WorldWideScience

Sample records for models results revealed

  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. VEMAP 1: Selected Model Results

    Data.gov (United States)

    National Aeronautics and Space Administration — The Vegetation/Ecosystem Modeling and Analysis Project (VEMAP) was a multi-institutional, international effort addressing the response of biogeography and...

  4. VEMAP 1: Selected Model Results

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: The Vegetation/Ecosystem Modeling and Analysis Project (VEMAP) was a multi-institutional, international effort addressing the response of biogeography and...

  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. 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

  7. 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.

  8. 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 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...... 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....

  9. The Danish national passenger modelModel specification and results

    DEFF Research Database (Denmark)

    Rich, Jeppe; Hansen, Christian Overgaard

    2016-01-01

    , 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...... function types and it is indicated that the spline-function provides a better description of the data. Results are also provided in the form of a back-casting exercise where the model is tested in a back-casting scenario to 2002....

  10. Sandfish numerical model reveals optimal swimming in sand

    Science.gov (United States)

    Maladen, Ryan; Ding, Yang; Kamor, Adam; Slatton, Andrew; Goldman, Daniel

    2009-11-01

    Motivated by experiment and theory examining the undulatory swimming of the sandfish lizard within granular media footnotetextMaladen et. al, Science, 325, 314, 2009, we study a numerical model of the sandfish as it swims within a validated soft sphere Molecular Dynamics granular media simulation. We hypothesize that features of its morphology and undulatory kinematics, and the granular media contribute to effective sand swimming. Our results agree with a resistive force model of the sandfish and show that speed and transport cost are optimized at a ratio of wave amplitude to wavelength of 0.2, irrespective of media properties and preparation. At this ratio, the entry of the animal into the media is fastest at an angle of 20^o, close to the angle of repose. We also find that the sandfish cross-sectional body shape reduces motion induced buoyancy within the granular media and that wave efficiency is sensitive to body-particle friction but independent of particle-particle friction.

  11. Multiplex model of mental lexicon reveals explosive learning in humans.

    Science.gov (United States)

    Stella, Massimo; Beckage, Nicole M; Brede, Markus; De Domenico, Manlio

    2018-02-02

    Word similarities affect language acquisition and use in a multi-relational way barely accounted for in the literature. We propose a multiplex network representation of this mental lexicon of word similarities as a natural framework for investigating large-scale cognitive patterns. Our representation accounts for semantic, taxonomic, and phonological interactions and it identifies a cluster of words which are used with greater frequency, are identified, memorised, and learned more easily, and have more meanings than expected at random. This cluster emerges around age 7 through an explosive transition not reproduced by null models. We relate this explosive emergence to polysemy - redundancy in word meanings. Results indicate that the word cluster acts as a core for the lexicon, increasing both lexical navigability and robustness to linguistic degradation. Our findings provide quantitative confirmation of existing conjectures about core structure in the mental lexicon and the importance of integrating multi-relational word-word interactions in psycholinguistic frameworks.

  12. 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.

  13. 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.

  14. 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

  15. Geometry of the Farallon Slab Revealed by Joint Interpretation of Wavefield Imaging and Tomography Results from the Earthscope Transportable Array

    Science.gov (United States)

    Pavlis, G. L.; Wang, Y.

    2015-12-01

    A significant number of P and S wave tomography models have been produced in the past decade using various subsets of data from the Earthscope USArray and different inversion algorithms. We focus here on published tomography results that span large portions of the final footprint of the USArray. We use 3D visualization techniques to search for common features in different tomography models. We also compare tomography results to features seen in our current generation wavefield images. Recent innovations of our plane wave migration method have yielded what is arguably the highest resolution image ever produced of the mantle in the vicinity of the transition zone. The new results reveal a rich collection of coherent, dipping structures seen throughout the upper mantle and transition zone. These dipping interfaces are judged significant according to a coherence metric. We treat these surfaces as strain markers to assess proposed models for geometry of the 3D geometry of the Farallon Slab under North America. We find the following geologic interpretations are well supported by independent results: 1. The old Farallon under eastern North America and below the base of transition zone is universally seen as a high velocity anomaly. 2. All results support a simple, 3D kinematic model of the updip limit of the Farallon slab window that follows a track from Cape Mendocino, across Nevada, and northern Arizona and New Mexico. 3. All models show a strong low-velocity mantle under the southwestern U.S. 4. A low-velocity features is universally seen related to the Yellowstone-Snake River system. Shorter wavelength features observed in different tomography models are inconsistent showing that the theme of this session is very important to understand what features are in current results are real. Isopach maps of the thickness of the transition show a systematic difference in transition zone thickness in the western and eastern US. The transition zone thickens in the eastern US in

  16. Revisiting Runoff Model Calibration: Airborne Snow Observatory Results Allow Improved Modeling Results

    Science.gov (United States)

    McGurk, B. J.; Painter, T. H.

    2014-12-01

    Deterministic snow accumulation and ablation simulation models are widely used by runoff managers throughout the world to predict runoff quantities and timing. Model fitting is typically based on matching modeled runoff volumes and timing with observed flow time series at a few points in the basin. In recent decades, sparse networks of point measurements of the mountain snowpacks have been available to compare with modeled snowpack, but the comparability of results from a snow sensor or course to model polygons of 5 to 50 sq. km is suspect. However, snowpack extent, depth, and derived snow water equivalent have been produced by the NASA/JPL Airborne Snow Observatory (ASO) mission for spring of 20013 and 2014 in the Tuolumne River basin above Hetch Hetchy Reservoir. These high-resolution snowpack data have exposed the weakness in a model calibration based on runoff alone. The U.S. Geological Survey's Precipitation Runoff Modeling System (PRMS) calibration that was based on 30-years of inflow to Hetch Hetchy produces reasonable inflow results, but modeled spatial snowpack location and water quantity diverged significantly from the weekly measurements made by ASO during the two ablation seasons. The reason is that the PRMS model has many flow paths, storages, and water transfer equations, and a calibrated outflow time series can be right for many wrong reasons. The addition of a detailed knowledge of snow extent and water content constrains the model so that it is a better representation of the actual watershed hydrology. The mechanics of recalibrating PRMS to the ASO measurements will be described, and comparisons in observed versus modeled flow for both a small subbasin and the entire Hetch Hetchy basin will be shown. The recalibrated model provided a bitter fit to the snowmelt recession, a key factor for water managers as they balance declining inflows with demand for power generation and ecosystem releases during the final months of snow melt runoff.

  17. 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)

  18. 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.

  19. 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

  20. Modeling and Field Results from Seismic Stimulation

    International Nuclear Information System (INIS)

    Majer, E.; Pride, S.; Lo, W.; Daley, T.; Nakagawa, Seiji; Sposito, Garrison; Roberts, P.

    2006-01-01

    Modeling the effect of seismic stimulation employing Maxwell-Boltzmann theory shows that the important component of stimulation is mechanical rather than fluid pressure effects. Modeling using Biot theory (two phases) shows that the pressure effects diffuse too quickly to be of practical significance. Field data from actual stimulation will be shown to compare to theory

  1. Mechanical models of sandfish locomotion reveal principles of high performance subsurface sand-swimming

    OpenAIRE

    Maladen, Ryan D.; Ding, Yang; Umbanhowar, Paul B.; Kamor, Adam; Goldman, Daniel I.

    2011-01-01

    We integrate biological experiment, empirical theory, numerical simulation and a physical model to reveal principles of undulatory locomotion in granular media. High-speed X-ray imaging of the sandfish lizard, Scincus scincus, in 3 mm glass particles shows that it swims within the medium without using its limbs by propagating a single-period travelling sinusoidal wave down its body, resulting in a wave efficiency, η, the ratio of its average forward speed to the wave speed, of approximately 0...

  2. Coupled Michigan MHD - Rice Convection Model Results

    Science.gov (United States)

    de Zeeuw, D.; Sazykin, S.; Wolf, D.; Gombosi, T.; Powell, K.

    2002-12-01

    A new high performance Rice Convection Model (RCM) has been coupled to the adaptive-grid Michigan MHD model (BATSRUS). This fully coupled code allows us to self-consistently simulate the physics in the inner and middle magnetosphere. A study will be presented of the basic characteristics of the inner and middle magnetosphere in the context of a single coupled-code run for idealized storm inputs. The analysis will include region-2 currents, shielding of the inner magnetosphere, partial ring currents, pressure distribution, magnetic field inflation, and distribution of pV^gamma.

  3. 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

  4. 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)

  5. Modeling clicks beyond the first result page

    NARCIS (Netherlands)

    Chuklin, A.; Serdyukov, P.; de Rijke, M.

    2013-01-01

    Most modern web search engines yield a list of documents of a fixed length (usually 10) in response to a user query. The next ten search results are usually available in one click. These documents either replace the current result page or are appended to the end. Hence, in order to examine more

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

    Science.gov (United States)

    Klein, Colin; Clutton, Peter; Polito, Vince

    2018-01-01

    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. PMID:29515501

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

    Science.gov (United States)

    Klein, Colin; Clutton, Peter; Polito, Vince

    2018-01-01

    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.

  8. 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.

  9. 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...

  10. 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.).

  11. Animal Model Reveals Potential Waterborne Transmission of Helicobacter pylori Infection.

    Science.gov (United States)

    Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2015-10-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.

  12. 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.

  13. Interactive Visualization and Navigation of Web Search Results Revealing Community Structures and Bridges

    OpenAIRE

    Sallaberry, Arnaud; Zaidi, Faraz; Pich, C.; Melançon, Guy

    2010-01-01

    International audience; With the information overload on the Internet, organization and visualization of web search results so as to facilitate faster access to information is a necessity. The classical methods present search results as an ordered list of web pages ranked in terms of relevance to the searched topic. Users thus have to scan text snippets or navigate through various pages before finding the required information. In this paper we present an interactive visualization system for c...

  14. 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.

  15. Pluto Revealed: First Results from the Historic 1st Fly-By Space Mission

    Science.gov (United States)

    Smith, Kimberly Ennico

    2015-01-01

    On July 14, 2015, after a 9.5 year trek across the solar system, NASAs New Horizons spacecraft successfully flew by the dwarf planet Pluto and its system of moons, taking imagery, spectra and in-situ particle data. Data obtained by New Horizons will address numerous outstanding questions on the geology and composition of Pluto and Charon, plus measurements of Plutos atmosphere, and provide revised understanding of the formation and evolution of Pluto and Charon and its smaller moons. This data set is an invaluable glimpse into the outer Third Zone of the Solar System. Data from the intense July 14th fly-by sequence will be downlinked to Earth over a period of 16 months, the duration set by the large data set (over 60 GBits), tempered by limited transmission bandwidth rates (1-2 kbps) and sharing the three 70m DSN assets. This presentation summarizes the New Horizons mission and early science results.

  16. 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.

  17. Clustering reveals limits of parameter identifiability in multi-parameter models of biochemical dynamics.

    Science.gov (United States)

    Nienałtowski, Karol; Włodarczyk, Michał; Lipniacki, Tomasz; Komorowski, Michał

    2015-09-29

    Compared to engineering or physics problems, dynamical models in quantitative biology typically depend on a relatively large number of parameters. Progress in developing mathematics to manipulate such multi-parameter models and so enable their efficient interplay with experiments has been slow. Existing solutions are significantly limited by model size. In order to simplify analysis of multi-parameter models a method for clustering of model parameters is proposed. It is based on a derived statistically meaningful measure of similarity between groups of parameters. The measure quantifies to what extend changes in values of some parameters can be compensated by changes in values of other parameters. The proposed methodology provides a natural mathematical language to precisely communicate and visualise effects resulting from compensatory changes in values of parameters. As a results, a relevant insight into identifiability analysis and experimental planning can be obtained. Analysis of NF-κB and MAPK pathway models shows that highly compensative parameters constitute clusters consistent with the network topology. The method applied to examine an exceptionally rich set of published experiments on the NF-κB dynamics reveals that the experiments jointly ensure identifiability of only 60% of model parameters. The method indicates which further experiments should be performed in order to increase the number of identifiable parameters. We currently lack methods that simplify broadly understood analysis of multi-parameter models. The introduced tools depict mutually compensative effects between parameters to provide insight regarding role of individual parameters, identifiability and experimental design. The method can also find applications in related methodological areas of model simplification and parameters estimation.

  18. Mechanical models of sandfish locomotion reveal principles of high performance subsurface sand-swimming.

    Science.gov (United States)

    Maladen, Ryan D; Ding, Yang; Umbanhowar, Paul B; Kamor, Adam; Goldman, Daniel I

    2011-09-07

    We integrate biological experiment, empirical theory, numerical simulation and a physical model to reveal principles of undulatory locomotion in granular media. High-speed X-ray imaging of the sandfish lizard, Scincus scincus, in 3 mm glass particles shows that it swims within the medium without using its limbs by propagating a single-period travelling sinusoidal wave down its body, resulting in a wave efficiency, η, the ratio of its average forward speed to the wave speed, of approximately 0.5. A resistive force theory (RFT) that balances granular thrust and drag forces along the body predicts η close to the observed value. We test this prediction against two other more detailed modelling approaches: a numerical model of the sandfish coupled to a discrete particle simulation of the granular medium, and an undulatory robot that swims within granular media. Using these models and analytical solutions of the RFT, we vary the ratio of undulation amplitude to wavelength (A/λ) and demonstrate an optimal condition for sand-swimming, which for a given A results from the competition between η and λ. The RFT, in agreement with the simulated and physical models, predicts that for a single-period sinusoidal wave, maximal speed occurs for A/λ ≈ 0.2, the same kinematics used by the sandfish.

  19. A Multi-Scale Model of Hepcidin Promoter Regulation Reveals Factors Controlling Systemic Iron Homeostasis

    Science.gov (United States)

    Muckenthaler, Martina U.; Legewie, Stefan

    2014-01-01

    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. PMID:24391488

  20. 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.

  1. Fibrinogen adsorption mechanisms at the gold substrate revealed by QCM-D measurements and RSA modeling.

    Science.gov (United States)

    Kubiak, Katarzyna; Adamczyk, Zbigniew; Cieśla, Michał

    2016-03-01

    Adsorption kinetics of fibrinogen at a gold substrate at various pHs was thoroughly studied using the QCM-D method. The experimental were interpreted in terms of theoretical calculations performed according to the random sequential adsorption model (RSA). In this way, the hydration functions and water factors of fibrinogen monolayers were quantitatively evaluated at various pHs. It was revealed that for the lower range of fibrinogen coverage the hydration function were considerably lower than previously obtained for the silica sensor [33]. The lower hydration of fibrinogen monolayers on the gold sensor was attributed to its higher roughness. However, for higher fibrinogen coverage the hydration functions for both sensors became identical exhibiting an universal behavior. By using the hydration functions, the fibrinogen adsorption/desorption runs derived from QCM-D measurements were converted to the Γd vs. the time relationships. This allowed to precisely determine the maximum coverage that varied between 1.6mgm(-2) at pH 3.5 and 4.5mgm(-2) at pH 7.4 (for ionic strength of 0.15M). These results agree with theoretical eRSA modeling and previous experimental data derived by using ellipsometry, OWLS and TIRF. Various fibrinogen adsorption mechanisms were revealed by exploiting the maximum coverage data. These results allow one to develop a method for preparing fibrinogen monolayers of well-controlled coverage and molecule orientation. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

    Science.gov (United States)

    Zhang, Xiuming; Mormino, Elizabeth C.; Sun, Nanbo; Sperling, Reisa A.; Sabuncu, Mert R.; Yeo, B. T. Thomas

    2016-01-01

    We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research. PMID:27702899

  3. Comparison of blade-strike modeling results with empirical data

    Energy Technology Data Exchange (ETDEWEB)

    Ploskey, Gene R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carlson, Thomas J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2004-03-01

    This study is the initial stage of further investigation into the dynamics of injury to fish during passage through a turbine runner. As part of the study, Pacific Northwest National Laboratory (PNNL) estimated the probability of blade strike, and associated injury, as a function of fish length and turbine operating geometry at two adjacent turbines in Powerhouse 1 of Bonneville Dam. Units 5 and 6 had identical intakes, stay vanes, wicket gates, and draft tubes, but Unit 6 had a new runner and curved discharge ring to minimize gaps between the runner hub and blades and between the blade tips and discharge ring. We used a mathematical model to predict blade strike associated with two Kaplan turbines and compared results with empirical data from biological tests conducted in 1999 and 2000. Blade-strike models take into consideration the geometry of the turbine blades and discharges as well as fish length, orientation, and distribution along the runner. The first phase of this study included a sensitivity analysis to consider the effects of difference in geometry and operations between families of turbines on the strike probability response surface. The analysis revealed that the orientation of fish relative to the leading edge of a runner blade and the location that fish pass along the blade between the hub and blade tip are critical uncertainties in blade-strike models. Over a range of discharges, the average prediction of injury from blade strike was two to five times higher than average empirical estimates of visible injury from shear and mechanical devices. Empirical estimates of mortality may be better metrics for comparison to predicted injury rates than other injury measures for fish passing at mid-blade and blade-tip locations.

  4. 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.

  5. Identifying habitats at risk: simple models can reveal complex ecosystem dynamics.

    Science.gov (United States)

    Maxwell, Paul S; Pitt, Kylie A; Olds, Andrew D; Rissik, David; Connolly, Rod M

    2015-03-01

    The relationship between ecological impact and ecosystem structure is often strongly nonlinear, so that small increases in impact levels can cause a disproportionately large response in ecosystem structure. Nonlinear ecosystem responses can be difficult to predict because locally relevant data sets can be difficult or impossible to obtain. Bayesian networks (BN) are an emerging tool that can help managers to define ecosystem relationships using a range of data types from comprehensive quantitative data sets to expert opinion. We show how a simple BN can reveal nonlinear dynamics in seagrass ecosystems using ecological relationships sourced from the literature. We first developed a conceptual diagram by cataloguing the ecological responses of seagrasses to a range of drivers and impacts. We used the conceptual diagram to develop a BN populated with values sourced from published studies. We then applied the BN to show that the amount of initial seagrass biomass has a mitigating effect on the level of impact a meadow can withstand without loss, and that meadow recovery can often require disproportionately large improvements in impact levels. This mitigating effect resulted in the middle ranges of impact levels having a wide likelihood of seagrass presence, a situation known as bistability. Finally, we applied the model in a case study to identify the risk of loss and the likelihood of recovery for the conservation and management of seagrass meadows in Moreton Bay, Queensland, Australia. We used the model to predict the likelihood of bistability in 23 locations in the Bay. The model predicted bistability in seven locations, most of which have experienced seagrass loss at some stage in the past 25 years providing essential information for potential future restoration efforts. Our results demonstrate the capacity of simple, flexible modeling tools to facilitate collation and synthesis of disparate information. This approach can be adopted in the initial stages of

  6. 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.

  7. Some results regarding the comparison of the Earth's atmospheric models

    Directory of Open Access Journals (Sweden)

    Šegan S.

    2005-01-01

    Full Text Available In this paper we examine air densities derived from our realization of aeronomic atmosphere models based on accelerometer measurements from satellites in a low Earth's orbit (LEO. Using the adapted algorithms we derive comparison parameters. The first results concerning the adjustment of the aeronomic models to the total-density model are given.

  8. 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.)

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

    Science.gov (United States)

    Huang, Sijia; Chong, Nicole; Lewis, Nathan E; Jia, Wei; Xie, Guoxiang; Garmire, Lana X

    2016-03-31

    More accurate diagnostic methods are pressingly needed to diagnose breast cancer, the most common malignant cancer in women worldwide. Blood-based metabolomics is a promising diagnostic method for breast cancer. However, many metabolic biomarkers are difficult to replicate among studies. We propose that higher-order functional representation of metabolomics data, such as pathway-based metabolomic features, can be used as robust biomarkers for breast cancer. Towards this, we have developed a new computational method that uses personalized pathway dysregulation scores for disease diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under the Curve, a receiver operating characteristic curve) of 0.968 and 0.934, sensitivities of 0.946 and 0.954, and specificities of 0.934 and 0.918. These two metabolomics-based pathway models are further validated by RNA-Seq-based TCGA (The Cancer Genome Atlas) breast cancer data, with AUCs of 0.995 and 0.993. 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. 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 diagnosis.

  10. Modelling of Yeast Mating Reveals Robustness Strategies for Cell-Cell Interactions.

    Directory of Open Access Journals (Sweden)

    Weitao Chen

    2016-07-01

    Full Text Available Mating of budding yeast cells is a model system for studying cell-cell interactions. Haploid yeast cells secrete mating pheromones that are sensed by the partner which responds by growing a mating projection toward the source. The two projections meet and fuse to form the diploid. Successful mating relies on precise coordination of dynamic extracellular signals, signaling pathways, and cell shape changes in a noisy background. It remains elusive how cells mate accurately and efficiently in a natural multi-cell environment. Here we present the first stochastic model of multiple mating cells whose morphologies are driven by pheromone gradients and intracellular signals. Our novel computational framework encompassed a moving boundary method for modeling both a-cells and α-cells and their cell shape changes, the extracellular diffusion of mating pheromones dynamically coupled with cell polarization, and both external and internal noise. Quantification of mating efficiency was developed and tested for different model parameters. Computer simulations revealed important robustness strategies for mating in the presence of noise. These strategies included the polarized secretion of pheromone, the presence of the α-factor protease Bar1, and the regulation of sensing sensitivity; all were consistent with data in the literature. In addition, we investigated mating discrimination, the ability of an a-cell to distinguish between α-cells either making or not making α-factor, and mating competition, in which multiple a-cells compete to mate with one α-cell. Our simulations were consistent with previous experimental results. Moreover, we performed a combination of simulations and experiments to estimate the diffusion rate of the pheromone a-factor. In summary, we constructed a framework for simulating yeast mating with multiple cells in a noisy environment, and used this framework to reproduce mating behaviors and to identify strategies for robust cell

  11. 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.

  12. Coordinating Role of RXRα in Downregulating Hepatic Detoxification during Inflammation Revealed by Fuzzy-Logic Modeling.

    Directory of Open Access Journals (Sweden)

    Roland Keller

    2016-01-01

    Full Text Available During various inflammatory processes circulating cytokines including IL-6, IL-1β, and TNFα elicit a broad and clinically relevant impairment of hepatic detoxification that is based on the simultaneous downregulation of many drug metabolizing enzymes and transporter genes. To address the question whether a common mechanism is involved we treated human primary hepatocytes with IL-6, the major mediator of the acute phase response in liver, and characterized acute phase and detoxification responses in quantitative gene expression and (phospho-proteomics data sets. Selective inhibitors were used to disentangle the roles of JAK/STAT, MAPK, and PI3K signaling pathways. A prior knowledge-based fuzzy logic model comprising signal transduction and gene regulation was established and trained with perturbation-derived gene expression data from five hepatocyte donors. Our model suggests a greater role of MAPK/PI3K compared to JAK/STAT with the orphan nuclear receptor RXRα playing a central role in mediating transcriptional downregulation. Validation experiments revealed a striking similarity of RXRα gene silencing versus IL-6 induced negative gene regulation (rs = 0.79; P<0.0001. These results concur with RXRα functioning as obligatory heterodimerization partner for several nuclear receptors that regulate drug and lipid metabolism.

  13. Steel Containment Vessel Model Test: Results and Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Costello, J.F.; Hashimote, T.; Hessheimer, M.F.; Luk, V.K.

    1999-03-01

    A high pressure test of the steel containment vessel (SCV) model was conducted on December 11-12, 1996 at Sandia National Laboratories, Albuquerque, NM, USA. The test model is a mixed-scaled model (1:10 in geometry and 1:4 in shell thickness) of an improved Mark II boiling water reactor (BWR) containment. A concentric steel contact structure (CS), installed over the SCV model and separated at a nominally uniform distance from it, provided a simplified representation of a reactor shield building in the actual plant. The SCV model and contact structure were instrumented with strain gages and displacement transducers to record the deformation behavior of the SCV model during the high pressure test. This paper summarizes the conduct and the results of the high pressure test and discusses the posttest metallurgical evaluation results on specimens removed from the SCV model.

  14. 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.

  15. 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.

  16. 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.

  17. Results on the symmetries of integrable fermionic models on chains

    International Nuclear Information System (INIS)

    Dolcini, F.; Montorsi, A.

    2001-01-01

    We investigate integrable fermionic models within the scheme of the graded quantum inverse scattering method, and prove that any symmetry imposed on the solution of the Yang-Baxter equation reflects on the constants of motion of the model; generalizations with respect to known results are discussed. This theorem is shown to be very effective when combined with the polynomial R-matrix technique (PRT): we apply both of them to the study of the extended Hubbard models, for which we find all the subcases enjoying several kinds of (super)symmetries. In particular, we derive a geometrical construction expressing any gl(2,1)-invariant model as a linear combination of EKS and U-supersymmetric models. Further, we use the PRT to obtain 32 integrable so(4)-invariant models. By joint use of the Sutherland's species technique and η-pairs construction we propose a general method to derive their physical features, and we provide some explicit results

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Enlarging the collective model of household behaviour: a revealed preference analysis

    OpenAIRE

    d'Aspremont-Lynden, Claude; Dos Santos Ferreira, Rodolphe

    2017-01-01

    We use a comprehensive model of strategic household behaviour in which the spouses' expenditure on each public good is decomposed into autonomous spending and coordinated spending à la Lindahl. We obtain a continuum of semi-cooperative regimes parameterized by the relative weights put on autonomous spending, by each spouse and for each public good, nesting full cooperative and non-cooperative regimes as limit cases. Testing is approached through revealed preference analysis, by looking for ra...

  3. Convergence models for cylindrical caverns and the resulting ground subsidence

    Energy Technology Data Exchange (ETDEWEB)

    Haupt, W.; Sroka, A.; Schober, F.

    1983-02-01

    The authors studied the effects of different convergence characteristics on surface soil response for the case of narrow, cylindrical caverns. Maximum ground subsidence - a parameter of major importance in this type of cavern - was calculated for different convergence models. The models were established without considering the laws of rock mechanics and rheology. As a result, two limiting convergence models were obtained that describe an interval of expectation into which all other models fit. This means that ground movements over cylindrical caverns can be calculated ''on the safe side'', correlating the trough resulting on the surface with the convergence characterisitcs of the cavern. Among other applications, the method thus permits monitoring of caverns.

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

    DEFF Research Database (Denmark)

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

    . However, recent developments in numerical weather prediction (NWP) include probabilistic forecasting techniques, which can be utilised also for atmospheric dispersion models. The ensemble statistical methods developed and applied to NWP models aim at describing the inherent uncertainties......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...... of the meteorological model results. These uncertainties stem from e.g. limits in meteorological obser-vations used to initialise meteorological forecast series. By perturbing the initial state of an NWP model run in agreement with the available observa-tional data, an ensemble of meteorological forecasts is produced...

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

    DEFF Research Database (Denmark)

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

    ’ 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......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...... 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...

  6. The 2013 European Seismic Hazard Model: key components and results

    OpenAIRE

    Jochen Woessner; Danciu Laurentiu; Domenico Giardini; Helen Crowley; Fabrice Cotton; G. Grünthal; Gianluca Valensise; Ronald Arvidsson; Roberto Basili; Mine Betül Demircioglu; Stefan Hiemer; Carlo Meletti; Roger W. Musson; Andrea N. Rovida; Karin Sesetyan

    2015-01-01

    The 2013 European Seismic Hazard Model (ESHM13) results from a community-based probabilistic seismic hazard assessment supported by the EU-FP7 project “Seismic Hazard Harmonization in Europe” (SHARE, 2009–2013). The ESHM13 is a consistent seismic hazard model for Europe and Turkey which overcomes the limitation of national borders and includes a through quantification of the uncertainties. It is the first completed regional effort contributing to the “Global Earthquake Model” initiative. It m...

  7. Hydroclimatology of the Nile: results from a regional climate model

    Directory of Open Access Journals (Sweden)

    Y. A. Mohamed

    2005-01-01

    Full Text Available This paper presents the result of the regional coupled climatic and hydrologic model of the Nile Basin. For the first time the interaction between the climatic processes and the hydrological processes on the land surface have been fully coupled. The hydrological model is driven by the rainfall and the energy available for evaporation generated in the climate model, and the runoff generated in the catchment is again routed over the wetlands of the Nile to supply moisture for atmospheric feedback. The results obtained are quite satisfactory given the extremely low runoff coefficients in the catchment. The paper presents the validation results over the sub-basins: Blue Nile, White Nile, Atbara river, the Sudd swamps, and the Main Nile for the period 1995 to 2000. Observational datasets were used to evaluate the model results including radiation, precipitation, runoff and evaporation data. The evaporation data were derived from satellite images over a major part of the Upper Nile. Limitations in both the observational data and the model are discussed. It is concluded that the model provides a sound representation of the regional water cycle over the Nile. The sources of atmospheric moisture to the basin, and location of convergence/divergence fields could be accurately illustrated. The model is used to describe the regional water cycle in the Nile basin in terms of atmospheric fluxes, land surface fluxes and land surface-climate feedbacks. The monthly moisture recycling ratio (i.e. locally generated/total precipitation over the Nile varies between 8 and 14%, with an annual mean of 11%, which implies that 89% of the Nile water resources originates from outside the basin physical boundaries. The monthly precipitation efficiency varies between 12 and 53%, and the annual mean is 28%. The mean annual result of the Nile regional water cycle is compared to that of the Amazon and the Mississippi basins.

  8. Results of a model for premixed combustion oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Janus, M.C.; Richards, G.A.

    1996-09-01

    Combustion oscillations are receiving renewed research interest due to increasing use of lean premix (LPM) combustion to gas turbines. A simple, nonlinear model for premixed combustion is described in this paper. The model was developed to help explain specific experimental observations and to provide guidance for development of active control schemes based on nonlinear concepts. The model can be used to quickly examine instability trends associated with changes in equivalence ratio, mass flow rate, geometry, ambient conditions, etc. The model represents the relevant processes occurring in a fuel nozzle and combustor which are analogous to current LPM turbine combustors. Conservation equations for the fuel nozzle and combustor are developed from simple control volume analysis, providing a set of ordinary differential equations that can be solved on a personal computer. Combustion is modeled as a stirred reactor, with a bimolecular reaction rate between fuel and air. A variety of numerical results and comparisons to experimental data are presented to demonstrate the utility of the model. Model results are used to understand the fundamental mechanisms which drive combustion oscillations, effects of inlet air temperature and nozzle geometry on instability, and effectiveness of open loop control schemes.

  9. Summary of FY15 results of benchmark modeling activities

    Energy Technology Data Exchange (ETDEWEB)

    Arguello, J. Guadalupe [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    Sandia is participating in the third phase of an is a contributing partner to a U.S.-German "Joint Project" entitled "Comparison of current constitutive models and simulation procedures on the basis of model calculations of the thermo-mechanical behavior and healing of rock salt." The first goal of the project is to check the ability of numerical modeling tools to correctly describe the relevant deformation phenomena in rock salt under various influences. Achieving this goal will lead to increased confidence in the results of numerical simulations related to the secure storage of radioactive wastes in rock salt, thereby enhancing the acceptance of the results. These results may ultimately be used to make various assertions regarding both the stability analysis of an underground repository in salt, during the operating phase, and the long-term integrity of the geological barrier against the release of harmful substances into the biosphere, in the post-operating phase.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Marginal production in the Gulf of Mexico - II. Model results

    International Nuclear Information System (INIS)

    Kaiser, Mark J.; Yu, Yunke

    2010-01-01

    In the second part of this two-part article on marginal production in the Gulf of Mexico, we estimate the number of committed assets in water depth less than 1000 ft that are expected to be marginal over a 60-year time horizon. We compute the expected quantity and value of the production and gross revenue streams of the gulf's committed asset inventory circa. January 2007 using a probabilistic model framework. Cumulative hydrocarbon production from the producing inventory is estimated to be 1056 MMbbl oil and 13.3 Tcf gas. Marginal production from the committed asset inventory is expected to contribute 4.1% of total oil production and 5.4% of gas production. A meta-evaluation procedure is adapted to present the results of sensitivity analysis. Model results are discussed along with a description of the model framework and limitations of the analysis. (author)

  15. Marginal production in the Gulf of Mexico - II. Model results

    Energy Technology Data Exchange (ETDEWEB)

    Kaiser, Mark J.; Yu, Yunke [Center for Energy Studies, Louisiana State University, Baton Rouge, LA 70803 (United States)

    2010-08-15

    In the second part of this two-part article on marginal production in the Gulf of Mexico, we estimate the number of committed assets in water depth less than 1000 ft that are expected to be marginal over a 60-year time horizon. We compute the expected quantity and value of the production and gross revenue streams of the gulf's committed asset inventory circa. January 2007 using a probabilistic model framework. Cumulative hydrocarbon production from the producing inventory is estimated to be 1056 MMbbl oil and 13.3 Tcf gas. Marginal production from the committed asset inventory is expected to contribute 4.1% of total oil production and 5.4% of gas production. A meta-evaluation procedure is adapted to present the results of sensitivity analysis. Model results are discussed along with a description of the model framework and limitations of the analysis. (author)

  16. Structural Model of RNA Polymerase II Elongation Complex with Complete Transcription Bubble Reveals NTP Entry Routes.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    2015-07-01

    Full Text Available The RNA polymerase II (Pol II is a eukaryotic enzyme that catalyzes the synthesis of the messenger RNA using a DNA template. Despite numerous biochemical and biophysical studies, it remains elusive whether the "secondary channel" is the only route for NTP to reach the active site of the enzyme or if the "main channel" could be an alternative. On this regard, crystallographic structures of Pol II have been extremely useful to understand the structural basis of transcription, however, the conformation of the unpaired non-template DNA part of the full transcription bubble (TB is still unknown. Since diffusion routes of the nucleoside triphosphate (NTP substrate through the main channel might overlap with the TB region, gaining structural information of the full TB is critical for a complete understanding of Pol II transcription process. In this study, we have built a structural model of Pol II with a complete transcription bubble based on multiple sources of existing structural data and used Molecular Dynamics (MD simulations together with structural analysis to shed light on NTP entry pathways. Interestingly, we found that although both channels have enough space to allow NTP loading, the percentage of MD conformations containing enough space for NTP loading through the secondary channel is twice higher than that of the main channel. Further energetic study based on MD simulations with NTP loaded in the channels has revealed that the diffusion of the NTP through the main channel is greatly disfavored by electrostatic repulsion between the NTP and the highly negatively charged backbones of nucleotides in the non-template DNA strand. Taken together, our results suggest that the secondary channel is the major route for NTP entry during Pol II transcription.

  17. 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.

  18. Fuel assembly bow: analytical modeling and resulting design improvements

    International Nuclear Information System (INIS)

    Stabel, J.; Huebsch, H.P.

    1995-01-01

    The bowing of fuel assemblies may result in a contact between neighbouring fuel assemblies and in connection with a vibration to a resulting wear or even perforation at the corners of the spacer grids of neighbouring assemblies. Such events allowed reinsertion of a few fuel assemblies in Germany only after spacer repair. In order to identify the most sensitive parameters causing the observed bowing of fuel assemblies a new computer model was develop which takes into a account the highly nonlinear behaviour of the interaction between fuel rods and spacers. As a result of the studies performed with this model, design improvements such as a more rigid connection between guide thimbles and spacer grids, could be defined. First experiences with this improved design show significantly better fuel behaviour. (author). 5 figs., 1 tabs

  19. 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.

  20. Modeling vertical loads in pools resulting from fluid injection. [BWR

    Energy Technology Data Exchange (ETDEWEB)

    Lai, W.; McCauley, E.W.

    1978-06-15

    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 /sup 1///sub 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.

  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. Some results on the dynamics generated by the Bazykin model

    Directory of Open Access Journals (Sweden)

    Georgescu, R M

    2006-07-01

    Full Text Available A predator-prey model formerly proposed by A. Bazykin et al. [Bifurcation diagrams of planar dynamical systems (1985] is analyzed in the case when two of the four parameters are kept fixed. Dynamics and bifurcation results are deduced by using the methods developed by D. K. Arrowsmith and C. M. Place [Ordinary differential equations (1982], S.-N. Chow et al. [Normal forms and bifurcation of planar fields (1994], Y. A. Kuznetsov [Elements of applied bifurcation theory (1998], and A. Georgescu [Dynamic bifurcation diagrams for some models in economics and biology (2004]. The global dynamic bifurcation diagram is constructed and graphically represented. The biological interpretation is presented, too.

  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. 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.

  6. Interaction between subducting plates: results from numerical and analogue modeling

    Science.gov (United States)

    Kiraly, Agnes; Capitanio, Fabio A.; Funiciello, Francesca; Faccenna, Claudio

    2016-04-01

    The tectonic setting of the Alpine-Mediterranean area is achieved during the late Cenozoic subduction, collision and suturing of several oceanic fragments and continental blocks. In this stage, processes such as interactions among subducting slabs, slab migrations and related mantle flow played a relevant role on the resulting tectonics. Here, we use numerical models to first address the mantle flow characteristic in 3D. During the subduction of a single plate the strength of the return flow strongly depends on the slab pull force, that is on the plate's buoyancy, however the physical properties of the slab, such as density, viscosity or width, do not affect largely the morphology of the toroidal cell. Instead, dramatic effects on the geometry and the dynamics of the toroidal cell result in models where the thickness of the mantle is varied. The vertical component of the vorticity vector is used to define the characteristic size of the toroidal cell, which is ~1.2-1.3 times the mantle depth. This latter defines the range of viscous stress propagation through the mantle and consequent interactions with other slabs. We thus further investigate on this setup where two separate lithospheric plates subduct in opposite sense, developing opposite polarities and convergent slab retreat, and model different initial sideways distance between the plates. The stress profiles in time illustrate that the plates interacts when slabs are at the characteristic distance and the two slabs toroidal cells merge. Increased stress and delayed slab migrations are the results. Analogue models of double-sided subduction show similar maximum distance and allow testing the additional role of stress propagated through the plates. We use a silicon plate subducting on its two opposite margins, which is either homogeneous or comprises oceanic and continental lithospheres, differing in buoyancy. The modeling results show that the double-sided subduction is strongly affected by changes in plate

  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. Workshop to transfer VELMA watershed model results to ...

    Science.gov (United States)

    An EPA Western Ecology Division (WED) watershed modeling team has been working with the Snoqualmie Tribe Environmental and Natural Resources Department to develop VELMA watershed model simulations of the effects of historical and future restoration and land use practices on streamflow, stream temperature, and other habitat characteristics affecting threatened salmon populations in the 100 square mile Tolt River watershed in Washington state. To date, the WED group has fully calibrated the watershed model to simulate Tolt River flows with a high degree of accuracy under current and historical conditions and practices, and is in the process of simulating long-term responses to specific watershed restoration practices conducted by the Snoqualmie Tribe and partners. On July 20-21 WED Researchers Bob McKane, Allen Brookes and ORISE Fellow Jonathan Halama will be attending a workshop at the Tolt River site in Carnation, WA, to present and discuss modeling results with the Snoqualmie Tribe and other Tolt River watershed stakeholders and land managers, including the Washington Departments of Ecology and Natural Resources, U.S. Forest Service, City of Seattle, King County, and representatives of the Northwest Indian Fisheries Commission. The workshop is being co-organized by the Snoqualmie Tribe, EPA Region 10 and WED. The purpose of this 2-day workshop is two-fold. First, on Day 1, the modeling team will perform its second site visit to the watershed, this time focus

  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. Some results on hyperscaling in the 3D Ising model

    Energy Technology Data Exchange (ETDEWEB)

    Baker, G.A. Jr. [Los Alamos National Lab., NM (United States). Theoretical Div.; Kawashima, Naoki [Univ. of Tokyo (Japan). Dept. of Physics

    1995-09-01

    The authors review exact studies on finite-sized 2 dimensional Ising models and show that the point for an infinite-sized model at the critical temperature is a point of nonuniform approach in the temperature-size plane. They also illuminate some strong effects of finite-size on quantities which do not diverge at the critical point. They then review Monte Carlo studies for 3 dimensional Ising models of various sizes (L = 2--100) at various temperatures. From these results they find that the data for the renormalized coupling constant collapses nicely when plotted against the correlation length, determined in a system of edge length L, divided by L. They also find that {zeta}{sub L}/L {ge} 0.26 is definitely too large for reliable studies of the critical value, g*, of the renormalized coupling constant. They have reasonable evidence that {zeta}{sub L}/L {approx} 0.1 is adequate for results that are within one percent of those for the infinite system size. On this basis, they have conducted a series of Monte Carlo calculations with this condition imposed. These calculations were made practical by the development of improved estimators for use in the Swendsen-Wang cluster method. The authors found from these results, coupled with a reversed limit computation (size increases with the temperature fixed at the critical temperature), that g* > 0, although there may well be a sharp downward drop in g as the critical temperature is approached in accord with the predictions of series analysis. The results support the validity of hyperscaling in the 3 dimensional Ising model.

  11. Presenting results of software model checker via debugging interface

    OpenAIRE

    Kohan, Tomáš

    2012-01-01

    Title: Presenting results of software model checker via debugging interface Author: Tomáš Kohan Department: Department of Software Engineering Supervisor of the master thesis: RNDr. Ondřej Šerý, Ph.D., Department of Distributed and Dependable Systems Abstract: This thesis is devoted to design and implementation of the new debugging interface of the Java PathFinder application. As a suitable inte- face container was selected the Eclipse development environment. The created interface should vis...

  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. Challenges in validating model results for first year ice

    Science.gov (United States)

    Melsom, Arne; Eastwood, Steinar; Xie, Jiping; Aaboe, Signe; Bertino, Laurent

    2017-04-01

    In order to assess the quality of model results for the distribution of first year ice, a comparison with a product based on observations from satellite-borne instruments has been performed. Such a comparison is not straightforward due to the contrasting algorithms that are used in the model product and the remote sensing product. The implementation of the validation is discussed in light of the differences between this set of products, and validation results are presented. The model product is the daily updated 10-day forecast from the Arctic Monitoring and Forecasting Centre in CMEMS. The forecasts are produced with the assimilative ocean prediction system TOPAZ. Presently, observations of sea ice concentration and sea ice drift are introduced in the assimilation step, but data for sea ice thickness and ice age (or roughness) are not included. The model computes the age of the ice by recording and updating the time passed after ice formation as sea ice grows and deteriorates as it is advected inside the model domain. Ice that is younger than 365 days is classified as first year ice. The fraction of first-year ice is recorded as a tracer in each grid cell. The Ocean and Sea Ice Thematic Assembly Centre in CMEMS redistributes a daily product from the EUMETSAT OSI SAF of gridded sea ice conditions which include "ice type", a representation of the separation of regions between those infested by first year ice, and those infested by multi-year ice. The ice type is parameterized based on data for the gradient ratio GR(19,37) from SSMIS observations, and from the ASCAT backscatter parameter. This product also includes information on ambiguity in the processing of the remote sensing data, and the product's confidence level, which have a strong seasonal dependency.

  14. 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.

  15. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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 {times} 10{sup {minus}5} and the annual probability of flooding associated with loss of spent fuel pool cooling scenarios is 1 {times} 10{sup {minus}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.

  17. 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.

  18. 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

  19. 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

    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......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...

  20. 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

  1. Impact Flash Physics: Modeling and Comparisons With Experimental Results

    Science.gov (United States)

    Rainey, E.; Stickle, A. M.; Ernst, C. M.; Schultz, P. H.; Mehta, N. L.; Brown, R. C.; Swaminathan, P. K.; Michaelis, C. H.; Erlandson, R. E.

    2015-12-01

    horizontal. High-speed radiometer measurements were made of the time-dependent impact flash at wavelengths of 350-1100 nm. We will present comparisons between these measurements and the output of APL's model. The results of this validation allow us to determine basic relationships between observed optical signatures and impact conditions.

  2. 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.

  3. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.

    Science.gov (United States)

    Schur, Florian K M; Obr, Martin; Hagen, Wim J H; Wan, William; Jakobi, Arjen J; Kirkpatrick, Joanna M; Sachse, Carsten; Kräusslich, Hans-Georg; Briggs, John A G

    2016-07-29

    Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs. We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra- and intermolecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease. We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1. Copyright © 2016, American Association for the Advancement of Science.

  4. Complex patterns of divergence among green-sensitive (RH2a African cichlid opsins revealed by Clade model analyses

    Directory of Open Access Journals (Sweden)

    Weadick Cameron J

    2012-10-01

    Full Text Available Abstract Background Gene duplications play an important role in the evolution of functional protein diversity. Some models of duplicate gene evolution predict complex forms of paralog divergence; orthologous proteins may diverge as well, further complicating patterns of divergence among and within gene families. Consequently, studying the link between protein sequence evolution and duplication requires the use of flexible substitution models that can accommodate multiple shifts in selection across a phylogeny. Here, we employed a variety of codon substitution models, primarily Clade models, to explore how selective constraint evolved following the duplication of a green-sensitive (RH2a visual pigment protein (opsin in African cichlids. Past studies have linked opsin divergence to ecological and sexual divergence within the African cichlid adaptive radiation. Furthermore, biochemical and regulatory differences between the RH2aα and RH2aβ paralogs have been documented. It thus seems likely that selection varies in complex ways throughout this gene family. Results Clade model analysis of African cichlid RH2a opsins revealed a large increase in the nonsynonymous-to-synonymous substitution rate ratio (ω following the duplication, as well as an even larger increase, one consistent with positive selection, for Lake Tanganyikan cichlid RH2aβ opsins. Analysis using the popular Branch-site models, by contrast, revealed no such alteration of constraint. Several amino acid sites known to influence spectral and non-spectral aspects of opsin biochemistry were found to be evolving divergently, suggesting that orthologous RH2a opsins may vary in terms of spectral sensitivity and response kinetics. Divergence appears to be occurring despite intronic gene conversion among the tandemly-arranged duplicates. Conclusions Our findings indicate that variation in selective constraint is associated with both gene duplication and divergence among orthologs in African

  5. Cooperative Metabolism in a Three-Partner Insect-Bacterial Symbiosis Revealed by Metabolic Modeling.

    Science.gov (United States)

    Ankrah, Nana Y D; Luan, Junbo; Douglas, Angela E

    2017-08-01

    An important factor determining the impact of microbial symbionts on their animal hosts is the balance between the cost of nutrients consumed by the symbionts and the benefit of nutrients released back to the host, but the quantitative significance of nutrient exchange in symbioses involving multiple microbial partners has rarely been addressed. In this study on the association between two intracellular bacterial symbionts, " Candidatus Portiera aleyrodidarum" and " Candidatus Hamiltonella defensa," and their animal host, the whitefly Bemisia tabaci , we apply metabolic modeling to investigate host-symbiont nutrient exchange. Our in silico analysis revealed that >60% of the essential amino acids and related metabolites synthesized by " Candidatus Portiera aleyrodidarum" are utilized by the host, including a substantial contribution of nitrogen recycled from host nitrogenous waste, and that these interactions are required for host growth. In contrast, " Candidatus Hamiltonella defensa" retains most or all of the essential amino acids and B vitamins that it is capable of synthesizing. Furthermore, " Candidatus Hamiltonella defensa" suppresses host growth in silico by competition with " Candidatus Portiera aleyrodidarum" for multiple host nutrients, by suppressing " Candidatus Portiera aleyrodidarum" growth and metabolic function, and also by consumption of host nutrients that would otherwise be allocated to host growth. The interpretation from these modeling outputs that " Candidatus Hamiltonella defensa" is a nutritional parasite could not be inferred reliably from gene content alone but requires consideration of constraints imposed by the structure of the metabolic network. Furthermore, these quantitative models offer precise predictions for future experimental study and the opportunity to compare the functional organization of metabolic networks in different symbioses. IMPORTANCE The metabolic functions of unculturable intracellular bacteria with much reduced

  6. Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency.

    Science.gov (United States)

    Theodoris, Christina V; Li, Molong; White, Mark P; Liu, Lei; He, Daniel; Pollard, Katherine S; Bruneau, Benoit G; Srivastava, Deepak

    2015-03-12

    The mechanisms by which transcription factor haploinsufficiency alters the epigenetic and transcriptional landscape in human cells to cause disease are unknown. Here, we utilized human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) to show that heterozygous nonsense mutations in NOTCH1 that cause aortic valve calcification disrupt the epigenetic architecture, resulting in derepression of latent pro-osteogenic and -inflammatory gene networks. Hemodynamic shear stress, which protects valves from calcification in vivo, activated anti-osteogenic and anti-inflammatory networks in NOTCH1(+/+), but not NOTCH1(+/-), iPSC-derived ECs. NOTCH1 haploinsufficiency altered H3K27ac at NOTCH1-bound enhancers, dysregulating downstream transcription of more than 1,000 genes involved in osteogenesis, inflammation, and oxidative stress. Computational predictions of the disrupted NOTCH1-dependent gene network revealed regulatory nodes that, when modulated, restored the network toward the NOTCH1(+/+) state. Our results highlight how alterations in transcription factor dosage affect gene networks leading to human disease and reveal nodes for potential therapeutic intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Study results of picking high amplitude reflectors in turbidite channel to reveal detail of methane hydrate concentrated zone

    Energy Technology Data Exchange (ETDEWEB)

    Shimoda, N.; Saeki, T.; Inamori, T.; Kobayashi, T.; Fujii, T. [Japan Oil, Gas and Metals National Corp., Mihama-ku, Chiba (Japan). Technology Research Center

    2008-07-01

    Bottom simulating reflectors are found extensively in the eastern Nankai Trough. BSR is considered as a bottom of methane hydrate bearing sediments. High resolution three-dimensional seismic surveys were conducted in 2002 and a multi-well drilling campaign was executed in 2004. This paper discussed the resource potential of methane hydrate in this area. The paper discussed an evaluation of more than 10 methane hydrate concentrated zones in the Nankai Trough. Methane hydrated concentrated zones in this area are roughly classified into 2 types of turbidite sedimentary facies from the seismic geomorphological point of view known as lobe and channel. This paper attempted to interpret a detailed structure of a channel type methane hydrate concentrated zone. High amplitude reflector patches may indicate sand dominated bodies with high methane hydrate concentration. It was concluded that picked reflector patches demonstrated that the methane hydrate concentrated zone was biforked at a lower current area. Detailed observations also revealed that the methane hydrate concentrated zone was developed in a channel complex of which fluid migration was slowly shifted.

  8. 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

  9. 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

  10. Position-sensitive transition edge sensor modeling and results

    Energy Technology Data Exchange (ETDEWEB)

    Hammock, Christina E-mail: chammock@milkyway.gsfc.nasa.gov; Figueroa-Feliciano, Enectali; Apodaca, Emmanuel; Bandler, Simon; Boyce, Kevin; Chervenak, Jay; Finkbeiner, Fred; Kelley, Richard; Lindeman, Mark; Porter, Scott; Saab, Tarek; Stahle, Caroline

    2004-03-11

    We report the latest design and experimental results for a Position-Sensitive Transition-Edge Sensor (PoST). The PoST is motivated by the desire to achieve a larger field-of-view without increasing the number of readout channels. A PoST consists of a one-dimensional array of X-ray absorbers connected on each end to a Transition Edge Sensor (TES). Position differentiation is achieved through a comparison of pulses between the two TESs and X-ray energy is inferred from a sum of the two signals. Optimizing such a device involves studying the available parameter space which includes device properties such as heat capacity and thermal conductivity as well as TES read-out circuitry parameters. We present results for different regimes of operation and the effects on energy resolution, throughput, and position differentiation. Results and implications from a non-linear model developed to study the saturation effects unique to PoSTs are also presented.

  11. Spatial Structure of a Braided River: Metric Resolution Hydrodynamic Modeling Reveals What SWOT Might See

    Science.gov (United States)

    Schubert, J.; Sanders, B. F.; Andreadis, K.

    2013-12-01

    The Surface Water and Ocean Topography (SWOT) mission, currently under study by NASA (National Aeronautics and Space Administration) and CNES (Centre National d'Etudes Spatiales), is designed to provide global spatial measurements of surface water properties at resolutions better than 10 m and with centimetric accuracy. The data produced by SWOT will include irregularly spaced point clouds of the water surface height, with point spacings from roughly 2-50 m depending on a point's location within SWOT's swath. This could offer unprecedented insight into the spatial structure of rivers. Features that may be resolved include backwater profiles behind dams, drawdown profiles, uniform flow sections, critical flow sections, and even riffle-pool flow structures. In the event that SWOT scans a river during a major flood, it becomes possible to delineate the limits of the flood as well as the spatial structure of the water surface elevation, yielding insight into the dynamic interaction of channels and flood plains. The Platte River in Nebraska, USA, is a braided river with a width and slope of approximately 100 m and 100 cm/km, respectively. A 1 m resolution Digital Terrain Model (DTM) of the river basin, based on airborne lidar collected during low-flow conditions, was used to parameterize a two-dimensional, variable resolution, unstructured grid, hydrodynamic model that uses 3 m resolution triangles in low flow channels and 10 m resolution triangles in the floodplain. Use of a fine resolution mesh guarantees that local variability in topography is resolved, and after applying the hydrodynamic model, the effects of topographic variability are expressed as variability in the water surface height, depth-averaged velocity and flow depth. Flow is modeled over a reach length of 10 km for multi-day durations to capture both frequent (diurnal variations associated with regulated flow) and infrequent (extreme flooding) flow phenomena. Model outputs reveal a number of interesting

  12. Differential chromosome conformations as hallmarks of cellular identity revealed by mathematical polymer modeling.

    Directory of Open Access Journals (Sweden)

    Imen Lassadi

    2015-06-01

    Full Text Available Inherently dynamic, chromosomes adopt many different conformations in response to DNA metabolism. Models of chromosome organization in the yeast nucleus obtained from genome-wide chromosome conformation data or biophysical simulations provide important insights into the average behavior but fail to reveal features from dynamic or transient events that are only visible in a fraction of cells at any given moment. We developed a method to determine chromosome conformation from relative positions of three fluorescently tagged DNA in living cells imaged in 3D. Cell type specific chromosome folding properties could be assigned based on positional combinations between three loci on yeast chromosome 3. We determined that the shorter left arm of chromosome 3 is extended in MATα cells, but can be crumpled in MATa cells. Furthermore, we implemented a new mathematical model that provides for the first time an estimate of the relative physical constraint of three linked loci related to cellular identity. Variations in this estimate allowed us to predict functional consequences from chromatin structural alterations in asf1 and recombination enhancer deletion mutant cells. The computational method is applicable to identify and characterize dynamic chromosome conformations in any cell type.

  13. 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

  14. Combining experimental and mathematical modeling to reveal mechanisms of macrophage-dependent left ventricular remodeling

    Directory of Open Access Journals (Sweden)

    Dai Qiuxia

    2011-05-01

    Full Text Available Abstract Background Progressive remodeling of the left ventricle (LV following myocardial infarction (MI can lead to congestive heart failure, but the underlying initiation factors remain poorly defined. The objective of this study, accordingly, was to determine the key factors and elucidate the regulatory mechanisms of LV remodeling using integrated computational and experimental approaches. Results By examining the extracellular matrix (ECM gene expression and plasma analyte levels in C57/BL6J mice LV post-MI and ECM gene responses to transforming growth factor (TGF-β1 in cultured cardiac fibroblasts, we found that key factors in LV remodeling included macrophages, fibroblasts, transforming growth factor-β1, matrix metalloproteinase-9 (MMP-9, and specific collagen subtypes. We established a mathematical model to study LV remodeling post-MI by quantifying the dynamic balance between ECM construction and destruction. The mathematical model incorporated the key factors and demonstrated that TGF-β1 stimuli and MMP-9 interventions with different strengths and intervention times lead to different LV remodeling outcomes. The predictions of the mathematical model fell within the range of experimental measurements for these interventions, providing validation for the model. Conclusions In conclusion, our results demonstrated that the balance between ECM synthesis and degradation, controlled by interactions of specific key factors, determines the LV remodeling outcomes. Our mathematical model, based on the balance between ECM construction and destruction, provides a useful tool for studying the regulatory mechanisms and for predicting LV remodeling outcomes.

  15. 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.

  16. 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.

  17. Computational Analysis Reveals the Association of Threonine 118 Methionine Mutation in PMP22 Resulting in CMT-1A

    Directory of Open Access Journals (Sweden)

    Chundi Vinay Kumar

    2014-01-01

    Full Text Available The T118M mutation in PMP22 gene is associated with Charcot Marie Tooth, type 1A (CMT1A. CMT1A is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Mutations in CMT related disorder are seen to increase the stability of the protein resulting in the diseased state. We performed SNP analysis for all the nsSNPs of PMP22 protein and carried out molecular dynamics simulation for T118M mutation to compare the stability difference between the wild type protein structure and the mutant protein structure. The mutation T118M resulted in the overall increase in the stability of the mutant protein. The superimposed structure shows marked structural variation between the wild type and the mutant protein structures.

  18. Results of EPRI/ANL DCH investigations and model development

    International Nuclear Information System (INIS)

    Spencer, B.W.; Sienicki, J.J.; Sehgal, B.R.; Merilo, M.

    1988-01-01

    The results of a series of five experiments are described addressing the severity and mitigation of direct containment heating. The tests were performed in a 1:30 linear scale mockup of the Zion PWR containment system using a reactor-material corium melt consisting of 60% UO 2 , 16% ZrO 2 , 24% SSt at nominally 2800C initial temperature. A ''worst-case'' type test involving unimpeded corium dispersal through an air atmosphere in a closed vessel produced an atmosphere heatup of 323K, equivalent to a DCH efficiency of 62%. With the addition of structural features which impeded the corium dispersal, representative of dispersal pathway features at Zion, the DCH efficiency was reduced to 1--5%. (This important result is scale dependent and requires larger scale tests such as the SURTSEY program at SNL plus mechanistic modeling for application to the reactor system.) With the addition of water in the cavity region, there was no measurable heatup of the atmosphere. This was attributable to the vigorous codispersal of water with corium which prevented the temperature of the atmosphere from significantly exceeding T/sub sat/. In this case the DCH load was replaced by the more benign ''steam spike'' from corium quench. Significant oxidation of the corium constituents occurred in the tests, adding chemical energy to the system and producing hydrogen. Overall, the results suggest that with consideration of realistic, plant specific, mitigating features, DCH may be no worse and possibly far less severe than the previously examined steam spike. Implications for accident management are addressed. 17 refs., 7 figs., 4 tabs

  19. 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.

  20. Cell type-specific functions of period genes revealed by novel adipocyte and hepatocyte circadian clock models.

    Directory of Open Access Journals (Sweden)

    Chidambaram Ramanathan

    2014-04-01

    Full Text Available In animals, circadian rhythms in physiology and behavior result from coherent rhythmic interactions between clocks in the brain and those throughout the body. Despite the many tissue specific clocks, most understanding of the molecular core clock mechanism comes from studies of the suprachiasmatic nuclei (SCN of the hypothalamus and a few other cell types. Here we report establishment and genetic characterization of three cell-autonomous mouse clock models: 3T3 fibroblasts, 3T3-L1 adipocytes, and MMH-D3 hepatocytes. Each model is genetically tractable and has an integrated luciferase reporter that allows for longitudinal luminescence recording of rhythmic clock gene expression using an inexpensive off-the-shelf microplate reader. To test these cellular models, we generated a library of short hairpin RNAs (shRNAs against a panel of known clock genes and evaluated their impact on circadian rhythms. Knockdown of Bmal1, Clock, Cry1, and Cry2 each resulted in similar phenotypes in all three models, consistent with previous studies. However, we observed cell type-specific knockdown phenotypes for the Period and Rev-Erb families of clock genes. In particular, Per1 and Per2, which have strong behavioral effects in knockout mice, appear to play different roles in regulating period length and amplitude in these peripheral systems. Per3, which has relatively modest behavioral effects in knockout mice, substantially affects period length in the three cellular models and in dissociated SCN neurons. In summary, this study establishes new cell-autonomous clock models that are of particular relevance to metabolism and suitable for screening for clock modifiers, and reveals previously under-appreciated cell type-specific functions of clock genes.

  1. Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability

    Directory of Open Access Journals (Sweden)

    Vernon Suzanne D

    2007-02-01

    Full Text Available Abstract Background The body's primary stress management system is the hypothalamic pituitary adrenal (HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. Results We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR. This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS. Conclusion Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis.

  2. 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.

  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. Complex mean circulation over the inner shelf south of Martha's Vineyard revealed by observations and a high-resolution model

    Science.gov (United States)

    Ganju, Neil K.; Lentz, Steven J.; Kirincich, Anthony R.; Farrar, J. Thomas

    2011-01-01

    Inner-shelf circulation is governed by the interaction between tides, baroclinic forcing, winds, waves, and frictional losses; the mean circulation ultimately governs exchange between the coast and ocean. In some cases, oscillatory tidal currents interact with bathymetric features to generate a tidally rectified flow. Recent observational and modeling efforts in an overlapping domain centered on the Martha's Vineyard Coastal Observatory (MVCO) provided an opportunity to investigate the spatial and temporal complexity of circulation on the inner shelf. ADCP and surface radar observations revealed a mean circulation pattern that was highly variable in the alongshore and cross-shore directions. Nested modeling incrementally improved representation of the mean circulation as grid resolution increased and indicated tidal rectification as the generation mechanism of a counter-clockwise gyre near the MVCO. The loss of model skill with decreasing resolution is attributed to insufficient representation of the bathymetric gradients (Δh/h), which is important for representing nonlinear interactions between currents and bathymetry. The modeled momentum balance was characterized by large spatial variability of the pressure gradient and horizontal advection terms over short distances, suggesting that observed inner-shelf momentum balances may be confounded. Given the available observational and modeling data, this work defines the spatially variable mean circulation and its formation mechanism—tidal rectification—and illustrates the importance of model resolution for resolving circulation and constituent exchange near the coast. The results of this study have implications for future observational and modeling studies near the MVCO and other inner-shelf locations with alongshore bathymetric variability.

  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. 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.)

  7. 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.

  8. Dynamic habitat suitability modelling reveals rapid poleward distribution shift in a mobile apex predator.

    Science.gov (United States)

    Hill, Nicholas J; Tobin, Andrew J; Reside, April E; Pepperell, Julian G; Bridge, Tom C L

    2016-03-01

    Many taxa are undergoing distribution shifts in response to anthropogenic climate change. However, detecting a climate signal in mobile species is difficult due to their wide-ranging, patchy distributions, often driven by natural climate variability. For example, difficulties associated with assessing pelagic fish distributions have rendered fisheries management ill-equipped to adapt to the challenges posed by climate change, leaving pelagic species and ecosystems vulnerable. Here, we demonstrate the value of citizen science data for modelling the dynamic habitat suitability of a mobile pelagic predator (black marlin, Istiompax indica) within the south-west Pacific Ocean. The extensive spatial and temporal coverage of our occurrence data set (n = 18 717), collected at high resolution (~1.85 km(2) ), enabled identification of suitable habitat at monthly time steps over a 16-year period (1998-2013). We identified considerable monthly, seasonal and interannual variability in the extent and distribution of suitable habitat, predominately driven by chlorophyll a and sea surface height. Interannual variability correlated with El Nino Southern Oscillation (ENSO) events, with suitable habitat extending up to ~300 km further south during La Nina events. Despite the strong influence of ENSO, our model revealed a rapid poleward shift in the geometric mean of black marlin habitat, occurring at 88.2 km decade(-1) . By incorporating multiple environmental factors at monthly time steps, we were able to demonstrate a rapid distribution shift in a mobile pelagic species. Our findings suggest that the rapid velocity of climate change in the south-west Pacific Ocean is likely affecting mobile pelagic species, indicating that they may be more vulnerable to climate change than previously thought. © 2015 John Wiley & Sons Ltd.

  9. Robust hierarchical state-space models reveal diel variation in travel rates of migrating leatherback turtles.

    Science.gov (United States)

    Jonsen, Ian D; Myers, Ransom A; James, Michael C

    2006-09-01

    1. Biological and statistical complexity are features common to most ecological data that hinder our ability to extract meaningful patterns using conventional tools. Recent work on implementing modern statistical methods for analysis of such ecological data has focused primarily on population dynamics but other types of data, such as animal movement pathways obtained from satellite telemetry, can also benefit from the application of modern statistical tools. 2. We develop a robust hierarchical state-space approach for analysis of multiple satellite telemetry pathways obtained via the Argos system. State-space models are time-series methods that allow unobserved states and biological parameters to be estimated from data observed with error. We show that the approach can reveal important patterns in complex, noisy data where conventional methods cannot. 3. Using the largest Atlantic satellite telemetry data set for critically endangered leatherback turtles, we show that the diel pattern in travel rates of these turtles changes over different phases of their migratory cycle. While foraging in northern waters the turtles show similar travel rates during day and night, but on their southward migration to tropical waters travel rates are markedly faster during the day. These patterns are generally consistent with diving data, and may be related to changes in foraging behaviour. Interestingly, individuals that migrate southward to breed generally show higher daytime travel rates than individuals that migrate southward in a non-breeding year. 4. Our approach is extremely flexible and can be applied to many ecological analyses that use complex, sequential data.

  10. 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.

  11. Atmosphere-Ionosphere Response to the M9 Tohoku Earthquake Revealed by Joined Satellite and Ground Observations. Preliminary Results

    Science.gov (United States)

    Ouzounov, Dimitar; Pulinets, Sergey; Romanov, Alexey; Tsybulya, Konstantin; Davidenko, Dimitri; Kafatos, Menas; Taylor, Patrick

    2011-01-01

    The recent M9 Tohoku Japan earthquake of March 11, 2011 was the largest recorded earthquake ever to hit this nation. We retrospectively analyzed the temporal and spatial variations of four different physical parameters - outgoing long wave radiation (OLR), GPS/TEC, Low-Earth orbit tomography and critical frequency foF2. These changes characterize the state of the atmosphere and ionosphere several days before the onset of this earthquake. Our first results show that on March 8th a rapid increase of emitted infrared radiation was observed from the satellite data and an anomaly developed near the epicenter. The GPS/TEC data indicate an increase and variation in electron density reaching a maximum value on March 8. Starting on this day in the lower ionospheric there was also confirmed an abnormal TEC variation over the epicenter. From March 3-11 a large increase in electron concentration was recorded at all four Japanese ground based ionosondes, which return to normal after the main earthquake. We found a positive correlation between the atmospheric and ionospheric anomalies and the Tohoku earthquake. This study may lead to a better understanding of the response of the atmosphere/ionosphere to the Great Tohoku earthquake.

  12. Deep scientific drilling results from Koyna and Killari earthquake regions reveal why Indian shield lithosphere is unusual, thin and warm

    Directory of Open Access Journals (Sweden)

    O.P. Pandey

    2016-09-01

    Full Text Available The nature of crustal and lithospheric mantle evolution of the Archean shields as well as their subsequent deformation due to recent plate motions and sustained intraplate geodynamic activity, has been a subject of considerable interest. In view of this, about three decades ago, a new idea was put forward suggesting that out of all shield terrains, the Indian shield has an extremely thin lithosphere (∼100 km, compared to 250–350 km, elsewhere, apart from being warm, non-rigid, sheared and deformed. As expected, it met with scepticism by heat flow and the emerging seismic tomographic study groups, who on the contrary suggested that the Indian shield has a cool crust, besides a coherent and thick lithosphere (as much as 300–400 km like any other shield. However, recently obtained integrated geological and geophysical findings from deep scientific drillings in 1993 Killari (Mw: 6.3 and 1967 Koyna (Mw: 6.3 earthquake zones, as well as newly acquired geophysical data over other parts of Indian shield terrain, have provided a totally new insight to this debate. Beneath Killari, the basement was found consisting of high density, high velocity mid crustal amphibolite to granulite facies rocks due to exhumation of the deeper crustal layers and sustained granitic upper crustal erosion. Similar type of basement appears to be present in Koyna region too, which is characterized by considerably high upper crustal temperatures. Since, such type of crust is depleted in radiogenic elements, it resulted into lowering of heat flow at the surface, increase in heat flow contribution from the mantle, and upwarping of the lithosphere-asthenosphere boundary. Consequently, the Indian shield lithosphere has become unusually thin and warm. This study highlights the need of an integrated geological, geochemical and geophysical approach in order to accurately determine deep crust-mantle thermal regime in continental areas.

  13. Blade element momentum modeling of inflow with shear in comparison with advanced model results

    DEFF Research Database (Denmark)

    Aagaard Madsen, Helge; Riziotis, V.; Zahle, Frederik

    2012-01-01

    shear is present in the inflow. This gives guidance to how the BEM modeling of shear should be implemented. Another result from the advanced vortex model computations is a clear indication of influence of the ground, and the general tendency is a speed up effect of the flow through the rotor giving...

  14. 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.)

  15. 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

  16. Effect of geometry of rice kernels on drying modeling results

    Science.gov (United States)

    Geometry of rice grain is commonly represented by sphere, spheroid or ellipsoid shapes in the drying models. Models using simpler shapes are easy to solve mathematically, however, deviation from the true grain shape might lead to large errors in predictions of drying characteristics such as, moistur...

  17. 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

  18. Quark cluster model of nuclei and lepton scattering results

    International Nuclear Information System (INIS)

    Vary, J.P.; Iowa State Univ. of Science and Technology, Ames

    1984-01-01

    A review of the quark cluster model (QCM) of nuclei is presented along with applications to deep inelastic lepton scattering and elastic lepton scattering experiments. In addition a sample comparison is made with high momentum transfer (p, π) data. The QCM prediction for the ratio of nuclear structure functions in the x > 1 domain is discussed as a critical test of the model

  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. 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.

  1. 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.

  2. 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.

  3. 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

    2016-01-01

    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. PMID:27021558

  4. 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.

  5. Wave-current interactions: model development and preliminary results

    Science.gov (United States)

    Mayet, Clement; Lyard, Florent; Ardhuin, Fabrice

    2013-04-01

    The coastal area concentrates many uses that require integrated management based on diagnostic and predictive tools to understand and anticipate the future of pollution from land or sea, and learn more about natural hazards at sea or activity on the coast. The realistic modelling of coastal hydrodynamics needs to take into account various processes which interact, including tides, surges, and sea state (Wolf [2008]). These processes act at different spatial scales. Unstructured-grid models have shown the ability to satisfy these needs, given that a good mesh resolution criterion is used. We worked on adding a sea state forcing in a hydrodynamic circulation model. The sea state model is the unstructured version of WAVEWATCH III c (Tolman [2008]) (which version is developed at IFREMER, Brest (Ardhuin et al. [2010]) ), and the hydrodynamic model is the 2D barotropic module of the unstructured-grid finite element model T-UGOm (Le Bars et al. [2010]). We chose to use the radiation stress approach (Longuet-Higgins and Stewart [1964]) to represent the effect of surface waves (wind waves and swell) in the barotropic model, as previously done by Mastenbroek et al. [1993]and others. We present here some validation of the model against academic cases : a 2D plane beach (Haas and Warner [2009]) and a simple bathymetric step with analytic solution for waves (Ardhuin et al. [2008]). In a second part we present realistic application in the Ushant Sea during extreme event. References Ardhuin, F., N. Rascle, and K. Belibassakis, Explicit wave-averaged primitive equations using a generalized Lagrangian mean, Ocean Modelling, 20 (1), 35-60, doi:10.1016/j.ocemod.2007.07.001, 2008. Ardhuin, F., et al., Semiempirical Dissipation Source Functions for Ocean Waves. Part I: Definition, Calibration, and Validation, J. Phys. Oceanogr., 40 (9), 1917-1941, doi:10.1175/2010JPO4324.1, 2010. Haas, K. A., and J. C. Warner, Comparing a quasi-3D to a full 3D nearshore circulation model: SHORECIRC and

  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. SAMI2 model results for the quiet time low latitude ionosphere over India

    Science.gov (United States)

    Rao, S. S.; Sharma, Shweta; Pandey, R.

    2018-04-01

    Efficacy of SAMI2 model for the Indian low latitude region around 75°E longitudes has been tested for different levels of solar flux. With a slight modification of the plasma drift velocity the SAMI2 model has been successful in reproducing quiet time ionospheric low latitude features like Equatorial Ionization Anomaly. We have also showed the formation of electron hole in the topside equatorial ionosphere in the Indian sector. Simulation results show the formation of electron hole in the altitude range 800-2500 km over the magnetic equator. Indian zone results reveal marked differences with regard to the time of occurrence, seasonal appearances and strength of the electron hole vis-a-vis those reported for the American equatorial region.

  8. Evolutionary profiling reveals the heterogeneous origins of classes of human disease genes: implications for modeling disease genetics in animals.

    Science.gov (United States)

    Maxwell, Evan K; Schnitzler, Christine E; Havlak, Paul; Putnam, Nicholas H; Nguyen, Anh-Dao; Moreland, R Travis; Baxevanis, Andreas D

    2014-10-04

    The recent expansion of whole-genome sequence data available from diverse animal lineages provides an opportunity to investigate the evolutionary origins of specific classes of human disease genes. Previous studies have observed that human disease genes are of particularly ancient origin. While this suggests that many animal species have the potential to serve as feasible models for research on genes responsible for human disease, it is unclear whether this pattern has meaningful implications and whether it prevails for every class of human disease. We used a comparative genomics approach encompassing a broad phylogenetic range of animals with sequenced genomes to determine the evolutionary patterns exhibited by human genes associated with different classes of disease. Our results support previous claims that most human disease genes are of ancient origin but, more importantly, we also demonstrate that several specific disease classes have a significantly large proportion of genes that emerged relatively recently within the metazoans and/or vertebrates. An independent assessment of the synonymous to non-synonymous substitution rates of human disease genes found in mammals reveals that disease classes that arose more recently also display unexpected rates of purifying selection between their mammalian and human counterparts. Our results reveal the heterogeneity underlying the evolutionary origins of (and selective pressures on) different classes of human disease genes. For example, some disease gene classes appear to be of uncommonly recent (i.e., vertebrate-specific) origin and, as a whole, have been evolving at a faster rate within mammals than the majority of disease classes having more ancient origins. The novel patterns that we have identified may provide new insight into cases where studies using traditional animal models were unable to produce results that translated to humans. Conversely, we note that the larger set of disease classes do have ancient origins

  9. New analytic results for speciation times in neutral models.

    Science.gov (United States)

    Gernhard, Tanja

    2008-05-01

    In this paper, we investigate the standard Yule model, and a recently studied model of speciation and extinction, the "critical branching process." We develop an analytic way-as opposed to the common simulation approach-for calculating the speciation times in a reconstructed phylogenetic tree. Simple expressions for the density and the moments of the speciation times are obtained. Methods for dating a speciation event become valuable, if for the reconstructed phylogenetic trees, no time scale is available. A missing time scale could be due to supertree methods, morphological data, or molecular data which violates the molecular clock. Our analytic approach is, in particular, useful for the model with extinction, since simulations of birth-death processes which are conditioned on obtaining n extant species today are quite delicate. Further, simulations are very time consuming for big n under both models.

  10. 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....

  11. New Results in Optical Modelling of Quantum Well Solar Cells

    Directory of Open Access Journals (Sweden)

    Silvian Fara

    2012-01-01

    Full Text Available This project brought further advancements to the quantum well solar cell concept proposed by Keith Barnham. In this paper, the optical modelling of MQW solar cells was analyzed and we focussed on the following topics: (i simulation of the refraction index and the reflectance, (ii simulation of the absorption coefficient, (iii simulation of the quantum efficiency for the absorption process, (iv discussion and modelling of the quantum confinement effect, and (v evaluation of datasheet parameters of the MQW cell.

  12. 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 ...

  13. Integrated population modeling reveals the impact of climate on the survival of juvenile emperor penguins.

    Science.gov (United States)

    Abadi, Fitsum; Barbraud, Christophe; Gimenez, Olivier

    2017-03-01

    Early-life demographic traits are poorly known, impeding our understanding of population processes and sensitivity to climate change. Survival of immature individuals is a critical component of population dynamics and recruitment in particular. However, obtaining reliable estimates of juvenile survival (i.e., from independence to first year) remains challenging, as immatures are often difficult to observe and to monitor individually in the field. This is particularly acute for seabirds, in which juveniles stay at sea and remain undetectable for several years. In this work, we developed a Bayesian integrated population model to estimate the juvenile survival of emperor penguins (Aptenodytes forsteri), and other demographic parameters including adult survival and fecundity of the species. Using this statistical method, we simultaneously analyzed capture-recapture data of adults, the annual number of breeding females, and the number of fledglings of emperor penguins collected at Dumont d'Urville, Antarctica, for the period 1971-1998. We also assessed how climate covariates known to affect the species foraging habitats and prey [southern annular mode (SAM), sea ice concentration (SIC)] affect juvenile survival. Our analyses revealed that there was a strong evidence for the positive effect of SAM during the rearing period (SAMR) on juvenile survival. Our findings suggest that this large-scale climate index affects juvenile emperor penguins body condition and survival through its influence on wind patterns, fast ice extent, and distance to open water. Estimating the influence of environmental covariates on juvenile survival is of major importance to understand the impacts of climate variability and change on the population dynamics of emperor penguins and seabirds in general and to make robust predictions on the impact of climate change on marine predators. © 2016 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Conspecific plants are better 'nurses' than rocks: consistent results revealing intraspecific facilitation as a process that promotes establishment in a hyper-arid environment.

    Science.gov (United States)

    Loayza, Andrea P; Herrera-Madariaga, Marisol A; Carvajal, Danny E; García-Guzmán, Patricio; Squeo, Francisco A

    2017-11-01

    Harsh environmental conditions in arid ecosystems limit seedling recruitment to microhabitats under nurse structures, such as shrubs or rocks. These structures, however, do not necessarily afford the same benefits to plants because nurse rocks provide only physical nurse effects, whereas nurse plants can provide both physical and biological nurse effects. Nevertheless, if the nurse plant is a conspecific, the benefits it provides may be outweighed by higher mortality due to negative density-dependent processes; consequently, negative density-dependence is expected to limit plants from acting as nurses to their own seedlings. The degree to which an abiotic nurse may be more beneficial than a conspecific one remains largely unexplored. Here, we examine the role and elucidate the mechanisms by which conspecific plants and rocks promote plant establishment in a hyper-arid desert. For 4 years, we examined establishment patterns of Myrcianthes coquimbensis (Myrtaceae), a threatened desert shrub that recruits solely in rock cavities and under conspecific shrubs. Specifically, we characterized these microhabitats, as well as open interspaces for comparison, and conducted germination, seed removal and seedling survival experiments. Our results revealed that conspecific shrubs and nurse rocks modified environmental conditions in similar ways; soil and air temperatures were lower, and water availability was higher than in open interspaces. We found no evidence on negative density-dependent recruitment: seed removal was lowest and seedling emergence highest under conspecific plants, moreover seedling survival probabilities were similar in rock cavities and under conspecific plants. We conclude that the probability of establishment was highest under conspecific plants than in other microhabitats, contrasting what is expected under the Janzen-Connell recruitment model. We suggest that for species living in stressful environments, population regulation may be a function of

  20. 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.

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

    Indian Academy of Sciences (India)

    J Tomkinson heterobicyclic molecules could form a reasonable base of model compounds to un- derstand the eigenvectors of one interesting molecular system; the nitrogenous het- erocyclic bases of the nucleotides. Low energy molecular vibrational eigenvectors involve atomic displacements over the molecule as a whole ...

  2. 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

    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...

  3. 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.

  4. Some results for the dynamic (s, S) inventory model *

    NARCIS (Netherlands)

    H.C. Tijms

    1971-01-01

    textabstractSummary The periodic review, single item, stationary (s, S) inventory model is considered. There is a fixed lead time, a linear purchase cost, a fixed set‐up cost, a holding and shortage cost function, a discount factor 0 < α≤ 1 and backlogging of unfilled demand. The solution for the

  5. 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.).

  6. 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

  7. 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.

  8. 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.

  9. Application of the steepest slope model reveals different perfusion territories within the mouse placenta.

    Science.gov (United States)

    Remus, C C; Sedlacik, J; Wedegaertner, U; Arck, P; Hecher, K; Adam, G; Forkert, N D

    2013-10-01

    The steepest slope model is a numerically robust and fast method for perfusion quantification. The purpose of this study was to evaluate if the steepest slope model can be used for quantifying placental perfusion in mice based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) datasets. T1-weighted DCE MRI was performed in 5 pregnant BALB/c mice on gestation day (gd) 14.5 and in 5 mice on gd 16.5 using a 7T small animal MRI scanner. The placentas were manually delineated in the DCE datasets and the arterial input function (AIF) was selected from the kidney hilus. Placental perfusion was determined on a voxel-by-voxel basis using the steepest slope model. Perfusion was averaged over the entire placenta as well as separately calculated for the high-flow compartment within the central labyrinth zone and for the remaining low-flow placenta tissue. The AIF selection was independently performed by two observers for assessment of inter-observer differences. Mean perfusion on gd 14.5 was 135 ml/min/100 ml (standard deviation SD: 29 ml/min/100 ml placenta) and 112 ml/min/100 ml on gd 16.5 for the whole placenta (SD: 32 ml/min/100 ml). Perfusion in the high flow compartment in the central labyrinth was significantly higher (p ≤ 0.002) than in the low-flow compartment including the remaining placenta tissue: 184 ml/min/100 ml (SD: 39 ml/min/100 ml) vs. 119 ml/min/100 ml (SD 28 ml/min/100 ml) on gd 14.5 and 158 ml/min/100 ml (SD: 58 ml/min/100 ml) vs. 114 ml/min/100 ml (SD: 52 ml/min/100 ml of placenta) on gd 16.5. The mean relative inter-rater observer difference was 6%. The steepest slope model is a computationally simple method, which allows perfusion quantification in the mouse placenta. Furthermore, the results of this work indicate that the different placental compartments should be analyzed separately to prevent biased results due to averaging. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. N-gram analysis of 970 microbial organisms reveals presence of biological language models

    Directory of Open Access Journals (Sweden)

    Ganapathiraju Madhavi K

    2011-01-01

    Full Text Available Abstract Background It has been suggested previously that genome and proteome sequences show characteristics typical of natural-language texts such as "signature-style" word usage indicative of authors or topics, and that the algorithms originally developed for natural language processing may therefore be applied to genome sequences to draw biologically relevant conclusions. Following this approach of 'biological language modeling', statistical n-gram analysis has been applied for comparative analysis of whole proteome sequences of 44 organisms. It has been shown that a few particular amino acid n-grams are found in abundance in one organism but occurring very rarely in other organisms, thereby serving as genome signatures. At that time proteomes of only 44 organisms were available, thereby limiting the generalization of this hypothesis. Today nearly 1,000 genome sequences and corresponding translated sequences are available, making it feasible to test the existence of biological language models over the evolutionary tree. Results We studied whole proteome sequences of 970 microbial organisms using n-gram frequencies and cross-perplexity employing the Biological Language Modeling Toolkit and Patternix Revelio toolkit. Genus-specific signatures were observed even in a simple unigram distribution. By taking statistical n-gram model of one organism as reference and computing cross-perplexity of all other microbial proteomes with it, cross-perplexity was found to be predictive of branch distance of the phylogenetic tree. For example, a 4-gram model from proteome of Shigellae flexneri 2a, which belongs to the Gammaproteobacteria class showed a self-perplexity of 15.34 while the cross-perplexity of other organisms was in the range of 15.59 to 29.5 and was proportional to their branching distance in the evolutionary tree from S. flexneri. The organisms of this genus, which happen to be pathotypes of E.coli, also have the closest perplexity values with

  11. 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

  12. 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

  13. Integrating Kinetic Model of E. coli with Genome Scale Metabolic Fluxes Overcomes Its Open System Problem and Reveals Bistability in Central Metabolism.

    Directory of Open Access Journals (Sweden)

    Ahmad A Mannan

    Full Text Available An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, limiting the size of the system that can be modelled. Furthermore, the subsystem of the metabolic network whose dynamics can be modelled is faced with three problems: how to parameterize the model with mostly incomplete steady state data, how to close what is now an inherently open system, and how to account for the impact on growth. In this study we address these challenges of kinetic modelling by capitalizing on multi-'omics' steady state data and a genome-scale metabolic network model. We use these to generate parameters that integrate knowledge embedded in the genome-scale metabolic network model, into the most comprehensive kinetic model of the central carbon metabolism of E. coli realized to date. As an application, we performed a dynamical systems analysis of the resulting enriched model. This revealed bistability of the central carbon metabolism and thus its potential to express two distinct metabolic states. Furthermore, since our model-informing technique ensures both stable states are constrained by the same thermodynamically feasible steady state growth rate, the ensuing bistability represents a temporal coexistence of the two states, and by extension, reveals the emergence of a phenotypically heterogeneous population.

  14. Integrating Kinetic Model of E. coli with Genome Scale Metabolic Fluxes Overcomes Its Open System Problem and Reveals Bistability in Central Metabolism

    Science.gov (United States)

    Mannan, Ahmad A.; Toya, Yoshihiro; Shimizu, Kazuyuki; McFadden, Johnjoe; Kierzek, Andrzej M.; Rocco, Andrea

    2015-01-01

    An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, limiting the size of the system that can be modelled. Furthermore, the subsystem of the metabolic network whose dynamics can be modelled is faced with three problems: how to parameterize the model with mostly incomplete steady state data, how to close what is now an inherently open system, and how to account for the impact on growth. In this study we address these challenges of kinetic modelling by capitalizing on multi-‘omics’ steady state data and a genome-scale metabolic network model. We use these to generate parameters that integrate knowledge embedded in the genome-scale metabolic network model, into the most comprehensive kinetic model of the central carbon metabolism of E. coli realized to date. As an application, we performed a dynamical systems analysis of the resulting enriched model. This revealed bistability of the central carbon metabolism and thus its potential to express two distinct metabolic states. Furthermore, since our model-informing technique ensures both stable states are constrained by the same thermodynamically feasible steady state growth rate, the ensuing bistability represents a temporal coexistence of the two states, and by extension, reveals the emergence of a phenotypically heterogeneous population. PMID:26469081

  15. Dynamic model of the electrorheological fluid based on measurement results

    International Nuclear Information System (INIS)

    Krivenkov, K; Ulrich, S; Bruns, R

    2013-01-01

    To develop modern applications for vibration decoupling based on electrorheological fluids with suitable control strategies, an appropriate mathematical model of the ERF is necessary. The devices mostly used have annular-shape electrorheological valves. This requires the use of flow channels to measure the static and dynamic properties of the electrorheological fluids in similar flow conditions. Particularly for the identification of the dynamic behavior of the fluids, the influences of the non-electrorheological properties on the overall system must be taken into account. In this contribution three types of parameters with several nonlinear dependencies for the mapping of the static and dynamic properties of the ERF are considered: electro-rheological, hydraulic and electrical. The mathematical model introduced can precisely demonstrate the static and dynamic behavior of the electrorheological fluid and can be used for the future design of real systems for vibration decoupling or other systems with high dynamic requirements.

  16. 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

  17. 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.

  18. Sharing brain mapping statistical results with the neuroimaging data model

    Science.gov (United States)

    Maumet, Camille; Auer, Tibor; Bowring, Alexander; Chen, Gang; Das, Samir; Flandin, Guillaume; Ghosh, Satrajit; Glatard, Tristan; Gorgolewski, Krzysztof J.; Helmer, Karl G.; Jenkinson, Mark; Keator, David B.; Nichols, B. Nolan; Poline, Jean-Baptiste; Reynolds, Richard; Sochat, Vanessa; Turner, Jessica; Nichols, Thomas E.

    2016-01-01

    Only a tiny fraction of the data and metadata produced by an fMRI study is finally conveyed to the community. This lack of transparency not only hinders the reproducibility of neuroimaging results but also impairs future meta-analyses. In this work we introduce NIDM-Results, a format specification providing a machine-readable description of neuroimaging statistical results along with key image data summarising the experiment. NIDM-Results provides a unified representation of mass univariate analyses including a level of detail consistent with available best practices. This standardized representation allows authors to relay methods and results in a platform-independent regularized format that is not tied to a particular neuroimaging software package. Tools are available to export NIDM-Result graphs and associated files from the widely used SPM and FSL software packages, and the NeuroVault repository can import NIDM-Results archives. The specification is publically available at: http://nidm.nidash.org/specs/nidm-results.html. PMID:27922621

  19. Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma.

    Science.gov (United States)

    Kling, Teresia; Ferrarese, Roberto; Ó hAilín, Darren; Johansson, Patrik; Heiland, Dieter Henrik; Dai, Fangping; Vasilikos, Ioannis; Weyerbrock, Astrid; Jörnsten, Rebecka; Carro, Maria Stella; Nelander, Sven

    2016-10-01

    Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2) as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell-like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes. Copyright © 2016. Published by Elsevier B.V.

  20. Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma

    Directory of Open Access Journals (Sweden)

    Teresia Kling

    2016-10-01

    Full Text Available Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2 as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell-like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes.

  1. Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    2016-09-01

    Full Text Available Cancer genomics has provided an unprecedented opportunity for understanding genetic causes of human cancer. However, distinguishing which mutations are functionally relevant to cancer pathogenesis remains a major challenge. We describe here a mammary stem cell (MaSC organoid-based approach for rapid generation of somatic genetically engineered mouse models (GEMMs. By using RNAi and CRISPR-mediated genome engineering in MaSC-GEMMs, we have discovered that inactivation of Ptpn22 or Mll3, two genes mutated in human breast cancer, greatly accelerated PI3K-driven mammary tumorigenesis. Using these tumor models, we have also identified genetic alterations promoting tumor metastasis and causing resistance to PI3K-targeted therapy. Both Ptpn22 and Mll3 inactivation resulted in disruption of mammary gland differentiation and an increase in stem cell activity. Mechanistically, Mll3 deletion enhanced stem cell activity through activation of the HIF pathway. Thus, our study has established a robust in vivo platform for functional cancer genomics and has discovered functional breast cancer mutations.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. A unifying mathematical model of lipid droplet metabolism reveals key molecular players in the development of hepatic steatosis.

    Science.gov (United States)

    Wallstab, Christin; Eleftheriadou, Dimitra; Schulz, Theresa; Damm, Georg; Seehofer, Daniel; Borlak, Jürgen; Holzhütter, Hermann-Georg; Berndt, Nikolaus

    2017-10-01

    The liver responds to elevated plasma concentrations of free fatty acids (FFAs) with an enhanced uptake of FFAs and their esterification to triacylglycerol (TAG). On the long term, this may result in massive hepatic TAG accumulation called steatosis hepatitis. In hepatocytes, the poor water-soluble TAG is packed in specialized organelles: Lipid droplets (LDs) serving as transient cellular deposit and lipoproteins (LPs) transporting TAG and cholesterol esters to extra-hepatic tissues. The dynamics of these organelles is controlled by a variety of regulatory surface proteins (RSPs). Assembly and export of VLDLs are mainly regulated by the microsomal transfer protein (MTP) and apoprotein B100. Formation and lipolysis of LDs are regulated by several RSPs. The best studied regulators belong to the PAT (Perilipin/Adipophilin/TIP47) and CIDE families. Knockdown or overexpression of SRPs may significantly affect the total number and size distribution of LDs. Intriguingly, a large cell-to-cell heterogeneity with respect to the number and size of LDs has been found in various cell types including hepatocytes. These findings suggest that the extent of cellular lipid accumulation is determined not only by the imbalance between lipid supply and utilization but also by variations in the expression of RSPs and metabolic enzymes. To better understand the relative regulatory impact of individual processes involved in the cellular TAG turnover, we developed a comprehensive kinetic model encompassing the pathways of the fatty acid and triglyceride metabolism and the main molecular processes governing the dynamics of LDs. The model was parametrized such that a large number of experimental in vitro and in vivo findings are correctly recapitulated. A control analysis of the model revealed that variations in the activity of FFA uptake, diacylglycerol acyltransferase (DGAT) 2, and adipose triglyceride lipase (ATGL) have the strongest influence on the cellular TAG level. We used the model

  9. Aerodynamic modelling of a Cretaceous bird reveals thermal soaring capabilities during early avian evolution.

    Science.gov (United States)

    Serrano, Francisco José; Chiappe, Luis María

    2017-07-01

    Several flight modes are thought to have evolved during the early evolution of birds. Here, we use a combination of computational modelling and morphofunctional analyses to infer the flight properties of the raven-sized, Early Cretaceous bird Sapeornis chaoyangensis -a likely candidate to have evolved soaring capabilities. Specifically, drawing information from (i) mechanical inferences of the deltopectoral crest of the humerus, (ii) wing shape (i.e. aspect ratio), (iii) estimations of power margin (i.e. difference between power required for flight and available power from muscles), (iv) gliding behaviour (i.e. forward speed and sinking speed), and (v) palaeobiological evidence, we conclude that S. chaoyangensis was a thermal soarer with an ecology similar to that of living South American screamers. Our results indicate that as early as 125 Ma, some birds evolved the morphological and aerodynamic requirements for soaring on continental thermals, a conclusion that highlights the degree of ecological, functional and behavioural diversity that resulted from the first major evolutionary radiation of birds. © 2017 The Author(s).

  10. 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

  11. Combining forming results via weld models to powerful numerical assemblies

    NARCIS (Netherlands)

    Kose, K.; Rietman, Bert

    2004-01-01

    Forming simulations generally give satisfying results with respect to thinning, stresses, changed material properties and, with a proper springback calculation, the geometric form. The joining of parts by means of welding yields an extra change of the material properties and the residual stresses.

  12. 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.

  13. 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.

  14. A mathematical model of mechanotransduction reveals how mechanical memory regulates mesenchymal stem cell fate decisions.

    Science.gov (United States)

    Peng, Tao; Liu, Linan; MacLean, Adam L; Wong, Chi Wut; Zhao, Weian; Nie, Qing

    2017-05-16

    Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts. We study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates. We present a continuous model that is able to describe the cell fate transitions that occur during differentiation, and analyze its dynamics with tools from multistability, bifurcation, and cell fate landscape analysis, and via stochastic simulation. Whereas experimentally, memory has only been observed during osteogenic differentiation, this model predicts that memory regions can exist for each of the four MSC-derived cell lineages. We can predict the substrate stiffness ranges over which memory drives differentiation; these are directly testable in an experimental setting. Furthermore, we quantitatively predict how substrate stiffness and culture duration co-regulate the fate of a stem cell, and we find that the feedbacks from the differentiating MSC onto its substrate are critical to preserve mechanical memory. Strikingly, we show that re-seeding MSCs onto a sufficiently soft substrate increases the number of cell fates accessible. Control of MSC differentiation is crucial for the success of much-lauded regenerative therapies based on MSCs. We have predicted new memory regions that will directly impact this control, and have quantified the size of the memory region for osteoblasts, as well as the co-regulatory effects on cell fates of substrate stiffness and culture duration. Taken together, these results can be used to develop novel strategies to better control the fates of MSCs in vitro and following transplantation.

  15. 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

    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 laten...

  16. Results from ITMIX - the Ice Thickness Models Intercomparison eXperiment

    Science.gov (United States)

    Farinotti, Daniel; Itmix Consortium, The

    2017-04-01

    Knowledge about the ice thickness distribution of a given glacier or ice cap is essential for a number of glaciological and hydrological applications. Yet, the ice thickness of the majority of worlds' ice masses remains poorly constrained. Recently, significant advances have been made in numerical methods that infer glacier ice thickness from surface characteristics, and a number of approaches have been proposed. A comprehensive assessment of their performance, however, is missing to date. Here, we present results from ITMIX - the Ice Thickness Models Intercomparison eXperiment - which was the first coordinated effort to assess the relative strengths and weaknesses of individual approaches. Operating in a working group of the International Association of Cryospheric Sciences, we present results from a total of 17 different models, applied over 21 test cases including glaciers, ice caps, and synthetic geometries. We show that the results from individual approaches can differ largely, but that combining them into an ensemble-estimate can yield significantly improvements. Comparison against direct ice thickness measurements reveals that ensemble solution can achieve accuracies in the order of 10 ± 24 % of the mean ice thickness. We additionally highlight how input-data quality can affect the estimates, and argue that better accounting for input-data uncertainty will be a key for an improved next generation of ice thickness estimation models.

  17. Testing the AGN unification model in the infrared. First results with GTC/CanariCam

    Science.gov (United States)

    Ramos Almeida, C.

    2015-05-01

    The unified model for Active Galactic Nuclei (AGN) accounts for a variety of observational differences in terms of viewing geometry alone. However, from the fitting of high spatial resolution infrared (IR) data with clumpy torus models, it has been hinted that the immediate dusty surroundings of Type-1 and 2 Seyfert nuclei might be intrinsically different in terms of covering factor (torus width and number of clouds). Moreover, these torus covering factors also showed variations among objects belonging to the same type, in contradiction with simple unification. Interestingly, these intrinsic differences in Seyfert tori could explain, for example, the lack of broad optical lines in the polarized spectra of about half of the brightest Seyfert 2 galaxies. On the other hand, recent IR interferometry studies have revealed that, in at least four Seyfert galaxies, the mid-IR emission is elongated in the polar direction. These results are difficult to reconcile with unified models, which claim that the bulk of the mid-IR emission comes from the torus. In this invited contribution I summarize the latest results on high angular resolution IR studies of AGN, which constitute a crucial test for AGN unification. These results include those from the mid-infrared instrument CanariCam on the 10.4 m Gran Telescopio CANARIAS (GTC), which are starting to be published by the CanariCam AGN team, Los Piratas (https://sites.google.com/site/piratasrelatedpublications).

  18. 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.

  19. 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.

  20. Results from the coupled Michigan MHD model and the Rice Convection Model

    Science.gov (United States)

    de Zeeuw, D.; Sazykin, S.; Wolf, R.; Gombosi, T.; Powell, K.

    A new high performance Rice Convection Model (RCM) has been coupled to the adaptive-grid Michigan MHD model (BATSRUS). This fully coupled code allows us to self-consistently simulate the physics in the inner and middle magnetosphere. A study will be presented of the basic characteristics of the inner and middle magnetosphere in the context of a single coupled-code run with steady inputs. The analysis will include region-2 currents, shielding of the inner magnetosphere, partial ring currents, pressure distribution, magnetic field inflation, and distribution of pV^gamma. The coupled-code simulation will be compared with results from RCM runs and algorithms.

  1. The Intrinsic Dynamics and Unfolding Process of an Antibody Fab Fragment Revealed by Elastic Network Model

    Directory of Open Access Journals (Sweden)

    Ji-Guo Su

    2015-12-01

    Full Text Available Antibodies have been increasingly used as pharmaceuticals in clinical treatment. Thermal stability and unfolding process are important properties that must be considered in antibody design. In this paper, the structure-encoded dynamical properties and the unfolding process of the Fab fragment of the phosphocholine-binding antibody McPC603 are investigated by use of the normal mode analysis of Gaussian network model (GNM. Firstly, the temperature factors for the residues of the protein were calculated with GNM and then compared with the experimental measurements. A good result was obtained, which provides the validity for the use of GNM to study the dynamical properties of the protein. Then, with this approach, the mean-square fluctuation (MSF of the residues, as well as the MSF in the internal distance (MSFID between all pairwise residues, was calculated to investigate the mobility and flexibility of the protein, respectively. It is found that the mobility and flexibility of the constant regions are higher than those of the variable regions, and the six complementarity-determining regions (CDRs in the variable regions also exhibit relative large mobility and flexibility. The large amplitude motions of the CDRs are considered to be associated with the immune function of the antibody. In addition, the unfolding process of the protein was simulated by iterative use of the GNM. In our method, only the topology of protein native structure is taken into account, and the protein unfolding process is simulated through breaking the native contacts one by one according to the MSFID values between the residues. It is found that the flexible regions tend to unfold earlier. The sequence of the unfolding events obtained by our method is consistent with the hydrogen-deuterium exchange experimental results. Our studies imply that the unfolding behavior of the Fab fragment of antibody McPc603 is largely determined by the intrinsic dynamics of the protein.

  2. 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

  3. 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

  4. A spastic paraplegia mouse model reveals REEP1-dependent ER shaping.

    Science.gov (United States)

    Beetz, Christian; Koch, Nicole; Khundadze, Mukhran; Zimmer, Geraldine; Nietzsche, Sandor; Hertel, Nicole; Huebner, Antje-Kathrin; Mumtaz, Rizwan; Schweizer, Michaela; Dirren, Elisabeth; Karle, Kathrin N; Irintchev, Andrey; Alvarez, Victoria; Redies, Christoph; Westermann, Martin; Kurth, Ingo; Deufel, Thomas; Kessels, Michael M; Qualmann, Britta; Hübner, Christian A

    2013-10-01

    Axonopathies are a group of clinically diverse disorders characterized by the progressive degeneration of the axons of specific neurons. In hereditary spastic paraplegia (HSP), the axons of cortical motor neurons degenerate and cause a spastic movement disorder. HSP is linked to mutations in several loci known collectively as the spastic paraplegia genes (SPGs). We identified a heterozygous receptor accessory protein 1 (REEP1) exon 2 deletion in a patient suffering from the autosomal dominantly inherited HSP variant SPG31. We generated the corresponding mouse model to study the underlying cellular pathology. Mice with heterozygous deletion of exon 2 in Reep1 displayed a gait disorder closely resembling SPG31 in humans. Homozygous exon 2 deletion resulted in the complete loss of REEP1 and a more severe phenotype with earlier onset. At the molecular level, we demonstrated that REEP1 is a neuron-specific, membrane-binding, and membrane curvature-inducing protein that resides in the ER. We further show that Reep1 expression was prominent in cortical motor neurons. In REEP1-deficient mice, these neurons showed reduced complexity of the peripheral ER upon ultrastructural analysis. Our study connects proper neuronal ER architecture to long-term axon survival.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Stress Resultant Based Elasto-Viscoplastic Thick Shell Model

    Directory of Open Access Journals (Sweden)

    Pawel Woelke

    2012-01-01

    Full Text Available The current paper presents enhancement introduced to the elasto-viscoplastic shell formulation, which serves as a theoretical base for the finite element code EPSA (Elasto-Plastic Shell Analysis [1–3]. The shell equations used in EPSA are modified to account for transverse shear deformation, which is important in the analysis of thick plates and shells, as well as composite laminates. Transverse shear forces calculated from transverse shear strains are introduced into a rate-dependent yield function, which is similar to Iliushin's yield surface expressed in terms of stress resultants and stress couples [12]. The hardening rule defined by Bieniek and Funaro [4], which allows for representation of the Bauschinger effect on a moment-curvature plane, was previously adopted in EPSA and is used here in the same form. Viscoplastic strain rates are calculated, taking into account the transverse shears. Only non-layered shells are considered in this work.

  10. 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.

  11. Error statistics of hidden Markov model and hidden Boltzmann model results

    Directory of Open Access Journals (Sweden)

    Newberg Lee A

    2009-07-01

    Full Text Available Abstract Background Hidden Markov models and hidden Boltzmann models are employed in computational biology and a variety of other scientific fields for a variety of analyses of sequential data. Whether the associated algorithms are used to compute an actual probability or, more generally, an odds ratio or some other score, a frequent requirement is that the error statistics of a given score be known. What is the chance that random data would achieve that score or better? What is the chance that a real signal would achieve a given score threshold? Results Here we present a novel general approach to estimating these false positive and true positive rates that is significantly more efficient than are existing general approaches. We validate the technique via an implementation within the HMMER 3.0 package, which scans DNA or protein sequence databases for patterns of interest, using a profile-HMM. Conclusion The new approach is faster than general naïve sampling approaches, and more general than other current approaches. It provides an efficient mechanism by which to estimate error statistics for hidden Markov model and hidden Boltzmann model results.

  12. Modeling results for a linear simulator of a divertor

    Energy Technology Data Exchange (ETDEWEB)

    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.

    1993-06-23

    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 {approximately} 1 Gw/m{sup 2} along the magnetic fieldlines and > 10 MW/m{sup 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.

  13. 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

  14. 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...

  15. Seeing the forest and the trees: multilevel models reveal both species and community patterns

    Science.gov (United States)

    Michelle M. Jackson; Monica G. Turner; Scott M. Pearson; Anthony R. Ives

    2012-01-01

    Studies designed to understand species distributions and community assemblages typically use separate analytical approaches (e.g., logistic regression and ordination) to model the distribution of individual species and to relate community composition to environmental variation. Multilevel models (MLMs) offer a promising strategy for integrating species and community-...

  16. Different human gut models reveal the distinct fermentation patterns of arabinoxylan versus inulin

    NARCIS (Netherlands)

    Abbeele, P. van den; Venema, K.; Wiele, T. van de; Verstraete, W.; Possemiers, S.

    2013-01-01

    Different in vitro models have been developed to assess how food compounds affect the human gut microbiota. Using two such models (SHIME(R) and TIM-2), we compared how long-chain arabinoxylan (LC-AX), a wheat-derived potentially prebiotic fiber, and inulin (IN), a well-established prebiotic

  17. 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

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

    Science.gov (United States)

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

    2016-01-01

    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...

  19. Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals.

    Science.gov (United States)

    Koon, Yen Ling; Koh, Cheng Gee; Chiam, Keng-Hwee

    2014-01-01

    Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational modeling to study the strategies of protein transport in the context of JNK (c-JUN NH2-terminal kinase) transport along microtubules to the terminals of neuronal cells. One such strategy for protein transport is for the proteins of the JNK signaling cascade to bind to scaffolds, and to have the whole protein-scaffold cargo transported by kinesin motors along microtubules. We show how this strategy outperforms protein transport by diffusion alone, using metrics such as signaling rate and signal amplification. We find that there exists a range of scaffold concentrations for which JNK transport is optimal. Increase in scaffold concentration increases signaling rate and signal amplification but an excess of scaffolds results in the dilution of reactants. Similarly, there exists a range of kinesin motor speeds for which JNK transport is optimal. Signaling rate and signal amplification increases with kinesin motor speed until the speed of motor translocation becomes faster than kinase/scaffold-motor binding. Finally, we suggest experiments that can be performed to validate whether, in physiological conditions, neuronal cells do indeed adopt such an optimal strategy. Understanding cytoskeletal-assisted protein transport is crucial since axonal and cell body accumulation of organelles and proteins is a histological feature in many human neurodegenerative diseases. In this paper, we have shown that axonal transport performance changes with altered transport component concentrations and transport speeds wherein these aspects can be modulated to improve axonal efficiency and prevent or slowdown axonal deterioration.

  20. Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals.

    Directory of Open Access Journals (Sweden)

    Yen Ling Koon

    Full Text Available Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational modeling to study the strategies of protein transport in the context of JNK (c-JUN NH2-terminal kinase transport along microtubules to the terminals of neuronal cells. One such strategy for protein transport is for the proteins of the JNK signaling cascade to bind to scaffolds, and to have the whole protein-scaffold cargo transported by kinesin motors along microtubules. We show how this strategy outperforms protein transport by diffusion alone, using metrics such as signaling rate and signal amplification. We find that there exists a range of scaffold concentrations for which JNK transport is optimal. Increase in scaffold concentration increases signaling rate and signal amplification but an excess of scaffolds results in the dilution of reactants. Similarly, there exists a range of kinesin motor speeds for which JNK transport is optimal. Signaling rate and signal amplification increases with kinesin motor speed until the speed of motor translocation becomes faster than kinase/scaffold-motor binding. Finally, we suggest experiments that can be performed to validate whether, in physiological conditions, neuronal cells do indeed adopt such an optimal strategy. Understanding cytoskeletal-assisted protein transport is crucial since axonal and cell body accumulation of organelles and proteins is a histological feature in many human neurodegenerative diseases. In this paper, we have shown that axonal transport performance changes with altered transport component concentrations and transport speeds wherein these aspects can be modulated to improve axonal efficiency and prevent or slowdown axonal deterioration.

  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. Metabolite Profiling Reveals the Effect of Dietary Rubus coreanus Vinegar on Ovariectomy-Induced Osteoporosis in a Rat Model.

    Science.gov (United States)

    Lee, Mee Youn; Kim, Hyang Yeon; Singh, Digar; Yeo, Soo Hwan; Baek, Seong Yeol; Park, Yoo Kyoung; Lee, Choong Hwan

    2016-01-26

    The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats, high-dose RC vinegar (HRV)-treated OVX rats and alendronate (ALEN)-treated OVX rats. The efficacy of RC vinegar was evaluated using physical, biochemical, histological and metabolomic parameters. Compared to the OVX rats, the LRV and HRV groups showed positive effects on the aforementioned parameters, indicating estrogen regulation. Plasma metabolome analysis of the groups using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole-TOF-MS (UPLC-Q-TOF-MS) with multivariate analysis revealed 19 and 16 metabolites, respectively. Notably, the levels of butyric acid, phenylalanine, glucose, tryptophan and some lysophosphatidylcholines were marginally increased in RC vinegar-treated groups compared to OVX. However, the pattern of metabolite levels in RC vinegar-treated groups was found similar to ALEN, but differed significantly from that in sham group. The results highlight the prophylactic and curative potential of dietary vinegar against postmenopausal osteoporosis. RC vinegar could be an effective natural alternative for the prevention of postmenopausal osteoporosis.

  3. A Murine Model for Human ECO Syndrome Reveals a Critical Role of Intestinal Cell Kinase in Skeletal Development.

    Science.gov (United States)

    Ding, Mengmeng; Jin, Li; Xie, Lin; Park, So Hyun; Tong, Yixin; Wu, Di; Chhabra, A Bobby; Fu, Zheng; Li, Xudong

    2018-03-01

    An autosomal-recessive inactivating mutation R272Q in the human intestinal cell kinase (ICK) gene caused profound multiplex developmental defects in human endocrine-cerebro-osteodysplasia (ECO) syndrome. ECO patients exhibited a wide variety of skeletal abnormalities, yet the underlying mechanisms by which ICK regulates skeletal development remained largely unknown. The goal of this study was to understand the structural and mechanistic basis underlying skeletal anomalies caused by ICK dysfunction. Ick R272Q knock-in transgenic mouse model not only recapitulated major ECO skeletal defects such as short limbs and polydactyly but also revealed a deformed spine with defective intervertebral disk. Loss of ICK function markedly reduced mineralization in the spinal column, ribs, and long bones. Ick mutants showed a significant decrease in the proliferation zone of long bones and the number of type X collagen-expressing hypertrophic chondrocytes in the spinal column and the growth plate of long bones. These results implicate that ICK plays an important role in bone and cartilage development by promoting chondrocyte proliferation and maturation. Our findings provided new mechanistic insights into the skeletal phenotype of human ECO and ECO-like syndromes.

  4. 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

    , prediction errors for growth rate and metabolic fluxes were 69% and 14% lower, respectively. The sector-constrained ME model thus represents a generalist ME model reflecting both growth rate maximization and "hedging" against uncertain environments and stresses, as indicated by significant enrichment...... 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......-related protein groups) as demonstrated here. This flexible formalism provides an accessible approach for narrowing the gap between the complexity captured by omics data and governing principles of proteome allocation described by systems-level models....

  5. 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

  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. 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

  8. 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.

  9. Integrating fossils, phylogenies, and niche models into biogeography to reveal ancient evolutionary history: the case of Hypericum (hypericaceae).

    Science.gov (United States)

    Meseguer, Andrea S; Lobo, Jorge M; Ree, Richard; Beerling, David J; Sanmartín, Isabel

    2015-03-01

    In disciplines such as macroevolution that are not amenable to experimentation, scientists usually rely on current observations to test hypotheses about historical events, assuming that "the present is the key to the past." Biogeographers, for example, used this assumption to reconstruct ancestral ranges from the distribution of extant species. Yet, under scenarios of high extinction rates, the biodiversity we observe today might not be representative of the historical diversity and this could result in incorrect biogeographic reconstructions. Here, we introduce a new approach to incorporate into biogeographic inference the temporal, spatial, and environmental information provided by the fossil record, as a direct evidence of the extinct biodiversity fraction. First, inferences of ancestral ranges for those nodes in the phylogeny calibrated with the fossil record are constrained to include the geographic distribution of the fossil. Second, we use fossil distribution and past climate data to reconstruct the climatic preferences and potential distribution of ancestral lineages over time, and use this information to build a biogeographic model that takes into account "ecological connectivity" through time. To show the power of this approach, we reconstruct the biogeographic history of the large angiosperm genus Hypericum, which has a fossil record extending back to the Early Cenozoic. Unlike previous reconstructions based on extant species distributions, our results reveal that Hypericum stem lineages were already distributed in the Holarctic before diversification of its crown-group, and that the geographic distribution of the genus has been relatively stable throughout the climatic oscillations of the Cenozoic. Geographical movement was mediated by the existence of climatic corridors, like Beringia, whereas the equatorial tropical belt acted as a climatic barrier, preventing Hypericum lineages to reach the southern temperate regions. Our study shows that an

  10. 3D radiation belt diffusion model results using new empirical models of whistler chorus and hiss

    Science.gov (United States)

    Cunningham, G.; Chen, Y.; Henderson, M. G.; Reeves, G. D.; Tu, W.

    2012-12-01

    3D diffusion codes model the energization, radial transport, and pitch angle scattering due to wave-particle interactions. Diffusion codes are powerful but are limited by the lack of knowledge of the spatial & temporal distribution of waves that drive the interactions for a specific event. We present results from the 3D DREAM model using diffusion coefficients driven by new, activity-dependent, statistical models of chorus and hiss waves. Most 3D codes parameterize the diffusion coefficients or wave amplitudes as functions of magnetic activity indices like Kp, AE, or Dst. These functional representations produce the average value of the wave intensities for a given level of magnetic activity; however, the variability of the wave population at a given activity level is lost with such a representation. Our 3D code makes use of the full sample distributions contained in a set of empirical wave databases (one database for each wave type, including plasmaspheric hiss, lower and upper hand chorus) that were recently produced by our team using CRRES and THEMIS observations. The wave databases store the full probability distribution of observed wave intensity binned by AE, MLT, MLAT and L*. In this presentation, we show results that make use of the wave intensity sample probability distributions for lower-band and upper-band chorus by sampling the distributions stochastically during a representative CRRES-era storm. The sampling of the wave intensity probability distributions produces a collection of possible evolutions of the phase space density, which quantifies the uncertainty in the model predictions caused by the uncertainty of the chorus wave amplitudes for a specific event. A significant issue is the determination of an appropriate model for the spatio-temporal correlations of the wave intensities, since the diffusion coefficients are computed as spatio-temporal averages of the waves over MLT, MLAT and L*. The spatiotemporal correlations cannot be inferred from the

  11. Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI.

    Science.gov (United States)

    Woodhead, J L; Yang, K; Brouwer, K L R; Siler, S Q; Stahl, S H; Ambroso, J L; Baker, D; Watkins, P B; Howell, B A

    2014-07-09

    Bile salt export pump (BSEP) inhibition has been proposed to be an important mechanism for drug-induced liver injury (DILI). Modeling can prioritize knowledge gaps concerning bile acid (BA) homeostasis and thus help guide experimentation. A submodel of BA homeostasis in rats and humans was constructed within DILIsym, a mechanistic model of DILI. In vivo experiments in rats with glibenclamide were conducted, and data from these experiments were used to validate the model. The behavior of DILIsym was analyzed in the presence of a simulated theoretical BSEP inhibitor. BSEP inhibition in humans is predicted to increase liver concentrations of conjugated chenodeoxycholic acid (CDCA) and sulfate-conjugated lithocholic acid (LCA) while the concentration of other liver BAs remains constant or decreases. On the basis of a sensitivity analysis, the most important unknowns are the level of BSEP expression, the amount of intestinal synthesis of LCA, and the magnitude of farnesoid-X nuclear receptor (FXR)-mediated regulation.

  12. 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...

  13. Revealing spatial pattern dynamics in aquatic ecosystem modelling with Multi-Agent Systems in Lake Veluwe

    NARCIS (Netherlands)

    Li, H.; Mynett, A.; Penning, E.; Qi, H.

    2010-01-01

    Aquatic ecosystems are among the most complex due to the highly nonlinearity, randomness, as well as interactive multi-processes in multi-scales. Besides, highly limited understanding and very limited measurement data make the modelling of such kind of systems a very challenging task, which needs to

  14. Gray box modeling of MSW degradation : Revealing its dominant (bio)chemical mechanism

    NARCIS (Netherlands)

    Van Turnhout, A.G.; Heimovaara, T.J.; Kleerebezem, R.

    2013-01-01

    In this paper we present an approach to describe organic degradation within immobile water regions of Municipal Solid Waste (MSW) landfills which is best described by the term “gray box” model. We use a simplified set of dominant (bio)chemical and physical reactions and realistic environmental

  15. Model-based reasoning: using visual tools to reveal student learning.

    Science.gov (United States)

    Luckie, Douglas; Harrison, Scott H; Ebert-May, Diane

    2011-03-01

    Using visual models is common in science and should become more common in classrooms. Our research group has developed and completed studies on the use of a visual modeling tool, the Concept Connector. This modeling tool consists of an online concept mapping Java applet that has automatic scoring functions we refer to as Robograder. The Concept Connector enables students in large introductory science courses to visualize their thinking through online model building. The Concept Connector's flexible scoring system, based on tested grading schemes as well as instructor input, has enabled >1,000 physiology students to build maps of their ideas about plant and animal physiology with the guidance of automatic and immediate online scoring of homework. Criterion concept maps developed by instructors in this project contain numerous expert-generated or "correct" propositions connecting two concept words together with a linking phrase. In this study, holistic algorithms were used to test automated methods of scoring concept maps that might work as well as a human grader.

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

    NARCIS (Netherlands)

    Ettema, J.|info:eu-repo/dai/nl/304831913; van den Broeke, M.R.|info:eu-repo/dai/nl/073765643; van Meijgaard, E.; van de Berg, W.J.|info:eu-repo/dai/nl/304831611; Bamber, Jonathan L.; Box, J.E.; Bales, R.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. Using fuzzy logic models to reveal farmers' motives to integrate livestock, fish, and crops

    NARCIS (Netherlands)

    Bosma, R.H.

    2007-01-01

    Rural extension services have changed paradigm and shifted to more participatory approaches, whereas in common mathematical models of farming systems, farmers’ motivation is solely represented by ‘utility maximisation’. While globally, farmers specialise, in Vietnam the rice-based systems have

  18. Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation.

    Science.gov (United States)

    Manousopoulou, A; Koutmani, Y; Karaliota, S; Woelk, C H; Manolakos, E S; Karalis, K; Garbis, S D

    2016-04-25

    This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation. Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group; n=7) or a HFD (HFD group; n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR. Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased. High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms

  19. Distribution of glass transition temperatures Tg in polystyrene thin films as revealed by low-energy muon spin relaxation: A comparison with neutron reflectivity results.

    Science.gov (United States)

    Kanaya, Toshiji; Ogawa, Hiroki; Kishimoto, Mizuki; Inoue, Rintaro; Suter, Andreas; Prokscha, Thomas

    2015-08-01

    In a previous paper [Phys. Rev. E 83, 021801 (2011)] we performed neutron reflectivity (NR) measurements on a five-layer polystyrene (PS) thin film consisting of alternatively stacked deuterated polystyrene (dPS) and hydrogenated polystyrene (hPS) layers (dPS/hPS/dPS/hPS/dPS, ∼100 nm thick) on a Si substrate to reveal the distribution of Tg along the depth direction. Information on the Tg distribution is very useful to understand the interesting but unusual properties of polymer thin films. However, one problem that we have to clarify is if there are effects of deuterium labeling on Tg or not. To tackle the problem we performed low-energy muon spin relaxation (μSR) measurements on the above-mentioned deuterium-labeled five-layer PS thin film as well as dPS and hPS single-layer thin films ∼100 nm thick as a function of muon implantation energy. It was found that the deuterium labeling had no significant effects on the Tg distribution, guaranteeing that we can safely discuss the unusual thin film properties based on the Tg distribution revealed by NR on the deuterium-labeled thin films. In addition, the μSR result suggested that the higher Tg near the Si substrate is due to the strong orientation of phenyl rings.

  20. Conserved intergenic sequences revealed by CTAG-profiling in Salmonella: thermodynamic modeling for function prediction

    Science.gov (United States)

    Tang, Le; Zhu, Songling; Mastriani, Emilio; Fang, Xin; Zhou, Yu-Jie; Li, Yong-Guo; Johnston, Randal N.; Guo, Zheng; Liu, Gui-Rong; Liu, Shu-Lin

    2017-03-01

    Highly conserved short sequences help identify functional genomic regions and facilitate genomic annotation. We used Salmonella as the model to search the genome for evolutionarily conserved regions and focused on the tetranucleotide sequence CTAG for its potentially important functions. In Salmonella, CTAG is highly conserved across the lineages and large numbers of CTAG-containing short sequences fall in intergenic regions, strongly indicating their biological importance. Computer modeling demonstrated stable stem-loop structures in some of the CTAG-containing intergenic regions, and substitution of a nucleotide of the CTAG sequence would radically rearrange the free energy and disrupt the structure. The postulated degeneration of CTAG takes distinct patterns among Salmonella lineages and provides novel information about genomic divergence and evolution of these bacterial pathogens. Comparison of the vertically and horizontally transmitted genomic segments showed different CTAG distribution landscapes, with the genome amelioration process to remove CTAG taking place inward from both terminals of the horizontally acquired segment.

  1. Integrative modeling reveals the principles of multi-scale chromatin boundary formation in human nuclear organization.

    Science.gov (United States)

    Moore, Benjamin L; Aitken, Stuart; Semple, Colin A

    2015-05-27

    Interphase chromosomes adopt a hierarchical structure, and recent data have characterized their chromatin organization at very different scales, from sub-genic regions associated with DNA-binding proteins at the order of tens or hundreds of bases, through larger regions with active or repressed chromatin states, up to multi-megabase-scale domains associated with nuclear positioning, replication timing and other qualities. However, we have lacked detailed, quantitative models to understand the interactions between these different strata. Here we collate large collections of matched locus-level chromatin features and Hi-C interaction data, representing higher-order organization, across three human cell types. We use quantitative modeling approaches to assess whether locus-level features are sufficient to explain higher-order structure, and identify the most influential underlying features. We identify structurally variable domains between cell types and examine the underlying features to discover a general association with cell-type-specific enhancer activity. We also identify the most prominent features marking the boundaries of two types of higher-order domains at different scales: topologically associating domains and nuclear compartments. We find parallel enrichments of particular chromatin features for both types, including features associated with active promoters and the architectural proteins CTCF and YY1. We show that integrative modeling of large chromatin dataset collections using random forests can generate useful insights into chromosome structure. The models produced recapitulate known biological features of the cell types involved, allow exploration of the antecedents of higher-order structures and generate testable hypotheses for further experimental studies.

  2. Interstitial void structure in Cu Sn liquid alloy as revealed from reverse Monte Carlo modelling

    Science.gov (United States)

    Hoyer, W.; Kleinhempel, R.; Lorinczi, A.; Pohlers, A.; Popescu, M.; Sava, F.

    2005-02-01

    A model for the structure of copper-tin liquid alloy has been developed using the standard reverse Monte Carlo method. The interstitial void structure (size distribution) was analysed. The effects of various kinds of voids (small size and large size) on the interference function and radial distribution function were investigated. Predictions related to the formation of some ternary alloys by filling the interstices of the basic alloy were advanced.

  3. Crust and Mantle Deformation Revealed from High-Resolution Radially Anisotropic Velocity Models

    Science.gov (United States)

    Li, A.; Dave, R.; Yao, Y.

    2017-12-01

    Love wave tomography, which can achieve a similar model resolution as Rayleigh wave, so far has limited applications to the USArray data. Recently, we have developed high-resolution Love wave phase velocity maps in the Wyoming craton and Texas using data at the Transportable Array stations. 3-D, radially anisotropic velocity models are obtained by jointly inverting Love and Rayleigh wave phase velocities. A high-velocity anomaly extending to about 200 km depth beneath central Wyoming correlates with negative radial anisotropy (Vsv>Vsh), suggesting that mantle downwelling develops under the cratonic lithosphere. Surprisingly, the significantly low velocity beneath the Yellowstone hotspot, which has been interpreted as partial melting and asthenospheric upwelling, is associated with the largest radial anisotropy (Vsh>Vsv) in the area. This observation does not support mantle upwelling. Instead, it indicates that the upper mantle beneath the hotspot has experienced strong shear deformation probably by the plate motion and large-scale mantle flow. In Texas, positive radial anisotropy in the lower crust extends from the coast to the Ouachita belt, which is characterized by high velocity and negative radial anisotropy. In the upper mantle, large variations of velocity and anisotropy exit under the coastal plain. A common feature in these anisotropic models is that high-velocity anomalies in the upper mantle often correlate with negative anisotropy (Vsv>Vsh) while low-velocity anomalies are associated with positive anisotropy (Vsh>Vsv). The manifestation of mantle downweling as negative radial anisotropy is largely due to the relatively high viscosity of the high-velocity mantle block, which is less affected by the surrounding large-scale horizontal flow. However, mantle upwelling, which is often associated with low-velocity anomalies, presumably low-viscosity mantle blocks, is invisible in radial anisotropy models. Such upwelling may happen too quickly to make last

  4. State-space modelling reveals proximate causes of harbour seal population declines.

    Science.gov (United States)

    Matthiopoulos, Jason; Cordes, Line; Mackey, Beth; Thompson, David; Duck, Callan; Smout, Sophie; Caillat, Marjolaine; Thompson, Paul

    2014-01-01

    Declines in large vertebrate populations are widespread but difficult to detect from monitoring data and hard to understand due to a multiplicity of plausible biological explanations. In parts of Scotland, harbour seals (Phoca vitulina) have been in decline for 10 years. To evaluate the contributions of different proximate causes (survival, fecundity, observation artefacts) to this decline, we collated behavioural, demographic and population data from one intensively studied population in part of the Moray Firth (north-east Scotland). To these, we fit a state-space model comprising age-structured dynamics and a detailed account of observation errors. After accounting for culling (estimated by our model as 14% of total mortality), the main driver of the historical population decline was a decreasing trend in survival of young individuals combined with (previously unrecognised) low levels of pupping success. In more recent years, the model provides evidence for considerable increases in breeding success and consistently high levels of adult survival. However, breeding success remains the most volatile demographic component of the population. Forecasts from the model indicate a slow population recovery, providing cautious support for recent management measures. Such investigations of the proximate causes of population change (survival, fecundity and observation errors) provide valuable short-term support for the management of population declines, helping to focus future data collection on those ultimate causal mechanisms that are not excluded by the demographic evidence. The contribution of specific ultimate drivers (e.g. shooting mortality or competitors) can also be quantified by including them as covariates to survival or fecundity.

  5. Phylogenetic structural equation modelling reveals no need for an 'origin' of the leaf economics spectrum.

    Science.gov (United States)

    Mason, Chase M; Goolsby, Eric W; Humphreys, Devon P; Donovan, Lisa A

    2016-01-01

    The leaf economics spectrum (LES) is a prominent ecophysiological paradigm that describes global variation in leaf physiology across plant ecological strategies using a handful of key traits. Nearly a decade ago, Shipley et al. (2006) used structural equation modelling to explore the causal functional relationships among LES traits that give rise to their strong global covariation. They concluded that an unmeasured trait drives LES covariation, sparking efforts to identify the latent physiological trait underlying the 'origin' of the LES. Here, we use newly developed phylogenetic structural equation modelling approaches to reassess these conclusions using both global LES data as well as data collected across scales in the genus Helianthus. For global LES data, accounting for phylogenetic non-independence indicates that no additional unmeasured traits are required to explain LES covariation. Across datasets in Helianthus, trait relationships are highly variable, indicating that global-scale models may poorly describe LES covariation at non-global scales. © 2015 John Wiley & Sons Ltd/CNRS.

  6. Pollution history of a tropical estuary revealed by combined hydrodynamic modelling and sediment geochemistry

    Science.gov (United States)

    Andrews, J. E.; Greenaway, A. M.; Bigg, G. R.; Webber, D. F.; Dennis, P. F.; Guthrie, G. A.

    1999-01-01

    Hydrodynamic modelling of water movement in Hunts Bay, a protected part of Kingston Harbour, Jamaica, shows that depth averaged tidal flows are very low. In the northeast corner of Hunts Bay, water is essentially stagnant. Even under high flow conditions, much of the Bay bottom water is `bypassed' by buoyant, lower salinity surface flows. The muddy sediments of Hunts Bay reflect these sluggish to stagnant conditions; sediment cores from the northeast corner of the Bay contain progressively higher amounts of organic matter in their upper parts (˜last 15-20 years sedimentation). Combined C/N ratios and stable carbon isotope compositions of this organic matter imply a sewage origin. Both lead and chromium metal concentrations and enrichment factors relative to average crustal shales show geographically related patterns that reflect hydrodynamic circulation predicted by modelling. In particular, metal concentrations and enrichment factors are highest at the northern end of the bay, especially in the northeast corner. Modelling confirms that stagnant conditions would occur in the northeast part of the bay even without the presence of a major causeway. The causeway may contribute to low flow conditions, but is not the principal cause of organic contamination, which is simply an excessive input of sewage.

  7. The NMR-Rosetta capsid model of M13 bacteriophage reveals a quadrupled hydrophobic packing epitope.

    Science.gov (United States)

    Morag, Omry; Sgourakis, Nikolaos G; Baker, David; Goldbourt, Amir

    2015-01-27

    Filamentous phage are elongated semiflexible ssDNA viruses that infect bacteria. The M13 phage, belonging to the family inoviridae, has a length of ∼1 μm and a diameter of ∼7 nm. Here we present a structural model for the capsid of intact M13 bacteriophage using Rosetta model building guided by structure restraints obtained from magic-angle spinning solid-state NMR experimental data. The C5 subunit symmetry observed in fiber diffraction studies was enforced during model building. The structure consists of stacked pentamers with largely alpha helical subunits containing an N-terminal type II β-turn; there is a rise of 16.6-16.7 Å and a tilt of 36.1-36.6° between consecutive pentamers. The packing of the subunits is stabilized by a repeating hydrophobic stacking pocket; each subunit participates in four pockets by contributing different hydrophobic residues, which are spread along the subunit sequence. Our study provides, to our knowledge, the first magic-angle spinning NMR structure of an intact filamentous virus capsid and further demonstrates the strength of this technique as a method of choice to study noncrystalline, high-molecular-weight molecular assemblies.

  8. 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

  9. 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.

  10. Active backstop faults in the Mentawai region of Sumatra, Indonesia, revealed by teleseismic broadband waveform modeling

    Science.gov (United States)

    Wang, Xin; Bradley, Kyle Edward; Wei, Shengji; Wu, Wenbo

    2018-02-01

    Two earthquake sequences that affected the Mentawai islands offshore of central Sumatra in 2005 (Mw 6.9) and 2009 (Mw 6.7) have been highlighted as evidence for active backthrusting of the Sumatran accretionary wedge. However, the geometry of the activated fault planes is not well resolved due to large uncertainties in the locations of the mainshocks and aftershocks. We refine the locations and focal mechanisms of medium size events (Mw > 4.5) of these two earthquake sequences through broadband waveform modeling. In addition to modeling the depth-phases for accurate centroid depths, we use teleseismic surface wave cross-correlation to precisely relocate the relative horizontal locations of the earthquakes. The refined catalog shows that the 2005 and 2009 "backthrust" sequences in Mentawai region actually occurred on steeply (∼60 degrees) landward-dipping faults (Masilo Fault Zone) that intersect the Sunda megathrust beneath the deepest part of the forearc basin, contradicting previous studies that inferred slip on a shallowly seaward-dipping backthrust. Static slip inversion on the newly-proposed fault fits the coseismic GPS offsets for the 2009 mainshock equally well as previous studies, but with a slip distribution more consistent with the mainshock centroid depth (∼20 km) constrained from teleseismic waveform inversion. Rupture of such steeply dipping reverse faults within the forearc crust is rare along the Sumatra-Java margin. We interpret these earthquakes as 'unsticking' of the Sumatran accretionary wedge along a backstop fault separating imbricated material from the stronger Sunda lithosphere. Alternatively, the reverse faults may have originated as pre-Miocene normal faults of the extended continental crust of the western Sunda margin. Our waveform modeling approach can be used to further refine global earthquake catalogs in order to clarify the geometries of active faults.

  11. Future change of the global monsoon revealed from 19 CMIP5 models

    Science.gov (United States)

    Hsu, Pang-chi; Li, Tim; Murakami, Hiroyuki; Kitoh, Akio

    2013-02-01

    The variability of global monsoon area (GMA), global monsoon precipitation (GMP), and global monsoon intensity (GMI) in the present climate (1979-2003) and the future warmer climate (2075-2099) under Representative Concentration Pathways 4.5 (RCP4.5) scenario was examined based on 19 Coupled Model Intercomparison Project Phase 5 (CMIP5) simulations. In the present-day simulations, the ensemble mean precipitation reproduces the observed GMA, GMP, and GMI, although the spread of individual models is large. In the RCP4.5 simulations, most (17 of 19) of the CMIP5 models project enhanced global monsoon activity, with the increases of GMA, GMP, and GMI by 1.9%, 3.2%, and 1.3%, respectively, per 1 K of surface warming. The diagnosis of a column-integrated moisture budget indicates that the increase in GMP is primarily attributed to the increases of moisture convergence and surface evaporation, whereas horizontal moisture advection has little effect. A further separation of dynamic and thermodynamic factors shows that increase of the moisture convergence comes mainly from the increase of water vapor, but is partly offset by the convergence effect. The increase of the surface evaporation is caused by the increase of sea-air specific humidity difference, while the change in surface wind speed plays a minor role. The GMP experiences a great year-to-year variation, and it is significantly negatively correlated with the Niño3.4 index averaged over a typical monsoon year (defined from May to the following April) in the pre-industrial control and present-day simulations, similar to observations. Under the RCP4.5 warming, such rainfall variability is intensified, and the relationship between monsoon and El Niño strengthens. A large proportion of intensification in the year-to-year monsoon rainfall variability arises from the land monsoon region.

  12. Mathematical modeling of atopic dermatitis reveals "double-switch" mechanisms underlying 4 common disease phenotypes.

    Science.gov (United States)

    Domínguez-Hüttinger, Elisa; Christodoulides, Panayiotis; Miyauchi, Kosuke; Irvine, Alan D; Okada-Hatakeyama, Mariko; Kubo, Masato; Tanaka, Reiko J

    2017-06-01

    The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical, and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data. We sought to develop a multiscale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress, and immune dysregulation and use it to achieve a coherent mechanistic understanding of the onset, progression, and prevention of AD. We mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form. Our model analysis identified a "double switch," with 2 concatenated bistable switches, as a key network motif that dictates AD pathogenesis: the first switch is responsible for the reversible onset of inflammation, and the second switch is triggered by long-lasting or frequent activation of the first switch, causing irreversible onset of systemic T H 2 sensitization and worsening of AD symptoms. Our mathematical analysis of the bistable switch predicts that genetic risk factors decrease the threshold of environmental stressors to trigger systemic T H 2 sensitization. This analysis predicts and explains 4 common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically demonstrated preventive effects of emollient treatments against development of AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. REVEALING THE ACTIVATION PATHWAY FOR TMEM16A CHLORIDE CHANNELS FROM MACROSCOPIC CURRENTS AND KINETIC MODELS

    Science.gov (United States)

    Contreras-Vite, Juan A.; Cruz-Rangel, Silvia; De Jesús-Pérez, José J.; Aréchiga Figueroa, Iván A.; Rodríguez-Menchaca, Aldo A.; Pérez-Cornejo, Patricia; Hartzell, H. Criss; Arreola, Jorge

    2017-01-01

    TMEM16A (ANO1), the pore-forming subunit of calcium-activated chloride channels, regulates several physiological and pathophysiological processes such as smooth muscle contraction, cardiac and neuronal excitability, salivary secretion, tumour growth, and cancer progression. Gating of TMEM16A is complex because it involves the interplay between increases in intracellular calcium concentration ([Ca2+]i), membrane depolarization, extracellular Cl− or permeant anions, and intracellular protons. Our goal here was to understand how these variables regulate TMEM16A gating and to explain four observations. a) TMEM16A is activated by voltage in the absence of intracellular Ca2+. b) The Cl− conductance is decreased after reducing extracellular Cl− concentration ([Cl−]o). c) ICl is regulated by physiological concentrations of [Cl−]o. d) In cells dialyzed with 0.2 µM [Ca2+]i, Cl− has a bimodal effect: at [Cl−]o < 30 mM TMEM16A current activates with a monoexponential time course, but above 30 mM [Cl−]o ICl activation displays fast and slow kinetics. To explain the contribution of Vm, Ca2+ and Cl− to gating, we developed a 12-state Markov chain model. This model explains TMEM16A activation as a sequential, direct, and Vm-dependent binding of two Ca2+ ions coupled to a Vm-dependent binding of an external Cl− ion, with Vm-dependent transitions between states. Our model predicts that extracellular Cl− does not alter the apparent Ca2+ affinity of TMEM16A, which we corroborated experimentally. Rather, extracellular Cl− acts by stabilizing the open configuration induced by Ca2+ and by contributing to the Vm dependence of activation. PMID:27138167

  14. Large-scale Models Reveal the Two-component Mechanics of Striated Muscle

    Directory of Open Access Journals (Sweden)

    Robert Jarosch

    2008-12-01

    Full Text Available This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit. Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation. Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with forceregulating sites for Ca2+ binding, the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

  15. 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

  16. Using simulations and kinetic network models to reveal the dynamics and functions of riboswitches.

    Science.gov (United States)

    Lin, Jong-Chin; Yoon, Jeseong; Hyeon, Changbong; Thirumalai, D

    2015-01-01

    Riboswitches, RNA elements found in the untranslated region, regulate gene expression by binding to target metaboloites with exquisite specificity. Binding of metabolites to the conserved aptamer domain allosterically alters the conformation in the downstream expression platform. The fate of gene expression is determined by the changes in the downstream RNA sequence. As the metabolite-dependent cotranscriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate both the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolite. Single molecule force experiments that decipher the free energy landscape of riboswitches from their mechanical responses, theoretical and computational studies have recently shed light on the distinct mechanism of folding dynamics in different classes of riboswitches. Here, we first discuss the dynamics of water around riboswitch, highlighting that water dynamics can enhance the fluctuation of nucleic acid structure. To go beyond native state fluctuations, we used the Self-Organized Polymer model to predict the dynamics of add adenine riboswitch under mechanical forces. In addition to quantitatively predicting the folding landscape of add-riboswitch, our simulations also explain the difference in the dynamics between pbuE adenine- and add adenine-riboswitches. In order to probe the function in vivo, we use the folding landscape to propose a system level kinetic network model to quantitatively predict how gene expression is regulated for riboswitches that are under kinetic control. © 2015 Elsevier Inc. All rights reserved.

  17. 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)

  18. Probabilistic modelling of chromatin code landscape reveals functional diversity of enhancer-like chromatin states

    Science.gov (United States)

    Zhou, Jian; Troyanskaya, Olga G.

    2016-01-01

    Interpreting the functional state of chromatin from the combinatorial binding patterns of chromatin factors, that is, the chromatin codes, is crucial for decoding the epigenetic state of the cell. Here we present a systematic map of Drosophila chromatin states derived from data-driven probabilistic modelling of dependencies between chromatin factors. Our model not only recapitulates enhancer-like chromatin states as indicated by widely used enhancer marks but also divides these states into three functionally distinct groups, of which only one specific group possesses active enhancer activity. Moreover, we discover a strong association between one specific enhancer state and RNA Polymerase II pausing, linking transcription regulatory potential and chromatin organization. We also observe that with the exception of long-intron genes, chromatin state transition positions in transcriptionally active genes align with an absolute distance to their corresponding transcription start site, regardless of gene length. Using our method, we provide a resource that helps elucidate the functional and spatial organization of the chromatin code landscape. PMID:26841971

  19. Generalized additive models reveal the intrinsic complexity of wood formation dynamics.

    Science.gov (United States)

    Cuny, Henri E; Rathgeber, Cyrille B K; Kiessé, Tristan Senga; Hartmann, Felix P; Barbeito, Ignacio; Fournier, Meriem

    2013-04-01

    The intra-annual dynamics of wood formation, which involves the passage of newly produced cells through three successive differentiation phases (division, enlargement, and wall thickening) to reach the final functional mature state, has traditionally been described in conifers as three delayed bell-shaped curves followed by an S-shaped curve. Here the classical view represented by the 'Gompertz function (GF) approach' was challenged using two novel approaches based on parametric generalized linear models (GLMs) and 'data-driven' generalized additive models (GAMs). These three approaches (GFs, GLMs, and GAMs) were used to describe seasonal changes in cell numbers in each of the xylem differentiation phases and to calculate the timing of cell development in three conifer species [Picea abies (L.), Pinus sylvestris L., and Abies alba Mill.]. GAMs outperformed GFs and GLMs in describing intra-annual wood formation dynamics, showing two left-skewed bell-shaped curves for division and enlargement, and a right-skewed bimodal curve for thickening. Cell residence times progressively decreased through the season for enlargement, whilst increasing late but rapidly for thickening. These patterns match changes in cell anatomical features within a tree ring, which allows the separation of earlywood and latewood into two distinct cell populations. A novel statistical approach is presented which renews our understanding of xylogenesis, a dynamic biological process in which the rate of cell production interplays with cell residence times in each developmental phase to create complex seasonal patterns.

  20. 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.

  1. Dissociable perceptual-learning mechanisms revealed by diffusion-model analysis.

    Science.gov (United States)

    Petrov, Alexander A; Van Horn, Nicholas M; Ratcliff, Roger

    2011-06-01

    Performance on perceptual tasks improves with practice. Most theories address only accuracy data and tacitly assume that perceptual learning is a monolithic phenomenon. The present study pioneers the use of response time distributions in perceptual learning research. The 27 observers practiced a visual motion-direction discrimination task with filtered-noise textures for four sessions with feedback. Session 5 tested whether the learning effects transferred to the orthogonal direction. The diffusion model (Ratcliff, Psychological Review, 85, 59-108, 1978) achieved good fits to the individual response time distributions from each session and identified two distinct learning mechanisms with markedly different specificities. A stimulus-specific increase in the drift-rate parameter indicated improved sensory input to the decision process, and a stimulus-general decrease in nondecision time variability suggested improved timing of the decision process onset relative to stimulus onset (which was preceded by a beep). A traditional d' analysis would miss the latter effect, but the diffusion-model analysis identified it in the response time data.

  2. 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.

  3. 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'.

  4. Structure of naturally hydrated ferrihydrite revealed through neutron diffraction and first-principles modeling

    Science.gov (United States)

    Chappell, Helen F.; Thom, William; Bowron, Daniel T.; Faria, Nuno; Hasnip, Philip J.; Powell, Jonathan J.

    2017-08-01

    Ferrihydrite, with a ``two-line'' x-ray diffraction pattern (2L-Fh), is the most amorphous of the iron oxides and is ubiquitous in both terrestrial and aquatic environments. It also plays a central role in the regulation and metabolism of iron in bacteria, algae, higher plants, and animals, including humans. In this study, we present a single-phase model for ferrihydrite that unifies existing analytical data while adhering to fundamental chemical principles. The primary particle is small (20-50 Å) and has a dynamic and variably hydrated surface, which negates long-range order; collectively, these features have hampered complete characterization and frustrated our understanding of the mineral's reactivity and chemical/biochemical function. Near and intermediate range neutron diffraction (NIMROD) and first-principles density functional theory (DFT) were employed in this study to generate and interpret high-resolution data of naturally hydrated, synthetic 2L-Fh at standard temperature. The structural optimization overcomes transgressions of coordination chemistry inherent within previously proposed structures, to produce a robust and unambiguous single-phase model.

  5. A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.

    Directory of Open Access Journals (Sweden)

    Maren Mönnich

    Full Text Available The human developmental diseases Cornelia de Lange Syndrome (CdLS and Roberts Syndrome (RBS are both caused by mutations in proteins responsible for sister chromatid cohesion. Cohesion is mediated by a multi-subunit complex called cohesin, which is loaded onto chromosomes by NIPBL. Once on chromosomes, cohesin binding is stabilized in S phase upon acetylation by ESCO2. CdLS is caused by heterozygous mutations in NIPBL or cohesin subunits SMC1A and SMC3, and RBS is caused by homozygous mutations in ESCO2. The genetic cause of both CdLS and RBS reside within the chromosome cohesion apparatus, and therefore they are collectively known as "cohesinopathies". However, the two syndromes have distinct phenotypes, with differences not explained by their shared ontology. In this study, we have used the zebrafish model to distinguish between developmental pathways downstream of cohesin itself, or its acetylase ESCO2. Esco2 depleted zebrafish embryos exhibit features that resemble RBS, including mitotic defects, craniofacial abnormalities and limb truncations. A microarray analysis of Esco2-depleted embryos revealed that different subsets of genes are regulated downstream of Esco2 when compared with cohesin subunit Rad21. Genes downstream of Rad21 showed significant enrichment for transcriptional regulators, while Esco2-regulated genes were more likely to be involved the cell cycle or apoptosis. RNA in situ hybridization showed that runx1, which is spatiotemporally regulated by cohesin, is expressed normally in Esco2-depleted embryos. Furthermore, myca, which is downregulated in rad21 mutants, is upregulated in Esco2-depleted embryos. High levels of cell death contributed to the morphology of Esco2-depleted embryos without affecting specific developmental pathways. We propose that cell proliferation defects and apoptosis could be the primary cause of the features of RBS. Our results show that mutations in different elements of the cohesion apparatus have

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

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    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.

  7. 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.

  8. 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

  9. Mesoscopic models for DNA stretching under force: New results and comparison with experiments.

    Science.gov (United States)

    Manghi, Manoel; Destainville, Nicolas; Palmeri, John

    2012-10-01

    Single-molecule experiments on double-stranded B-DNA stretching have revealed one or two structural transitions, when increasing the external force. They are characterized by a sudden increase of DNA contour length and a decrease of the bending rigidity. The nature and the critical forces of these transitions depend on DNA base sequence, loading rate, salt conditions and temperature. It has been proposed that the first transition, at forces of 60-80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA, while the second one, at stronger forces, is a strand peeling resulting in single-stranded DNAs (ssDNA), similar to thermal denaturation. But due to experimental conditions these two transitions can overlap, for instance for poly(dA-dT). In an attempt to propose a coherent picture compatible with this variety of experimental observations, we derive an analytical formula using a coupled discrete worm-like chain-Ising model. Our model takes into account bending rigidity, discreteness of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit of zero force, this model simplifies into a coupled model already developed by us for studying thermal DNA melting, establishing a connection with previous fitting parameter values for denaturation profiles. Our results are summarized as follows: i) ssDNA is fitted, using an analytical formula, over a nano-Newton range with only three free parameters, the contour length, the bending modulus and the monomer size; ii) a surprisingly good fit on this force range is possible only by choosing a monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase length; iii) mesoscopic models are not able to fit B to ssDNA (or S to ss) transitions; iv) an analytical formula for fitting B to S transitions is derived in the strong force approximation and for long DNAs, which is in excellent agreement with exact transfer matrix calculations; v) this formula fits perfectly well poly(dG-dC) and

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Jérôme R D Soiné

    2015-03-01

    Full Text Available 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.

  12. Computational modeling of the hematopoietic erythroid-myeloid switch reveals insights into cooperativity, priming, and irreversibility.

    Directory of Open Access Journals (Sweden)

    Vijay Chickarmane

    2009-01-01

    Full Text Available Hematopoietic stem cell lineage choices are decided by genetic networks that are turned ON/OFF in a switch-like manner. However, prior to lineage commitment, genes are primed at low expression levels. Understanding the underlying molecular circuitry in terms of how it governs both a primed state and, at the other extreme, a committed state is of relevance not only to hematopoiesis but also to developmental systems in general. We develop a computational model for the hematopoietic erythroid-myeloid lineage decision, which is determined by a genetic switch involving the genes PU.1 and GATA-1. Dynamical models based upon known interactions between these master genes, such as mutual antagonism and autoregulation, fail to make the system bistable, a desired feature for robust lineage determination. We therefore suggest a new mechanism involving a cofactor that is regulated as well as recruited by one of the master genes to bind to the antagonistic partner that is necessary for bistability and hence switch-like behavior. An interesting fallout from this architecture is that suppression of the cofactor through external means can lead to a loss of cooperativity, and hence to a primed state for PU.1 and GATA-1. The PU.1-GATA-1 switch also interacts with another mutually antagonistic pair, C/EBPalpha-FOG-1. The latter pair inherits the state of its upstream master genes and further reinforces the decision due to several feedback loops, thereby leading to irreversible commitment. The genetic switch, which handles the erythroid-myeloid lineage decision, is an example of a network that implements both a primed and a committed state by regulating cooperativity through recruitment of cofactors. Perturbing the feedback between the master regulators and downstream targets suggests potential reprogramming strategies. The approach points to a framework for lineage commitment studies in general and could aid the search for lineage-determining genes.

  13. Recovery or decline of the Black Sea: A societal choice revealed by socio-ecological modelling

    NARCIS (Netherlands)

    Langmead, O.; McQuatters-Gollop, A.; Mee, L.; Friedrich, J.; Gilbert, A.J.; Gormoiu, M.-T.; Jackson, E. L.; Knudsen, S.; Minicheva, G.; Todorova, V.

    2009-01-01

    During recent decades anthropogenic activities have dramatically impacted the Black Sea ecosystem. High levels of riverine nutrient input during the 1970s and 1980s caused eutrophic conditions including intense algal blooms resulting in hypoxia and the subsequent collapse of benthic habitats on the

  14. Dansgaard Oeschger Dynamics: Clearly Revealed in a Comprehensive Model of Glacial Climate

    Science.gov (United States)

    Peltier, W. Richard; Vettoretti, Guido

    2017-04-01

    More than 30 years ago, Willi Dansgaard in Copenhagen and Hans Oeschger in Bern established the existence of millennium timescale oscillations in oxygen isotope stratigraphies from Greenland ice cores. This isotopic signal was interpreted as implying large amplitude variations in surface air temperature. Until the publication of Peltier and Vettoretti (2014, GRL) the prevalent view had been that this exclusively ice-age phenomenon, thought to be linked to variability in the strength of the Atlantic MOC, was considered to be forced by the episodic release of freshwater from the continental ice sheets, each oscillation requiring its own freshwater input. In Peltier and Vettoretti (2014) this phenomenon was recovered for the first time in a comprehensive model of glacial climate, specifically the CESM1 model of the NCAR laboratory. Attention was drawn to the fact that individual D-O oscillations, or Bond Cycle clusters of such oscillations, were inevitably preceded by individual Heinrich events. In Peltier and Vettoretti (2014) it was shown that, following the "spin-up" of CESM1 into the glacial state, with continental ice sheet volume held fixed, a sequence of nonlinear unforced and therefor "free" oscillations of the MOC occurred, following a sharp Heinrich event-like sharp suppression of MOC strength. All of the salient characteristics of the D-O process inferred on the basis of ice core evidence from both hemispheres were fully captured in these high (CMIP5) resolution simulations, namely: (i) the pulse shape of the individual oscillations characterized by an extremely rapid shift from cold stadial to warm interstadial conditions followed by a slow return to the stadial state, (ii) the peak-to-peak variations in Greenland surface air temperature of 10-15 degrees Centigrade during individual oscillations, (iii) the "bi-polar see saw" connection between this Northern Hemisphere process and that recorded in the EDML and WAIS Divide ice cores from Antarctica, (iv) the

  15. Surface-based morphometry reveals the neuroanatomical basis of the five-factor model of personality.

    Science.gov (United States)

    Riccelli, Roberta; Toschi, Nicola; Nigro, Salvatore; Terracciano, Antonio; Passamonti, Luca

    2017-04-01

    The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project.Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal-temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal-parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders. © The Author (2017). Published by Oxford University Press.

  16. Revealing chemophoric sites in organophosphorus insecticides through the MIA-QSPR modeling of soil sorption data.

    Science.gov (United States)

    Daré, Joyce K; Silva, Cristina F; Freitas, Matheus P

    2017-10-01

    Soil sorption of insecticides employed in agriculture is an important parameter to probe the environmental fate of organic chemicals. Therefore, methods for the prediction of soil sorption of new agrochemical candidates, as well as for the rationalization of the molecular characteristics responsible for a given sorption profile, are extremely beneficial for the environment. A quantitative structure-property relationship method based on chemical structure images as molecular descriptors provided a reliable model for the soil sorption prediction of 24 widely used organophosphorus insecticides. By means of contour maps obtained from the partial least squares regression coefficients and the variable importance in projection scores, key molecular moieties were targeted for possible structural modification, in order to obtain novel and more environmentally friendly insecticide candidates. The image-based descriptors applied encode molecular arrangement, atoms connectivity, groups size, and polarity; consequently, the findings in this work cannot be achieved by a simple relationship with hydrophobicity, usually described by the octanol-water partition coefficient. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Sector analysis and predictive modelling reveal iterative shoot-like development in fern fronds.

    Science.gov (United States)

    Sanders, Heather L; Darrah, Peter R; Langdale, Jane A

    2011-07-01

    Plants colonized the terrestrial environment over 450 million years ago. Since then, shoot architecture has evolved in response to changing environmental conditions. Our current understanding of the innovations that altered shoot morphology is underpinned by developmental studies in a number of plant groups. However, the least is known about mechanisms that operate in ferns--a key group for understanding the evolution of plant development. Using a novel combination of sector analysis, conditional probability modelling methods and histology, we show that shoots, fronds ('leaves') and pinnae ('leaflets') of the fern Nephrolepis exaltata all develop from single apical initial cells. Shoot initials cleave on three faces to produce a pool of cells from which individual frond apical initials are sequentially specified. Frond initials then cleave in two planes to produce a series of lateral merophyte initials that each contributes a unit of three pinnae to half of the mediolateral frond axis. Notably, this iterative pattern in both shoots and fronds is similar to the developmental process that operates in shoots of other plant groups. Pinnae initials first cleave in two planes to generate lateral marginal initials. The apical and marginal initials then divide in three planes to coordinately generate the determinate pinna. These findings impact both on our understanding of fundamental plant developmental processes and on our perspective of how shoot systems evolved.

  18. Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models.

    Science.gov (United States)

    Dourado, Keina M C; Baik, June; Oliveira, Vanessa K P; Beltrame, Miriam; Yamamoto, Ami; Theuer, Charles P; Figueiredo, Camila A V; Verneris, Michael R; Perlingeiro, Rita C R

    2017-05-04

    Endoglin (CD105), a receptor of the transforming growth factor-β superfamily, has been reported to identify functional long-term repopulating hematopoietic stem cells, and has been detected in certain subtypes of acute leukemias. Whether this receptor plays a functional role in leukemogenesis remains unknown. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105 + blasts are endowed with superior leukemogenic activity compared with the CD105 - population. We test the effect of targeting this receptor using the monoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemia progression following disease establishment, but in B-ALL, TRC105 alone was ineffective due to the shedding of soluble CD105. However, in both B-ALL and AML, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis, indicating that TRC105 may represent a novel therapeutic option for B-ALL and AML. © 2017 by The American Society of Hematology.

  19. New insight into motor adaptation to pain revealed by a combination of modelling and empirical approaches.

    Science.gov (United States)

    Hodges, P W; Coppieters, M W; MacDonald, D; Cholewicki, J

    2013-09-01

    Movement changes in pain. Unlike the somewhat stereotypical response of limb muscles to pain, trunk muscle responses are highly variable when challenged by pain in that region. This has led many to question the existence of a common underlying theory to explain the adaptation. Here, we tested the hypotheses that (1) adaptation in muscle activation in acute pain leads to enhanced spine stability, despite variation in the pattern of muscle activation changes; and (2) individuals would use a similar 'signature' pattern for tasks with different mechanical demands. In 17 healthy individuals, electromyography recordings were made from a broad array of anterior and posterior trunk muscles while participants moved slowly between trunk flexion and extension with and without experimentally induced back pain. Hypotheses were tested by estimating spine stability (Stability Index) with an electromyography-driven spine model and analysis of individual and overall (net) adaptations in muscle activation. The Stability Index (P individuals used the same pattern of adaptation in muscle activity. For most, the adaptation was similar between movement directions despite opposite movement demands. These data provide the first empirical confirmation that, in most individuals, acute back pain leads to increased spinal stability and that the pattern of muscle activity is not stereotypical, but instead involves an individual-specific response to pain. This adaptation is likely to provide short-term benefit to enhance spinal protection, but could have long-term consequences for spinal health. © 2013 European Federation of International Association for the Study of Pain Chapters.

  20. Systems analysis of eleven rodent disease models reveals an inflammatome signature and key drivers.

    Science.gov (United States)

    Wang, I-Ming; Zhang, Bin; Yang, Xia; Zhu, Jun; Stepaniants, Serguei; Zhang, Chunsheng; Meng, Qingying; Peters, Mette; He, Yudong; Ni, Chester; Slipetz, Deborah; Crackower, Michael A; Houshyar, Hani; Tan, Christopher M; Asante-Appiah, Ernest; O'Neill, Gary; Luo, Mingjuan Jane; Thieringer, Rolf; Yuan, Jeffrey; Chiu, Chi-Sung; Lum, Pek Yee; Lamb, John; Boie, Yves; Wilkinson, Hilary A; Schadt, Eric E; Dai, Hongyue; Roberts, Christopher

    2012-07-17

    Common inflammatome gene signatures as well as disease-specific signatures were identified by analyzing 12 expression profiling data sets derived from 9 different tissues isolated from 11 rodent inflammatory disease models. The inflammatome signature significantly overlaps with known drug targets and co-expressed gene modules linked to metabolic disorders and cancer. A large proportion of genes in this signature are tightly connected in tissue-specific Bayesian networks (BNs) built from multiple independent mouse and human cohorts. Both the inflammatome signature and the corresponding consensus BNs are highly enriched for immune response-related genes supported as causal for adiposity, adipokine, diabetes, aortic lesion, bone, muscle, and cholesterol traits, suggesting the causal nature of the inflammatome for a variety of diseases. Integration of this inflammatome signature with the BNs uncovered 151 key drivers that appeared to be more biologically important than the non-drivers in terms of their impact on disease phenotypes. The identification of this inflammatome signature, its network architecture, and key drivers not only highlights the shared etiology but also pinpoints potential targets for intervention of various common diseases.

  1. 3D gravity modelling reveals off-axis crustal thickness variations along the western Gakkel Ridge (Arctic Ocean)

    Science.gov (United States)

    Schmidt-Aursch, Mechita C.; Jokat, Wilfried

    2016-11-01

    Near-orthogonal ultra-slow (13.3 mm yr- 1 to 6.5 mm yr- 1) sea floor spreading in the absence of large transform faults make the Arctic Gakkel Ridge ideally suited for the study of magmatic processes. To enable this, we generated a three-dimensional gravity model of crustal thickness over the ridge and parts of the adjacent Nansen and Amundsen basins west of 65° E. The model shows that oceanic crust accreted prior to chrons C5/C6 is generally very thin (1-3 km). Magnetic anomalies over this thin crust are highly variable both parallel and perpendicular to the ridge axis. This is the result of amagmatic or weakly volcanic spreading that started with the opening of the basins 56 Ma ago. The separation of Greenland from Svalbard at chron C5/C6 led to the inflow of North Atlantic mantle into the western Eurasia Basin leading to a change in the mantle convection system and the establishment of a magmatic dichotomy along the Gakkel Ridge. Robust magmatism was established in the Western Volcanic Zone (6° 30‧ W-3° 30‧ E), leading to creation of a 6.6 km thick igneous crust, characterized by a strong positive axial magnetic anomaly, numerous volcanic cones, and widespread thick mid-ocean ridge basalts. The transition to the neighbouring Sparsely Magmatic (3° 30‧ E-29° E) and Eastern Volcanic (29° E-85° E) zones is sharp. Peridotites cover the central valley and the inner rift flanks, the central magnetic anomaly vanishes and crustal thickness decreases to 1-4 km. Transverse basement ridges, extending for as much as 100 km into the adjacent basins, intersect the central valley. Although partly of tectonic origin, the transverse ridges are also an expression of long-living magmatic centres, as revealed by increased magnetic anomaly intensities and local thickening of the crust to values as great as 5.9 km.

  2. 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.

  3. 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

  4. Diversity and distribution of nuclease bacteriocins in bacterial genomes revealed using Hidden Markov Models.

    Directory of Open Access Journals (Sweden)

    Connor Sharp

    2017-07-01

    Full Text Available Bacteria exploit an arsenal of antimicrobial peptides and proteins to compete with each other. Three main competition systems have been described: type six secretion systems (T6SS; contact dependent inhibition (CDI; and bacteriocins. Unlike T6SS and CDI systems, bacteriocins do not require contact between bacteria but are diffusible toxins released into the environment. Identified almost a century ago, our understanding of bacteriocin distribution and prevalence in bacterial populations remains poor. In the case of protein bacteriocins, this is because of high levels of sequence diversity and difficulties in distinguishing their killing domains from those of other competition systems. Here, we develop a robust bioinformatics pipeline exploiting Hidden Markov Models for the identification of nuclease bacteriocins (NBs in bacteria of which, to-date, only a handful are known. NBs are large (>60 kDa toxins that target nucleic acids (DNA, tRNA or rRNA in the cytoplasm of susceptible bacteria, usually closely related to the producing organism. We identified >3000 NB genes located on plasmids or on the chromosome from 53 bacterial species distributed across different ecological niches, including human, animals, plants, and the environment. A newly identified NB predicted to be specific for Pseudomonas aeruginosa (pyocin Sn was produced and shown to kill P. aeruginosa thereby validating our pipeline. Intriguingly, while the genes encoding the machinery needed for NB translocation across the cell envelope are widespread in Gram-negative bacteria, NBs are found exclusively in γ-proteobacteria. Similarity network analysis demonstrated that NBs fall into eight groups each with a distinct arrangement of protein domains involved in import. The only structural feature conserved across all groups was a sequence motif critical for cell-killing that is generally not found in bacteriocins targeting the periplasm, implying a specific role in translocating the

  5. 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.

  6. 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

  7. Photospheric Current Spikes And Their Possible Association With Flares - Results from an HMI Data Driven Model

    Science.gov (United States)

    Goodman, M. L.; Kwan, C.; Ayhan, B.; Eric, S. L.

    2016-12-01

    A data driven, near photospheric magnetohydrodynamic model predicts spikes in the horizontal current density, and associated resistive heating rate. The spikes appear as increases by orders of magnitude above background values in neutral line regions (NLRs) of active regions (ARs). The largest spikes typically occur a few hours to a few days prior to M or X flares. The spikes correspond to large vertical derivatives of the horizontal magnetic field. The model takes as input the photospheric magnetic field observed by the Helioseismic & Magnetic Imager (HMI) on the Solar Dynamics Observatory (SDO) satellite. This 2.5 D field is used to determine an analytic expression for a 3 D magnetic field, from which the current density, vector potential, and electric field are computed in every AR pixel for 14 ARs. The field is not assumed to be force-free. The spurious 6, 12, and 24 hour Doppler periods due to SDO orbital motion are filtered out of the time series of the HMI magnetic field for each pixel. The subset of spikes analyzed at the pixel level are found to occur on HMI and granulation scales of 1 arcsec and 12 minutes. Spikes are found in ARs with and without M or X flares, and outside as well as inside NLRs, but the largest spikes are localized in the NLRs of ARs with M or X flares. The energy to drive the heating associated with the largest current spikes comes from bulk flow kinetic energy, not the electromagnetic field, and the current density is highly non-force free. The results suggest that, in combination with the model, HMI is revealing strong, convection driven, non-force free heating events on granulation scales, and it is plausible these events are correlated with subsequent M or X flares. More and longer time series need to be analyzed to determine if such a correlation exists.

  8. Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.

    Science.gov (United States)

    Williams, Stephen R; Zies, Deborah; Mullegama, Sureni V; Grotewiel, Michael S; Elsea, Sarah H

    2012-06-08

    Haploinsufficiency of RAI1 results in Smith-Magenis syndrome (SMS), a disorder characterized by intellectual disability, multiple congenital anomalies, obesity, neurobehavioral abnormalities, and a disrupted circadian sleep-wake pattern. An inverted melatonin rhythm (i.e., melatonin peaks during the day instead of at night) and associated sleep-phase disturbances in individuals with SMS, as well as a short-period circadian rhythm in mice with a chromosomal deletion of Rai1, support SMS as a circadian-rhythm-dysfunction disorder. However, the molecular cause of the circadian defect in SMS has not been described. The circadian oscillator temporally orchestrates metabolism, physiology, and behavior largely through transcriptional modulation. Data support RAI1 as a transcriptional regulator, but the genes it might regulate are largely unknown. Investigation into the role that RAI1 plays in the regulation of gene transcription and circadian maintenance revealed that RAI1 regulates the transcription of circadian locomotor output cycles kaput (CLOCK), a key component of the mammalian circadian oscillator that transcriptionally regulates many critical circadian genes. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others. These data suggest that heterozygous mutation of RAI1 and Rai1 leads to a disrupted circadian rhythm and thus results in an abnormal sleep-wake cycle, which can contribute to an abnormal feeding pattern and dependent cognitive performance. Finally, we conclude that RAI1 is a positive transcriptional regulator of CLOCK, pinpointing a novel and important role for this gene in the circadian oscillator. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. 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.

  10. 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...

  11. Revealing a cancer diagnosis to patients: attitudes of patients, families, friends, nurses, and physicians in Lebanon—results of a cross-sectional study

    Science.gov (United States)

    Farhat, F.; Othman, A.; el Baba, G.; Kattan, J.

    2015-01-01

    Background Disclosure of a cancer diagnosis to patients is a major problem for physicians in Lebanon. Our survey aimed to identify the attitudes of patients, families and friends, nurses, and physicians regarding disclosure of a cancer diagnosis. Methods Study participants included 343 physicians, nurses, cancer patients, families, and friends from clinics in two major hospitals in Lebanon. All completed a 29-item questionnaire that assessed, by demographic group, the information provided about cancer, opinions about the disclosure of the diagnosis to cancer patients, perceived consequences to patients, and the roles of family, friends, and religion. Results Overall, 7.8% of the patients were convinced that cancer is incurable. Nearly 82% preferred to be informed about their diagnosis. Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to their patients. However, only 14% of the physicians said that they revealed the truth to the patients themselves, with only 9% doing so immediately after confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred before the start of the treatment by 59% of the patients and immediately after confirmation of the diagnosis by 72% of the physicians. Overall, 86% of physicians, 51% of nurses, and 69% of patients and their families believed that religion helped with the acceptance of a cancer diagnosis. A role for family in accepting the diagnosis was reported by 74% of the patients, 56% of the nurses, and 88% of the physicians. All participants considered that fear was the most difficult feeling (63%) experienced by cancer patients, followed by pain (29%), pity (8%), and death (1%), with no statistically significant difference between the answers given by the participant groups. Conclusions The social background in Lebanese society is the main obstacle to revealing the truth to cancer patients. Lebanese patients seem to prefer direct communication of the truth, but families take the opposite

  12. Integrating social model principles into broad-based treatment: results of a program evaluation.

    Science.gov (United States)

    Polcin, Douglas L; Prindle, Suzi D; Bostrom, Alan

    2002-11-01

    Although traditional social model recovery programs appear to be decreasing, some aspects of social model recovery continue to exert a strong influence in broad-based, integrated programs. This article describes a four-week program that integrates licensed therapists, certified counselors, psychiatric consultation, and social model recovery principles into a broad-based treatment approach. The Social Model Philosophy Scale revealed a low overall rating on social model philosophy. However, social model principles that were heavily stressed included practicing 12-step recovery, the importance of getting a 12-step sponsor, staff-client interactions outside a formal office, employing staff who are in recovery, and emphasizing a goal of abstinence. Three- and six-month follow-up revealed significant improvement in alcohol and drug use, heavy alcohol use, satisfaction with family relationships, 12-step involvement, illegal behaviors, arrests, unsafe sex, self-esteem, use of medical resources, and health status. Findings provide a rationale for larger, multi-site studies that assess the effectiveness of social model characteristics using multivariate techniques.

  13. Regression mixture models : Does modeling the covariance between independent variables and latent classes improve the results?

    NARCIS (Netherlands)

    Lamont, A.E.; Vermunt, J.K.; Van Horn, M.L.

    2016-01-01

    Regression mixture models are increasingly used as an exploratory approach to identify heterogeneity in the effects of a predictor on an outcome. In this simulation study, we tested the effects of violating an implicit assumption often made in these models; that is, independent variables in the

  14. Modeling drifting snow in Antarctica with a regional climate model: 2. Results

    NARCIS (Netherlands)

    Lenaerts, J.T.M.; van den Broeke, M.R.

    2012-01-01

    This paper presents a model study of the impact of drifting snow on the lower atmosphere, surface snow characteristics, and surface mass balance of Antarctica. We use the regional atmospheric climate model RACMO2.1/ANT with a high horizontal resolution (27 km), equipped with a drifting snow routine

  15. 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

  16. The MARINA model (Model to Assess River Inputs of Nutrients to seAs): Model description and results for China.

    Science.gov (United States)

    Strokal, Maryna; Kroeze, Carolien; Wang, Mengru; Bai, Zhaohai; Ma, Lin

    2016-08-15

    Chinese agriculture has been developing fast towards industrial food production systems that discharge nutrient-rich wastewater into rivers. As a result, nutrient export by rivers has been increasing, resulting in coastal water pollution. We developed a Model to Assess River Inputs of Nutrients to seAs (MARINA) for China. The MARINA Nutrient Model quantifies river export of nutrients by source at the sub-basin scale as a function of human activities on land. MARINA is a downscaled version for China of the Global NEWS-2 (Nutrient Export from WaterSheds) model with an improved approach for nutrient losses from animal production and population. We use the model to quantify dissolved inorganic and organic nitrogen (N) and phosphorus (P) export by six large rivers draining into the Bohai Gulf (Yellow, Hai, Liao), Yellow Sea (Yangtze, Huai) and South China Sea (Pearl) in 1970, 2000 and 2050. We addressed uncertainties in the MARINA Nutrient model. Between 1970 and 2000 river export of dissolved N and P increased by a factor of 2-8 depending on sea and nutrient form. Thus, the risk for coastal eutrophication increased. Direct losses of manure to rivers contribute to 60-78% of nutrient inputs to the Bohai Gulf and 20-74% of nutrient inputs to the other seas in 2000. Sewage is an important source of dissolved inorganic P, and synthetic fertilizers of dissolved inorganic N. Over half of the nutrients exported by the Yangtze and Pearl rivers originated from human activities in downstream and middlestream sub-basins. The Yellow River exported up to 70% of dissolved inorganic N and P from downstream sub-basins and of dissolved organic N and P from middlestream sub-basins. Rivers draining into the Bohai Gulf are drier, and thus transport fewer nutrients. For the future we calculate further increases in river export of nutrients. The MARINA Nutrient model quantifies the main sources of coastal water pollution for sub-basins. This information can contribute to formulation of

  17. Report on the results of studies on revised ECCS evaluation models for LWR power plants

    International Nuclear Information System (INIS)

    1978-01-01

    For evaluating the function and performance of emergency core cooling systems of LWR power plants, the use of the ECCS evaluation models of GE and westinghouse are permitted. For the models, however, the formulae of correlation with higher accuracy were developed along with the accumulation of results of experimental and theoretical studies in the field. Revision to the models has thus been proposed on the basis of the results of researches both in Japan and abroad. Such alterations and the results of the studies thereon are described. The following matters are described: on the evaluation models for BWR ECCS, CCFL model, low flow rate film boiling heat transfer coefficient, radiation heat transfer model, and critical flow model; on the evaluation models, for PWR ECCS, heat radiation, between fuel rods, accumulator injection pressure loss in reflooding, rupture of cladding tubes, hot wall delay, model of steam cooling in reflooding 17 x 17 core ELECHT correlation, and temperature at reactor vessel top. (Mori, K.)

  18. 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.

  19. 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.

  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. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Channel Verification Results for the SCME models in a Multi-Probe Based MIMO OTA Setup

    DEFF Research Database (Denmark)

    Fan, Wei; Carreño, Xavier; S. Ashta, Jagjit

    2013-01-01

    , where the focus is on comparing results from various proposed methods. Channel model verification is necessary to ensure that the target channel models are correctly implemented inside the test area. This paper shows that the all the key parameters of the SCME models, i.e., power delay profile, temporal...

  8. Recent trends of extreme precipitation indices in the Iberian Peninsula using observations and WRF model results

    Science.gov (United States)

    Bartolomeu, S.; Carvalho, M. J.; Marta-Almeida, M.; Melo-Gonçalves, P.; Rocha, A.

    2016-08-01

    Spatial and temporal distributions of the trends of extreme precipitation indices were analysed between 1986 and 2005, over the Iberian Peninsula (IP). The knowledge of the patterns of extreme precipitation is important for impacts assessment, development of adaptation and mitigation strategies. As such, there is a growing need for a more detailed knowledge of precipitation climate change. This analysis was performed for Portuguese and Spanish observational datasets and results performed by the Weather Research and Forecast (WRF) model forced by the ERA-Interim reanalysis. Extreme precipitation indices recommended by the Expert Team for Climate Change Detection Monitoring and Indices were computed, by year and season. Then, annual and seasonal trends of the indices were estimated by Theil-Sen method and their significance was tested by the Mann-Kendal test. Additionally, a second simulation forced by the Max Planck Institute Earth System Model (MPI-ESM), was considered. This second modelling configuration was created in order to assess its performance when simulating extremes of precipitation. The annual trends estimated for the 1986-2005, from the observational datasets and from the ERA-driven simulation reveal: 1) negative statistically significant trends of the CWD index in the Galicia and in the centre of the IP; 2) positive statistically significant trends of the CDD index over the south of the IP and negative statistically significant trends in Galicia, north and centre of Portugal; 3) positive statistically significant trends of the R75p index in some regions of the north of the IP; 4) positive statistically significant trends in the R95pTOT index in the Central Mountains Chain, Leon Mountains and in the north of Portugal. Seasonally, negative statistically significant trends of the CWD index were found in Galicia, in winter and in the south of the IP, in summer. Positive statistically significant trends of the CWD index were identified in the Leon Mountains

  9. 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

  10. Dynamical implications of prescribing part of a coupled system: Results from a low-order model

    Directory of Open Access Journals (Sweden)

    A. T. Wittenberg

    1998-01-01

    Full Text Available It is a common procedure in climate modelling to specify dynamical system components from an external source; a prominent example is the forcing of an atmospheric model with observed sea surface temperatures. In this paper, we examine the dynamics of such forced models using a simple prototype climate system. A particular fully coupled run of the model is designated the "true" solution, and an ensemble of perturbed initial states is generated by adding small errors to the "true" initial state. The perturbed ensemble is then integrated for the same period as the true solution, using both the fully-coupled model and a model in which the ocean is prescribed exactly from the true solution at every time step. Although the prescribed forcing is error-free, the forced-atmosphere ensemble is shown to converge to spurious solutions. Statistical tests show that neither the time-mean state nor the variability of the forced ensemble is consistent with the fully-coupled system. A stability analysis reveals the source of the inconsistency, and suggests that such behaviour may be a more general feature of models with prescribed subsystems. Possible implications for model validation and predictability are discussed.

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

    Science.gov (United States)

    Trnka, Miroslav; Eitzinger, Josef; Kapler, Pavel; Dubrovský, Martin; Semerádová, Daniela; Žalud, Zdeněk; Formayer, Herbert

    2007-10-16

    The results of previous studies have suggested that estimated daily globalradiation (R G ) values contain an error that could compromise the precision of subsequentcrop model applications. The following study presents a detailed site and spatial analysis ofthe R G 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 R G values were available as a reference, withseven methods for R G estimation being tested, and ii) for the agricultural areas of the CzechRepublic using daily data from 52 weather stations, with five R G estimation methods. In thelatter case the R G values estimated from the hours of sunshine using the ångström-Prescottformula were used as the standard method because of the lack of measured R G data. At thesite level we found that even the use of methods based on hours of sunshine, which showedthe lowest bias in R G estimates, led to a significant distortion of the key crop model outputs.When the ångström-Prescott method was used to estimate R G , 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 R G 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 R G 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 R G data uncertainty propagation over the winter wheat yields also revealed significant differences within the study area. We found that R G estimates based on

  12. 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

  13. A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

    Science.gov (United States)

    Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

    2017-01-01

    The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs. DOI: http://dx.doi.org/10.7554/eLife.22772.001 PMID:28695824

  14. Integrated biology approach reveals molecular and pathological interactions among Alzheimer's Aβ42, Tau, TREM2, and TYROBP in Drosophila models.

    Science.gov (United States)

    Sekiya, Michiko; Wang, Minghui; Fujisaki, Naoki; Sakakibara, Yasufumi; Quan, Xiuming; Ehrlich, Michelle E; De Jager, Philip L; Bennett, David A; Schadt, Eric E; Gandy, Sam; Ando, Kanae; Zhang, Bin; Iijima, Koichi M

    2018-03-29

    Cerebral amyloidosis, neuroinflammation, and tauopathy are key features of Alzheimer's disease (AD), but interactions among these features remain poorly understood. Our previous multiscale molecular network models of AD revealed TYROBP as a key driver of an immune- and microglia-specific network that was robustly associated with AD pathophysiology. Recent genetic studies of AD further identified pathogenic mutations in both TREM2 and TYROBP. In this study, we systematically examined molecular and pathological interactions among Aβ, tau, TREM2, and TYROBP by integrating signatures from transgenic Drosophila models of AD and transcriptome-wide gene co-expression networks from two human AD cohorts. Glial expression of TREM2/TYROBP exacerbated tau-mediated neurodegeneration and synergistically affected pathways underlying late-onset AD pathology, while neuronal Aβ42 and glial TREM2/TYROBP synergistically altered expression of the genes in synaptic function and immune modules in AD. The comprehensive pathological and molecular data generated through this study strongly validate the causal role of TREM2/TYROBP in driving molecular networks in AD and AD-related phenotypes in flies.

  15. Norfolk Harbor and Channels Deepening Study. Report 1. Physical Model Results. Chesapeake Bay Hydraulic Model Investigation.

    Science.gov (United States)

    1983-06-01

    These mechanisms consist of a feedback system that is entirely self-contained and is not dependent on computer feedback for adjustment. The system...reproducing a variable hydro- graph freshwater inflow through the use of positive feedback control of river discharges. Fresh water normally enters the model...juni of the I IOW patter-1 it Lte in, aI t he )Jillls . ’Ihe othle r t o .Lames ranges , JN02 arnd JG63 , show s I i gilt dt-( I 1ae 1. IAm If I I iti

  16. 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.

  17. 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

    2015-05-21

    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.

  18. 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.

  19. 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.

  20. 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.)

  1. Low-resolution molecular models reveal the oligomeric state of the PPAR and the conformational organization of its domains in solution.

    Directory of Open Access Journals (Sweden)

    Amanda Bernardes

    Full Text Available The peroxisome proliferator-activated receptors (PPARs regulate genes involved in lipid and carbohydrate metabolism, and are targets of drugs approved for human use. Whereas the crystallographic structure of the complex of full length PPARγ and RXRα is known, structural alterations induced by heterodimer formation and DNA contacts are not well understood. Herein, we report a small-angle X-ray scattering analysis of the oligomeric state of hPPARγ alone and in the presence of retinoid X receptor (RXR. The results reveal that, in contrast with other studied nuclear receptors, which predominantly form dimers in solution, hPPARγ remains in the monomeric form by itself but forms heterodimers with hRXRα. The low-resolution models of hPPARγ/RXRα complexes predict significant changes in opening angle between heterodimerization partners (LBD and extended and asymmetric shape of the dimer (LBD-DBD as compared with X-ray structure of the full-length receptor bound to DNA. These differences between our SAXS models and the high-resolution crystallographic structure might suggest that there are different conformations of functional heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange experiments reveal that the heterodimer binding to DNA promotes more compact and less solvent-accessible conformation of the receptor complex.

  2. 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

  3. 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.

  4. Striatal and Hippocampal Entropy and Recognition Signals in Category Learning: Simultaneous Processes Revealed by Model-Based fMRI

    Science.gov (United States)

    Davis, Tyler; Love, Bradley C.; Preston, Alison R.

    2012-01-01

    Category learning is a complex phenomenon that engages multiple cognitive processes, many of which occur simultaneously and unfold dynamically over time. For example, as people encounter objects in the world, they simultaneously engage processes to determine their fit with current knowledge structures, gather new information about the objects, and adjust their representations to support behavior in future encounters. Many techniques that are available to understand the neural basis of category learning assume that the multiple processes that subserve it can be neatly separated between different trials of an experiment. Model-based functional magnetic resonance imaging offers a promising tool to separate multiple, simultaneously occurring processes and bring the analysis of neuroimaging data more in line with category learning’s dynamic and multifaceted nature. We use model-based imaging to explore the neural basis of recognition and entropy signals in the medial temporal lobe and striatum that are engaged while participants learn to categorize novel stimuli. Consistent with theories suggesting a role for the anterior hippocampus and ventral striatum in motivated learning in response to uncertainty, we find that activation in both regions correlates with a model-based measure of entropy. Simultaneously, separate subregions of the hippocampus and striatum exhibit activation correlated with a model-based recognition strength measure. Our results suggest that model-based analyses are exceptionally useful for extracting information about cognitive processes from neuroimaging data. Models provide a basis for identifying the multiple neural processes that contribute to behavior, and neuroimaging data can provide a powerful test bed for constraining and testing model predictions. PMID:22746951

  5. 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

  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. Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity

    OpenAIRE

    Peng, Mengling; Li, Shengnan; He, Qianian; Zhao, Jinlong; Li, Longlong; Ma, Haitian

    2018-01-01

    Background Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. Results In this study, the abundances of 293 hepatic proteins...

  8. 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

  9. 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.

  10. The temporal-spatial dynamics of feature maps during monocular deprivation revealed by chronic imaging and self-organization model simulation.

    Science.gov (United States)

    Tong, Lei; Xie, Yang; Yu, Hongbo

    2016-12-17

    Experiments on the adult visual cortex of cats, ferrets and monkeys have revealed organized spatial relationships between multiple feature maps which can also be reproduced by the Kohonen and elastic net self-organization models. However, attempts to apply these models to simulate the temporal kinetics of monocular deprivation (MD) during the critical period, and their effects on the spatial arrangement of feature maps, have led to conflicting results. In this study, we performed MD and chronic imaging in the ferret visual cortex during the critical period of ocular dominance (OD) plasticity. We also used the Kohonen model to simulate the effects of MD on OD and orientation map development. Both the experiments and simulations demonstrated two general parameter-insensitive findings. Specifically, our first finding demonstrated that the OD index shift resulting from MD, and its subsequent recovery during binocular vision (BV), were both nonlinear, with a significantly stronger shift occurring during the initial period. Meanwhile, spatial reorganization of feature maps led to globally unchanged but locally shifted map patterns. In detail, we found that the periodicity of OD and orientation maps remained unchanged during, and after, deprivation. Relationships between OD and orientation maps remained similar but were significantly weakened due to OD border shifts. These results indicate that orthogonal gradient relationships between maps may be preset and are only mildly modifiable during the critical period. The Kohonen model was able to reproduce these experimental results, hence its role is further extended to the description of cortical feature map dynamics during development. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b.

    Science.gov (United States)

    Vogelgesang, Steffen; Niebert, Sabine; Renner, Ute; Möbius, Wiebke; Hülsmann, Swen; Manzke, Till; Niebert, Marcus

    2017-01-01

    Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). Although alteration in serotonin levels have been reported in RTT patients, the molecular mechanisms underlying these defects are not well understood. Therefore, we chose to investigate the serotonergic system in hippocampus and brainstem of male Mecp2 -/y knock-out mice in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The serotonergic system in mouse is comprised of 16 genes, whose mRNA expression profile was analyzed by quantitative RT-PCR. Mecp2 -/y mice are an established animal model for RTT displaying most of the cognitive and physical impairments of human patients and the selected areas receive significant modulation through serotonin. Using anatomically and functional characterized areas, we found region-specific differential expression between wild type and Mecp2 -/y mice at post-natal day 40. In brainstem, we found five genes to be dysregulated, while in hippocampus, two genes were dysregulated. The one gene dysregulated in both brain regions was dopamine decarboxylase, but of special interest is the serotonin receptor 5b (5-ht 5b ), which showed 75-fold dysregulation in brainstem of Mecp2 -/y mice. This dysregulation was not due to upregulation, but due to failure of down-regulation in Mecp2 -/y mice during development. Detailed analysis of 5-ht 5b revealed a receptor that localizes to endosomes and interacts with G αi proteins.

  12. Revealing common disease mechanisms shared by tumors of different tissues of origin through semantic representation of genomic alterations and topic modeling.

    Science.gov (United States)

    Chen, Vicky; Paisley, John; Lu, Xinghua

    2017-03-14

    Cancer is a complex disease driven by somatic genomic alterations (SGAs) that perturb signaling pathways and consequently cellular function. Identifying patterns of pathway perturbations would provide insights into common disease mechanisms shared among tumors, which is important for guiding treatment and predicting outcome. However, identifying perturbed pathways is challenging, because different tumors can have the same perturbed pathways that are perturbed by different SGAs. Here, we designed novel semantic representations that capture the functional similarity of distinct SGAs perturbing a common pathway in different tumors. Combining this representation with topic modeling would allow us to identify patterns in altered signaling pathways. We represented each gene with a vector of words describing its function, and we represented the SGAs of a tumor as a text document by pooling the words representing individual SGAs. We applied the nested hierarchical Dirichlet process (nHDP) model to a collection of tumors of 5 cancer types from TCGA. We identified topics (consisting of co-occurring words) representing the common functional themes of different SGAs. Tumors were clustered based on their topic associations, such that each cluster consists of tumors sharing common functional themes. The resulting clusters contained mixtures of cancer types, which indicates that different cancer types can share disease mechanisms. Survival analysis based on the clusters revealed significant differences in survival among the tumors of the same cancer type that were assigned to different clusters. The results indicate that applying topic modeling to semantic representations of tumors identifies patterns in the combinations of altered functional pathways in cancer.

  13. Radiative effects of a CO2 increase: Results of a model comparison

    International Nuclear Information System (INIS)

    Luther, F.M.

    1992-01-01

    Many infrared (IR) radiative transfer models have been developed that range in complexity from line-by-line calculations to simplified parameterizations used in climate models and general circulation models. Assessment of the potential climatic effects of trace gases such as carbon dioxide requires first an evaluation of the radiative properties of each gas and determination of the perturbation to the radiative fluxes. The most detailed radiative transfer models are well suited for this application. The perturbed radiative fluxes lead to climatic effects that are evaluated using models that couple radiative, dynamic transport, and hydrological processes. Recently, chemical interactions have also been included in the assessments. It is desirable that a better understanding be developed of the differences in model approaches used by various modeling groups and how these differences affect model sensitivity to perturbations such as increased carbon dioxide. Since many factors affect model sensitivity, a practical approach is to start with a comparison of the basic physical processes without feedbacks and couplings, then to build in complexity. Because increases in carbon dioxide leads to radiative forcing, the treatment of radiative processes is a natural starting point for comparison. A comparison of infrared radiative transfer models has begun under the auspices of the US Department of Energy's Carbon Dioxide Research Program. The results of the IR model comparison will be included in the state-of-the-art report on climate modeling

  14. Results and Comparison from the SAM Linear Fresnel Technology Performance Model: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, M. J.

    2012-04-01

    This paper presents the new Linear Fresnel technology performance model in NREL's System Advisor Model. The model predicts the financial and technical performance of direct-steam-generation Linear Fresnel power plants, and can be used to analyze a range of system configurations. This paper presents a brief discussion of the model formulation and motivation, and provides extensive discussion of the model performance and financial results. The Linear Fresnel technology is also compared to other concentrating solar power technologies in both qualitative and quantitative measures. The Linear Fresnel model - developed in conjunction with the Electric Power Research Institute - provides users with the ability to model a variety of solar field layouts, fossil backup configurations, thermal receiver designs, and steam generation conditions. This flexibility aims to encompass current market solutions for the DSG Linear Fresnel technology, which is seeing increasing exposure in fossil plant augmentation and stand-alone power generation applications.

  15. Metabolic and transcriptomic analysis of Huntington’s disease model reveal changes in intracellular glucose levels and related genes

    Directory of Open Access Journals (Sweden)

    Gepoliano Chaves

    2017-08-01

    Full Text Available Huntington’s Disease (HD is a neurodegenerative disorder caused by an expansion in a CAG-tri-nucleotide repeat that introduces a poly-glutamine stretch into the huntingtin protein (mHTT. Mutant huntingtin (mHTT has been associated with several phenotypes including mood disorders and depression. Additionally, HD patients are known to be more susceptible to type II diabetes mellitus (T2DM, and HD mice model develops diabetes. However, the mechanism and pathways that link Huntington’s disease and diabetes have not been well established. Understanding the underlying mechanisms can reveal potential targets for drug development in HD. In this study, we investigated the transcriptome of mHTT cell populations alongside intracellular glucose measurements using a functionalized nanopipette. Several genes related to glucose uptake and glucose homeostasis are affected. We observed changes in intracellular glucose concentrations and identified altered transcript levels of certain genes including Sorcs1, Hh-II and Vldlr. Our data suggest that these can be used as markers for HD progression. Sorcs1 may not only have a role in glucose metabolism and trafficking but also in glutamatergic pathways affecting trafficking of synaptic components.

  16. A novel approach to PTSD modeling in rats reveals alternating patterns of limbic activity in different types of stress reaction.

    Science.gov (United States)

    Ritov, G; Boltyansky, B; Richter-Levin, G

    2016-05-01

    Human reactions to trauma exposure are extremely diverse, with some individuals exhibiting only time-limited distress and others qualifying for posttraumatic stress disorder diagnosis (PTSD). Furthermore, whereas most PTSD patients mainly display fear-based symptoms, a minority of patients display a co-morbid anhedonic phenotype. We employed an individual profiling approach to model these intriguing facets of the psychiatric condition in underwater-trauma exposed rats. Based on long-term assessments of anxiety-like and anhedonic behaviors, our analysis uncovered three separate phenotypes of stress response; an anxious, fear-based (38%), a co-morbid, fear-anhedonic (15%), and an exposed-unaffected group (47%). Immunohistochemical assessments for cellular activation (c-Fos) and activation of inhibition (c-Fos+GAD67) revealed a differential involvement of limbic regions and distinct co-activity patterns for each of these phenotypes, validating the behavioral categorization. In accordance with recent neurocognitive hypotheses for posttraumatic depression, we show that enhanced pretrauma anxiety predicts the progression of posttraumatic anhedonia only in the fear-anhedonic phenotype.

  17. 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.

  18. An outcome-based learning model to identify emerging threats : experimental and simulation results.

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Moyano, I. J.; Conrad, S. H.; Andersen, D. F.; Decision and Information Sciences; SNL; Univ. at Albany

    2007-01-01

    The authors present experimental and simulation results of an outcome-based learning model as it applies to the identification of emerging threats. This model integrates judgment, decision making, and learning theories to provide an integrated framework for the behavioral study of emerging threats.

  19. The European Integrated Tokamak Modelling (ITM) effort: achievements and first physics results

    NARCIS (Netherlands)

    G.L. Falchetto,; Coster, D.; Coelho, R.; Scott, B. D.; Figini, L.; Kalupin, D.; Nardon, E.; Nowak, S.; L.L. Alves,; Artaud, J. F.; Basiuk, V.; João P.S. Bizarro,; C. Boulbe,; Dinklage, A.; Farina, D.; B. Faugeras,; Ferreira, J.; Figueiredo, A.; Huynh, P.; Imbeaux, F.; Ivanova-Stanik, I.; Jonsson, T.; H.-J. Klingshirn,; Konz, C.; Kus, A.; Marushchenko, N. B.; Pereverzev, G.; M. Owsiak,; Poli, E.; Peysson, Y.; R. Reimer,; Signoret, J.; Sauter, O.; Stankiewicz, R.; Strand, P.; Voitsekhovitch, I.; Westerhof, E.; T. Zok,; Zwingmann, W.; ITM-TF contributors,; ASDEX Upgrade team,; JET-EFDA Contributors,

    2014-01-01

    A selection of achievements and first physics results are presented of the European Integrated Tokamak Modelling Task Force (EFDA ITM-TF) simulation framework, which aims to provide a standardized platform and an integrated modelling suite of validated numerical codes for the simulation and

  20. 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.

  1. Modelling of water potential and water uptake rate of tomato plants in the greenhouse: preliminary results.

    NARCIS (Netherlands)

    Bruggink, G.T.; Schouwink, H.E.; Gieling, Th.H.

    1988-01-01

    A dynamic model is presented which predicts water potential and water uptake rate of greenhouse tomato plants using transpiration rate as input. The model assumes that water uptake is the resultant of water potential and hydraulic resistance, and that water potential is linearly related to water

  2. Mobile satellite propagation measurements and modeling: A review of results for systems engineers

    Science.gov (United States)

    Stutzman, W. L. (Editor); Barts, R. M.; Bostian, C. W.; Butterworth, J. S.; Campbell, R.; Goldhirsh, J.; Vogel, W. J.

    1988-01-01

    An overview of Mobile Satellite System (MSS) propagation measurements and modeling is given, including a summary of results. The simple models presented should be of some use to systems engineers. A complete summary of propagation experiments with literature references is included.

  3. 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

  4. 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.

  5. 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,...

  6. 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.

  7. 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.

  8. Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method.

    Directory of Open Access Journals (Sweden)

    Martin Meier-Schellersheim

    2006-07-01

    Full Text Available The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential activation/deactivation of membrane-bound and cytosolic components. As such, it provides particularly interesting challenges for a combined computational and experimental analysis. We developed a novel detailed molecular signaling model that, when used to simulate the response to the attractant cyclic adenosine monophosphate (cAMP, made nontrivial predictions about Dictyostelium chemosensing. These predictions, including the unexpected existence of spatially asymmetrical, multiphasic, cyclic adenosine monophosphate-induced PTEN translocation and phosphatidylinositol-(3,4,5P3 generation, were experimentally verified by quantitative single-cell microscopy leading us to propose significant modifications to the current standard model for chemoattractant-induced biochemical polarization in this organism. Key to this successful modeling effort was the use of "Simmune," a new software package that supports the facile development and testing of detailed computational representations of cellular behavior. An intuitive interface allows user definition of complex signaling networks based on the definition of specific molecular binding site interactions and the subcellular localization of molecules. It automatically translates such inputs into spatially resolved simulations and dynamic graphical representations of the resulting signaling network that can be explored in a manner that closely parallels wet lab experimental procedures. These features of Simmune were critical to the model development and analysis presented here and are likely to be useful in the computational investigation of many aspects of cell biology.

  9. 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.

  10. 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.

  11. High-speed video gait analysis reveals early and characteristic locomotor phenotypes in mouse models of neurodegenerative movement disorders.

    Science.gov (United States)

    Preisig, Daniel F; Kulic, Luka; Krüger, Maik; Wirth, Fabian; McAfoose, Jordan; Späni, Claudia; Gantenbein, Pascal; Derungs, Rebecca; Nitsch, Roger M; Welt, Tobias

    2016-09-15

    Neurodegenerative diseases of the central nervous system frequently affect the locomotor system resulting in impaired movement and gait. In this study we performed a whole-body high-speed video gait analysis in three different mouse lines of neurodegenerative movement disorders to investigate the motor phenotype. Based on precise computerized motion tracking of all relevant joints and the tail, a custom-developed algorithm generated individual and comprehensive locomotor profiles consisting of 164 spatial and temporal parameters. Gait changes observed in the three models corresponded closely to the classical clinical symptoms described in these disorders: Muscle atrophy due to motor neuron loss in SOD1 G93A transgenic mice led to gait characterized by changes in hind-limb movement and positioning. In contrast, locomotion in huntingtin N171-82Q mice modeling Huntington's disease with basal ganglia damage was defined by hyperkinetic limb movements and rigidity of the trunk. Harlequin mutant mice modeling cerebellar degeneration showed gait instability and extensive changes in limb positioning. Moreover, model specific gait parameters were identified and were shown to be more sensitive than conventional motor tests. Altogether, this technique provides new opportunities to decipher underlying disease mechanisms and test novel therapeutic approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. 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

    . 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...... grains per unit A(V), and not only in the starlight intensity. These results show that some of the physical assumptions of the DL model will need to be revised. To circumvent the model deficiency, we propose an empirical renormalization of the DL A(V) estimate, dependent of U-min, which compensates...

  13. 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.

  14. Age, introduction of solid feed and weaning are more important determinants of gut bacterial succession in piglets than breed and nursing mother as revealed by a reciprocal cross-fostering model

    NARCIS (Netherlands)

    Bian, Gaorui; Ma, Shouqing; Zhu, Zhigang; Su, Yong; Zoetendal, Erwin G.; Mackie, Roderick; Liu, Junhua; Mu, Chunlong; Huang, Ruihua; Smidt, Hauke; Zhu, Weiyun

    2016-01-01

    A reciprocal cross-fostering model with an obese typical Chinese piglet breed and a lean Western breed was used to identify genetic and maternal effects on the acquisition and development gut bacteria from birth until after weaning. Pyrosequencing of 16S rRNA genes results revealed an age- and

  15. Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

    NARCIS (Netherlands)

    H. Wesseling (Hendrik); P.C. Guest (Paul); C.-M. Lee (Chi-Ming); E.H.F. Wong (Erik); H. Rahmoune (Hassan); S. Bahn (Sabine)

    2014-01-01

    textabstractBackground: Over the last decade, the transgenic N-methyl-D-aspartate receptor (NMDAR) NR1-knockdown mouse (NR1neo-/-) has been investigated as a glutamate hypofunction model for schizophrenia. Recent research has now revealed that the model also recapitulates cognitive and negative

  16. 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......, 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...... experiments need to be extrapolated to more general situations (e.g. to real houses or even to other soil–gas pollutants). Finally, models provide a cost-effective test bench for improved designs of radon prevention systems. The paper includes a summary of transport equations and boundary conditions...

  17. 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)

  18. RELATIONSHIP BETWEEN ISO 9001 CERTIFICATION MATURITY AND EFQM BUSINESS EXCELLENCE MODEL RESULTS

    Directory of Open Access Journals (Sweden)

    Luis Miguel Fonseca

    2015-07-01

    Full Text Available Purpose: This exploratory research evaluates if there a relationship between the number of years since an organization has achieved ISO 9001 certification and the highest level of recognition received by the same organization with the EFQM Business Excellence Model.Methodology/Approach: After state of the art review a detailed comparison between both models was made. Fifty two Portuguese organizations were considered and Correlation coefficient Spearman Rho was used to investigate the possible relationships.Findings: Conclusion is that there is indeed a moderate positive correlation between these two variables, the higher the number of years of ISO 9001 certification, the higher the results of the organization EFQM model evaluation and recognition. This supports the assumption that ISO 9001 International Standard by incorporating many of the principles present in the EFQM Business Excellence Model is consistent with this model and can be considered as a step towards that direction.Research Limitation/implication: Due to the dynamic nature of these models that might change over time and the possible time delays between implementation and results, more in-depth studies like experimental design or a longitudinal quasi-experimental design could be used to confirm the results of this investigation.Originality/Value of paper: This research gives additional insights on conjunct studies of both models. The use of external evaluation results carried out by the independent EFQM assessors minimizes the possible bias of previous studies accessing the value of ISO 9001 certification.

  19. Radiation Transfer Model Intercomparison (RAMI) exercise: Results from the second phase

    Science.gov (United States)

    Pinty, B.; Widlowski, J.-L.; Taberner, M.; Gobron, N.; Verstraete, M. M.; Disney, M.; Gascon, F.; Gastellu, J.-P.; Jiang, L.; Kuusk, A.; Lewis, P.; Li, X.; Ni-Meister, W.; Nilson, T.; North, P.; Qin, W.; Su, L.; Tang, S.; Thompson, R.; Verhoef, W.; Wang, H.; Wang, J.; Yan, G.; Zang, H.

    2004-03-01

    The Radiation Transfer Model Intercomparison (RAMI) initiative is a community-driven exercise to benchmark the models of radiation transfer (RT) used to represent the reflectance of terrestrial surfaces. Systematic model intercomparisons started in 1999 as a self-organized, open-access, voluntary activity of the RT modeling community. The results of the first phase were published by [2001]. The present paper describes the benchmarking protocol and the results achieved during the second phase, which took place during 2002. This second phase included two major components: The first one included a rerun of all direct-mode tests proposed during the first phase, to accommodate the evaluation of models that have been upgraded since, and the participation of new models into the entire exercise. The second component was designed to probe the performance of three-dimensional models in complex heterogeneous environments, which closely mimic the observations of actual space instruments operating at various spatial resolutions over forest canopy systems. Phases 1 and 2 of RAMI both confirm not only that a majority of the radiation transfer models participating in RAMI are in good agreement between themselves for relatively simple radiation transfer problems but also that these models exhibit significant discrepancies when considering more complex but nevertheless realistic geophysical scenarios. Specific recommendations are provided to guide the future of this benchmarking program (Phase 3 and beyond).

  20. [Analysis of the model OPM3®application and results for health area].

    Science.gov (United States)

    Augusto Dos Santos, Luis; de Fátima Marin, Heimar

    2011-01-01

    This research sought to analyze if a questionnaire model created by an international community of project management is applicable to health organizations. The model OPM3 ® (Organizational Project Management Maturity Model) was created in order that organizations of any area or size can identify the presence or absence of good management practices. The aim of applying this model is to always evaluate the organization and not the interviewee. In this paper, one presents the results of employing this model in an organization that has information technology products and services applied to health area. This study verified that the model is rapidly applicable and that the analyzed organization has an expressive number of good practices.

  1. A New Explanation and Proof of the Paradoxical Scoring Results in Multidimensional Item Response Models.

    Science.gov (United States)

    Jordan, Pascal; Spiess, Martin

    2017-10-13

    In multidimensional item response models, paradoxical scoring effects can arise, wherein correct answers are penalized and incorrect answers are rewarded. For the most prominent class of IRT models, the class of linearly compensatory models, a general derivation of paradoxical scoring effects based on the geometry of item discrimination vectors is given, which furthermore corrects an error in an established theorem on paradoxical results. This approach highlights the very counterintuitive way in which item discrimination parameters (and also factor loadings) have to be interpreted in terms of their influence on the latent ability estimate. It is proven that, despite the error in the original proof, the key result concerning the existence of paradoxical effects remains true-although the actual relation to the item parameters is shown to be a more complicated function than previous results suggested. The new proof enables further insights into the actual mathematical causation of the paradox and generalizes the findings within the class of linearly compensatory models.

  2. 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)

  3. A Tower Model for Lightning Overvoltage Studies Based on the Result of an FDTD Simulation

    Science.gov (United States)

    Noda, Taku

    This paper describes a method for deriving a transmission tower model for EMTP lightning overvoltage studies from a numerical electromagnetic simulation result obtained by the FDTD (Finite Difference Time Domain) method. The FDTD simulation carried out in this paper takes into account the following items which have been ignored or over-simplified in previously-presented simulations: (i) resistivity of the ground soil; (ii) arms, major slant elements, and foundations of the tower; (iii) development speed of the lightning return stroke. For validation purpose a pulse test of a 500-kV transmission tower is simulated, and a comparison with the measured result shows that the present FDTD simulation gives a sufficiently accurate result. Using this validated FDTD-based simulation method the insulator-string voltages of a tower for a lightning stroke are calculated, and based on the simulation result the parameter values of the proposed tower model for EMTP studies are determined in a systematic way. Since previously-presented models include trial-and-error process in the parameter determination, it can be said that the proposed model is more general in this regard. As an illustrative example, the 500-kV transmission tower mentioned above is modeled, and it is shown that the derived model closely reproduces the FDTD simulation result.

  4. Revealing a cancer diagnosis to patients: attitudes of patients, families, friends, nurses, and physicians in Lebanon-results of a cross-sectional study.

    Science.gov (United States)

    Farhat, F; Othman, A; El Baba, G; Kattan, J

    2015-08-01

    Disclosure of a cancer diagnosis to patients is a major problem for physicians in Lebanon. Our survey aimed to identify the attitudes of patients, families and friends, nurses, and physicians regarding disclosure of a cancer diagnosis. Study participants included 343 physicians, nurses, cancer patients, families, and friends from clinics in two major hospitals in Lebanon. All completed a 29-item questionnaire that assessed, by demographic group, the information provided about cancer, opinions about the disclosure of the diagnosis to cancer patients, perceived consequences to patients, and the roles of family, friends, and religion. Overall, 7.8% of the patients were convinced that cancer is incurable. Nearly 82% preferred to be informed about their diagnosis. Similarly, 83% of physicians were in favour of disclosing a cancer diagnosis to their patients. However, only 14% of the physicians said that they revealed the truth to the patients themselves, with only 9% doing so immediately after confirmation of the diagnosis. Disclosure of a cancer diagnosis was preferred before the start of the treatment by 59% of the patients and immediately after confirmation of the diagnosis by 72% of the physicians. Overall, 86% of physicians, 51% of nurses, and 69% of patients and their families believed that religion helped with the acceptance of a cancer diagnosis. A role for family in accepting the diagnosis was reported by 74% of the patients, 56% of the nurses, and 88% of the physicians. All participants considered that fear was the most difficult feeling (63%) experienced by cancer patients, followed by pain (29%), pity (8%), and death (1%), with no statistically significant difference between the answers given by the participant groups. The social background in Lebanese society is the main obstacle to revealing the truth to cancer patients. Lebanese patients seem to prefer direct communication of the truth, but families take the opposite approach. Physicians also prefer to

  5. A systems biology model of the regulatory network in Populus leaves reveals interacting regulators and conserved regulation

    Directory of Open Access Journals (Sweden)

    Hvidsten Torgeir R

    2011-01-01

    Full Text Available Abstract Background Green plant leaves have always fascinated biologists as hosts for photosynthesis and providers of basic energy to many food webs. Today, comprehensive databases of gene expression data enable us to apply increasingly more advanced computational methods for reverse-engineering the regulatory network of leaves, and to begin to understand the gene interactions underlying complex emergent properties related to stress-response and development. These new systems biology methods are now also being applied to organisms such as Populus, a woody perennial tree, in order to understand the specific characteristics of these species. Results We present a systems biology model of the regulatory network of Populus leaves. The network is reverse-engineered from promoter information and expression profiles of leaf-specific genes measured over a large set of conditions related to stress and developmental. The network model incorporates interactions between regulators, such as synergistic and competitive relationships, by evaluating increasingly more complex regulatory mechanisms, and is therefore able to identify new regulators of leaf development not found by traditional genomics methods based on pair-wise expression similarity. The approach is shown to explain available gene function information and to provide robust prediction of expression levels in new data. We also use the predictive capability of the model to identify condition-specific regulation as well as conserved regulation between Populus and Arabidopsis. Conclusions We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions

  6. 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

  7. 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

  8. 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.

  9. Deriving user-informed climate information from climate model ensemble results

    Directory of Open Access Journals (Sweden)

    H. Huebener

    2017-07-01

    Full Text Available 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.

  10. Use of the LQ model with large fraction sizes results in underestimation of isoeffect doses

    International Nuclear Information System (INIS)

    Sheu, Tommy; Molkentine, Jessica; Transtrum, Mark K.; Buchholz, Thomas A.; Withers, Hubert Rodney; Thames, Howard D.; Mason, Kathy A.

    2013-01-01

    Purpose: To test the appropriateness of the linear-quadratic (LQ) model to describe survival of jejunal crypt clonogens after split doses with variable (small 1–6 Gy, large 8–13 Gy) first dose, as a model of its appropriateness for both small and large fraction sizes. Methods: C3Hf/KamLaw mice were exposed to whole body irradiation using 300 kVp X-rays at a dose rate of 1.84 Gy/min, and the number of viable jejunal crypts was determined using the microcolony assay. 14 Gy total dose was split into unequal first and second fractions separated by 4 h. Data were analyzed using the LQ model, the lethal potentially lethal (LPL) model, and a repair-saturation (RS) model. Results: Cell kill was greater in the group receiving the larger fraction first, creating an asymmetry in the plot of survival vs size of first dose, as opposed to the prediction of the LQ model of a symmetric response. There was a significant difference in the estimated βs (higher β after larger first doses), but no significant difference in the αs, when large doses were given first vs small doses first. This difference results in underestimation (based on present data by approximately 8%) of isoeffect doses using LQ model parameters based on small fraction sizes. While the LPL model also predicted a symmetric response inconsistent with the data, the RS model results were consistent with the observed asymmetry. Conclusion: The LQ model underestimates doses for isoeffective crypt-cell survival with large fraction sizes (in the present setting, >9 Gy)

  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

    Ten months of data from ESA's Swarm mission, together with recent ground observatory monthly means, are used to update the CHAOS series of geomagnetic field models with a focus on time-changes of the core field. As for previous CHAOS field models quiet-time, night-side, data selection criteria......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...... fit obtained to both the Swarm data and the CHAMP data. The new model also provides a good description of observatory secular variation, capturing rapid field evolution events during the past decade. Maps of the core surface field and its secular variation can already be extracted in the Swarm-era. We...

  12. 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)

  13. 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.

  14. 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.

  15. Expression of ERCC1, p53, and class III β-tubulin do not reveal chemoresistance in endometrial cancer: results from an immunohistochemical study.

    Science.gov (United States)

    Vandenput, Ingrid; Capoen, An; Coenegrachts, Lieve; Verbist, Godelieve; Moerman, Philippe; Vergote, Ignace; Amant, Frédéric

    2011-08-01

    In non-small cell lung cancer, expression of excision repair cross-complementation group 1 (ERCC1) and p53 correlates with platinum resistance and class III β-tubulin with resistance to taxanes. The potential to personalize treatment in endometrial cancer remains uninvestigated. Patients received platinum-based chemotherapy, with or without paclitaxel. Patients were divided into 2 groups: group A (n = 33) consisted of patients with early-stage endometrial cancer treated with adjuvant chemotherapy. Group B (n = 116) included cases with primary advanced or recurrent disease. Immunohistochemistry was performed to analyze the expression of ERCC1 and p53, for all cases, and class III β-tubulin for cases treated with paclitaxel. The findings were correlated with response according to Response Criteria in Solid Tumors; recurrence-free, disease-specific survival; and established prognostic markers. The mean age of 149 patients was 64 years (range, 31-84 years). Distribution of histopathologic subtypes was as follows: 44 endometrioid (30%), 92 serous/clear cell (62%), and 13 carcinosarcomas (8%).In group A, 11 (33%) and 19 patients (58%) showed expression for ERCC1 and p53, respectively. Seven (78%) of nine patients receiving paclitaxel were positive for class III β-tubulin. There was no correlation between expression of ERCC1, p53, or class III β-tubulin and recurrence or survival. In group B, 25 (22%) and 61 patients (64%) were positive for ERCC1 and p53, respectively. Fifty-two (74%) of seventy patients receiving paclitaxel were positive for class III β-tubulin. Only p53 expression correlated with survival (P = 0.01). In contrast to theoretical assumptions, the current study did not reveal evidence that the expression of ERCC1 and class III β-tubulin predicts response to cytotoxic treatment and patient outcome in endometrial cancer.

  16. 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.

  17. Satellite data for systematic validation of wave model results in the Black Sea

    Science.gov (United States)

    Behrens, Arno; Staneva, Joanna

    2017-04-01

    The Black Sea is with regard to the availability of traditional in situ wave measurements recorded by usual waverider buoys a data sparse semi-enclosed sea. The only possibility for systematic validations of wave model results in such a regional area is the use of satellite data. In the frame of the COPERNICUS Marine Evolution System for the Black Sea that requires wave predictions, the third-generation spectral wave model WAM is used. The operational system is demonstrated based on four years' systematic comparisons with satellite data. The aim of this investigation was to answer two questions. Is the wave model able to provide a reliable description of the wave conditions in the Black Sea and are the satellite measurements suitable for validation purposes on such a regional scale ? Detailed comparisons between measured data and computed model results for the Black Sea including yearly statistics have been done for about 300 satellite overflights per year. The results discussed the different verification schemes needed to review the forecasting skills of the operational system. The good agreement between measured and modeled data supports the expectation that the wave model provides reasonable results and that the satellite data is of good quality and offer an appropriate validation alternative to buoy measurements. This is the required step towards further use of those satellite data for assimilation into the wave fields to improve the wave predictions. Additional support for the good quality of the wave predictions is provided by comparisons between ADCP measurements that are available for a short time period in February 2012 and the corresponding model results at a location near the Bulgarian coast in the western Black Sea. Sensitivity tests with different wave model options and different driving wind fields have been done which identify the appropriate model configuration that provides the best wave predictions. In addition to the comparisons between measured

  18. Uncertainty quantification and sensitivity analysis of volcanic columns models: Results from the integral model PLUME-MoM

    Science.gov (United States)

    de'Michieli Vitturi, M.; Engwell, S. L.; Neri, A.; Barsotti, S.

    2016-10-01

    The behavior of plumes associated with explosive volcanic eruptions is complex and dependent on eruptive source parameters (e.g. exit velocity, gas fraction, temperature and grain-size distribution). It is also well known that the atmospheric environment interacts with volcanic plumes produced by explosive eruptions in a number of ways. The wind field can bend the plume but also affect atmospheric air entrainment into the column, enhancing its buoyancy and in some cases, preventing column collapse. In recent years, several numerical simulation tools and observational systems have investigated the action of eruption parameters and wind field on volcanic column height and column trajectory, revealing an important influence of these variables on plume behavior. In this study, we assess these dependencies using the integral model PLUME-MoM, whereby the continuous polydispersity of pyroclastic particles is described using a quadrature-based moment method, an innovative approach in volcanology well-suited for the description of the multiphase nature of magmatic mixtures. Application of formalized uncertainty quantification and sensitivity analysis techniques enables statistical exploration of the model, providing information on the extent to which uncertainty in the input or model parameters propagates to model output uncertainty. In particular, in the framework of the IAVCEI Commission on tephra hazard modeling inter-comparison study, PLUME-MoM is used to investigate the parameters exerting a major control on plume height, applying it to a weak plume scenario based on 26 January 2011 Shinmoe-dake eruptive conditions and a strong plume scenario based on the climatic phase of the 15 June 1991 Pinatubo eruption.

  19. 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.

  20. SModelS: A Tool for Making Systematic Use of Simplified Models Results

    Science.gov (United States)

    Waltenberger, Wolfgang; SModelS Group

    2016-10-01

    We present an automated software tool ”SModelS” to systematically confront theories Beyond the Standard Model (BSM) with experimental data. The tool consists of a general procedure to decompose such BSM theories into their Simplified Models Spectra (SMS). In addition, SModelS features a database containing the majority of the published SMS results of CMS and ATLAS. These results consist of the 95% confidence level upper limits on signal production cross sections. The two components together allow us to quickly confront any BSM model with LHC results. As a show-case example we will briefly discuss an application of our procedure to a specific supersymmetric model. It is one of our ongoing efforts to extend the framework to include also efficiency maps produced either by the experimental collaborations, by efforts performed within the phenomenological groups, or possibly also by ourselves. While the current implementation can handle null results only, it is our ultimate goal to build the Next Standard Model in a bottom-up fashion from both negative and positive results of several experiments. The implementation is open source, written in python, and available from http://smodels.hephy.at.

  1. Updating Finite Element Model of a Wind Turbine Blade Section Using Experimental Modal Analysis Results

    Directory of Open Access Journals (Sweden)

    Marcin Luczak

    2014-01-01

    Full Text Available This paper presents selected results and aspects of the multidisciplinary and interdisciplinary research oriented for the experimental and numerical study of the structural dynamics of a bend-twist coupled full scale section of a wind turbine blade structure. The main goal of the conducted research is to validate finite element model of the modified wind turbine blade section mounted in the flexible support structure accordingly to the experimental results. Bend-twist coupling was implemented by adding angled unidirectional layers on the suction and pressure side of the blade. Dynamic test and simulations were performed on a section of a full scale wind turbine blade provided by Vestas Wind Systems A/S. The numerical results are compared to the experimental measurements and the discrepancies are assessed by natural frequency difference and modal assurance criterion. Based on sensitivity analysis, set of model parameters was selected for the model updating process. Design of experiment and response surface method was implemented to find values of model parameters yielding results closest to the experimental. The updated finite element model is producing results more consistent with the measurement outcomes.

  2. 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

  3. 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...

  4. Mathematical Modeling in Tobacco Control Research: Initial Results From a Systematic Review.

    Science.gov (United States)

    Feirman, Shari P; Donaldson, Elisabeth; Glasser, Allison M; Pearson, Jennifer L; Niaura, Ray; Rose, Shyanika W; Abrams, David B; Villanti, Andrea C

    2016-03-01

    The US Food and Drug Administration has expressed interest in using mathematical models to evaluate potential tobacco policies. The goal of this systematic review was to synthesize data from tobacco control studies that employ mathematical models. We searched five electronic databases on July 1, 2013 to identify published studies that used a mathematical model to project a tobacco-related outcome and developed a data extraction form based on the ISPOR-SMDM Modeling Good Research Practices. We developed an organizational framework to categorize these studies and identify models employed across multiple papers. We synthesized results qualitatively, providing a descriptive synthesis of included studies. The 263 studies in this review were heterogeneous with regard to their methodologies and aims. We used the organizational framework to categorize each study according to its objective and map the objective to a model outcome. We identified two types of study objectives (trend and policy/intervention) and three types of model outcomes (change in tobacco use behavior, change in tobacco-related morbidity or mortality, and economic impact). Eighteen models were used across 118 studies. This paper extends conventional systematic review methods to characterize a body of literature on mathematical modeling in tobacco control. The findings of this synthesis can inform the development of new models and the improvement of existing models, strengthening the ability of researchers to accurately project future tobacco-related trends and evaluate potential tobacco control policies and interventions. These findings can also help decision-makers to identify and become oriented with models relevant to their work. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. 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....

  6. A Calibration of the Wierzbicki-Xue Damage Model Using Charpy Test Results

    Directory of Open Access Journals (Sweden)

    Kim Jong-Bong

    2015-01-01

    Full Text Available Damage models are frequently used to predict fractures in large deformation problems such as penetration of a projectile into a target. Though many damage models have been proposed so far, coefficients of each model have been provided for only a few materials. In this study, the coefficients of the Wierzbicki-Xue (2005 damage model for tungsten heavy alloy (DX2HCMF are determined using the Charpy impact test. The Wierzbicki-Xue fracture criterion is implemented into NET3D code in which a node-split algorithm is built in. By comparing the energy absorbed in the Charpy test with the results of finite element analysis, the fracture model coefficients are determined.

  7. Quantifying Uncertainty in Model Predictions for the Pliocene (Plio-QUMP): Initial results

    Science.gov (United States)

    Pope, J.O.; Collins, M.; Haywood, A.M.; Dowsett, H.J.; Hunter, S.J.; Lunt, D.J.; Pickering, S.J.; Pound, M.J.

    2011-01-01

    Examination of the mid-Pliocene Warm Period (mPWP; ~. 3.3 to 3.0. Ma BP) provides an excellent opportunity to test the ability of climate models to reproduce warm climate states, thereby assessing our confidence in model predictions. To do this it is necessary to relate the uncertainty in model simulations of mPWP climate to uncertainties in projections of future climate change. The uncertainties introduced by the model can be estimated through the use of a Perturbed Physics Ensemble (PPE). Developing on the UK Met Office Quantifying Uncertainty in Model Predictions (QUMP) Project, this paper presents the results from an initial investigation using the end members of a PPE in a fully coupled atmosphere-ocean model (HadCM3) running with appropriate mPWP boundary conditions. Prior work has shown that the unperturbed version of HadCM3 may underestimate mPWP sea surface temperatures at higher latitudes. Initial results indicate that neither the low sensitivity nor the high sensitivity simulations produce unequivocally improved mPWP climatology relative to the standard. Whilst the high sensitivity simulation was able to reconcile up to 6 ??C of the data/model mismatch in sea surface temperatures in the high latitudes of the Northern Hemisphere (relative to the standard simulation), it did not produce a better prediction of global vegetation than the standard simulation. Overall the low sensitivity simulation was degraded compared to the standard and high sensitivity simulations in all aspects of the data/model comparison. The results have shown that a PPE has the potential to explore weaknesses in mPWP modelling simulations which have been identified by geological proxies, but that a 'best fit' simulation will more likely come from a full ensemble in which simulations that contain the strengths of the two end member simulations shown here are combined. ?? 2011 Elsevier B.V.

  8. 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...

  9. Ares I Scale Model Acoustic Test Above Deck Water Sound Suppression Results

    Science.gov (United States)

    Counter, Douglas D.; Houston, Janice D.

    2011-01-01

    The Ares I Scale Model Acoustic Test (ASMAT) program test matrix was designed to determine the acoustic reduction for the Liftoff acoustics (LOA) environment with an above deck water sound suppression system. The scale model test can be used to quantify the effectiveness of the water suppression system as well as optimize the systems necessary for the LOA noise reduction. Several water flow rates were tested to determine which rate provides the greatest acoustic reductions. Preliminary results are presented.

  10. 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

  11. [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.

  12. Building a Global Groundwater Model fromScratch - Concepts and Results

    Science.gov (United States)

    Reinecke, R.; Song, Q.; Foglia, L.; Mehl, S.; Doll, P. M.

    2016-12-01

    To represent groundwater-surface water interactions as well as the impact of capillary rise on evapotranspiration in global-scale hydrological models, it is necessary to simulate the location and temporal variation of the groundwater table. This requires to replace simulation of groundwater dynamics by calculating groundwater storage variations in individual grid cells (independent from the storage variation in neighboring cells) by hydraulic head gradient-based groundwater modeling. Based on the experience of two research groups who have published different approaches for global-scale groundwater modeling, we present first results of our effort to develop a transient global groundwater model that is to replace the simple storage-based ground-water module of the global hydrological model WaterGAP. The following three technical and conceptual aspects of this endeavour arediscussed: (1) A software engineering approach to build a new hydraulic head based global groundwater model from scratch with the goal of maximizing performance and extensibility. (2) Comparison to other model approaches and their inherent problems. (3) Global-data deficits and how to deal with them. Furthermore, this poster presents and discusses first results and provides an outlook on future developments.

  13. 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.

  14. 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

  15. Phase Partitioning of Common Alcohols With BTEX Compounds in Water: Comparison Between Modeling and Experimental Results

    Science.gov (United States)

    Lee, K. Y.

    2007-12-01

    This study compares the modeling and experimental results on the equilibrium phase partitioning behavior of three common alcohols (ethanol, isopropanol, and methanol) in a two-phase system consisting of water and a BTEX compound. A previously developed computer program is used to generate ternary phase diagrams for each alcohol-water-NAPL mixture combination, where the required activity coefficients are estimated using the UNIFAC model. A set of laboratory experiments is conducted to determine the maximum single-phase water content for every alcohol-water-NAPL mixture combination considered in this study, where the initial volume composition is 85 percent alcohol and 15 percent NAPL. Comparison of experimental results against UNIFAC- derived modeling results shows good agreement for mixtures containing ethanol and methanol, but relatively poor agreement for mixtures containing isopropanol.

  16. Confined placental origin of the circulating cell free fetal DNA revealed by a discordant non-invasive prenatal test result in a trisomy 18 pregnancy.

    Science.gov (United States)

    Mao, Jun; Wang, Ting; Wang, Ben-Jing; Liu, Ying-Hua; Li, Hong; Zhang, Jianguang; Cram, David; Chen, Ying

    2014-06-10

    Non-invasive prenatal testing (NIPT) by massively parallel sequencing is a useful clinical test for the detection of common fetal aneuploidies. While the accuracy of aneuploidy detection can approach 100%, results discordant with the fetus are occasionally reported. In this study we investigated the basis of a discordant T21 positive and T18 negative NIPT result associated with a T18 fetus confirmed by karyotyping. Massively parallel sequencing was used to detect fetal DNA in maternal circulating plasma. The parental origin and nature of the fetal and placental aneuploidies were investigated by quantitative fluorescent PCR of short tandem repeat (STR) sequences and by copy number variation (CNV) sequencing. There was no evidence of T21 maternal mosaicism, T21 microchimerism or a vanishing twin to explain the discordant NIPT result. However, examination of multiple placental biopsies showed both T21 and T18 mosaicism, including one confined region with a significantly higher proportion of T21 cells. Based on fetal DNA fractions and average mosaicism levels, the effective T21 and T18 fetal DNA fractions should have been sufficient for the detection of both trisomies. In this pregnancy, we speculate that confined placental region(s) with higher proportions of T21 cells were preferentially releasing fetal DNAs into the maternal circulation. This study highlights placental mosaicism as a significant risk factor for discordant NIPT results. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Latest results from the EU project AVATAR: Aerodynamic modelling of 10 MW wind turbines

    DEFF Research Database (Denmark)

    Schepers O. Ceyhan, J. G.; Boorsma, K.; Gonzalez, A.

    2016-01-01

    This paper presents the most recent results from the EU project AVATAR in which aerodynamic models are improved and validated for wind turbines on a scale of 10 MW and more. Measurements on a DU 00-W-212 airfoil are presented which have been taken in the pressurized DNW-HDG wind tunnel up...... to a Reynolds number of 15 Million. These measurements are compared with measurements in the LM wind tunnel for Reynolds numbers of 3 and 6 Million and with calculational results. In the analysis of results special attention is paid to high Reynolds numbers effects. CFD calculations on airfoil performance...... results from 3D rotor models where a comparison is made between results from vortex wake methods and BEM methods at yawed conditions....

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Modeling of soil nitrification responses to temperature reveals thermodynamic differences between ammonia-oxidizing activity of archaea and bacteria.

    Science.gov (United States)

    Taylor, Anne E; Giguere, Andrew T; Zoebelein, Conor M; Myrold, David D; Bottomley, Peter J

    2017-04-01

    Soil nitrification potential (NP) activities of ammonia-oxidizing archaea and bacteria (AOA and AOB, respectively) were evaluated across a temperature gradient (4-42 °C) imposed upon eight soils from four different sites in Oregon and modeled with both the macromolecular rate theory and the square root growth models to quantify the thermodynamic responses. There were significant differences in response by the dominant AOA and AOB contributing to the NPs. The optimal temperatures (T opt ) for AOA- and AOB-supported NPs were significantly different (P12 °C greater than AOB. The change in heat capacity associated with the temperature dependence of nitrification (ΔC P ‡ ) was correlated with T opt across the eight soils, and the ΔC P ‡ of AOB activity was significantly more negative than that of AOA activity (Ptemperature (T min ) and different, albeit very similar, maximum temperature (T max ) values for AOB than for AOA activity. The results also suggested that there may be different forms of AOA AMO that are active over different temperature ranges with different T min , but no evidence of multiple T min values within the AOB. Fundamental differences in temperature-influenced properties of nitrification driven by AOA and AOB provides support for the idea that the biochemical processes associated with NH 3 oxidation in AOA and AOB differ thermodynamically from each other, and that also might account for the difficulties encountered in attempting to model the response of nitrification to temperature change in soil environments.

  5. Optical polarization tractography revealed significant fiber disarray in skeletal muscles of a mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Wang, Y; Zhang, K; Wasala, N B; Duan, D; Yao, G

    2015-02-01

    Optical polarization tractography (OPT) was recently developed to visualize tissue fiber architecture with cellular-level resolution and accuracy. In this study, we explored the feasibility of using OPT to study muscle disease in the mdx4cv mouse model of Duchenne muscular dystrophy. The freshly dissected tibialis anterior muscles of mdx4cv and normal mice were imaged. A "fiber disarray index" (FDI) was developed to quantify the myofiber disorganization. In necrotic muscle regions of the mdx4cv mice, the FDI was significantly elevated and can be used to segment the 3D necrotic regions for assessing the overall muscle damage. These results demonstrated the OPT's capability for imaging microscopic fiber alternations in muscle research.

  6. 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.

  7. Adsorption of arsenic and phosphate onto the surface of calcite as revealed by batch experiments and surface complexation modelling

    DEFF Research Database (Denmark)

    Sø, Helle Ugilt

    in sorption edges, pKa’s and geometry of the two anions. The adsorption of arsenate and phosphate in the single sorbate systems was modelled successfully using either the constant capacitance model (CCM) for calcite or the CD-MUSIC model for calcite. Generally the models capture the variation in arsenate...

  8. Toxic pyrene metabolism in Mycobacterium gilvum PYR-GCK results in the expression of mammalian cell entry genes as revealed by transcriptomics study.

    Science.gov (United States)

    Badejo, Abimbola Comfort; Chung, Won Hyong; Kim, Nam Shin; Kim, Se Kye; Chai, Jin Choul; Lee, Young Seek; Jung, Kyoung Hwa; Kim, Hyo Joon; Chai, Young Gyu

    2014-09-01

    Mycobacterium gilvum PYR-GCK is a bacterial strain under study for its bioremediation use on heavy hydrocarbon pollutants in the environment. During the course of our study, mammalian cell entry (mce) genes, known to facilitate pathogenicity in M. tuberculosis, were highly expressed during a comparative and substrate-related cultural global transcriptomic study. RNA sequencing of the global transcriptome of the test strain in two different substrates, pyrene and glucose, showed high expression of the mce genes based on the differential results. After validating the expression of these genes with quantitative real-time PCR, we arrived at the conclusion that the genes were expressed based on the pyrene substrate (a phytosterol compound), and sterol metabolism is said to activate the expression of the mce genes in some actinomycetes bacteria, M. gilvum PYR-GCK in this case. This study is believed to be important based on the fact that some mycobacterial strains are undergoing a continuous research as a result of their use in practical bioremediation of anthropogenic exposure of toxic organic wastes in the environment.

  9. 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.

  10. 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 and

  11. Comparison of TS and ANN Models with the Results of Emission Scenarios in Rainfall Prediction

    Directory of Open Access Journals (Sweden)

    S. Babaei Hessar

    2016-02-01

    Full Text Available Introduction: Precipitation is one of the most important and sensitive parameters of the tropical climate that influence the catchments hydrological regime. The prediction of rainfall is vital for strategic planning and water resources management. Despite its importance, statistical rainfall forecasting, especially for long-term, has been proven to be a great challenge due to the dynamic nature of climate phenomena and random fluctuations involved in the process. Various methods, such as time series and artificial neural network models, have been proposed to predict the level of rainfall. But there is not enough attention to global warming and climate change issues. The main aim of this study is to investigate the conformity of artificial neural network and time series models with climate scenarios. Materials and Methods: For this study, 50 years of daily rainfall data (1961 to 2010 of the synoptic station of Urmia, Tabriz and Khoy was investigated. Data was obtained from Meteorological Organization of Iran. In the present study, the results of two Artificial Neural Network (ANN and Time Seri (TS methods were compared with the result of the Emission Scenarios (A2 & B1. HadCM3 model in LARS-WG software was used to generate rainfall for the next 18 years (2011-2029. The results of models were compared with climate scenarios over the next 18 years in the three synoptic stations located in the basin of the Lake Urmia. At the first stage, the best model of time series method was selected. The precipitation was estimated for the next 18 years using these models. For the same period, precipitation was forecast using artificial neural networks. Finally, the results of two models were compared with data generated under two scenarios (B1 and A2 in LARS-WG. Results and Discussion: Different order of AR, MA and ARMA was examined to select the best model of TS The results show that AR(1 was suitable for Tabriz and Khoy stations .In the Urmia station MA(1 was

  12. Numerical modelling of CO2 migration in saline reservoirs using geoelectric and seismic techniques - first results

    Science.gov (United States)

    Hagrey, S. A. Al; Strahser, M. H. P.; Rabbel, W.

    2009-04-01

    The research project "CO2 MoPa" (modelling and parameterisation of CO2 storage in deep saline formations for dimensions and risk analysis) has been initiated in 2008 by partners from different disciplines (e.g. geology, hydrogeology, geochemistry, geophysics, geomechanics, hydraulic engineering and law). It deals with the parameterisation of virtual subsurface storage sites to characterise rock properties, with high pressure-temperature experiments to determine in situ hydro-petrophysical and mechanical parameters, and with modelling of processes related to CCS in deep saline reservoirs. One objective is the estimation of the sensitivity and the resolution of reflection seismic and geoelectrical time-lapse measurements in order to determine the underground distribution of CO2. Compared with seismic, electric resistivity tomography (ERT) has lower resolution, but its permanent installation and continuous monitoring can make it an economical alternative or complement. Seismic and ERT (in boreholes) applications to quantify changes of intrinsic aquifers properties with time are justified by the velocity and resistivity decrease related to CO2 injection. Our numerical 2D/3D modelling reveals the capability of the techniques to map CO2 plumes and changes as a function of thickness, concentration, receiver/electrode configuration, aspect ratio and modelling and inversion constraint parameters. Depending on these factors, some configurations are favoured due to their better spatial resolution and lower artefacts. Acknowledgements This work has been carried out in the framework of "CO2 MoPa" research project funded by the Federal German Ministry of Education and Research (BMBF) and a consortium of energy companies (E.ON Energy, EnBW AG, RWE Dea AG, Stadtwerke Kiel AG, Vattenfall Europe Technology Research GmbH and Wintershall Holding AG).

  13. 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.

  14. 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

  15. Modelling of the earth atmosphere contamination as result of cesium 137 deflation from contaminated territories

    International Nuclear Information System (INIS)

    Zhmura, G.M.; Zhmura, N.V.

    1998-01-01

    The results of calculation of cesium 137 average annual ground atmosphere concentrations on the Belarus territory in the knots of net (50*50) km are given. The calculations were made on the base of a model notions about dusting area sources. Analysis of the results shows that cesium 137 average annual ground atmosphere concentrations on the Belarus territory are varied more than two orders depending on a point of calculation from 1 to 400 micro Bq/m 3

  16. Army Sustainability Modelling Analysis and Reporting Tool Phase 1: User Manual and Results Interpretation Guide

    Science.gov (United States)

    2009-11-01

    Force Sustainability Modelling Tool Prototype GB Gigabyte GRES General Reserve HQ Headquarters HTA Hardening the Army JOLTS Joint Operational...Hardening the Army ( HTA ) proposed force structure.1 Following this work, the Director General Preparedness and Plans – Army (DGPP-A) approached DSTO to...that the different elements of the results for the corps have been identified, we can turn our attention to what the results say about the

  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. Evidence for Symplectic Symmetry in Ab Initio No-Core Shell Model Results for Light Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Dytrych, Tomas; Sviratcheva, Kristina D.; Bahri, Chairul; Draayer, Jerry P.; /Louisiana State U.; Vary, James P.; /Iowa State U. /LLNL, Livermore /SLAC

    2007-04-24

    Clear evidence for symplectic symmetry in low-lying states of {sup 12}C and {sup 16}O is reported. Eigenstates of {sup 12}C and {sup 16}O, determined within the framework of the no-core shell model using the JISP16 NN realistic interaction, typically project at the 85-90% level onto a few of the most deformed symplectic basis states that span only a small fraction of the full model space. The results are nearly independent of whether the bare or renormalized effective interactions are used in the analysis. The outcome confirms Elliott's SU(3) model which underpins the symplectic scheme, and above all, points to the relevance of a symplectic no-core shell model that can reproduce experimental B(E2) values without effective charges as well as deformed spatial modes associated with clustering phenomena in nuclei.

  19. Computer modeling reveals that modifications of the histone tail charges define salt-dependent interaction of the nucleosome core particles.

    Science.gov (United States)

    Yang, Ye; Lyubartsev, Alexander P; Korolev, Nikolay; Nordenskiöld, Lars

    2009-03-18

    Coarse-grained Langevin molecular dynamics computer simulations were conducted for systems that mimic solutions of nucleosome core particles (NCPs). The NCP was modeled as a negatively charged spherical particle representing the complex of DNA and the globular part of the histones combined with attached strings of connected charged beads modeling the histone tails. The size, charge, and distribution of the tails relative to the core were built to match real NCPs. Three models of NCPs were constructed to represent different extents of covalent modification on the histone tails: (nonmodified) recombinant (rNCP), acetylated (aNCP), and acetylated and phosphorylated (paNCP). The simulation cell contained 10 NCPs in a dielectric continuum with explicit mobile counterions and added salt. The NCP-NCP interaction is decisively dependent on the modification state of the histone tails and on salt conditions. Increasing the monovalent salt concentration (KCl) from salt-free to physiological concentration leads to NCP aggregation in solution for rNCP, whereas NCP associates are observed only occasionally in the system of aNCPs. In the presence of divalent salt (Mg(2+)), rNCPs form dense stable aggregates, whereas aNCPs form aggregates less frequently. Aggregates are formed via histone-tail bridging and accumulation of counterions in the regions of NCP-NCP contacts. The paNCPs do not show NCP-NCP interaction upon addition of KCl or in the presence of Mg(2+). Simulations for systems with a gradual substitution of K(+) for Mg(2+), to mimic the Mg(2+) titration of an NCP solution, were performed. The rNCP system showed stronger aggregation that occurred at lower concentrations of added Mg(2+), compared to the aNCP system. Additional molecular dynamics simulations performed with a single NCP in the simulation cell showed that detachment of the tails from the NCP core was modest under a wide range of salt concentrations. This implies that salt-induced tail dissociation of the

  20. 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).

  1. 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

  2. Modelling analysis and prediction of women javelin throw results in the years I946 — 2013

    Directory of Open Access Journals (Sweden)

    P Grycmann

    2016-01-01

    Full Text Available The main goals of our study of the women's javelin throw were twofold; first, to analyse the dynamics of female javelin throw results variability as a function of time (time period 1946-2014, second, to create a predictive model of the results during the upcoming 4 years. The study material consisted of databases covering the female track and field events obtained from the International Association of Athletics Federations. Prior to predicting the magnitude of results change dynamics in the time to follow, the adjustment of trend function to empirical data was tested using the coefficients of convergence. Phase ll of the investigation consisted of the construction of predictive models. The greatest decreases in result indexes were noted in 2000 (9.4%, 2005-2006 (8.7% and Z009 (7.4%. The trend increase was only noted in the years 2006-2008. In general, until 1998 the mean result improved by 54.6% (100% - results of 1946 whereas from 1999 through 2011 the result only increased by 1.3%. Based on data and results variability analysis it might be presumed that, in the nearest future (2015-2018, results variability will increase by approximately 9.7%. Percent improvement of javelin throw distance calculated on the basis of the 1999 raw input data is 1.4% (end of 2014.

  3. The Witten-Sakai-Sugimoto model: A brief review and some recent results

    Science.gov (United States)

    Rebhan, Anton

    2015-05-01

    A brief review of the Witten-Sakai-Sugimoto model is given, which is a top-down holographic model of low-energy QCD with chiral quarks derived from type-IIA superstring theory. The main predictions of the model, in particular concerning meson spectra, the gluon condensate, the QCD string tension, the mass of the η' and of baryons are discussed and compared quantitatively with available experimental and/or lattice results. Then some recent results of potential interest to the physics program at the future FAIR facility are presented: The spectrum of glueballs and their decay rates into pions, and the phase diagram of QCD at finite temperature, density, and magnetic field strength.

  4. The Witten-Sakai-Sugimoto model: A brief review and some recent results

    Directory of Open Access Journals (Sweden)

    Rebhan Anton

    2015-01-01

    Full Text Available A brief review of the Witten-Sakai-Sugimoto model is given, which is a top-down holographic model of low-energy QCD with chiral quarks derived from type-IIA superstring theory. The main predictions of the model, in particular concerning meson spectra, the gluon condensate, the QCD string tension, the mass of the η′ and of baryons are discussed and compared quantitatively with available experimental and/or lattice results. Then some recent results of potential interest to the physics program at the future FAIR facility are presented: The spectrum of glueballs and their decay rates into pions, and the phase diagram of QCD at finite temperature, density, and magnetic field strength.

  5. Comparative Results on 3D Navigation of Quadrotor using two Nonlinear Model based Controllers

    Science.gov (United States)

    Bouzid, Y.; Siguerdidjane, H.; Bestaoui, Y.

    2017-01-01

    Recently the quadrotors are being increasingly employed in both military and civilian areas where a broad range of nonlinear flight control techniques are successfully implemented. With this advancement, it has become necessary to investigate the efficiency of these flight controllers by studying theirs features and compare their performance. In this paper, the control of Unmanned Aerial Vehicle (UAV) quadrotor, using two different approaches, is presented. The first controller is Nonlinear PID (NLPID) whilst the second one is Nonlinear Internal Model Control (NLIMC) that are used for the stabilization as well as for the 3D trajectory tracking. The numerical simulations have shown satisfactory results using nominal system model or disturbed model for both of them. The obtained results are analyzed with respect to several criteria for the sake of comparison.

  6. Influence of Different Modeling Strategies for CFRP on Finite Element Simulation Results

    Directory of Open Access Journals (Sweden)

    Liu Xueshu

    2016-01-01

    Full Text Available Numerical simulation is used to predict the behavior and response of carbon fiber reinforced plastic (CFRP. Sometimes zero thickness of interface layer is introduced into the numerical model to investigate the inter-layer behavior like delamination. To investigate the influence of critical volume-type defect like void, usually appeared in matrix rich region at the interface between layers, on mechanical properties of CFRP, numerical models with different interface thickness were created and tensile property and three-point bending simulation results were compared to experimental ones. It is found that accurate result is obtained with increasing of the interface thickness and up to 20% that of layer thickness is recommended to model the matrix rich region.

  7. 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.

  8. 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.)

  9. Targeted liquid chromatography quadrupole ion trap mass spectrometry analysis of tachykinin related peptides reveals significant expression differences in a rat model of neuropathic pain.

    Science.gov (United States)

    Pailleux, Floriane; Vachon, Pascal; Lemoine, Jérôme; Beaudry, Francis

    2013-08-01

    Animal models are widely used to perform basic scientific research in pain. The rodent chronic constriction injury (CCI) model is widely used to study neuropathic pain. Animals were tested prior and after CCI surgery using behavioral tests (von Frey filaments and Hargreaves test) to evaluate pain. The brain and the lumbar enlargement of the spinal cord were collected from neuropathic and normal animals. Tachykinin related peptides were analyzed by high performance liquid chromatography quadrupole ion trap mass spectrometry. Our results reveal that the β-tachykinin₅₈₋₇₁, SP and SP₃₋₁₁ up-regulation are closely related to pain behavior. The spinal β-tachykinin₅₈₋₇₁, SP and SP₃₋₁₁ concentrations were significantly up-regulated in neuropathic animals compared with normal animals (ptachykinin₅₈₋₇₁ and SP concentrations were significantly up-regulated (ptachykinin₅₈₋₇₁, SP₁₋₇ and SP₆₋₁₁ (p>0.05). The β-tachykinin₅₈₋₇₁, SP and C-terminal SP metabolites could potentially serve as biomarkers in early drug discovery. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Latest results from the EU project AVATAR : Aerodynamic modelling of 10 MW wind turbines

    NARCIS (Netherlands)

    Ceyhan, J. G Schepers O; Ceyhan, O; Boorsma, K; Gonzalez, A; Munduate, X; Pires, O; Sørensen, Jens Nørkær; Simao Ferreira, C.; Sieros, G; Madsen, J.; Voutsinas, S.; Lutz, T.; Barakos, G.; Colonia, S.; Heißelmann, H.; Meng, F.; Croce, A.

    2016-01-01

    This paper presents the most recent results from the EU project AVATAR in which aerodynamic models are improved and validated for wind turbines on a scale of 10 MW and more. Measurements on a DU 00-W-212 airfoil are presented which have been taken in the pressurized DNW-HDG wind tunnel up to a

  11. Social Approval of the Community Assessment Model for Odor Dispersal: Results from a Citizen Survey

    Science.gov (United States)

    Tyndall, John C.; Grudens-Schuck, Nancy; Harmon, Jay D.; Hoff, Steve J.

    2012-08-01

    Odors emitted from US Midwest hog production facilities present farmers, residents, and state regulatory agencies with a set of complex challenges. To predict odor exposure from multiple swine production sources simultaneously, and to determine siting recommendations for proposed new or enlarged hog facilities, researchers at Iowa State University designed the community assessment model for odor dispersion (CAM). A three-county citizen survey conducted in Iowa examined the level of hypothetical social acceptance of the modeling process, and level of trust in CAM results. While 69 % of respondents approved of modeling as a way to determine the most socially appropriate location for production sites, only 35 % would trust the results if potential odor exposure from a new facility were proposed to be built near their home. We analyzed approval of the CAM model, and level of trust, across a number of demographic, attitudinal, and belief factors regarding environmental quality and the hog industry. Overall, trust in CAM was uneven and varied across respondents. Those residents who would not trust CAM tended to be more concerned with environmental quality and less inclined to believe that the hog industry is critically important economically. Those who would not trust CAM results also had significantly more direct experience with odors. Findings point to predominantly positive, yet equivocal acceptance of CAM results among the citizenry, which is not unexpected given conflict typical of siting decisions in industry and waste disposal arenas. Recommendations are offered regarding the interaction of trust, beliefs and attitudes and the utility of CAM.

  12. Evidence of Two Component Accretion Flows as revealed by time lag properties: Results of Long-Term RXTE/ASM Data Analysis

    Science.gov (United States)

    Ghosh, Arindam; Chakrabarti, Sandip Kumar

    2016-07-01

    Long-term RXTE/ASM X-ray data of several Galactic black hole candidates (BHCs) are analyzed. The results of this analysis show the existence of two component accretion flow (TCAF) in both low-mass and high-mass X-ray binaries (LMXBs & HMXBs). Large disks with long viscous timescales in the accreting matter with high angular momentum are prevalent in LMXBs due to processes like Roche lobe overflow, while small disks with little viscous delays are observed in HMXBs, primarily because of wind accretion. Two parameters are defined as photon indices, independent of the choice of a BHC, in order to find correlation between the two components, namely, the Keplerian disk component and the sub-Keplerian component, thereby estimating the time lag between two aforesaid timescales. Fluxes of hard and soft photons are observed to be anti-correlated with respect to these photon indices. The time lags give us an idea of the viscosity in the Keplerian component.

  13. Evaluation of the WAMME model surface fluxes using results from the AMMA land-surface model intercomparison project

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Aaron Anthony [GAME-CNRM, Meteo-France, Toulouse (France); Poccard-Leclercq, Isabelle [Universite de Nantes, LETG-Geolittomer, Nantes (France); Xue, Yongkang; Feng, Jinming [University of California at Los Angeles, Los Angeles, CA (United States); Rosnay, Patricia de [European Centre for Medium Range Weather Forecasting, Reading (United Kingdom)

    2010-07-15

    The West African monsoon (WAM) circulation and intensity have been shown to be influenced by the land surface in numerous numerical studies using regional scale and global scale atmospheric climate models (RCMs and GCMs, respectively) over the last several decades. The atmosphere-land surface interactions are modulated by the magnitude of the north-south gradient of the low level moist static energy, which is highly correlated with the steep latitudinal gradients of the vegetation characteristics and coverage, land use, and soil properties over this zone. The African Multidisciplinary Monsoon Analysis (AMMA) has organised comprehensive activities in data collection and modelling to further investigate the significance land-atmosphere feedbacks. Surface energy fluxes simulated by an ensemble of land surface models from AMMA Land-surface Model Intercomparison Project (ALMIP) have been used as a proxy for the best estimate of the ''real world'' values in order to evaluate GCM and RCM simulations under the auspices of the West African Monsoon Modelling Experiment (WAMME) project, since such large-scale observations do not exist. The ALMIP models have been forced in off-line mode using forcing based on a mixture of satellite, observational, and numerical weather prediction data. The ALMIP models were found to agree well over the region where land-atmosphere coupling is deemed to be most important (notably the Sahel), with a high signal to noise ratio (generally from 0.7 to 0.9) in the ensemble and a inter-model coefficient of variation between 5 and 15%. Most of the WAMME models simulated spatially averaged net radiation values over West Africa which were consistent with the ALMIP estimates, however, the partitioning of this energy between sensible and latent heat fluxes was significantly different: WAMME models tended to simulate larger (by nearly a factor of two) monthly latent heat fluxes than ALMIP. This results due to a positive precipitation

  14. 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.

  15. Characteristics of the Inner and Middle Magnetosphere: Results From the Coupled Michigan MHD Model and the Rice Convection Model

    Science.gov (United States)

    De Zeeuw, D.; Sazykin, S.; Wolf, D.; Gombosi, T.; Powell, K.

    2002-05-01

    A new high performance Rice Convection Model (RCM) has been coupled to the adaptive-grid Michigan MHD model (BATSRUS). This fully coupled code allows us to self-consistently simulate the physics in the inner and middle magnetosphere. A study will be presented of the basic characteristics of the inner and middle magnetosphere in the context of a single coupled-code run with steady inputs. The analysis will include region-2 currents, shielding of the inner magnetosphere, partial ring currents, pressure distribution, magnetic field inflation, and distribution of pV**gamma. The coupled-code simulation will be compared with results from RCM runs and algorithms.

  16. Assessment of Energy Removal Impacts on Physical Systems: Hydrodynamic Model Domain Expansion and Refinement, and Online Dissemination of Model Results

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Zhaoqing; Khangaonkar, Tarang; Wang, Taiping

    2010-08-01

    In this report we describe the 1) the expansion of the PNNL hydrodynamic model domain to include the continental shelf along the coasts of Washington, Oregon, and Vancouver Island; and 2) the approach and progress in developing the online/Internet disseminations of model results and outreach efforts in support of the Puget Sound Operational Forecast System (PS-OPF). Submittal of this report completes the work on Task 2.1.2, Effects of Physical Systems, Subtask 2.1.2.1, Hydrodynamics, for fiscal year 2010 of the Environmental Effects of Marine and Hydrokinetic Energy project.

  17. Assessment of Energy Removal Impacts on Physical Systems: Hydrodynamic Model Domain Expansion and Refinement, and Online Dissemination of Model Results

    International Nuclear Information System (INIS)

    Yang, Zhaoqing; Khangaonkar, Tarang; Wang, Taiping

    2010-01-01

    In this report we describe the (1) the expansion of the PNNL hydrodynamic model domain to include the continental shelf along the coasts of Washington, Oregon, and Vancouver Island; and (2) the approach and progress in developing the online/Internet disseminations of model results and outreach efforts in support of the Puget Sound Operational Forecast System (PS-OPF). Submittal of this report completes the work on Task 2.1.2, Effects of Physical Systems, Subtask 2.1.2.1, Hydrodynamics, for fiscal year 2010 of the Environmental Effects of Marine and Hydrokinetic Energy project.

  18. Dynamic analysis of ITER tokamak. Based on results of vibration test using scaled model

    International Nuclear Information System (INIS)

    Takeda, Nobukazu; Kakudate, Satoshi; Nakahira, Masataka

    2005-01-01

    The vibration experiments of the support structures with flexible plates for the ITER major components such as toroidal field coil (TF coil) and vacuum vessel (VV) were performed using small-sized flexible plates aiming to obtain its basic mechanical characteristics such as dependence of the stiffness on the loading angle. The experimental results were compared with the analytical ones in order to estimate an adequate analytical model for ITER support structure with flexible plates. As a result, the bolt connection of the flexible plates on the base plate strongly affected on the stiffness of the flexible plates. After studies of modeling the connection of the bolts, it is found that the analytical results modeling the bolts with finite stiffness only in the axial direction and infinite stiffness in the other directions agree well with the experimental ones. Based on this, numerical analysis regarding the actual support structure of the ITER VV and TF coil was performed. The support structure composed of flexible plates and connection bolts was modeled as a spring composed of only two spring elements simulating the in-plane and out-of-plane stiffness of the support structure with flexible plates including the effect of connection bolts. The stiffness of both spring models for VV and TF coil agree well with that of shell models, simulating actual structures such as flexible plates and connection bolts based on the experimental results. It is therefore found that the spring model with the only two values of stiffness enables to simplify the complicated support structure with flexible plates for the dynamic analysis of the VV and TF coil. Using the proposed spring model, the dynamic analysis of the VV and TF coil for the ITER were performed to estimate the integrity under the design earthquake. As a result, it is found that the maximum relative displacement of 8.6 mm between VV and TF coil is much less than 100 mm, so that the integrity of the VV and TF coil of the

  19. Furthering our Understanding of Land Surface Interactions using SVAT modelling: Results from SimSphere's Validation

    Science.gov (United States)

    North, Matt; Petropoulos, George; Ireland, Gareth; Rendal, Daisy; Carlson, Toby

    2015-04-01

    With current predicted climate change, there is an increased requirement to gain knowledge on the terrestrial biosphere, for numerous agricultural, hydrological and meteorological applications. To this end, Soil Vegetation Atmospheric Transfer (SVAT) models are quickly becoming the preferred scientific tool to monitor, at fine temporal and spatial resolutions, detailed information on numerous parameters associated with Earth system interactions. Validation of any model is critical to assess its accuracy, generality and realism to distinctive ecosystems and subsequently acts as important step before its operational distribution. In this study, the SimSphere SVAT model has been validated to fifteen different sites of the FLUXNET network, where model performance was statistically evaluated by directly comparing the model predictions vs in situ data, for cloud free days with a high energy balance closure. Specific focus is given to the models ability to simulate parameters associated with the energy balance, namely Shortwave Incoming Solar Radiation (Rg), Net Radiation (Rnet), Latent Heat (LE), Sensible Heat (H), Air Temperature at 1.3m (Tair 1.3m) and Air temperature at 50m (Tair 50m). Comparisons were performed for a number distinctive ecosystem types and for 150 days in total using in-situ data from ground observational networks acquired from the year 2011 alone. Evaluation of the models' coherence to reality was evaluated on the basis of a series of statistical parameters including RMSD, R2, Scatter, Bias, MAE , NASH index, Slope and Intercept. Results showed good to very good agreement between predicted and observed datasets, particularly so for LE, H, Tair 1.3m and Tair 50m where mean error distribution values indicated excellent model performance. Due to the systematic underestimation, poorer simulation accuracies were exhibited for Rg and Rnet, yet all values reported are still analogous to other validatory studies of its kind. In overall, the model

  20. Atmospheric boundary layer characteristics over the Pearl River Delta, China, during the summer of 2006: measurement and model results

    Directory of Open Access Journals (Sweden)

    S. J. Fan

    2011-07-01

    Full Text Available As part of the PRIDE-PRD2006 intensive campaign, atmospheric boundary layer (ABL measurements were performed in Qingyuan, Panyu, and Xinken over the Pearl River Delta (PRD on 1–30 July 2006. During the summer, the surface winds over the PRD are generally controlled by the south, usually with vertical wind shear at a height of approximately 800 m. Subsidence and precipitation from a tropical cyclone affects the air quality of the PRD. Under subsidence, wind speed in the ABL and the height of the ABL decrease and result in high-level concentrations. When the background wind speed is small or calm, the wind profile in Panyu and Xinken changes dramatically with height, which is perhaps caused by local circulation, such as sea-land breezes. To better understand the ABL of the PRD, simulations that used the Weather Research and Forecasting (WRF mesoscale model were utilized to analyze the ABL characteristics over the PRD. Based on three types of weather condition simulations (i.e., subsidence days, rainy days, and sunny days, the WRF model revealed that the simulated temperature and wind fields in these three cases were moderately consistent with the measurements. The results showed that diurnal variations of the ABL height on subsidence days and sunny days were obvious, but diurnal variations of the ABL height on rainy days were not apparent. The ABL is obviously affected by local circulation, and the ABL features are different at various stations. A simulation focused on a high pollution episode during the subsidence days on 12–15 July 2006, occurred under high-pressure conditions, accompanied by the tropical cyclone "Bilis". A comparison of the simulated vertical wind fields and temperature structure with the ABL measurements at Xinken, Panyu, and Qingyuan stations found that the modeled and measured atmospheric fields revealed two different types of ABL characteristics over the PRD. When the surface winds over the PRD were light or nearly calm

  1. Results from a 2 x CO2 simulation with the Canadian Climate Centre general circulation model

    International Nuclear Information System (INIS)

    Boer, G.J.

    1990-01-01

    The Canadian Climate Centre's general circulation model (GCM), GCMII, was used to simulate a doubling of atmospheric carbon dioxide concentration. The experiment was a standard greenhouse gas climate change study, using a three-dimensional atmospheric circulation model coupled to a simple 'slab' ocean and a thermodynamic ice model. This standard experiment retains the sophistication and generality of an atmospheric GCM, is straightforward in its use of simplified ocean and ice models, is comparatively economical of computer time, and permits comparison of results from different models. Features of the second generation GCMII include: higher resolution at T32L10 with a transform grid of 3.75 x 3.75 degree; full diurnal and annual cycles; ocean and sea ice treatment involving specification of ocean transports; modified treatment of land surface processes and hydrology; a parameterization of cloud optical feedback; and a retention of the special application data sets of surface parameters for North America and Europe. Results of the simulation were a globally averaged surface temperature increase of 3.5 degree C; a precipitation and evaporation increase of 3%; an average decrease in soil moisture of 6.6%; a decrease in cloud cover of 2.2%; a 66% decrease in mass of sea ice; and marked changes in other quantities in the polar region. 2 refs., 2 figs., 2 tabs

  2. Implementing a continuum of care model for older people - results from a Swedish case study

    Directory of Open Access Journals (Sweden)

    Anna Duner

    2011-11-01

    Full Text Available Introduction: There is a need for integrated care and smooth collaboration between care-providing organisations and professions to create a continuum of care for frail older people. However, collaboration between organisations and professions is often problematic. The aim of this study was to examine the process of implementing a new continuum of care model in a complex organisational context, and illuminate some of the challenges involved. The introduced model strived to connect three organisations responsible for delivering health and social care to older people: the regional hospital, primary health care and municipal eldercare.Methods: The actions of the actors involved in the process of implementing the model were understood to be shaped by the actors' understanding, commitment and ability. This article is based on 44 qualitative interviews performed on four occasions with 26 key actors at three organisational levels within these three organisations.Results and conclusions: The results point to the importance of paying regard to the different cultures of the organisations when implementing a new model. The role of upper management emerged as very important. Furthermore, to be accepted, the model has to be experienced as effectively dealing with real problems in the everyday practice of the actors in the organisations, from the bottom to the top.

  3. Response of a laminar premixed flame to flow oscillations: A kinematic model and thermoacoustic instability results

    Energy Technology Data Exchange (ETDEWEB)

    Fleifil, M.; Annaswamy, A.M.; Ghoneim, A.F. [Massachusetts Inst. of Technology, Cambridge, MA (United States); Ghoneim, Z.A. [Ain Shams Univ., Abassia (Egypt)

    1996-09-01

    Combustion instability is a resonance phenomenon that arises due to the coupling between the system acoustics and the unsteady heat release. The constructive feedback between the two processes, which is known to occur as a certain phase relationship between the pressure and the unsteady heat release rate is satisfied, depends on many parameters among which is the acoustic mode, the flame holder characteristics, and the dominant burning pattern. In this paper, the authors construct an analytical model to describe the dynamic response of a laminar premixed flame stabilized on the rim of a tube to velocity oscillation. They consider uniform and nonuniform velocity perturbations superimposed on a pipe flow velocity profile. The model results show that the magnitude of heat release perturbation and its phase with respect to the dynamic perturbation dependent primarily on the flame Strohal number, representing the ratio of the dominant frequency times the tube radius to the laminar burning velocity. In terms of this number, high-frequency perturbations pass through the flame while low frequencies lead to a strong response. The phase with respect to the velocity perturbation behaves in the opposite way. Results of this model are shown to agree with experimental observations and to be useful in determining how the combustion excited model is selected among all the acoustic unstable modes. The model is then used to obtain a time-domain differential equation describing the relationship between the velocity perturbation and the heat release response over the entire frequency range.

  4. Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

    OpenAIRE

    Wesseling, Hendrik; Guest, Paul; Lee, Chi-Ming; Wong, Erik; Rahmoune, Hassan; Bahn, Sabine

    2014-01-01

    textabstractBackground: Over the last decade, the transgenic N-methyl-D-aspartate receptor (NMDAR) NR1-knockdown mouse (NR1neo-/-) has been investigated as a glutamate hypofunction model for schizophrenia. Recent research has now revealed that the model also recapitulates cognitive and negative symptoms in the continuum of other psychiatric diseases, particularly autism spectrum disorders (ASD). As previous studies have mostly focussed on behavioural readouts, a molecular characterisation of ...

  5. Proteomic analysis of germinal vesicles in the domestic cat model reveals candidate nuclear proteins involved in oocyte competence acquisition.

    Science.gov (United States)

    Lee, P-C; Wildt, D E; Comizzoli, P

    2018-01-01

    Do nuclear proteins in the germinal vesicle (GV) contribute to oocyte competence acquisition during folliculogenesis? Proteomic analysis of GVs identified candidate proteins for oocyte competence acquisition, including a key RNA processing protein-heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1). The domestic cat GV, which is physiologically similar to the human GV, gains the intrinsic ability to resume meiosis and support early embryo development during the pre-antral-to-antral follicle transition. However, little is known about nuclear proteins that contribute to this developmental process. GVs were enriched from pre-antral (incompetent) and antral (competent) follicles from 802 cat ovaries. Protein lysates were subjected to quantitative proteomic analysis to identify differentially expressed proteins in GVs from the two follicular categories. Two biological replicates (from independent pools of ovaries) of pre-antral versus antral samples were labeled by tandem mass tags and then assessed by liquid chromatography-tandem mass spectrometry. Proteomic data were analyzed according to gene ontology and a protein-protein interaction network. Immunofluorescent staining and protein inhibition assays were used for validation. A total of 174 nuclear proteins was identified, with 54 being up-regulated and 22 down-regulated (≥1.5-fold) after antrum formation. Functional protein analysis through gene ontology over-representation tests revealed that changes in molecular network within the GVs during this transitional phase were related to chromatin reorganization, gene transcription, and maternal RNA processing and storage. Protein inhibition assays verified that hnRNPA2B1, a key nuclear protein identified, was required for oocyte meiotic maturation and subsequent blastocyst formation. Data are available via ProteomeXchange with identifier PXD007211. Proteins identified by proteomic comparison may (i) be involved in processes other than competence acquisition

  6. An adult osteopetrosis model in medaka reveals the importance of osteoclast function for bone remodeling in teleost fish.

    Science.gov (United States)

    To, Thuy Thanh; Witten, Paul Eckhard; Huysseune, Ann; Winkler, Christoph

    2015-12-01

    Osteoclasts play important roles during bone growth and in maintaining bone health and bone homeostasis. Dysfunction or lack of osteoclasts leads to increased bone mass and osteopetrosis phenotypes in mouse and human. Here we report a severe osteopetrosis-like phenotype in transgenic medaka fish, in which membrane bound EGFP (mEGFP) was expressed in osteoclasts under control of the cathepsin K promoter (ctsk:mEGFP). In contrast to reporter lines with GFP expression in the cytoplasm of osteoclasts, adult fish of the mEGFP line developed bone defects indicative for an osteoclast dysfunction. Activity of tartrate-resistant acid phosphatase (TRAP) was down-regulated and excess bone was observed in most parts of the skeleton. The osteopetrotic phenotype was particularly obvious at the neural and haemal arches that failed to increase their volume in growing fish. Excess bone caused severe constriction of the spinal cord and the ventral aorta. The continuation of tooth development and the failure to shed teeth resulted in severe hyperdontia. Interestingly, at the vertebral column vertebral body arches displayed a severe osteopetrosis, while vertebral centra had no or only a mild osteopetrotic phenotype. This confirms previous reports from cichlids that, different from the arches, allometric growth of fish vertebral centra initially does not depend on the action of osteoclasts. Independent developmental mechanism that shapes arches and vertebral centra can also lend support to the hypothesis that vertebral centra and arches function as independent developmental modules. Together, this medaka osteopetrosis model confirms the importance of proper osteoclast function during normal skeletal development in teleost fish that requires bone modeling and remodeling. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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.

  8. Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling

    Science.gov (United States)

    Jarvis, Gavin E.; Barbosa, Roseli

    2016-01-01

    Citral, eucalyptol, and linalool are widely used as flavorings, fragrances, and cosmetics. Here, we examined their effects on electrophysiological and binding properties of human 5-HT3 receptors expressed in Xenopus oocytes and human embryonic kidney 293 cells, respectively. Data were analyzed using nonlinear mixed-effects modeling to account for random variance in the peak current response between oocytes. The oils caused an insurmountable inhibition of 5‐HT–evoked currents (citral IC50 = 120 µM; eucalyptol = 258 µM; linalool = 141 µM) and did not compete with fluorescently labeled granisetron, suggesting a noncompetitive mechanism of action. Inhibition was not use‐dependent but required a 30-second preapplication. Compound washout caused a slow (∼180 seconds) but complete recovery. Coapplication of the oils with bilobalide or diltiazem indicated they did not bind at the same locations as these channel blockers. Homology modeling and ligand docking predicted binding to a transmembrane cavity at the interface of adjacent subunits. Liquid chromatography coupled to mass spectrometry showed that an essential oil extracted from Lippia alba contained 75.9% citral. This inhibited expressed 5‐HT3 receptors (IC50 = 45 µg ml−1) and smooth muscle contractions in rat trachea (IC50 = 200 µg ml−1) and guinea pig ileum (IC50 = 20 µg ml−1), providing a possible mechanistic explanation for why this oil has been used to treat gastrointestinal and respiratory ailments. These results demonstrate that citral, eucalyptol, and linalool inhibit 5-HT3 receptors, and their binding to a conserved cavity suggests a valuable target for novel allosteric modulators. PMID:26669427

  9. Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity.

    Science.gov (United States)

    Peng, Mengling; Li, Shengnan; He, Qianian; Zhao, Jinlong; Li, Longlong; Ma, Haitian

    2018-01-08

    Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development. In this study, the abundances of 293 hepatic proteins in 19-day old of chicken embryos compared with 14-day old and 160 hepatic proteins at hatching compared with 19-day old embryos were significantly changed. Pathway analysis showed that fatty acid degradation (upregulated ACAA2, CPT1A, and ACOX1), protein folding (upregulated PDIs, CALR3, LMAN1, and UBQLN1) and gluconeogenesis (upregulated ACSS1, AKR1A1, ALDH3A2, ALDH7A1, and FBP2) were enhanced from embryonic day 14 (E14) to E19 of chicken embryo development. Analysis of the differentially abundant proteins indicated that glycolysis was not the main way to produce energy from E19 to hatching day during chicken embryo development. In addition, purine metabolism was enhanced, as deduced from increased IMPDH2, NT5C, PGM2, and XDH abundances, and the decrease of growth rate could be overcome by increasing the abundance of ribosomal proteins from E19 to the hatching day. The levels of certain proteins were coordinated with each other to regulate the changes in metabolic pathways to satisfy the requirement for growth and development at different stages of chicken embryo development. Importantly, ACAA2, CPT1A, and ACOX1 might be key factors to control fat deposition during chicken embryonic development. These results provided information showing that chicken is a useful model to further investigate the mechanism of obesity and insulin resistance in humans.

  10. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Progress and Preliminary Results

    Science.gov (United States)

    Rosenzweig, C.

    2011-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a distributed climate-scenario simulation exercise for historical model intercomparison and future climate change conditions with participation of multiple crop and agricultural trade modeling groups around the world. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Recent progress and the current status of AgMIP will be presented, highlighting three areas of activity: preliminary results from crop pilot studies, outcomes from regional workshops, and emerging scientific challenges. AgMIP crop modeling efforts are being led by pilot studies, which have been established for wheat, maize, rice, and sugarcane. These crop-specific initiatives have proven instrumental in testing and contributing to AgMIP protocols, as well as creating preliminary results for aggregation and input to agricultural trade models. Regional workshops are being held to encourage collaborations and set research activities in motion for key agricultural areas. The first of these workshops was hosted by Embrapa and UNICAMP and held in Campinas, Brazil. Outcomes from this meeting have informed crop modeling research activities within South America, AgMIP protocols, and future regional workshops. Several scientific challenges have emerged and are currently being addressed by AgMIP researchers. Areas of particular interest include geospatial weather generation, ensemble methods for climate scenarios and crop models, spatial aggregation of field-scale yields to regional and global production, and characterization of future changes in climate variability.

  11. Results of an interactively coupled atmospheric chemistry – general circulation model: Comparison with observations

    Directory of Open Access Journals (Sweden)

    R. Hein

    2001-04-01

    Full Text Available The coupled climate-chemistry model ECHAM4.L39(DLR/CHEM is presented which enables a simultaneous treatment of meteorology and atmospheric chemistry and their feedbacks. This is the first model which interactively combines a general circulation model with a chemical model, employing most of the important reactions and species necessary to describe the stratospheric and upper tropospheric ozone chemistry, and which is computationally fast enough to allow long-term integrations with currently available computer resources. This is possible as the model time-step used for the chemistry can be chosen as large as the integration time-step for the dynamics. Vertically the atmosphere is discretized by 39 levels from the surface up to the top layer which is centred at 10 hPa, with a relatively high vertical resolution of approximately 700 m near the extra-tropical tropopause. We present the results of a control simulation representing recent conditions (1990 and compare it to available observations. The focus is on investigations of stratospheric dynamics and chemistry relevant to describe the stratospheric ozone layer. ECHAM4.L39(DLR/CHEM reproduces main features of stratospheric dynamics in the arctic vortex region, including stratospheric warming events. This constitutes a major improvement compared to earlier 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 inter-hemispheric differences are reproduced. Considering methane oxidation as part of the dynamic-chemistry feedback results in an improved representation of the spatial distribution of stratospheric water vapour concentrations. The current model constitutes a powerful tool to investigate, for instance, the combined direct and indirect effects of anthropogenic

  12. Results of an interactively coupled atmospheric chemistry – general circulation model: Comparison with observations

    Directory of Open Access Journals (Sweden)

    R. Hein

    Full Text Available The coupled climate-chemistry model ECHAM4.L39(DLR/CHEM is presented which enables a simultaneous treatment of meteorology and atmospheric chemistry and their feedbacks. This is the first model which interactively combines a general circulation model with a chemical model, employing most of the important reactions and species necessary to describe the stratospheric and upper tropospheric ozone chemistry, and which is computationally fast enough to allow long-term integrations with currently available computer resources. This is possible as the model time-step used for the chemistry can be chosen as large as the integration time-step for the dynamics. Vertically the atmosphere is discretized by 39 levels from the surface up to the top layer which is centred at 10 hPa, with a relatively high vertical resolution of approximately 700 m near the extra-tropical tropopause. We present the results of a control simulation representing recent conditions (1990 and compare it to available observations. The focus is on investigations of stratospheric dynamics and chemistry relevant to describe the stratospheric ozone layer. ECHAM4.L39(DLR/CHEM reproduces main features of stratospheric dynamics in the arctic vortex region, including stratospheric warming events. This constitutes a major improvement compared to earlier 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 inter-hemispheric differences are reproduced. Considering methane oxidation as part of the dynamic-chemistry feedback results in an improved representation of the spatial distribution of stratospheric water vapour concentrations. The current model constitutes a powerful tool to investigate, for instance, the combined direct and indirect effects of anthropogenic

  13. Simple Stellar Population Modeling of Quasar Host Galaxies with Diffusion K-Means Test Results

    Science.gov (United States)

    Mosby, Gregory; Moravec, E. A.; Tremonti, C. A.; Wolf, M. J.

    2013-01-01

    In the last decade, the correlation of the masses of supermassive black holes (SMBHs) and their host galaxy stellar spheroid velocity dispersions (the M-sigma relation) was greeted as clear evidence for the co-evolution of host galaxies and their SMBHs. However, studies in the last five years have posited that this relation could arise from central-limit properties of hierarchical formation alone. To address the question of whether and how often the SMBHs evolve with their host galaxies, it is necessary to look at galaxies whose SMBHs are actively growing—quasars—and determine the host galaxy properties. The central nuclei of quasar host galaxies complicate this type of study because their high luminosity tends to wash out their host galaxies. But, by using 3-D spectroscopy with the integral field unit (IFU) Sparsepak on the WIYN telescope, we have shown that the quasar light can be mostly isolated to one fiber in order to obtain the spectra of the quasar and the host galaxy concurrently. We can then model simultaneously the scattered quasar light and the stellar populations in the host galaxy fiber using a new simple stellar population (SSP) modeling method called diffusion k-means (DFK). The objectives of the research presented in this poster are to model synthetic quasar host galaxies using a DFK basis and a more traditional basis, compare the accuracy of both modeling methods, and test the affects of various prescriptions for masking the quasar lines in the host galaxy fiber. We present results from our SSP modeling and Markov Chain Monte Carlo (MCMC) results for DFK and traditional modeling schemes using synthetic data. By determining and then using the more robust stellar population modeling method, we can more confidently study quasar host galaxies to answer remaining questions in galaxy evolution. This work was partially supported by a National Science Foundation Graduate Fellowship (NSF Grant DGE-0718123) and through the NSF's REU program (NSF Award

  14. 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...

  15. A Compact Synchronous Cellular Model of Nonlinear Calcium Dynamics: Simulation and FPGA Synthesis Results.

    Science.gov (United States)

    Soleimani, Hamid; Drakakis, Emmanuel M

    2017-06-01

    Recent studies have demonstrated that calcium is a widespread intracellular ion that controls a wide range of temporal dynamics in the mammalian body. The simulation and validation of such studies using experimental data would benefit from a fast large scale simulation and modelling tool. This paper presents a compact and fully reconfigurable cellular calcium model capable of mimicking Hopf bifurcation phenomenon and various nonlinear responses of the biological calcium dynamics. The proposed cellular model is synthesized on a digital platform for a single unit and a network model. Hardware synthesis, physical implementation on FPGA, and theoretical analysis confirm that the proposed cellular model can mimic the biological calcium behaviors with considerably low hardware overhead. The approach has the potential to speed up large-scale simulations of slow intracellular dynamics by sharing more cellular units in real-time. To this end, various networks constructed by pipelining 10 k to 40 k cellular calcium units are compared with an equivalent simulation run on a standard PC workstation. Results show that the cellular hardware model is, on average, 83 times faster than the CPU version.

  16. Solar Deployment System (SolarDS) Model: Documentation and Sample Results

    Energy Technology Data Exchange (ETDEWEB)

    Denholm, P.; Drury, E.; Margolis, R.

    2009-09-01

    The Solar Deployment System (SolarDS) model is a bottom-up, market penetration model that simulates the potential adoption of photovoltaics (PV) on residential and commercial rooftops in the continental United States through 2030. NREL developed SolarDS to examine the market competitiveness of PV based on regional solar resources, capital costs, electricity prices, utility rate structures, and federal and local incentives. The model uses the projected financial performance of PV systems to simulate PV adoption for building types and regions then aggregates adoption to state and national levels. The main components of SolarDS include a PV performance simulator, a PV annual revenue calculator, a PV financial performance calculator, a PV market share calculator, and a regional aggregator. The model simulates a variety of installed PV capacity for a range of user-specified input parameters. PV market penetration levels from 15 to 193 GW by 2030 were simulated in preliminary model runs. SolarDS results are primarily driven by three model assumptions: (1) future PV cost reductions, (2) the maximum PV market share assumed for systems with given financial performance, and (3) PV financing parameters and policy-driven assumptions, such as the possible future cost of carbon emissions.

  17. Tabulation of Mie scattering calculation results for microwave radiative transfer modeling

    Science.gov (United States)

    Yeh, Hwa-Young M.; Prasad, N.

    1988-01-01

    In microwave radiative transfer model simulations, the Mie calculations usually consume the majority of the computer time necessary for the calculations (70 to 86 percent for frequencies ranging from 6.6 to 183 GHz). For a large array of atmospheric profiles, the repeated calculations of the Mie codes make the radiative transfer computations not only expensive, but sometimes impossible. It is desirable, therefore, to develop a set of Mie tables to replace the Mie codes for the designated ranges of temperature and frequency in the microwave radiative transfer calculation. Results of using the Mie tables in the transfer calculations show that the total CPU time (IBM 3081) used for the modeling simulation is reduced by a factor of 7 to 16, depending on the frequency. The tables are tested by computing the upwelling radiance of 144 atmospheric profiles generated by a 3-D cloud model (Tao, 1986). Results are compared with those using Mie quantities computed from the Mie codes. The bias and root-mean-square deviation (RMSD) of the model results using the Mie tables, in general, are less than 1 K except for 37 and 90 GHz. Overall, neither the bias nor RMSD is worse than 1.7 K for any frequency and any viewing angle.

  18. Deposition and removal of fugitive dust in the arid southwestern United States: measurements and model results.

    Science.gov (United States)

    Etyemezian, Vic; Ahonen, Sean; Nikolic, Djordje; Gillies, John; Kuhns, Hampden; Gillette, Dale; Veranth, John

    2004-09-01

    This work was motivated by the need to better reconcile emission factors for fugitive dust with the amount of geologic material found on ambient filter samples. The deposition of particulate matter with aerodynamic diameter less than or equal to 10 microm (PM10), generated by travel over an unpaved road, over the first 100 m of transport downwind of the road was examined at Ft. Bliss, near El Paso, TX. The field conditions, typical for warm days in the arid southwestern United States, represented sparsely vegetated terrain under neutral to unstable atmospheric conditions. Emission fluxes of PM10 dust were obtained from towers downwind of the unpaved road at 7, 50, and 100 m. The horizontal flux measurements at the 7 m and 100 m towers indicated that PM10 deposition to the vegetation and ground was too small to measure. The data indicated, with 95% confidence, that the loss of PM10 between the source of emission at the unpaved road, represented by the 7 m tower, and a point 100 m downwind was less than 9.5%. A Gaussian model was used to simulate the plume. Values of the vertical standard deviation sigma(z) and the deposition velocity Vd were similar to the U.S. Environmental Protection Agency (EPA) ISC3 model. For the field conditions, the model predicted that removal of PM10 unpaved road dust by deposition over the distance between the point of emission and 100 m downwind would be less than 5%. However, the model results also indicated that particles larger than 10 microm (aerodynamic diameter) would deposit more appreciably. The model was consistent with changes observed in size distributions between 7 m and 100 m downwind, which were measured with optical particle counters. The Gaussian model predictions were also compared with another study conducted over rough terrain and stable atmospheric conditions. Under such conditions, measured PM10 removal rates over 95 m of downwind transport were reported to be between 86% and 89%, whereas the Gaussian model predicted

  19. Recent results of searches for beyond Standard Model physics in ATLAS

    CERN Document Server

    Serkin, Leonid; The ATLAS collaboration

    2017-01-01

    Recent results of searches for beyond Standard Model physics in ATLAS are presented, with particular focus on searches for new phenomena in high jet multiplicity final states. These include searches for charged Higgs boson in the $H^{+} \\to tb $ decay channel, vector-like quark pair production, four-top-quark production in different signal benchmark scenarios and associated heavy Higgs boson production. No significant excess are observed in data and exclusion limits on cross sections and masses are given for the signal models in a number of benchmark scenarios, in most cases significantly extending the reach of previous searches.

  20. First Test Results of the 150 mm Aperture IR Quadrupole Models for the High Luminosity LHC

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosio, G. [Fermilab; Chlachidze, G. [Fermilab; Wanderer, P. [Brookhaven; Ferracin, P. [CERN; Sabbi, G. [LBNL, Berkeley

    2016-10-06

    The High Luminosity upgrade of the LHC at CERN will use large aperture (150 mm) quadrupole magnets to focus the beams at the interaction points. The high field in the coils requires Nb3Sn superconductor technology, which has been brought to maturity by the LHC Accelerator Re-search Program (LARP) over the last 10 years. The key design targets for the new IR quadrupoles were established in 2012, and fabrication of model magnets started in 2014. This paper discusses the results from the first single short coil test and from the first short quadrupole model test. Remaining challenges and plans to address them are also presented and discussed.

  1. First Test Results of the 150 mm Aperture IR Quadrupole Models for the High Luminosity LHC

    CERN Document Server

    Ambrosio, G; Wanderer, P; Ferracin, P; Sabbi, G

    2017-01-01

    The High Luminosity upgrade of the LHC at CERN will use large aperture (150 mm) quadrupole magnets to focus the beams at the interaction points. The high field in the coils requires Nb3Sn superconductor technology, which has been brought to maturity by the LHC Accelerator Re-search Program (LARP) over the last 10 years. The key design targets for the new IR quadrupoles were established in 2012, and fabrication of model magnets started in 2014. This paper discusses the results from the first single short coil test and from the first short quadrupole model test. Remaining challenges and plans to address them are also presented and discussed.

  2. A Module for Graphical Display of Model Results with the CBP Toolbox

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-04-21

    This report describes work performed by the Savannah River National Laboratory (SRNL) in fiscal year 2014 to add enhanced graphical capabilities to display model results in the Cementitious Barriers Project (CBP) Toolbox. Because Version 2.0 of the CBP Toolbox has just been released, the graphing enhancements described in this report have not yet been integrated into a new version of the Toolbox. Instead they have been tested using a standalone GoldSim model and, while they are substantially complete, may undergo further refinement before full implementation. Nevertheless, this report is issued to document the FY14 development efforts which will provide a basis for further development of the CBP Toolbox.

  3. Exact results for survival probability in the multistate Landau-Zener model

    International Nuclear Information System (INIS)

    Volkov, M V; Ostrovsky, V N

    2004-01-01

    An exact formula is derived for survival probability in the multistate Landau-Zener model in the special case where the initially populated state corresponds to the extremal (maximum or minimum) slope of a linear diabatic potential curve. The formula was originally guessed by S Brundobler and V Elzer (1993 J. Phys. A: Math. Gen. 26 1211) based on numerical calculations. It is a simple generalization of the expression for the probability of diabatic passage in the famous two-state Landau-Zener model. Our result is obtained via analysis and summation of the entire perturbation theory series

  4. Bayesian model of signal rewiring reveals mechanisms of gene dysregulation in acquired drug resistance in breast cancer.

    Directory of Open Access Journals (Sweden)

    A K M Azad

    Full Text Available Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks. Results were obtained using matched gene expression profiles under resistant and parental conditions. Using two lapatinib-treated ErbB2-positive breast cancer cell-lines: SKBR3 and BT474, our method identified similar dysregulated signaling pathways including EGFR-related pathways as well as other receptor-related pathways, many of which were reported previously as compensatory pathways of EGFR-inhibition via signaling cross-talk. A manual literature survey provided strong evidence that aberrant signaling activities in dysregulated pathways are closely related to acquired resistance in EGFR tyrosine kinase inhibitors. Our approach predicted literature-supported dysregulated pathways complementary to both node-centric (SPIA, DAVID, and GATHER and edge-centric (ESEA and PAGI methods. Moreover, by proposing a novel pattern of aberrant signaling called V-structures, we observed that genes were dysregulated in resistant-vs-sensitive conditions when they were involved in the switch of dependencies from targeted to bypass signaling events. A literature survey of some important V-structures suggested they play a role in breast cancer metastasis and/or acquired resistance to EGFR-TKIs, where the mRNA changes of TGFBR2, LEF1 and TP53 in resistant-vs-sensitive conditions were related to the dependency switch from targeted to

  5. Bayesian model of signal rewiring reveals mechanisms of gene dysregulation in acquired drug resistance in breast cancer

    Science.gov (United States)

    Azad, A. K. M.; Keith, Jonathan M.

    2017-01-01

    Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks. Results were obtained using matched gene expression profiles under resistant and parental conditions. Using two lapatinib-treated ErbB2-positive breast cancer cell-lines: SKBR3 and BT474, our method identified similar dysregulated signaling pathways including EGFR-related pathways as well as other receptor-related pathways, many of which were reported previously as compensatory pathways of EGFR-inhibition via signaling cross-talk. A manual literature survey provided strong evidence that aberrant signaling activities in dysregulated pathways are closely related to acquired resistance in EGFR tyrosine kinase inhibitors. Our approach predicted literature-supported dysregulated pathways complementary to both node-centric (SPIA, DAVID, and GATHER) and edge-centric (ESEA and PAGI) methods. Moreover, by proposing a novel pattern of aberrant signaling called V-structures, we observed that genes were dysregulated in resistant-vs-sensitive conditions when they were involved in the switch of dependencies from targeted to bypass signaling events. A literature survey of some important V-structures suggested they play a role in breast cancer metastasis and/or acquired resistance to EGFR-TKIs, where the mRNA changes of TGFBR2, LEF1 and TP53 in resistant-vs-sensitive conditions were related to the dependency switch from targeted to bypass signaling links

  6. AG Channel Measurement and Modeling Results for Over-Sea Conditions

    Science.gov (United States)

    Matolak, David; Sun, Rouyu

    2014-01-01

    This report describes results from flight tests conducted in an over-sea environment, for the purpose of characterizing the air-to-ground (AG) channel, for future unmanned aircraft system (UAS) communication system analysis and design. These results are for the first of a set of several flight tests conducted in different ground site (GS) environments. An ultimate aim of all these tests is the development of models for the AG channel that can be used in communication system evaluation. In this report we provide measured results for propagation path loss, root-mean square delay spread (RMS-DS), and the correlation coefficient of the primary received signal components on the four antennas (two antennas for C-band, two for L-band). For path loss, the curved-earth two-ray model provides a reasonable fit to the measured data, altered by several dB at the shortest link distances by aircraft antenna pattern effects. This two-ray model also accounts for the majority of measured RMS-DS results of a few tens of nanoseconds, except for the occasional intermittent reflections from surface objects. These intermittent reflections yield RMS-DS values up to several hundred nanoseconds. For portions of the flight path that were over a harbor area highly populated with boats, the channel was found to be more "continuously dispersive," with RMS-DS reaching approximately 250 ns. A separate model will be developed for this over-harbor setting. The correlation coefficient results are still undergoing analysis; preliminary observations are that correlation between signals on the same-band antennas is generally large (>0.6) for the C-band straight flight paths, whereas for the L-band signals and for the oval-shaped flight paths the correlation is generally small (below 0.4). Inter-band correlations are typically very small, and are well modeled as zero-mean Gaussian in distribution, with a standard deviation less than 0.2. Hence the over-sea channel effects in the two bands can be

  7. Preliminary Results from Electric Arc Furnace Off-Gas Enthalpy Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Nimbalkar, Sachin U [ORNL; Thekdi, Arvind [E3M Inc; Keiser, James R [ORNL; Storey, John Morse [ORNL

    2015-01-01

    This article describes electric arc furnace (EAF) off-gas enthalpy models developed at Oak Ridge National Laboratory (ORNL) to calculate overall heat availability (sensible and chemical enthalpy) and recoverable heat values (steam or power generation potential) for existing EAF operations and to test ORNL s new EAF waste heat recovery (WHR) concepts. ORNL s new EAF WHR concepts are: Regenerative Drop-out Box System and Fluidized Bed System. The two EAF off-gas enthalpy models described in this paper are: 1.Overall Waste Heat Recovery Model that calculates total heat availability in off-gases of existing EAF operations 2.Regenerative Drop-out Box System Model in which hot EAF off-gases alternately pass through one of two refractory heat sinks that store heat and then transfer it to another gaseous medium These models calculate the sensible and chemical enthalpy of EAF off-gases based on the off-gas chemical composition, temperature, and mass flow rate during tap to tap time, and variations in those parameters in terms of actual values over time. The models provide heat transfer analysis for the aforementioned concepts to confirm the overall system and major component sizing (preliminary) to assess the practicality of the systems. Real-time EAF off-gas composition (e.g., CO, CO2, H2, and H2O), volume flow, and temperature data from one EAF operation was used to test the validity and accuracy of the modeling work. The EAF off-gas data was used to calculate the sensible and chemical enthalpy of the EAF off-gases to generate steam and power. The article provides detailed results from the modeling work that are important to the success of ORNL s EAF WHR project. The EAF WHR project aims to develop and test new concepts and materials that allow cost-effective recovery of sensible and chemical heat from high-temperature gases discharged from EAFs.

  8. Atmosphere and permafrost in the Arctic: results from a new regional coupled atmosphere-land model

    Science.gov (United States)

    Matthes, Heidrun; Rinke, Annette; Zhou, Xu; Dethloff, Klaus

    2017-04-01

    Frozen ground is one of the key components of the land part of the Arctic climate system. A reliable representation of the exchanges of energy, water and gases (CO2 and CH4) between frozen ground and the atmosphere is essential for simulating the present day Arctic coupled climate system realistically and its future changes with some confidence. Regional atmosphere-snow-permafrost interactions can be best studied with Regional Climate Models (RCMs) due to their high horizontal resolution compared to Global Climate Models. For this purpose, the sophisticated land model CLM4 was integrated into the Arctic regional climate model HIRHAM5 (HIRHAM5-CLM4). To validate this model, it was run over the ERAInterim period (1979-2014) and the model results were compared to a similar simulation of HIRHAM5, using the inbuilt land model, as well as to station observations. The comparison focuses on the models ability to represent observations on permafrost like permafrost extent, active layer thickness (ALT) and soil temperature profiles, as well as on the representation of the Arctic atmosphere. The representation of ALT and soil temperature profiles is significantly improved in HIRHAM5-CLM4 compared to HIRHAM5. Averaged over the period 2000-2011, the bias to station observations of ALT is reduced from -1.3 m to -0.3 m, the Arctic wide winter soil temperature root mean square is reduced from up to 14.4K to a maximum of 5K. Arctic climatology of 2m air temperature and mean sea level pressure are well represented in both HIRHAM5-CLM4 and HIRHAM5, HIRHAM5-CLM4 reduces the air temperature bias averaged over 1979-2014 over Eastern and Central Siberia in winter by 0.5K. Using CLM4 in HIRHAM5 impacts the simulation of local circulation patterns and influences the occurrence of baroclinic cyclones.

  9. Analyzing Tropical Waves Using the Parallel Ensemble Empirical Model Decomposition Method: Preliminary Results from Hurricane Sandy

    Science.gov (United States)

    Shen, Bo-Wen; Cheung, Samson; Li, Jui-Lin F.; Wu, Yu-ling

    2013-01-01

    In this study, we discuss the performance of the parallel ensemble empirical mode decomposition (EMD) in the analysis of tropical waves that are associated with tropical cyclone (TC) formation. To efficiently analyze high-resolution, global, multiple-dimensional data sets, we first implement multilevel parallelism into the ensemble EMD (EEMD) and obtain a parallel speedup of 720 using 200 eight-core processors. We then apply the parallel EEMD (PEEMD) to extract the intrinsic mode functions (IMFs) from preselected data sets that represent (1) idealized tropical waves and (2) large-scale environmental flows associated with Hurricane Sandy (2012). Results indicate that the PEEMD is efficient and effective in revealing the major wave characteristics of the data, such as wavelengths and periods, by sifting out the dominant (wave) components. This approach has a potential for hurricane climate study by examining the statistical relationship between tropical waves and TC formation.

  10. 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

  11. 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

  12. ‘Get in early’; biofilm and wax moth (Galleria mellonella models reveal new insights into the therapeutic potential of Clostridium difficile bacteriophages

    Directory of Open Access Journals (Sweden)

    Janet Yakubu Nale

    2016-08-01

    Full Text Available Clostridium difficile infection (CDI is a global health threat associated with high rates of morbidity and mortality. Conventional antibiotic CDI therapy can result in treatment failure and recurrent infection. C. difficile produces biofilms which contribute to its virulence and impair antimicrobial activity. Some bacteriophages (phages can penetrate biofilms and thus could be developed to either replace or supplement antibiotics. Here, we determined the impact of a previously optimized 4-phage cocktail on C. difficile ribotype 014/020 biofilms, and additionally as adjunct to vancomycin treatment in Galleria mellonella larva CDI model. The phages were applied before or after biofilm establishment in vitro, and the impact was analyzed according to turbidity, viability counts and topography as observed using scanning electron and confocal microscopy. The infectivity profiles and efficacies of orally administered phages and/or vancomycin were ascertained by monitoring colonization levels and larval survival rates. Phages prevented biofilm formation, and penetrated established biofilms. A single phage application reduced colonization causing extended longevity in the remedial treatment and prevented disease in the prophylaxis group. Multiple phage doses significantly improved the larval remedial regimen, and this treatment is comparable to vancomycin and the combined treatments. Taken together, our data suggest that the phages significantly reduce C. difficile biofilms, and prevent colonization in the G. mellonella model when used alone or in combination with vancomycin. The phages appear to be highly promising therapeutics in the targeted eradication of CDI and the use of these models has revealed that prophylactic use could be a propitious therapeutic option.

  13. Inflation or deflation? New results for Mayon Volcano applying elastic-gravitational modeling

    Science.gov (United States)

    Fernández, J.; Tiampo, K. F.; Jentzsch, G.; Charco, M.; Rundle, J. B.

    Volcanic activity produces deformation and gravity changes that many times can be used as precursors of future eruptions. Applying geodetic techniques to monitoring activity involves interpretation using deformation models. Usually, the observed changes of the deformation and gravity fields are interpreted seperately, not in a joint inversion. It can be difficult, if not impossible, to interpret the data coherently or correctly in terms of the characteristics of the intrusion or the deflation derived from the gravity changes with purely elastic models, as in the case of Mayon Volcano, Phillipines. We show that elastic-gravitational models can be used to interpret these cases simultaneously leading to a result that is more plausible on the basis of the available information. Thus, we may need to change the philosophy normally used to interpret geodetic observations. Interpretation as proposed in this work can significantly improve the possibility of predicting future eruptions.

  14. The impact of air traffic in the NAFC. Model results and measurements

    Energy Technology Data Exchange (ETDEWEB)

    Wauben, W.M.F.; Velthoven, P.F.J. van; Kelder, H.M. [Koninklijk Nederlands Meteorologisch Inst., De Bilt (Netherlands)

    1997-12-31

    The impact of aircraft emissions on the atmospheric composition has been investigated with a global chemistry transport model. The model calculations show that aircraft emissions of nitrogen oxides contribute to about 40-80% of the background values of nitrogen oxides in the North Atlantic Flight Corridor (NAFC), and lead to an increase of the background ozone concentrations by about 3-4% in winter and 5-7% in summer. The three-dimensional distributions of ozone, nitrogen oxides and nitric acid, calculated by using analysed meteorological data, have been compared with airborne measurements performed in the North Atlantic Flight Corridor as part of the EC POLINAT project. The agreement between modelled results and observations is reasonably good for ozone, but worse for nitrogen oxides and nitric acid. (author) 12 refs.

  15. A comparison of solute-transport solution techniques and their effect on sensitivity analysis and inverse modeling results

    Science.gov (United States)

    Mehl, S.; Hill, M.C.

    2001-01-01

    Five common numerical techniques for solving the advection-dispersion equation (finite difference, predictor corrector, total variation diminishing, method of characteristics, and modified method of characteristics) were tested using simulations of a controlled conservative tracer-test experiment through a heterogeneous, two-dimensional sand tank. The experimental facility was constructed using disc