WorldWideScience

Sample records for residues molecular modeling

  1. Residue conservation and dimer-interface analysis of olfactory receptor molecular models

    Directory of Open Access Journals (Sweden)

    Ramanathan Sowdhamini

    2012-10-01

    Full Text Available Olfactory Receptors (ORs are members of the Class A rhodopsin like G-protein coupled receptors (GPCRs which are the initial players in the signal transduction cascade, leading to the generation of nerve impulses transmitted to the brain and resulting in the detection of odorant molecules. Despite the accumulation of thousands of olfactory receptor sequences, no crystal structures of ORs are known tο date. However, the recent availability of crystallographic models of a few GPCRs allows us to generate homology models of ORs and analyze their amino acid patterns, as there is a huge diversity in OR sequences. In this study, we have generated three-dimensional models of 100 representative ORs from Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Sacharomyces cerevisiae which were selected on the basis of a composite classification scheme and phylogenetic analysis. The crystal structure of bovine rhodopsin was used as a template and it was found that the full-length models have more than 90% of their residues in allowed regions of the Ramachandran plot. The structures were further used for analysis of conserved residues in the transmembrane and extracellular loop regions in order to identify functionally important residues. Several ORs are known to be functional as dimers and hence dimer interfaces were predicted for OR models to analyse their oligomeric functional state.

  2. PLS models for determination of SARA analysis of Colombian vacuum residues and molecular distillation fractions using MIR-ATR

    Directory of Open Access Journals (Sweden)

    Jorge A. Orrego-Ruiz

    2014-06-01

    Full Text Available In this work, prediction models of Saturates, Aromatics, Resins and Asphaltenes fractions (SARA from thirty-seven vacuum residues of representative Colombian crudes and eighteen fractions of molecular distillation process were obtained. Mid-Infrared (MIR Attenuated Total Reflection (ATR spectroscopy in combination with partial least squares (PLS regression analysis was used to estimate accurately SARA analysis in these kind of samples. Calibration coefficients of prediction models were for saturates, aromatics, resins and asphaltenes fractions, 0.99, 0.96, 0.97 and 0.99, respectively. This methodology permits to control the molecular distillation process since small differences in chemical composition can be detected. Total time elapsed to give the SARA analysis per sample is 10 minutes.

  3. Analysis and Ranking of Protein-Protein Docking Models Using Inter-Residue Contacts and Inter-Molecular Contact Maps

    KAUST Repository

    Oliva, Romina; Chermak, Edrisse; Cavallo, Luigi

    2015-01-01

    In view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available, protein-protein docking becomes the method of choice for predicting the arrangement of the complex. However, reliably scoring protein-protein docking poses is still an unsolved problem. As a consequence, the screening of many docking models is usually required in the analysis step, to possibly single out the correct ones. Here, making use of exemplary cases, we review our recently introduced methods for the analysis of protein complex structures and for the scoring of protein docking poses, based on the use of inter-residue contacts and their visualization in inter-molecular contact maps. We also show that the ensemble of tools we developed can be used in the context of rational drug design targeting protein-protein interactions.

  4. Analysis and Ranking of Protein-Protein Docking Models Using Inter-Residue Contacts and Inter-Molecular Contact Maps

    KAUST Repository

    Oliva, Romina

    2015-07-01

    In view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available, protein-protein docking becomes the method of choice for predicting the arrangement of the complex. However, reliably scoring protein-protein docking poses is still an unsolved problem. As a consequence, the screening of many docking models is usually required in the analysis step, to possibly single out the correct ones. Here, making use of exemplary cases, we review our recently introduced methods for the analysis of protein complex structures and for the scoring of protein docking poses, based on the use of inter-residue contacts and their visualization in inter-molecular contact maps. We also show that the ensemble of tools we developed can be used in the context of rational drug design targeting protein-protein interactions.

  5. Molecular Modeling

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 5. Molecular Modeling: A Powerful Tool for Drug Design and Molecular Docking. Rama Rao Nadendla. General Article Volume 9 Issue 5 May 2004 pp 51-60. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  7. MOLECULAR MODELING STUDY OF THE CONTRIBUTIONS OF SIDE AMINO ACID RESIDUES OF POLYMYXIN B3 TO ITS BINDING WITH E.COLI OUTER MEMBRANE LIPOPOLYSACCHARIDE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2014-12-01

    Full Text Available Last decades, antimicrobial peptides (AMPs are the subject of intense investigations aimed to develop effective drugs against extremely resistant nosocomial bacterial pathogens (especially Gram-negative bacteria. In particular, there has been greatly renewed interest to polymyxins, the representatives of AMPs which are specific and highly potent against Gram-negative bacteria, but have potential nephrotoxic side effect. A prerequisite of purposeful enhancement of therapeutic properties of polymyxins is a detailed knowledge of the molecular mechanisms of their interactions with cell targets. Lipopolysaccharide (LPS, the main component of the outer leaflet of outer membrane of gram-negative bacteria, is a primary cell target of polymyxins. The aim of the paper was to study the peculiarities of molecular interactions of polymyxin В3 with lipopolysaccharide of the outer membrane of gram-negative bacterium. Materials and methods The complexes of polymyxin В3 (PmВ3 and its alaninederivatives with E. coli outer membrane lipopolysaccharide were built and studied by molecular modeling methods (minimization, simulated annealing, docking. Atom coordinates of polymyxin В3 and LPS structures were taken from nuclear magnetic resonance and X-ray crystallography experiments, respectively. The AMBER03 force field was used with a 1.05 nm force cutoff. Longrange electrostatic interactions were treated by the Particle Mesh Ewald method. Results and discussion Alanine scanning of PmВ3 molecule has been carried out and the role of its side amino acid residues in the formation of complex with lipopolysaccharide has been investigated. It has been shown that substitutions of polymyxin’s Dab residues in positions 1, 3, 5, 8 and 9 for alanine markedly reduce the binding energy of PmB3-LPS complex, where as the similar substitutions of residues in positions 2, 6, 7 and 10 leave the binding energy virtually unchanged. Structural aspects of antimicrobial action of

  8. Molecular Dynamics Modeling of the Effect of Axial and Transverse Compression on the Residual Tensile Properties of Ballistic Fiber

    Directory of Open Access Journals (Sweden)

    Sanjib C. Chowdhury

    2017-02-01

    Full Text Available Ballistic impact induces multiaxial loading on Kevlar® and polyethylene fibers used in protective armor systems. The influence of multiaxial loading on fiber failure is not well understood. Experiments show reduction in the tensile strength of these fibers after axial and transverse compression. In this paper, we use molecular dynamics (MD simulations to explain and develop a fundamental understanding of this experimental observation since the property reduction mechanism evolves from the atomistic level. An all-atom MD method is used where bonded and non-bonded atomic interactions are described through a state-of-the-art reactive force field. Monotonic tension simulations in three principal directions of the models are conducted to determine the anisotropic elastic and strength properties. Then the models are subjected to multi-axial loads—axial compression, followed by axial tension and transverse compression, followed by axial tension. MD simulation results indicate that pre-compression distorts the crystal structure, inducing preloading of the covalent bonds and resulting in lower tensile properties.

  9. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  10. Residual Structures in Latent Growth Curve Modeling

    Science.gov (United States)

    Grimm, Kevin J.; Widaman, Keith F.

    2010-01-01

    Several alternatives are available for specifying the residual structure in latent growth curve modeling. Two specifications involve uncorrelated residuals and represent the most commonly used residual structures. The first, building on repeated measures analysis of variance and common specifications in multilevel models, forces residual variances…

  11. Spectrofluorometric and Molecular Modeling Studies on Binding of Nitrite Ion with Bovine Hemoglobin: Effect of Nitrite Ion on Amino Acid Residues

    Science.gov (United States)

    Madrakian, T.; Bagheri, H.; Afkhami, A.

    2015-05-01

    The interaction between nitrite ion and bovine hemoglobin was investigated by a spectrofluorometric technique. The experimental results indicated that the interaction causes a static quenching of the fluorescence of bovine hemoglobin, that the binding reaction is spontaneous, and that H-bonding interactions play a major role in binding of this ion to bovine hemoglobin. The formation constant for this interaction was calculated. Based on Förster's theory of nonradiative energy transfer, the binding distance between this ion and bovine hemoglobin was determined. Furthermore, the interaction of nitrite ion with tyrosine and tryptophan was investigated with synchronous fluorescence. There was no significant shift of the maximum emission wavelength with interactions of the mentioned ion with bovine hemoglobin, which implies that interaction of nitrite ion with bovine hemoglobin does not affect the microenvironment around the tryptophan and tyrosine residues. Furthermore, the effect of nitrite ion on amino acid residues of bovine hemoglobin was studied by a molecular docking technique.

  12. FINITE ELEMENT MODEL FOR PREDICTING RESIDUAL ...

    African Journals Online (AJOL)

    FINITE ELEMENT MODEL FOR PREDICTING RESIDUAL STRESSES IN ... the transverse residual stress in the x-direction (σx) had a maximum value of 375MPa ... the finite element method are in fair agreement with the experimental results.

  13. Development of a General Modelling Methodology for Vacuum Residue Hydroconversion

    Directory of Open Access Journals (Sweden)

    Pereira de Oliveira L.

    2013-11-01

    Full Text Available This work concerns the development of a methodology for kinetic modelling of refining processes, and more specifically for vacuum residue conversion. The proposed approach allows to overcome the lack of molecular detail of the petroleum fractions and to simulate the transformation of the feedstock molecules into effluent molecules by means of a two-step procedure. In the first step, a synthetic mixture of molecules representing the feedstock for the process is generated via a molecular reconstruction method, termed SR-REM molecular reconstruction. In the second step, a kinetic Monte-Carlo method (kMC is used to simulate the conversion reactions on this mixture of molecules. The molecular reconstruction was applied to several petroleum residues and is illustrated for an Athabasca (Canada vacuum residue. The kinetic Monte-Carlo method is then described in detail. In order to validate this stochastic approach, a lumped deterministic model for vacuum residue conversion was simulated using Gillespie’s Stochastic Simulation Algorithm. Despite the fact that both approaches are based on very different hypotheses, the stochastic simulation algorithm simulates the conversion reactions with the same accuracy as the deterministic approach. The full-scale stochastic simulation approach using molecular-level reaction pathways provides high amounts of detail on the effluent composition and is briefly illustrated for Athabasca VR hydrocracking.

  14. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

    Science.gov (United States)

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

    2014-12-12

    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Geostatistical methods applied to field model residuals

    DEFF Research Database (Denmark)

    Maule, Fox; Mosegaard, K.; Olsen, Nils

    consists of measurement errors and unmodelled signal), and is typically assumed to be uncorrelated and Gaussian distributed. We have applied geostatistical methods to analyse the residuals of the Oersted(09d/04) field model [http://www.dsri.dk/Oersted/Field_models/IGRF_2005_candidates/], which is based...

  16. Open source molecular modeling.

    Science.gov (United States)

    Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

    2016-09-01

    The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. An updated online version of this catalog can be found at https://opensourcemolecularmodeling.github.io. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Residuals and the Residual-Based Statistic for Testing Goodness of Fit of Structural Equation Models

    Science.gov (United States)

    Foldnes, Njal; Foss, Tron; Olsson, Ulf Henning

    2012-01-01

    The residuals obtained from fitting a structural equation model are crucial ingredients in obtaining chi-square goodness-of-fit statistics for the model. The authors present a didactic discussion of the residuals, obtaining a geometrical interpretation by recognizing the residuals as the result of oblique projections. This sheds light on the…

  18. Assessment of Molecular Modeling & Simulation

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-01-03

    This report reviews the development and applications of molecular and materials modeling in Europe and Japan in comparison to those in the United States. Topics covered include computational quantum chemistry, molecular simulations by molecular dynamics and Monte Carlo methods, mesoscale modeling of material domains, molecular-structure/macroscale property correlations like QSARs and QSPRs, and related information technologies like informatics and special-purpose molecular-modeling computers. The panel's findings include the following: The United States leads this field in many scientific areas. However, Canada has particular strengths in DFT methods and homogeneous catalysis; Europe in heterogeneous catalysis, mesoscale, and materials modeling; and Japan in materials modeling and special-purpose computing. Major government-industry initiatives are underway in Europe and Japan, notably in multi-scale materials modeling and in development of chemistry-capable ab-initio molecular dynamics codes.

  19. An Additive-Multiplicative Restricted Mean Residual Life Model

    DEFF Research Database (Denmark)

    Mansourvar, Zahra; Martinussen, Torben; Scheike, Thomas H.

    2016-01-01

    mean residual life model to study the association between the restricted mean residual life function and potential regression covariates in the presence of right censoring. This model extends the proportional mean residual life model using an additive model as its covariate dependent baseline....... For the suggested model, some covariate effects are allowed to be time-varying. To estimate the model parameters, martingale estimating equations are developed, and the large sample properties of the resulting estimators are established. In addition, to assess the adequacy of the model, we investigate a goodness...

  20. Predictive models of forest logging residues of Triplochiton ...

    African Journals Online (AJOL)

    The model developed indicated that logarithmic functions performed better than other form of equation. The findings of this study revealed that there is significant logging residues left to waste in the forest after timber harvest and quantifying this logging residue in terms of biomass model can serve as management tools in ...

  1. Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

    Science.gov (United States)

    Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

    2016-01-01

    Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

  2. Modelling of the Residual Stress State in a new Type of Residual Stress Specimen

    DEFF Research Database (Denmark)

    Jakobsen, Johnny; Andreasen, Jens Henrik

    2014-01-01

    forms the experimental case which is analysed. A FE model of the specimen is used for analysing the curing history and the residual stress build up. The model is validated against experimental strain data which are recorded by a Fibre Brag Grating sensor and good agreement has been achieved.......The paper presents a study on a new type residual stress specimen which is proposed as a simple way to conduct experimental validation for model predictions. A specimen comprising of a steel plate with circular hole embedded into a stack of CSM glass fibre and further infused with an epoxy resin...

  3. Magnetohydrodynamic Models of Molecular Tornadoes

    Science.gov (United States)

    Au, Kelvin; Fiege, Jason D.

    2017-07-01

    Recent observations near the Galactic Center (GC) have found several molecular filaments displaying striking helically wound morphology that are collectively known as molecular tornadoes. We investigate the equilibrium structure of these molecular tornadoes by formulating a magnetohydrodynamic model of a rotating, helically magnetized filament. A special analytical solution is derived where centrifugal forces balance exactly with toroidal magnetic stress. From the physics of torsional Alfvén waves we derive a constraint that links the toroidal flux-to-mass ratio and the pitch angle of the helical field to the rotation laws, which we find to be an important component in describing the molecular tornado structure. The models are compared to the Ostriker solution for isothermal, nonmagnetic, nonrotating filaments. We find that neither the analytic model nor the Alfvén wave model suffer from the unphysical density inversions noted by other authors. A Monte Carlo exploration of our parameter space is constrained by observational measurements of the Pigtail Molecular Cloud, the Double Helix Nebula, and the GC Molecular Tornado. Observable properties such as the velocity dispersion, filament radius, linear mass, and surface pressure can be used to derive three dimensionless constraints for our dimensionless models of these three objects. A virial analysis of these constrained models is studied for these three molecular tornadoes. We find that self-gravity is relatively unimportant, whereas magnetic fields and external pressure play a dominant role in the confinement and equilibrium radial structure of these objects.

  4. Magnetohydrodynamic Models of Molecular Tornadoes

    Energy Technology Data Exchange (ETDEWEB)

    Au, Kelvin; Fiege, Jason D., E-mail: fiege@physics.umanitoba.ca [Department of Physics and Astronomy, University of Manitoba Winnipeg, MB R3T 2N2 (Canada)

    2017-07-10

    Recent observations near the Galactic Center (GC) have found several molecular filaments displaying striking helically wound morphology that are collectively known as molecular tornadoes. We investigate the equilibrium structure of these molecular tornadoes by formulating a magnetohydrodynamic model of a rotating, helically magnetized filament. A special analytical solution is derived where centrifugal forces balance exactly with toroidal magnetic stress. From the physics of torsional Alfvén waves we derive a constraint that links the toroidal flux-to-mass ratio and the pitch angle of the helical field to the rotation laws, which we find to be an important component in describing the molecular tornado structure. The models are compared to the Ostriker solution for isothermal, nonmagnetic, nonrotating filaments. We find that neither the analytic model nor the Alfvén wave model suffer from the unphysical density inversions noted by other authors. A Monte Carlo exploration of our parameter space is constrained by observational measurements of the Pigtail Molecular Cloud, the Double Helix Nebula, and the GC Molecular Tornado. Observable properties such as the velocity dispersion, filament radius, linear mass, and surface pressure can be used to derive three dimensionless constraints for our dimensionless models of these three objects. A virial analysis of these constrained models is studied for these three molecular tornadoes. We find that self-gravity is relatively unimportant, whereas magnetic fields and external pressure play a dominant role in the confinement and equilibrium radial structure of these objects.

  5. finite element model for predicting residual stresses in shielded

    African Journals Online (AJOL)

    eobe

    This paper investigates the prediction of residual stresses developed ... steel plates through Finite Element Model simulation and experiments. ... The experimental values as measured by the X-Ray diffractometer were of ... Based on this, it can be concluded that Finite Element .... Comparison of Residual Stresses from X.

  6. The Ising model for prediction of disordered residues from protein sequence alone

    International Nuclear Information System (INIS)

    Lobanov, Michail Yu; Galzitskaya, Oxana V

    2011-01-01

    Intrinsically disordered regions serve as molecular recognition elements, which play an important role in the control of many cellular processes and signaling pathways. It is useful to be able to predict positions of disordered residues and disordered regions in protein chains using protein sequence alone. A new method (IsUnstruct) based on the Ising model for prediction of disordered residues from protein sequence alone has been developed. According to this model, each residue can be in one of two states: ordered or disordered. The model is an approximation of the Ising model in which the interaction term between neighbors has been replaced by a penalty for changing between states (the energy of border). The IsUnstruct has been compared with other available methods and found to perform well. The method correctly finds 77% of disordered residues as well as 87% of ordered residues in the CASP8 database, and 72% of disordered residues as well as 85% of ordered residues in the DisProt database

  7. Improvement and Validation of Weld Residual Stress Modelling Procedure

    International Nuclear Information System (INIS)

    Zang, Weilin; Gunnars, Jens; Dong, Pingsha; Hong, Jeong K.

    2009-06-01

    The objective of this work is to identify and evaluate improvements for the residual stress modelling procedure currently used in Sweden. There is a growing demand to eliminate any unnecessary conservatism involved in residual stress assumptions. The study was focused on the development and validation of an improved weld residual stress modelling procedure, by taking advantage of the recent advances in residual stress modelling and stress measurement techniques. The major changes applied in the new weld residual stress modelling procedure are: - Improved procedure for heat source calibration based on use of analytical solutions. - Use of an isotropic hardening model where mixed hardening data is not available. - Use of an annealing model for improved simulation of strain relaxation in re-heated material. The new modelling procedure is demonstrated to capture the main characteristics of the through thickness stress distributions by validation to experimental measurements. Three austenitic stainless steel butt-welds cases are analysed, covering a large range of pipe geometries. From the cases it is evident that there can be large differences between the residual stresses predicted using the new procedure, and the earlier procedure or handbook recommendations. Previously recommended profiles could give misleading fracture assessment results. The stress profiles according to the new procedure agree well with the measured data. If data is available then a mixed hardening model should be used

  8. Improvement and Validation of Weld Residual Stress Modelling Procedure

    Energy Technology Data Exchange (ETDEWEB)

    Zang, Weilin; Gunnars, Jens (Inspecta Technology AB, Stockholm (Sweden)); Dong, Pingsha; Hong, Jeong K. (Center for Welded Structures Research, Battelle, Columbus, OH (United States))

    2009-06-15

    The objective of this work is to identify and evaluate improvements for the residual stress modelling procedure currently used in Sweden. There is a growing demand to eliminate any unnecessary conservatism involved in residual stress assumptions. The study was focused on the development and validation of an improved weld residual stress modelling procedure, by taking advantage of the recent advances in residual stress modelling and stress measurement techniques. The major changes applied in the new weld residual stress modelling procedure are: - Improved procedure for heat source calibration based on use of analytical solutions. - Use of an isotropic hardening model where mixed hardening data is not available. - Use of an annealing model for improved simulation of strain relaxation in re-heated material. The new modelling procedure is demonstrated to capture the main characteristics of the through thickness stress distributions by validation to experimental measurements. Three austenitic stainless steel butt-welds cases are analysed, covering a large range of pipe geometries. From the cases it is evident that there can be large differences between the residual stresses predicted using the new procedure, and the earlier procedure or handbook recommendations. Previously recommended profiles could give misleading fracture assessment results. The stress profiles according to the new procedure agree well with the measured data. If data is available then a mixed hardening model should be used

  9. A proposed residual stress model for oblique turning

    International Nuclear Information System (INIS)

    Elkhabeery, M. M.

    2001-01-01

    A proposed mathematical model is presented for predicting the residual stresses caused by turning. Effects of change in tool free length, cutting speed, feed rate, and the tensile strength of work piece material on the maximum residual stress are investigated. The residual stress distribution in the surface region due to turning under unlubricated condition is determined using a deflection etching technique. To reduce the number of experiments required and build the mathematical model for these variables, Response Surface Methodology (RSM) is used. In addition, variance analysis and an experimental check are conducted to determine the prominent parameters and the adequacy of the model. The results show that the tensile stress of the work piece material, cutting speed, and feed rate have significant effects on the maximum residual stresses. The proposed model, that offering good correlation between the experimental and predicted results, is useful in selecting suitable cutting parameters for the machining of different materials. (author)

  10. Model-checking techniques based on cumulative residuals.

    Science.gov (United States)

    Lin, D Y; Wei, L J; Ying, Z

    2002-03-01

    Residuals have long been used for graphical and numerical examinations of the adequacy of regression models. Conventional residual analysis based on the plots of raw residuals or their smoothed curves is highly subjective, whereas most numerical goodness-of-fit tests provide little information about the nature of model misspecification. In this paper, we develop objective and informative model-checking techniques by taking the cumulative sums of residuals over certain coordinates (e.g., covariates or fitted values) or by considering some related aggregates of residuals, such as moving sums and moving averages. For a variety of statistical models and data structures, including generalized linear models with independent or dependent observations, the distributions of these stochastic processes tinder the assumed model can be approximated by the distributions of certain zero-mean Gaussian processes whose realizations can be easily generated by computer simulation. Each observed process can then be compared, both graphically and numerically, with a number of realizations from the Gaussian process. Such comparisons enable one to assess objectively whether a trend seen in a residual plot reflects model misspecification or natural variation. The proposed techniques are particularly useful in checking the functional form of a covariate and the link function. Illustrations with several medical studies are provided.

  11. Geochemical Testing And Model Development - Residual Tank Waste Test Plan

    International Nuclear Information System (INIS)

    Cantrell, K.J.; Connelly, M.P.

    2010-01-01

    This Test Plan describes the testing and chemical analyses release rate studies on tank residual samples collected following the retrieval of waste from the tank. This work will provide the data required to develop a contaminant release model for the tank residuals from both sludge and salt cake single-shell tanks. The data are intended for use in the long-term performance assessment and conceptual model development.

  12. Biomass yield and modeling of logging residues of Terminalia ...

    African Journals Online (AJOL)

    The use of Dbh as an independent variable in the prediction of models for estimating the biomass residues of the tree species was adjudged best because it performed well. The validation results showed that the selected models satisfied the assumptions of regression analysis. The practical implication of the models is that ...

  13. DEFECT MONITORING IN IRON CASTING USING RESIDUES OF AUTOREGRESSIVE MODELS

    Directory of Open Access Journals (Sweden)

    Vanusa Andrea Casarin

    2013-06-01

    Full Text Available The purpose of this study is to monitor the index of general waste irons forecasting nodular and gray using the residues originated from the methodology Box & Jenkins by means of X-bar and R control charts. Search is to find a general class of model ARIMA (p, d, q but as data have autocorrelation is found to the number of residues which allowed the application of charts. The found model was the model SARIMA (0,1,1(0,1,1 . In step of checking the stability of the model was found that some comments are out of control due to temperature and chemical composition.

  14. Technical note: Equivalent genomic models with a residual polygenic effect.

    Science.gov (United States)

    Liu, Z; Goddard, M E; Hayes, B J; Reinhardt, F; Reents, R

    2016-03-01

    Routine genomic evaluations in animal breeding are usually based on either a BLUP with genomic relationship matrix (GBLUP) or single nucleotide polymorphism (SNP) BLUP model. For a multi-step genomic evaluation, these 2 alternative genomic models were proven to give equivalent predictions for genomic reference animals. The model equivalence was verified also for young genotyped animals without phenotypes. Due to incomplete linkage disequilibrium of SNP markers to genes or causal mutations responsible for genetic inheritance of quantitative traits, SNP markers cannot explain all the genetic variance. A residual polygenic effect is normally fitted in the genomic model to account for the incomplete linkage disequilibrium. In this study, we start by showing the proof that the multi-step GBLUP and SNP BLUP models are equivalent for the reference animals, when they have a residual polygenic effect included. Second, the equivalence of both multi-step genomic models with a residual polygenic effect was also verified for young genotyped animals without phenotypes. Additionally, we derived formulas to convert genomic estimated breeding values of the GBLUP model to its components, direct genomic values and residual polygenic effect. Third, we made a proof that the equivalence of these 2 genomic models with a residual polygenic effect holds also for single-step genomic evaluation. Both the single-step GBLUP and SNP BLUP models lead to equal prediction for genotyped animals with phenotypes (e.g., reference animals), as well as for (young) genotyped animals without phenotypes. Finally, these 2 single-step genomic models with a residual polygenic effect were proven to be equivalent for estimation of SNP effects, too. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Development of residual stress prediction model in pipe weldment

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Yun Yong; Lim, Se Young; Choi, Kang Hyeuk; Cho, Young Sam; Lim, Jae Hyuk [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    2002-03-15

    When Leak Before Break(LBB) concepts is applied to high energy piping of nuclear power plants, residual weld stresses is a important variable. The main purpose of his research is to develop the numerical model which can predict residual weld stresses. Firstly, basic theories were described which need to numerical analysis of welding parts. Before the analysis of pipe, welding of a flat plate was analyzed and compared. Appling the data of used pipes, thermal/mechanical analysis were accomplished and computed temperature gradient and residual stress distribution. For thermal analysis, proper heat flux was regarded as the heat source and convection/radiation heat transfer were considered at surfaces. The residual stresses were counted from the computed temperature gradient and they were compared and verified with a result of another research.

  16. Molecular modeling of inorganic compounds

    National Research Council Canada - National Science Library

    Comba, Peter; Hambley, Trevor W; Martin, Bodo

    2009-01-01

    ... mechanics to inorganic and coordination compounds. Initially, simple metal complexes were modeled, but recently the field has been extended to include organometallic compounds, catalysis and the interaction of metal ions with biological macromolecules. The application of molecular mechanics to coordination compounds is complicated by the numbe...

  17. Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

    Science.gov (United States)

    Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

    2015-12-01

    Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

  18. Modeling of plates with multiple anisotropic layers and residual stress

    DEFF Research Database (Denmark)

    Engholm, Mathias; Pedersen, Thomas; Thomsen, Erik Vilain

    2016-01-01

    Usually the analytical approach for modeling of plates uses the single layer plate equation to obtain the deflection and does not take anisotropy and residual stress into account. Based on the stress–strain relation of each layer and balancing stress resultants and bending moments, a general...... multilayered anisotropic plate equation is developed for plates with an arbitrary number of layers. The exact deflection profile is calculated for a circular clamped plate of anisotropic materials with residual bi-axial stress.From the deflection shape the critical stress for buckling is calculated......, and an excellent agreement between the two models is seen with a relative difference of less than 2% for all calculations. The model was also used to extract the cell capacitance, the parasitic capacitance and the residual stress of a pressure sensor composed of a multilayered plate of silicon and silicon oxide...

  19. Modeling of CMUTs with Multiple Anisotropic Layers and Residual Stress

    DEFF Research Database (Denmark)

    Engholm, Mathias; Thomsen, Erik Vilain

    2014-01-01

    Usually the analytical approach for modeling CMUTs uses the single layer plate equation to obtain the deflection and does not take anisotropy and residual stress into account. A highly accurate model is developed for analytical characterization of CMUTs taking an arbitrary number of layers...... and residual stress into account. Based on the stress-strain relation of each layer and balancing stress resultants and bending moments, a general multilayered anisotropic plate equation is developed for plates with an arbitrary number of layers. The exact deflection profile is calculated for a circular...... clamped plate of anisotropic materials with residual bi-axial stress. From the deflection shape the critical stress for buckling is calculated and by using the Rayleigh-Ritz method the natural frequency is estimated....

  20. Human butyrylcholinesterase polymorphism: Molecular modeling.

    Science.gov (United States)

    Lushchekina, S; Delacour, H; Lockridge, O; Masson, P

    2015-01-01

    Prolonged apnoea following injection of ester-containing myoralaxants was first described in 1953. Because a large part of administered succinylcholine is shortly hydrolyzed by plasma butyrylcholinesterase (BChE) under normal conditions, prolonged apnoea was attributed to deficiency in BChE. It was found that BChE deficiency was due to genetic variations. Human BChE gene shows a large polyallelism. About 75 natural mutations of the BCHE gene have been documented so far [1]. Most of them cause alteration in BChE activity through point mutation effect on catalytic activity. Frame shifts and stop codons may also affect expression, or cause truncations in the sequence. Recently, two novel BChE "silent" variants, Val204Asp [2] and Ala34Val [3], causing prolonged neuromuscular block after administration of mivacurium, were discovered. Mutations were genetically and kinetically characterized. The aim of the current study was to understand how these mutations determine "silent" phenotype. Molecular dynamics studies were carried out with NAMD 2.9 software at the Lomonosov supercomputer. Charmm 36 force field was used, periodical boundary conditions, 1 atm pressure, 298 K. 100 ns molecular dynamics runs were performed for the wild-type BChE and its mutants Val204Asp and Ala34Val. Unlike wild-type BChE, which retained its operative catalytic triad through the whole MD simulation, the catalytic triad of mutants was disrupted, making chemical step impossible. Val204Asp mutation leads to reorganization of hydrogen bonding network around the catalytic triad, which in turn increases the distance between catalytic residue main chains. Mutation Ala34Val, located on the protein surface, leads to increased fluctuations in the Ω-loop and subsequent disruption of the gorge structure, including disruption of the catalytic triad and formation of new hydrogen bonds involving catalytic center residues. Comparative study of the "silent" Ala328Asp mutant and the catalytically active mutant

  1. Modeling Residual NAPL in Water-Wet Porous Media

    Directory of Open Access Journals (Sweden)

    R.J. Lenhard

    2002-06-01

    Full Text Available A model is outlined that predicts NAPL which is held in pore wedges and as films or lenses on solid and water surfaces and contributes negligibly to NAPL advection. This is conceptually referred to as residual NAPL. Since residual NAPL is immobile, it remains in the vadose zone after all free NAPL has drained. Residual NAPL is very important because it is a long-term source for groundwater contamination. Recent laboratory experiments have demonstrated that current models for predicting subsurface NAPL behavior are inadequate because they do not correctly predict residual NAPL. The main reason for the failure is a deficiency in the current constitutive theories for multiphase flow that are used in numerical simulators. Multiphase constitutive theory governs the relations among relative permeability, saturation, and pressure for fluid systems (i.e., air, NAPL, water. In this paper, we outline a model describing relations between fluid saturations and pressures that can be combined with existing multiphase constitutive theory to predict residual NAPL. We test the revised constitutive theory by applying it to a scenario involving NAPL imbibition and drainage, as well as water imbibition and drainage. The results suggest that the revised constitutive theory is able to predict the distribution of residual NAPL in the vadose zone as a function of saturation-path history. The revised model describing relations between fluid saturation and pressures will help toward developing or improving numerical multiphase flow simulators.

  2. Applied exposure modeling for residual radioactivity and release criteria

    International Nuclear Information System (INIS)

    Lee, D.W.

    1989-01-01

    The protection of public health and the environment from the release of materials with residual radioactivity for recycle or disposal as wastes without radioactive contents of concern presents a formidable challenge. Existing regulatory criteria are based on technical judgment concerning detectability and simple modeling. Recently, exposure modeling methodologies have been developed to provide a more consistent level of health protection. Release criteria derived from the application of exposure modeling methodologies share the same basic elements of analysis but are developed to serve a variety of purposes. Models for the support of regulations for all applications rely on conservative interpretations of generalized conditions while models developed to show compliance incorporate specific conditions not likely to be duplicated at other sites. Research models represent yet another type of modeling which strives to simulate the actual behavior of released material. In spite of these differing purposes, exposure modeling permits the application of sound and reasoned principles of radiation protection to the release of materials with residual levels of radioactivity. Examples of the similarities and differences of these models are presented and an application to the disposal of materials with residual levels of uranium contamination is discussed. 5 refs., 2 tabs

  3. Reconstruction for limited-projection fluorescence molecular tomography based on projected restarted conjugate gradient normal residual.

    Science.gov (United States)

    Cao, Xu; Zhang, Bin; Liu, Fei; Wang, Xin; Bai, Jing

    2011-12-01

    Limited-projection fluorescence molecular tomography (FMT) can greatly reduce the acquisition time, which is suitable for resolving fast biology processes in vivo but suffers from severe ill-posedness because of the reconstruction using only limited projections. To overcome the severe ill-posedness, we report a reconstruction method based on the projected restarted conjugate gradient normal residual. The reconstruction results of two phantom experiments demonstrate that the proposed method is feasible for limited-projection FMT. © 2011 Optical Society of America

  4. Modelling Of Residual Stresses Induced By High Speed Milling Process

    International Nuclear Information System (INIS)

    Desmaison, Olivier; Mocellin, Katia; Jardin, Nicolas

    2011-01-01

    Maintenance processes used in heavy industries often include high speed milling operations. The reliability of the post-process material state has to be studied. Numerical simulation appears to be a very interesting way to supply an efficient residual stresses (RS) distribution prediction.Because the adiabatic shear band and the serrated chip shaping are features of the austenitic stainless steel high speed machining, a 2D high speed orthogonal cutting model is briefly presented. This finite element model, developed on Forge registered software, is based on data taken from Outeiro and al.'s paper [1]. A new behaviour law fully coupling Johnson-Cook's constitutive law and Latham and Cockcroft's damage model is detailed in this paper. It ensures results that fit those found in literature.Then, the numerical tools used on the 2D model are integrated to a 3D high speed milling model. Residual stresses distribution is analysed, on the surface and into the depth of the material. Various revolutions and passes of the two teeth hemispheric mill on the workpiece are simulated. Thus the sensitivity of the residual stresses generation to the cutting conditions can be discussed. In order to validate the 3D model, a comparison of the cutting forces measured by EDF R and D to those given by numerical simulations is achieved.

  5. Benchmark on residual stress modeling in fracture mechanics assessment

    International Nuclear Information System (INIS)

    Marie, S.; Deschanels, H.; Chapuliot, S.; Le Delliou, P.

    2014-01-01

    In the frame of development in analytical defect assessment methods for the RSE-M and RCC-MRx codes, new work on the consideration of residual stresses is initiated by AREVA, CEA and EDF. The first step of this work is the realization of a database of F.E. reference cases. To validate assumptions and develop a good practice guideline for the consideration of residual stresses in finite element calculations, a benchmark between AREVA, CEA and EDF is going-on. A first application presented in this paper focuses on the analysis of the crack initiation of aged duplex stainless steel pipes submitted to an increasing pressure loading. Residual stresses are related to pipe fabrication process and act as shell bending condition. Two tests were performed: the first with an internal longitudinal semi-elliptical crack and the second with an external crack. The analysis first focuses on the ability to accurately estimate the measured pressure at the crack initiation of the two tests. For that purpose, the comparison of results obtained with different methods of taking into account the residual stresses (i.e. thermal fields or initial strain field). It then validates post-treatment procedures for J or G determination, and finally compares of the results obtained by the different partners. It is then shown that the numerical models can integrate properly the impact of residual stresses on the crack initiation pressure. Then, an excellent agreement is obtained between the different numerical evaluations of G provided by the participants to the benchmark so that best practice and reference F.E. solutions for residual stresses consideration can be provided based on that work. (authors)

  6. Model morphing and sequence assignment after molecular replacement

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov [Los Alamos National Laboratory, Mail Stop M888, Los Alamos, NM 87545 (United States); Read, Randy J. [University of Cambridge, Cambridge Institute for Medical Research, Cambridge CB2 0XY (United Kingdom); Adams, Paul D. [Lawrence Berkeley National Laboratory, One Cyclotron Road, Bldg 64R0121, Berkeley, CA 94720 (United States); Brunger, Axel T. [Stanford University, 318 Campus Drive West, Stanford, CA 94305 (United States); Afonine, Pavel V. [Lawrence Berkeley National Laboratory, One Cyclotron Road, Bldg 64R0121, Berkeley, CA 94720 (United States); Hung, Li-Wei [Los Alamos National Laboratory, Mail Stop M888, Los Alamos, NM 87545 (United States)

    2013-11-01

    A procedure for model building is described that combines morphing a model to match a density map, trimming the morphed model and aligning the model to a sequence. A procedure termed ‘morphing’ for improving a model after it has been placed in the crystallographic cell by molecular replacement has recently been developed. Morphing consists of applying a smooth deformation to a model to make it match an electron-density map more closely. Morphing does not change the identities of the residues in the chain, only their coordinates. Consequently, if the true structure differs from the working model by containing different residues, these differences cannot be corrected by morphing. Here, a procedure that helps to address this limitation is described. The goal of the procedure is to obtain a relatively complete model that has accurate main-chain atomic positions and residues that are correctly assigned to the sequence. Residues in a morphed model that do not match the electron-density map are removed. Each segment of the resulting trimmed morphed model is then assigned to the sequence of the molecule using information about the connectivity of the chains from the working model and from connections that can be identified from the electron-density map. The procedure was tested by application to a recently determined structure at a resolution of 3.2 Å and was found to increase the number of correctly identified residues in this structure from the 88 obtained using phenix.resolve sequence assignment alone (Terwilliger, 2003 ▶) to 247 of a possible 359. Additionally, the procedure was tested by application to a series of templates with sequence identities to a target structure ranging between 7 and 36%. The mean fraction of correctly identified residues in these cases was increased from 33% using phenix.resolve sequence assignment to 47% using the current procedure. The procedure is simple to apply and is available in the Phenix software package.

  7. Model morphing and sequence assignment after molecular replacement

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Read, Randy J.; Adams, Paul D.; Brunger, Axel T.; Afonine, Pavel V.; Hung, Li-Wei

    2013-01-01

    A procedure for model building is described that combines morphing a model to match a density map, trimming the morphed model and aligning the model to a sequence. A procedure termed ‘morphing’ for improving a model after it has been placed in the crystallographic cell by molecular replacement has recently been developed. Morphing consists of applying a smooth deformation to a model to make it match an electron-density map more closely. Morphing does not change the identities of the residues in the chain, only their coordinates. Consequently, if the true structure differs from the working model by containing different residues, these differences cannot be corrected by morphing. Here, a procedure that helps to address this limitation is described. The goal of the procedure is to obtain a relatively complete model that has accurate main-chain atomic positions and residues that are correctly assigned to the sequence. Residues in a morphed model that do not match the electron-density map are removed. Each segment of the resulting trimmed morphed model is then assigned to the sequence of the molecule using information about the connectivity of the chains from the working model and from connections that can be identified from the electron-density map. The procedure was tested by application to a recently determined structure at a resolution of 3.2 Å and was found to increase the number of correctly identified residues in this structure from the 88 obtained using phenix.resolve sequence assignment alone (Terwilliger, 2003 ▶) to 247 of a possible 359. Additionally, the procedure was tested by application to a series of templates with sequence identities to a target structure ranging between 7 and 36%. The mean fraction of correctly identified residues in these cases was increased from 33% using phenix.resolve sequence assignment to 47% using the current procedure. The procedure is simple to apply and is available in the Phenix software package

  8. Variational methods in molecular modeling

    CERN Document Server

    2017-01-01

    This book presents tutorial overviews for many applications of variational methods to molecular modeling. Topics discussed include the Gibbs-Bogoliubov-Feynman variational principle, square-gradient models, classical density functional theories, self-consistent-field theories, phase-field methods, Ginzburg-Landau and Helfrich-type phenomenological models, dynamical density functional theory, and variational Monte Carlo methods. Illustrative examples are given to facilitate understanding of the basic concepts and quantitative prediction of the properties and rich behavior of diverse many-body systems ranging from inhomogeneous fluids, electrolytes and ionic liquids in micropores, colloidal dispersions, liquid crystals, polymer blends, lipid membranes, microemulsions, magnetic materials and high-temperature superconductors. All chapters are written by leading experts in the field and illustrated with tutorial examples for their practical applications to specific subjects. With emphasis placed on physical unders...

  9. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  10. Modeling of residual stress state in turning of 304L

    International Nuclear Information System (INIS)

    Valiorgue, F.; Rech, J.; Bergheau, J.M.

    2010-01-01

    Research presented in this paper aims to link machining parameters to residual stress state and helps understanding mechanisms responsible of machined surface properties modifications. The first presented works are based on an experimental campaign. They reproduce the finishing turning operation of 304L and allow observing the residual stress state evolution at the work piece surface and for an affected depth of 0.2 mm for such processes. Then, the finishing turning operation is simulated numerically in order to realize the same sensitivity study to cutting parameters. This simulation is based on an hybrid approach mixing experimental data and numerical simulation. This method allows getting round the classical difficulties of turning simulation by applying equivalent thermo mechanical loadings onto the work piece surface without modeling the material separation phenomena. Moreover the numerical model uses an hardening law taking into account dynamic recrystallization phenomena. (authors)

  11. Predictive hydrogeochemical modelling of bauxite residue sand in field conditions.

    Science.gov (United States)

    Wissmeier, Laurin; Barry, David A; Phillips, Ian R

    2011-07-15

    The suitability of residue sand (the coarse fraction remaining from Bayer's process of bauxite refining) for constructing the surface cover of closed bauxite residue storage areas was investigated. Specifically, its properties as a medium for plant growth are of interest to ensure residue sand can support a sustainable ecosystem following site closure. The geochemical evolution of the residue sand under field conditions, its plant nutrient status and soil moisture retention were studied by integrated modelling of geochemical and hydrological processes. For the parameterization of mineral reactions, amounts and reaction kinetics of the mineral phases natron, calcite, tricalcium aluminate, sodalite, muscovite and analcime were derived from measured acid neutralization curves. The effective exchange capacity for ion adsorption was measured using three independent exchange methods. The geochemical model, which accounts for mineral reactions, cation exchange and activity corrected solution speciation, was formulated in the geochemical modelling framework PHREEQC, and partially validated in a saturated-flow column experiment. For the integration of variably saturated flow with multi-component solute transport in heterogeneous 2D domains, a coupling of PHREEQC with the multi-purpose finite-element solver COMSOL was established. The integrated hydrogeochemical model was applied to predict water availability and quality in a vertical flow lysimeter and a cover design for a storage facility using measured time series of rainfall and evaporation from southwest Western Australia. In both scenarios the sand was fertigated and gypsum-amended. Results show poor long-term retention of fertilizer ions and buffering of the pH around 10 for more than 5 y of leaching. It was concluded that fertigation, gypsum amendment and rainfall leaching alone were insufficient to render the geochemical conditions of residue sand suitable for optimal plant growth within the given timeframe. The

  12. Molecular modelling and radiopharmaceutical design

    International Nuclear Information System (INIS)

    Neves, M.; Gano, L.; Costa, M.C.; Raminhos, H.; Rosado, M.; Fausto, R.

    2002-01-01

    Aim: Among several headings for radiopharmaceuticals (RPs) design, molecular modelling (MM) could be used for the prediction of ligands and metal-complexes structures. Using MM it is also possible to simulate molecular interactions between predicted structures and specific biomolecules. Bisphosphonates (BPs) are ligands that are able to coordinate radioactive metals, such as 153 Sm, 166 Ho, 186 Re, etc., but they are all polymeric complexes difficult to characterize. It is reported that the bone uptake does not depend on the nature of metal center, but is primarily driven by the nature of the ligand, as in the case of HEDP-M (M= 99m Tc, 186 Re, 113 Sn). So, it would be interesting to estimate the relevant molecular properties of BPs by MM, simulate their interaction with hydroxyapatite (HAP) the main bone component, and then correlate the predicted molecular parameters with experimental data obtained from HAP binding and biodistribution studies of BPs carrying radioactive metals. Materials and Methods: The molecular structures and preferred conformations of BPs differing in the length of the aliphatic chain attached to their substituted amine groups (pami-dronate, olpadronate and ibandronate) were obtained using the second-generation CVFF 950 (version 1.01) force field of Hwang et al. Simulation of the interactions between the studied BPs and HAP were performed using a Cerius-2 system of programs running on a Silicon Graphics O2 workstation. BPs- 153 Sm complexes were synthesized and characterized by ITLC. Their binding to HAP and in vivo biodistribution studies were carried out as usual described in literature. Results: A direct correlation could be established between in vitro BPs affinity towards HAP and their corresponding energies from the Coulomb interactions involving the N and P atoms of the studied BPs bound to the HAP (0,0,1) surface and the nearest Ca atoms of HAP. The BPs- 153 Sm showing the highest binding to HAP and skeletal uptake are those which

  13. Influence of Hardening Model on Weld Residual Stress Distribution

    Energy Technology Data Exchange (ETDEWEB)

    Mullins, Jonathan; Gunnars, Jens (Inspecta Technology AB, Stockholm (Sweden))

    2009-06-15

    This study is the third stage of a project sponsored by the Swedish Radiation Safety Authority (SSM) to improve the weld residual stress modelling procedures currently used in Sweden. The aim of this study was to determine which material hardening model gave the best agreement with experimentally measured weld residual stress distributions. Two girth weld geometries were considered: 19mm and 65mm thick girth welds with Rin/t ratios of 10.5 and 2.8, respectively. The FE solver ABAQUS Standard v6.5 was used for analysis. As a preliminary step some improvements were made to the welding simulation procedure used in part one of the project. First, monotonic stress strain curves and a mixed isotropic/kinematic hardening model were sourced from the literature for 316 stainless steel. Second, more detailed information was obtained regarding the geometry and welding sequence for the Case 1 weld (compared with phase 1 of this project). Following the preliminary step, welding simulations were conducted using isotropic, kinematic and mixed hardening models. The isotropic hardening model gave the best overall agreement with experimental measurements; it is therefore recommended for future use in welding simulations. The mixed hardening model gave good agreement for predictions of the hoop stress but tended to under estimate the magnitude of the axial stress. It must be noted that two different sources of data were used for the isotropic and mixed models in this study and this may have contributed to the discrepancy in predictions. When defining a mixed hardening model it is difficult to delineate the relative contributions of isotropic and kinematic hardening and for the model used it may be that a greater isotropic hardening component should have been specified. The kinematic hardening model consistently underestimated the magnitude of both the axial and hoop stress and is not recommended for use. Two sensitivity studies were also conducted. In the first the effect of using a

  14. Influence of Hardening Model on Weld Residual Stress Distribution

    International Nuclear Information System (INIS)

    Mullins, Jonathan; Gunnars, Jens

    2009-06-01

    This study is the third stage of a project sponsored by the Swedish Radiation Safety Authority (SSM) to improve the weld residual stress modelling procedures currently used in Sweden. The aim of this study was to determine which material hardening model gave the best agreement with experimentally measured weld residual stress distributions. Two girth weld geometries were considered: 19mm and 65mm thick girth welds with Rin/t ratios of 10.5 and 2.8, respectively. The FE solver ABAQUS Standard v6.5 was used for analysis. As a preliminary step some improvements were made to the welding simulation procedure used in part one of the project. First, monotonic stress strain curves and a mixed isotropic/kinematic hardening model were sourced from the literature for 316 stainless steel. Second, more detailed information was obtained regarding the geometry and welding sequence for the Case 1 weld (compared with phase 1 of this project). Following the preliminary step, welding simulations were conducted using isotropic, kinematic and mixed hardening models. The isotropic hardening model gave the best overall agreement with experimental measurements; it is therefore recommended for future use in welding simulations. The mixed hardening model gave good agreement for predictions of the hoop stress but tended to under estimate the magnitude of the axial stress. It must be noted that two different sources of data were used for the isotropic and mixed models in this study and this may have contributed to the discrepancy in predictions. When defining a mixed hardening model it is difficult to delineate the relative contributions of isotropic and kinematic hardening and for the model used it may be that a greater isotropic hardening component should have been specified. The kinematic hardening model consistently underestimated the magnitude of both the axial and hoop stress and is not recommended for use. Two sensitivity studies were also conducted. In the first the effect of using a

  15. Quantifying and Visualizing Uncertainties in Molecular Models

    OpenAIRE

    Rasheed, Muhibur; Clement, Nathan; Bhowmick, Abhishek; Bajaj, Chandrajit

    2015-01-01

    Computational molecular modeling and visualization has seen significant progress in recent years with sev- eral molecular modeling and visualization software systems in use today. Nevertheless the molecular biology community lacks techniques and tools for the rigorous analysis, quantification and visualization of the associated errors in molecular structure and its associated properties. This paper attempts at filling this vacuum with the introduction of a systematic statistical framework whe...

  16. Model morphing and sequence assignment after molecular replacement.

    Science.gov (United States)

    Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Brunger, Axel T; Afonine, Pavel V; Hung, Li-Wei

    2013-11-01

    A procedure termed `morphing' for improving a model after it has been placed in the crystallographic cell by molecular replacement has recently been developed. Morphing consists of applying a smooth deformation to a model to make it match an electron-density map more closely. Morphing does not change the identities of the residues in the chain, only their coordinates. Consequently, if the true structure differs from the working model by containing different residues, these differences cannot be corrected by morphing. Here, a procedure that helps to address this limitation is described. The goal of the procedure is to obtain a relatively complete model that has accurate main-chain atomic positions and residues that are correctly assigned to the sequence. Residues in a morphed model that do not match the electron-density map are removed. Each segment of the resulting trimmed morphed model is then assigned to the sequence of the molecule using information about the connectivity of the chains from the working model and from connections that can be identified from the electron-density map. The procedure was tested by application to a recently determined structure at a resolution of 3.2 Å and was found to increase the number of correctly identified residues in this structure from the 88 obtained using phenix.resolve sequence assignment alone (Terwilliger, 2003) to 247 of a possible 359. Additionally, the procedure was tested by application to a series of templates with sequence identities to a target structure ranging between 7 and 36%. The mean fraction of correctly identified residues in these cases was increased from 33% using phenix.resolve sequence assignment to 47% using the current procedure. The procedure is simple to apply and is available in the Phenix software package.

  17. MODELLING DICLOFENAC AND IBUPROFEN RESIDUES IN MAJOR ESTONIAN SEASIDE CITIES

    Directory of Open Access Journals (Sweden)

    Erki Lember

    2016-06-01

    Full Text Available A theoretical model was developed to model the fate of two common pharmaceutical residues: diclofenac and ibuprofen in eight Estonian seaside cities that discharge their wastewaters directly into the Baltic Sea. The consumption rates of the active ingredients of diclofenac and ibuprofen from 2006-2014 were analysed. A decrease of 19.9% for diclofenac consumption and an increase of 14.1% for ibuprofen were found. The fate of diclofenac and ibuprofen were modelled by considering the human metabolism removal rate for pharmaceuticals, the removal rate of diclofenac and ibuprofen in activated sludge wastewater treatment plants (WWTP and annual flow rates. An average decrease from 1 to 0.8 µg/l (decrease of 20% for diclofenac and an increase from 11.4 to 13.4 µg/l (increase of 14.9% for ibuprofen for the concentration in the effluents of the WWTP were modelled. The model gives us a good overview about the theoretical concentrations of pharmaceutical residues in the environment and is helpful for evaluating environmental impacts.

  18. Chemical modelling of pore water composition from PFBC residues

    International Nuclear Information System (INIS)

    Karlsson, L.G.

    1991-01-01

    The concentration of trace elements varies depending on the source of the coal and also due to the combustion process used. Mercury is one important element among the trace elements in the coal residues, generally recognised as potentially harmful to the biological system. To predict the pore water concentrations of mercury and other important constituents leached from coal combustion residues disposal sites, mechanistic data on chemical reactions are required. The present study is an application of a basially thermodynamical approach using the geochemical code EQ3NR. The presence of discrete solid phases that control the aqueous concentrations of major elements such as aluminium, calcium and silicon are identified. Solid phases are modelled in equilibrium with a hypothetical pore water at a pH range of 7-11. In this study the thermodynamic database of EQ3NR has been complemented with data for cadmium, mercury and lead taken from the OECD/NEA Thermodynamic Database and from a compilation made by Lindsay. Possible solubility limiting phases for the important trace elements arsenic, cadmium, chromium, copper, mercury, nickel and lead have been identified. Concentrations of these trace elements as a function of pH in the hypothetical pore water were calculated using mechanistic thermodynamial data. The thermodynamical approach in this study seems justified because most solid residues that are either present or expected to form during weathering have relatively fast precipitation/dissolution kinetics. (21 refs., 18 figs., 5 tabs.)

  19. gRINN: a tool for calculation of residue interaction energies and protein energy network analysis of molecular dynamics simulations.

    Science.gov (United States)

    Serçinoglu, Onur; Ozbek, Pemra

    2018-05-25

    Atomistic molecular dynamics (MD) simulations generate a wealth of information related to the dynamics of proteins. If properly analyzed, this information can lead to new insights regarding protein function and assist wet-lab experiments. Aiming to identify interactions between individual amino acid residues and the role played by each in the context of MD simulations, we present a stand-alone software called gRINN (get Residue Interaction eNergies and Networks). gRINN features graphical user interfaces (GUIs) and a command-line interface for generating and analyzing pairwise residue interaction energies and energy correlations from protein MD simulation trajectories. gRINN utilizes the features of NAMD or GROMACS MD simulation packages and automatizes the steps necessary to extract residue-residue interaction energies from user-supplied simulation trajectories, greatly simplifying the analysis for the end-user. A GUI, including an embedded molecular viewer, is provided for visualization of interaction energy time-series, distributions, an interaction energy matrix, interaction energy correlations and a residue correlation matrix. gRINN additionally offers construction and analysis of Protein Energy Networks, providing residue-based metrics such as degrees, betweenness-centralities, closeness centralities as well as shortest path analysis. gRINN is free and open to all users without login requirement at http://grinn.readthedocs.io.

  20. 3D Printing of Molecular Models

    Science.gov (United States)

    Gardner, Adam; Olson, Arthur

    2016-01-01

    Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

  1. Neutron Scattering of Residual Hydrogen in 1,4-Dioxane-D8 Liquid. Understanding Measurements with Molecular Dynamics Simulations

    Energy Technology Data Exchange (ETDEWEB)

    de Almeida, Valmor F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Liu, Hongjun [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Herwig, Kenneth W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kidder, Michelle [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-01-25

    That incoherent scattering from protiated molecular liquids adds a constant background to the measured scattering intensity is well known, but less appreciated is the fact that coherent scattering is also induced by the presence of hydrogen in a deuterated liquid. In fact, the scattering intensity can be very sensitive, in the small-q region, with respect to the amounts and distribution of residual H in the system. We used 1,4-dioxane liquid to demonstrate that the partial structure factors of the HD and DD atom pairs contribute significantly to inter-molecular scattering and that uncertainty in the extent of deuteration account for discrepancies between simulations and measurements. Both contributions to uncertainty have similar magnitudes: scattering interference of the hydrogen-deuterium pair, and complementary interference from the deuterium-deuterium pair by virtue of chemical inhomogeneity. This situation arises in practice since deuteration of liquids is often 99% or less. A combined experimental and extensive computational study of static thermal neutron scattering of 1,4-dioxane demonstrates the foregoing. We show, through simulations, that the reason for the differences is the content of protiated dioxane (vendors quote 1%). We estimate that up to 5% (at 298K and at 343K) protiated mole fraction may be involved in generating the scattering differences. Finally, we find that the particular distribution of hydrogen in the protiated molecules affects the results significantly; here we considered molecules to be either fully protiated or fully deuterated. This scenario best reconciles the computational and experimental results, and leads us to speculate that the deuteration synthesis process tends to leave a molecule either fully deuterated or fully protiated. Although we have used 1,4-dioxane as a model liquid, the effects described in this study extend to similar liquids and similar systematic experimental/computational studies can be performed to either

  2. Model-based leakage localization in drinking water distribution networks using structured residuals

    OpenAIRE

    Puig Cayuela, Vicenç; Rosich, Albert

    2013-01-01

    In this paper, a new model based approach to leakage localization in drinking water networks is proposed based on generating a set of structured residuals. The residual evaluation is based on a numerical method based on an enhanced Newton-Raphson algorithm. The proposed method is suitable for water network systems because the non-linearities of the model make impossible to derive analytical residuals. Furthermore, the computed residuals are designed so that leaks are decoupled, which impro...

  3. The cognitive life of mechanical molecular models.

    Science.gov (United States)

    Charbonneau, Mathieu

    2013-12-01

    The use of physical models of molecular structures as research tools has been central to the development of biochemistry and molecular biology. Intriguingly, it has received little attention from scholars of science. In this paper, I argue that these physical models are not mere three-dimensional representations but that they are in fact very special research tools: they are cognitive augmentations. Despite the fact that they are external props, these models serve as cognitive tools that augment and extend the modeler's cognitive capacities and performance in molecular modeling tasks. This cognitive enhancement is obtained because of the way the modeler interacts with these models, the models' materiality contributing to the solving of the molecule's structure. Furthermore, I argue that these material models and their component parts were designed, built and used specifically to serve as cognitive facilitators and cognitive augmentations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Deep Generative Models for Molecular Science

    DEFF Research Database (Denmark)

    Jørgensen, Peter Bjørn; Schmidt, Mikkel Nørgaard; Winther, Ole

    2018-01-01

    Generative deep machine learning models now rival traditional quantum-mechanical computations in predicting properties of new structures, and they come with a significantly lower computational cost, opening new avenues in computational molecular science. In the last few years, a variety of deep...... generative models have been proposed for modeling molecules, which differ in both their model structure and choice of input features. We review these recent advances within deep generative models for predicting molecular properties, with particular focus on models based on the probabilistic autoencoder (or...

  5. Mathematical modeling of molecular motors

    OpenAIRE

    Keller, Peter

    2013-01-01

    Amongst the many complex processes taking place in living cells, transport of cargoes across the cytosceleton is fundamental to cell viability and activity. To move cargoes between the different cell parts, cells employ Molecular Motors. The motors operate by transporting cargoes along the so-called cellular micro-tubules, namely rope-like structures that connect, for instance, the cell-nucleus and outer membrane. We introduce a new Markov Chain, the killed Quasi-Random-Walk, for such transpo...

  6. Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

    2013-03-15

    Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

  7. A Numerical Model for Prediction of Residual Stress Using Rayleigh Waves

    International Nuclear Information System (INIS)

    Yuan, Mao Dan; Kang, To; Kim, Hak Joon; Song, Sung Jin

    2011-01-01

    In this work, a numerical model is proposed for the relation between the magnitudes and the depth residual stress with the velocity of Rayleigh wave. Three cases, stress-free, uniform stress and layered stress, are investigated for the change tendency of the Rayleigh wave speed. Using the simulated signal with variation of residual stress magnitude and depth, investigation of the parameters for fitting residual stress and velocity change are performed. The speed change of Rayleigh wave shows a linear relation with the magnitude and an exponential relation with the depth of residual stress. The combination of these two effects could be used for the depth profile evaluation of the residual stress

  8. Quantitative conformational analysis of the core region of N-glycans using residual dipolar couplings, aqueous molecular dynamics, and steric alignment

    International Nuclear Information System (INIS)

    Almond, Andrew; Duus, Jens O.

    2001-01-01

    A method is described for quantitatively investigating the dynamic conformation of small oligosaccharides containing an α(1 → 6) linkage. It was applied to the oligosaccharide Man-α(1 → 3) {Man-α (1 → 6)}Man-α-O-Me, which is a core region frequently observed in N-linked glycans. The approach tests an aqueous molecular dynamics simulation, capable of predicting microscopic dynamics, against experimental residual dipolar couplings, by assuming that alignment is caused purely by steric hindrance. The experimental constraints were heteronuclear and homonuclear residual dipolar couplings, and in particular those within the α(1 → 6) linkage itself. Powerful spin-state-selective pulse sequences and editing schemes were used to obtain the most relevant couplings for testing the model. Molecular dynamics simulations in water over a period of 50 ns were not able to predict the correct rotamer population at the α(1 → 6) linkage to agree with the experimental data. However, this sampling problem could be corrected using a simple maximum likelihood optimisation, indicating that the simulation was modelling local dynamics correctly. The maximum likelihood prediction of the residual dipolar couplings was found to be an almost equal population of the gg and gt rotamer conformations at the α(1 → 6) linkage, and the tg conformation was predicted to be unstable and unpopulated in aqueous solution. In this case all twelve measured residual dipolar couplings could be satisfied. This conformer population could also be used to make predictions of scalar couplings with the use of a previously derived empirical equation, and is qualitatively in agreement with previous predictions based on NMR, X-ray crystallography and optical data

  9. Integrated multiscale modeling of molecular computing devices

    International Nuclear Information System (INIS)

    Cummings, Peter T; Leng Yongsheng

    2005-01-01

    Molecular electronics, in which single organic molecules are designed to perform the functions of transistors, diodes, switches and other circuit elements used in current siliconbased microelecronics, is drawing wide interest as a potential replacement technology for conventional silicon-based lithographically etched microelectronic devices. In addition to their nanoscopic scale, the additional advantage of molecular electronics devices compared to silicon-based lithographically etched devices is the promise of being able to produce them cheaply on an industrial scale using wet chemistry methods (i.e., self-assembly from solution). The design of molecular electronics devices, and the processes to make them on an industrial scale, will require a thorough theoretical understanding of the molecular and higher level processes involved. Hence, the development of modeling techniques for molecular electronics devices is a high priority from both a basic science point of view (to understand the experimental studies in this field) and from an applied nanotechnology (manufacturing) point of view. Modeling molecular electronics devices requires computational methods at all length scales - electronic structure methods for calculating electron transport through organic molecules bonded to inorganic surfaces, molecular simulation methods for determining the structure of self-assembled films of organic molecules on inorganic surfaces, mesoscale methods to understand and predict the formation of mesoscale patterns on surfaces (including interconnect architecture), and macroscopic scale methods (including finite element methods) for simulating the behavior of molecular electronic circuit elements in a larger integrated device. Here we describe a large Department of Energy project involving six universities and one national laboratory aimed at developing integrated multiscale methods for modeling molecular electronics devices. The project is funded equally by the Office of Basic

  10. Limiting assumptions in molecular modeling: electrostatics.

    Science.gov (United States)

    Marshall, Garland R

    2013-02-01

    Molecular mechanics attempts to represent intermolecular interactions in terms of classical physics. Initial efforts assumed a point charge located at the atom center and coulombic interactions. It is been recognized over multiple decades that simply representing electrostatics with a charge on each atom failed to reproduce the electrostatic potential surrounding a molecule as estimated by quantum mechanics. Molecular orbitals are not spherically symmetrical, an implicit assumption of monopole electrostatics. This perspective reviews recent evidence that requires use of multipole electrostatics and polarizability in molecular modeling.

  11. Hanford tank residual waste - Contaminant source terms and release models

    International Nuclear Information System (INIS)

    Deutsch, William J.; Cantrell, Kirk J.; Krupka, Kenneth M.; Lindberg, Michael L.; Jeffery Serne, R.

    2011-01-01

    Highlights: → Residual waste from five Hanford spent fuel process storage tanks was evaluated. → Gibbsite is a common mineral in tanks with high Al concentrations. → Non-crystalline U-Na-C-O-P ± H phases are common in the U-rich residual. → Iron oxides/hydroxides have been identified in all residual waste samples. → Uranium release is highly dependent on waste and leachant compositions. - Abstract: Residual waste is expected to be left in 177 underground storage tanks after closure at the US Department of Energy's Hanford Site in Washington State, USA. In the long term, the residual wastes may represent a potential source of contamination to the subsurface environment. Residual materials that cannot be completely removed during the tank closure process are being studied to identify and characterize the solid phases and estimate the release of contaminants from these solids to water that might enter the closed tanks in the future. As of the end of 2009, residual waste from five tanks has been evaluated. Residual wastes from adjacent tanks C-202 and C-203 have high U concentrations of 24 and 59 wt.%, respectively, while residual wastes from nearby tanks C-103 and C-106 have low U concentrations of 0.4 and 0.03 wt.%, respectively. Aluminum concentrations are high (8.2-29.1 wt.%) in some tanks (C-103, C-106, and S-112) and relatively low ( 2 -saturated solution, or a CaCO 3 -saturated water. Uranium release concentrations are highly dependent on waste and leachant compositions with dissolved U concentrations one or two orders of magnitude higher in the tests with high U residual wastes, and also higher when leached with the CaCO 3 -saturated solution than with the Ca(OH) 2 -saturated solution. Technetium leachability is not as strongly dependent on the concentration of Tc in the waste, and it appears to be slightly more leachable by the Ca(OH) 2 -saturated solution than by the CaCO 3 -saturated solution. In general, Tc is much less leachable (<10 wt.% of the

  12. Molecular dynamics modeling of polymer flammability

    International Nuclear Information System (INIS)

    Nyden, M.R.; Brown, J.E.; Lomakin, S.M.

    1992-01-01

    Molecular dynamic simulations were used to identify factors which promote char formation during the thermal degradation of polymers. Computer movies based on these simulations, indicate that cross-linked model polymers tend to undergo further cross-linking when burned, eventually forming a high molecular weight, thermally stable char. This paper reports that the prediction was confirmed by char yield measurements made on γ and e - -irradiated polyethylene and chemically cross-linked poly(methyl methacrylate)

  13. Exploring RNA structure by integrative molecular modelling

    DEFF Research Database (Denmark)

    Masquida, Benoît; Beckert, Bertrand; Jossinet, Fabrice

    2010-01-01

    RNA molecular modelling is adequate to rapidly tackle the structure of RNA molecules. With new structured RNAs constituting a central class of cellular regulators discovered every year, the need for swift and reliable modelling methods is more crucial than ever. The pragmatic method based...... on interactive all-atom molecular modelling relies on the observation that specific structural motifs are recurrently found in RNA sequences. Once identified by a combination of comparative sequence analysis and biochemical data, the motifs composing the secondary structure of a given RNA can be extruded...

  14. Residue contacts predicted by evolutionary covariance extend the application of ab initio molecular replacement to larger and more challenging protein folds

    Directory of Open Access Journals (Sweden)

    Felix Simkovic

    2016-07-01

    Full Text Available For many protein families, the deluge of new sequence information together with new statistical protocols now allow the accurate prediction of contacting residues from sequence information alone. This offers the possibility of more accurate ab initio (non-homology-based structure prediction. Such models can be used in structure solution by molecular replacement (MR where the target fold is novel or is only distantly related to known structures. Here, AMPLE, an MR pipeline that assembles search-model ensembles from ab initio structure predictions (`decoys', is employed to assess the value of contact-assisted ab initio models to the crystallographer. It is demonstrated that evolutionary covariance-derived residue–residue contact predictions improve the quality of ab initio models and, consequently, the success rate of MR using search models derived from them. For targets containing β-structure, decoy quality and MR performance were further improved by the use of a β-strand contact-filtering protocol. Such contact-guided decoys achieved 14 structure solutions from 21 attempted protein targets, compared with nine for simple Rosetta decoys. Previously encountered limitations were superseded in two key respects. Firstly, much larger targets of up to 221 residues in length were solved, which is far larger than the previously benchmarked threshold of 120 residues. Secondly, contact-guided decoys significantly improved success with β-sheet-rich proteins. Overall, the improved performance of contact-guided decoys suggests that MR is now applicable to a significantly wider range of protein targets than were previously tractable, and points to a direct benefit to structural biology from the recent remarkable advances in sequencing.

  15. Medulloblastoma: Molecular Genetics and Animal Models

    Directory of Open Access Journals (Sweden)

    Corey Raffel

    2004-07-01

    Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

  16. HOMOLOGY MODELING AND MOLECULAR DYNAMICS STUDY OF MYCOBACTERIUM TUBERCULOSIS UREASE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2017-10-01

    Full Text Available Introduction. M. tuberculosis urease (MTU is an attractive target for chemotherapeutic intervention in tuberculosis by designing new safe and efficient enzyme inhibitors. A prerequisite for designing such inhibitors is an understanding of urease's three-dimensional (3D structure organization. 3D structure of M. tuberculosis urease is unknown. When experimental three-dimensional structure of a protein is not known, homology modeling, the most commonly used computational structure prediction method, is the technique of choice. This paper aimed to build a 3D-structure of M. tuberculosis urease by homology modeling and to study its stability by molecular dynamics simulations. Materials and methods. To build MTU model, five high-resolution X-ray structures of bacterial ureases with three-subunit composition (2KAU, 5G4H, 4UBP, 4СEU, and 4EPB have been selected as templates. For each template five stochastic alignments were created and for each alignment, a three-dimensional model was built. Then, each model was energy minimized and the models were ranked by quality Z-score. The MTU model with highest quality estimation amongst 25 potential models was selected. To further improve structure quality the model was refined by short molecular dynamics simulation that resulted in 20 snapshots which were rated according to their energy and the quality Z-score. The best scoring model having minimum energy was chosen as a final homology model of 3D structure for M. tuberculosis. The final model of MTU was also validated by using PDBsum and QMEAN servers. These checks confirmed good quality of MTU homology model. Results and discussion. Homology model of MTU is a nonamer (homotrimer of heterotrimers, (αβγ3 consisting of 2349 residues. In MTU heterotrimer, sub-units α, β, and γ tightly interact with each other at a surface of approximately 3000 Å2. Sub-unit α contains the enzyme active site with two Ni atoms coordinated by amino acid residues His347, His

  17. Proposed residual stress model for roller bent wide flange sections

    NARCIS (Netherlands)

    Spoorenberg, R.C.; Snijder, H.H.; Hoenderkamp, J.C.D.

    2011-01-01

    The manufacturing process of structural wide flange steel sections introduces residual stresses in the material. These stresses due to hot-rolling or welding influence the inelastic buckling response of structural steel members and need to be taken into account in the design. Based on experimental

  18. Analysis and modeling of simulated residual stress of mold injected plastic parts by using robust correlations

    OpenAIRE

    Vargas, Carlos; Sierra, Juan; Posada, Juan; Botero-Cadavid, Juan F.

    2017-01-01

    ABSTRACT The injection molding process is the most widely used processing technique for polymers. The analysis of residual stresses generated during this process is crucial for the part quality assessment. The present study evaluates the residual stresses in a tensile strength specimen using the simulation software Moldex3D for two polymers, polypropylene and polycarbonate. The residual stresses obtained under a simulated design of experiment were modeled using a robust multivariable regressi...

  19. New tyrosinase inhibitory decapeptide: Molecular insights into the role of tyrosine residues.

    Science.gov (United States)

    Ochiai, Akihito; Tanaka, Seiya; Imai, Yuta; Yoshida, Hisashi; Kanaoka, Takumi; Tanaka, Takaaki; Taniguchi, Masayuki

    2016-06-01

    Tyrosinase, a rate-limiting enzyme in melanin biosynthesis, catalyzes the hydroxylation of l-tyrosine to 3,4-dihydroxy-l-phenylalanine (l-dopa) (monophenolase reaction) and the subsequent oxidation of l-dopa to l-dopaquinone (diphenolase reaction). Thus, tyrosinase inhibitors have been proposed as skin-lightening agents; however, many of the existing inhibitors cannot be widely used in the cosmetic industry due to their high cytotoxicity and instability. On the other hand, some tyrosinase inhibitory peptides have been reported as safe. In this study, we found that the peptide TH10, which has a similar sequence to the characterized inhibitory peptide P4, strongly inhibits the monophenolase reaction with a half-maximal inhibitory concentration of 102 μM. Seven of the ten amino acid residues in TH10 were identical to P4; however, TH10 possesses one N-terminal tyrosine, whereas P4 contains three tyrosine residues located at its N-terminus, center, and C-terminus. Subsequent analysis using sequence-shuffled variants indicated that the tyrosine residues located at the N-terminus and center of P4 have little to no contribution to its inhibitory activity. Furthermore, docking simulation analysis of these peptides with mushroom tyrosinase demonstrated that the active tyrosine residue was positioned close to copper ions, suggesting that TH10 and P4 bind to tyrosinase as a substrate analogue. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Modeling crop residue burning experiments to evaluate smoke emissions and plume transport

    Science.gov (United States)

    Crop residue burning is a common land management practice that results in emissions of a variety of pollutants with negative health impacts. Modeling systems are used to estimate air quality impacts of crop residue burning to support retrospective regulatory assessments and also ...

  1. Assessing item fit for unidimensional item response theory models using residuals from estimated item response functions.

    Science.gov (United States)

    Haberman, Shelby J; Sinharay, Sandip; Chon, Kyong Hee

    2013-07-01

    Residual analysis (e.g. Hambleton & Swaminathan, Item response theory: principles and applications, Kluwer Academic, Boston, 1985; Hambleton, Swaminathan, & Rogers, Fundamentals of item response theory, Sage, Newbury Park, 1991) is a popular method to assess fit of item response theory (IRT) models. We suggest a form of residual analysis that may be applied to assess item fit for unidimensional IRT models. The residual analysis consists of a comparison of the maximum-likelihood estimate of the item characteristic curve with an alternative ratio estimate of the item characteristic curve. The large sample distribution of the residual is proved to be standardized normal when the IRT model fits the data. We compare the performance of our suggested residual to the standardized residual of Hambleton et al. (Fundamentals of item response theory, Sage, Newbury Park, 1991) in a detailed simulation study. We then calculate our suggested residuals using data from an operational test. The residuals appear to be useful in assessing the item fit for unidimensional IRT models.

  2. Modeling crop residue burning experiments to evaluate smoke emissions and plume transport

    Science.gov (United States)

    Luxi Zhou; Kirk R. Baker; Sergey L. Napelenok; George Pouliot; Robert Elleman; Susan M. O' Neill; Shawn P. Urbanski; David C. Wong

    2018-01-01

    Crop residue burning is a common land management practice that results in emissions of a variety of pollutants with negative health impacts. Modeling systems are used to estimate air quality impacts of crop residue burning to support retrospective regulatory assessments and also for forecasting purposes. Ground and airborne measurements from a recent field experiment...

  3. Grid computing in large pharmaceutical molecular modeling.

    Science.gov (United States)

    Claus, Brian L; Johnson, Stephen R

    2008-07-01

    Most major pharmaceutical companies have employed grid computing to expand their compute resources with the intention of minimizing additional financial expenditure. Historically, one of the issues restricting widespread utilization of the grid resources in molecular modeling is the limited set of suitable applications amenable to coarse-grained parallelization. Recent advances in grid infrastructure technology coupled with advances in application research and redesign will enable fine-grained parallel problems, such as quantum mechanics and molecular dynamics, which were previously inaccessible to the grid environment. This will enable new science as well as increase resource flexibility to load balance and schedule existing workloads.

  4. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    order to evaluate the importance of these interactions, students have proposed conservative or radical mutations at these sites. Once they have changed the amino acid residue and allowed the model to reach a new minimum energy, they can measure interatomic distances to determine whether or not a substrate can fit into the active site and/or form hydrogen bonds. A subtle variation on mutation of Trp 108 was a proposal to mutate an adjacent alanine residue, such as to displace the Trp further toward the helix and open up the active site. Other mutations, outside of the active site, have been proposed to change the overall stability of the protein (e.g., Gly to Ala within an a-helix, or loss of a disulfide bond). This exercise illustrates the possibilities of modeling proteins. Because it requires that the students set certain parameters and defaults for structural prediction, it helps them to understand the limitations of modeling. The final paper takes the form of a grant proposal. It presents the purification results, rationale for the desired mutation, relevance to previous studies, an overview of techniques applicable to the study of the mutant, predictions as to the characteristics of the engineered protein, and a plan for its purification. These proposals pass through at least one stage of peer review, and each student gives an oral presentation. This project serves to tie together many concepts learned during both the lecture and laboratory portions of the course. As noted above, we have been able to acquire workstations and software for modeling through funding from an NSF-ILI grant. However, the research proposal exercise can be modified, depending on facilities available and the goals of a particular course. A literature survey alone yields a wealth of information on this enzyme, and students can design experiments in biochemistry or molecular biology to follow up on the papers they have read. Some recent textbooks are accompanied by diskettes that allow

  5. Realistic molecular model of kerogen's nanostructure.

    Science.gov (United States)

    Bousige, Colin; Ghimbeu, Camélia Matei; Vix-Guterl, Cathie; Pomerantz, Andrew E; Suleimenova, Assiya; Vaughan, Gavin; Garbarino, Gaston; Feygenson, Mikhail; Wildgruber, Christoph; Ulm, Franz-Josef; Pellenq, Roland J-M; Coasne, Benoit

    2016-05-01

    Despite kerogen's importance as the organic backbone for hydrocarbon production from source rocks such as gas shale, the interplay between kerogen's chemistry, morphology and mechanics remains unexplored. As the environmental impact of shale gas rises, identifying functional relations between its geochemical, transport, elastic and fracture properties from realistic molecular models of kerogens becomes all the more important. Here, by using a hybrid experimental-simulation method, we propose a panel of realistic molecular models of mature and immature kerogens that provide a detailed picture of kerogen's nanostructure without considering the presence of clays and other minerals in shales. We probe the models' strengths and limitations, and show that they predict essential features amenable to experimental validation, including pore distribution, vibrational density of states and stiffness. We also show that kerogen's maturation, which manifests itself as an increase in the sp(2)/sp(3) hybridization ratio, entails a crossover from plastic-to-brittle rupture mechanisms.

  6. Molecular Simulation towards Efficient and Representative Subsurface Reservoirs Modeling

    KAUST Repository

    Kadoura, Ahmad Salim

    2016-01-01

    This dissertation focuses on the application of Monte Carlo (MC) molecular simulation and Molecular Dynamics (MD) in modeling thermodynamics and flow of subsurface reservoir fluids. At first, MC molecular simulation is proposed as a promising method

  7. Effect of heteroscedasticity treatment in residual error models on model calibration and prediction uncertainty estimation

    Science.gov (United States)

    Sun, Ruochen; Yuan, Huiling; Liu, Xiaoli

    2017-11-01

    The heteroscedasticity treatment in residual error models directly impacts the model calibration and prediction uncertainty estimation. This study compares three methods to deal with the heteroscedasticity, including the explicit linear modeling (LM) method and nonlinear modeling (NL) method using hyperbolic tangent function, as well as the implicit Box-Cox transformation (BC). Then a combined approach (CA) combining the advantages of both LM and BC methods has been proposed. In conjunction with the first order autoregressive model and the skew exponential power (SEP) distribution, four residual error models are generated, namely LM-SEP, NL-SEP, BC-SEP and CA-SEP, and their corresponding likelihood functions are applied to the Variable Infiltration Capacity (VIC) hydrologic model over the Huaihe River basin, China. Results show that the LM-SEP yields the poorest streamflow predictions with the widest uncertainty band and unrealistic negative flows. The NL and BC methods can better deal with the heteroscedasticity and hence their corresponding predictive performances are improved, yet the negative flows cannot be avoided. The CA-SEP produces the most accurate predictions with the highest reliability and effectively avoids the negative flows, because the CA approach is capable of addressing the complicated heteroscedasticity over the study basin.

  8. Molecular models and simulations of layered materials

    International Nuclear Information System (INIS)

    Kalinichev, Andrey G.; Cygan, Randall Timothy; Heinz, Hendrik; Greathouse, Jeffery A.

    2008-01-01

    The micro- to nano-sized nature of layered materials, particularly characteristic of naturally occurring clay minerals, limits our ability to fully interrogate their atomic dispositions and crystal structures. The low symmetry, multicomponent compositions, defects, and disorder phenomena of clays and related phases necessitate the use of molecular models and modern simulation methods. Computational chemistry tools based on classical force fields and quantum-chemical methods of electronic structure calculations provide a practical approach to evaluate structure and dynamics of the materials on an atomic scale. Combined with classical energy minimization, molecular dynamics, and Monte Carlo techniques, quantum methods provide accurate models of layered materials such as clay minerals, layered double hydroxides, and clay-polymer nanocomposites

  9. Modelling the Effects of Surface Residual Stresses on Fatigue Behavior of PM Disk Alloys, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — A finite element based model will be developed and validated to capture the evolution of residual stresses and cold work at machined features of compressor and...

  10. Molecular Modeling of Interfacial Behaviors of Nanomaterials

    Science.gov (United States)

    2007-05-01

    potential was originally designed for the modeling of mixed covalent- ionic bonding and was successfully used to describe oxides in crystalline, glassy, and...is separates from the bulk liquid polymer, i.e., the structure of this layer, as influenced by that of the meatal surface, is significantly more...Striolo, J. Kieffer, and P. Cummings, ’Evaluation of Force- fields for molecular simulation of polyhedral oligomeric silsesquioxanes,’ J. Phys. Chem

  11. Applications of Molecular and Materials Modeling

    Science.gov (United States)

    2002-01-01

    Chimica Industriale Molecular modeling of solvation Prof. Jacopo Tomasi http://www.dcci.unipi.it/attivita /attivita.html; http://www.dcci.unipi.it...solutions/ cases/notes/scale.html BNFL Sorption of gases in zeolites Dr. Scott L. Owens http://www.bnfl.co.uk/ BAE (British Aerospace Engineering) Rare...permeation of gases ; adhesion and interfacial interactions of siloxane networks; chemical reactivity and catalysis; environmental and cosmetics

  12. Fundamental and molecular composition characteristics of biochars produced from sugarcane and rice crop residues and by-products.

    Science.gov (United States)

    Jeong, Chang Yoon; Dodla, Syam K; Wang, Jim J

    2016-01-01

    Biochar conversion of sugarcane and rice harvest residues provides an alternative for managing these crop residues that are traditionally burned in open field. Sugarcane leaves, bagasse, rice straw and husk were converted to biochar at four pyrolysis temperatures (PTs) of 450 °C, 550 °C, 650 °C, and 750 °C and evaluated for various elemental, molecular and surface properties. The carbon content of biochars was highest for those produced at 650-750 °C. Biochars produced at 550 °C showed the characteristics of biochar that are commonly interpreted as being stable in soil, with low H/C and O/C ratios and pyrolysis fingerprints dominated by aromatic and polyaromatic hydrocarbons. At 550 °C, all biochars also exhibited maximum CEC values with sugarcane leaves biochar (SLB) > sugarcane bagasse biochar (SBB) > rice straw biochar (RSB) > rice husk biochar (RHB). The pore size distribution of biochars was dominated by pores of 20 nm and high PT increased both smaller and larger than 50 nm pores. Water holding capacity of biochars increased with PT but the magnitude of the increase was limited by feedstock types, likely related to the hydrophobicity of biochars as evident by molecular composition, besides pore volume properties of biochars. Py-GC/MS analysis revealed a clear destruction of lignin with decarboxylation and demethoxylation at 450 °C and dehydroxylation at above 550 °C. Overall, biochar molecular compositions became similar as PT increased, and the biochars produced at 550 °C demonstrated characteristics that have potential benefit as soil amendment for improving both C sequestration and nutrient dynamics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Observational Constraints for Modeling Diffuse Molecular Clouds

    Science.gov (United States)

    Federman, S. R.

    2014-02-01

    Ground-based and space-borne observations of diffuse molecular clouds suggest a number of areas where further improvements to modeling efforts is warranted. I will highlight those that have the widest applicability. The range in CO fractionation caused by selective isotope photodissociation, in particular the large 12C16O/13C16O ratios observed toward stars in Ophiuchus, is not reproduced well by current models. Our ongoing laboratory measurements of oscillator strengths and predissociation rates for Rydberg transitions in CO isotopologues may help clarify the situtation. The CH+ abundance continues to draw attention. Small scale structure seen toward ζ Per may provide additional constraints on the possible synthesis routes. The connection between results from optical transitions and those from radio and sub-millimeter wave transitions requires further effort. A study of OH+ and OH toward background stars reveals that these species favor different environments. This brings to focus the need to model each cloud along the line of sight separately, and to allow the physical conditions to vary within an individual cloud, in order to gain further insight into the chemistry. Now that an extensive set of data on molecular excitation is available, the models should seek to reproduce these data to place further constraints on the modeling results.

  14. COPRED: prediction of fold, GO molecular function and functional residues at the domain level.

    Science.gov (United States)

    López, Daniel; Pazos, Florencio

    2013-07-15

    Only recently the first resources devoted to the functional annotation of proteins at the domain level started to appear. The next step is to develop specific methodologies for predicting function at the domain level based on these resources, and to implement them in web servers to be used by the community. In this work, we present COPRED, a web server for the concomitant prediction of fold, molecular function and functional sites at the domain level, based on a methodology for domain molecular function prediction and a resource of domain functional annotations previously developed and benchmarked. COPRED can be freely accessed at http://csbg.cnb.csic.es/copred. The interface works in all standard web browsers. WebGL (natively supported by most browsers) is required for the in-line preview and manipulation of protein 3D structures. The website includes a detailed help section and usage examples. pazos@cnb.csic.es.

  15. Rapid Colorimetric Detection of Cartap Residues by AgNP Sensor with Magnetic Molecularly Imprinted Microspheres as Recognition Elements

    Directory of Open Access Journals (Sweden)

    Mao Wu

    2018-06-01

    Full Text Available The overuse of cartap in tea tree leads to hazardous residues threatening human health. A colorimetric determination was established to detect cartap residues in tea beverages by silver nanoparticles (AgNP sensor with magnetic molecularly imprinted polymeric microspheres (Fe3O4@mSiO2@MIPs as recognition elements. Using Fe3O4 as supporting core, mesoporous SiO2 as intermediate shell, methylacrylic acid as functional monomer, and cartap as template, Fe3O4@mSiO2@MIPs were prepared to selectively and magnetically separate cartap from tea solution before colorimetric determination by AgNP sensors. The core-shell Fe3O4@mSiO2@MIPs were also characterized by FT-IR, TEM, VSM, and experimental adsorption. The Fe3O4@mSiO2@MIPs could be rapidly separated by an external magnet in 10 s with good reusability (maintained 95.2% through 10 cycles. The adsorption process of cartap on Fe3O4@mSiO2@MIPs conformed to Langmuir adsorption isotherm with maximum adsorption capacity at 0.257 mmol/g and short equilibrium time of 30 min at 298 K. The AgNP colorimetric method semi-quantified cartap ≥5 mg/L by naked eye and quantified cartap 0.1–5 mg/L with LOD 0.01 mg/L by UV-vis spectroscopy. The AgNP colorimetric detection after pretreatment with Fe3O4@mSiO2@MIPs could be successfully utilized to recognize and detect cartap residues in tea beverages.

  16. Unveiling the Mechanism of Arginine Transport through AdiC with Molecular Dynamics Simulations: The Guiding Role of Aromatic Residues.

    Directory of Open Access Journals (Sweden)

    Eva-Maria Krammer

    Full Text Available Commensal and pathogenic enteric bacteria have developed several systems to adapt to proton leakage into the cytoplasm resulting from extreme acidic conditions. One such system involves arginine uptake followed by export of the decarboxylated product agmatine, carried out by the arginine/agmatine antiporter (AdiC, which thus works as a virtual proton pump. Here, using classical and targeted molecular dynamics, we investigated at the atomic level the mechanism of arginine transport through AdiC of E. coli. Overall, our MD simulation data clearly demonstrate that global rearrangements of several transmembrane segments are necessary but not sufficient for achieving transitions between structural states along the arginine translocation pathway. In particular, local structural changes, namely rotameric conversions of two aromatic residues, are needed to regulate access to both the outward- and inward-facing states. Our simulations have also enabled identification of a few residues, overwhelmingly aromatic, which are essential to guiding arginine in the course of its translocation. Most of them belong to gating elements whose coordinated motions contribute to the alternating access mechanism. Their conservation in all known E. coli acid resistance antiporters suggests that the transport mechanisms of these systems share common features. Last but not least, knowledge of the functional properties of AdiC can advance our understanding of the members of the amino acid-carbocation-polyamine superfamily, notably in eukaryotic cells.

  17. Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis

    Science.gov (United States)

    Anwar, Muhammad Ayaz; Choi, Sangdun

    2017-03-01

    Toll-like receptor 4 (TLR4), a vital innate immune receptor present on cell surfaces, initiates a signaling cascade during danger and bacterial intrusion. TLR4 needs to form a stable hexamer complex, which is necessary to dimerize the cytoplasmic domain. However, D299G and T399I polymorphism may abrogate the stability of the complex, leading to compromised TLR4 signaling. Crystallography provides valuable insights into the structural aspects of the TLR4 ectodomain; however, the dynamic behavior of polymorphic TLR4 is still unclear. Here, we employed molecular dynamics simulations (MDS), as well as principal component and residue network analyses, to decipher the structural aspects and signaling propagation associated with mutations in TLR4. The mutated complexes were less cohesive, displayed local and global variation in the secondary structure, and anomalous decay in rotational correlation function. Principal component analysis indicated that the mutated complexes also exhibited distinct low-frequency motions, which may be correlated to the differential behaviors of these TLR4 variants. Moreover, residue interaction networks (RIN) revealed that the mutated TLR4/myeloid differentiation factor (MD) 2 complex may perpetuate abnormal signaling pathways. Cumulatively, the MDS and RIN analyses elucidated the mutant-specific conformational alterations, which may help in deciphering the mechanism of loss-of-function mutations.

  18. Stress and Fatigue Life Modeling of Cannon Breech Closures Including Effects of Material Strength and Residual Stress

    National Research Council Canada - National Science Library

    Underwood, John

    2000-01-01

    ...; overload residual stress. Modeling of applied and residual stresses at the location of the fatigue failure site is performed by elastic-plastic finite element analysis using ABAQUS and by solid...

  19. A Residual Approach for Balanced Truncation Model Reduction (BTMR of Compartmental Systems

    Directory of Open Access Journals (Sweden)

    William La Cruz

    2014-05-01

    Full Text Available This paper presents a residual approach of the square root balanced truncation algorithm for model order reduction of continuous, linear and time-invariante compartmental systems. Specifically, the new approach uses a residual method to approximate the controllability and observability gramians, whose resolution is an essential step of the square root balanced truncation algorithm, that requires a great computational cost. Numerical experiences are included to highlight the efficacy of the proposed approach.

  20. Hydrodesulfurization and hydrodemetallization of different origin vacuum residues : new modeling approach.

    OpenAIRE

    Ferreira , Cristina; Tayakout-Fayolle , Melaz; Guibard , Isabelle; Lemos , Francisco

    2014-01-01

    International audience; In order to be able to upgrade the heaviest part of the crude oil one needs to remove several impurities, such as sulfur or metals. Residue hydrotreatment in fixed beds, under high hydrogen pressure can achieve high removal performances, with an industrial catalysts optimized staging. Despite the recent improvements, petroleum residues remain very difficult to describe and characterize in detail. Several kinetic models have been developed, but mostly they are feed depe...

  1. Molecular modeling of human neutral sphingomyelinase provides insight into its molecular interactions.

    Science.gov (United States)

    Dinesh; Goswami, Angshumala; Suresh, Panneer Selvam; Thirunavukkarasu, Chinnasamy; Weiergräber, Oliver H; Kumar, Muthuvel Suresh

    2011-01-01

    The neutral sphingomyelinase (N-SMase) is considered a major candidate for mediating the stress-induced production of ceramide, and it plays an important role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress responses. Recent studies have identified a small region at the very N-terminus of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced activation of N-SMase. There is no direct association between TNF-R55 NSD and N-SMase; instead, a protein named factor associated with N-SMase activation (FAN) has been reported to couple the TNF-R55 NSD to N-SMase. Since the three-dimensional fold of N-SMase is still unknown, we have modeled the structure using the protein fold recognition and threading method. Moreover, we propose models for the TNF-R55 NSD as well as the FAN protein in order to study the structural basis of N-SMase activation and regulation. Protein-protein interaction studies suggest that FAN is crucially involved in mediating TNF-induced activation of the N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses. Inhibition of N-SMase may lead to reduction of ceramide levels and hence may provide a novel therapeutic strategy for inflammation and autoimmune diseases. Molecular dynamics (MD) simulations were performed to check the stability of the predicted model and protein-protein complex; indeed, stable RMS deviations were obtained throughout the simulation. Furthermore, in silico docking of low molecular mass ligands into the active site of N-SMase suggests that His135, Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based on our results, these ligands are proposed to be potent and selective N-SMase inhibitors, which may ultimately prove useful as lead compounds for drug development.

  2. Molecular modeling of auxin transport inhibitors

    International Nuclear Information System (INIS)

    Gardner, G.; Black-Schaefer, C.; Bures, M.G.

    1990-01-01

    Molecular modeling techniques have been used to study the chemical and steric properties of auxin transport inhibitors. These bind to a specific site on the plant plasma membrane characterized by its affinity for N-1-naphthylphthalamic acid (NPA). A three-dimensional model was derived from critical features of ligands for the NPA receptor, and a suggested binding conformation is proposed. This model, along with three-dimensional structural searching techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the search criteria, 77 representative molecules were evaluated for their ability to compete for [ 3 H]NPA binding to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, from chemical classes not included in the original compound set, also inhibited polar auxin transport through corn coleoptile sections

  3. Modelling of Tool Wear and Residual Stress during Machining of AISI H13 Tool Steel

    Science.gov (United States)

    Outeiro, José C.; Umbrello, Domenico; Pina, José C.; Rizzuti, Stefania

    2007-05-01

    Residual stresses can enhance or impair the ability of a component to withstand loading conditions in service (fatigue, creep, stress corrosion cracking, etc.), depending on their nature: compressive or tensile, respectively. This poses enormous problems in structural assembly as this affects the structural integrity of the whole part. In addition, tool wear issues are of critical importance in manufacturing since these affect component quality, tool life and machining cost. Therefore, prediction and control of both tool wear and the residual stresses in machining are absolutely necessary. In this work, a two-dimensional Finite Element model using an implicit Lagrangian formulation with an automatic remeshing was applied to simulate the orthogonal cutting process of AISI H13 tool steel. To validate such model the predicted and experimentally measured chip geometry, cutting forces, temperatures, tool wear and residual stresses on the machined affected layers were compared. The proposed FE model allowed us to investigate the influence of tool geometry, cutting regime parameters and tool wear on residual stress distribution in the machined surface and subsurface of AISI H13 tool steel. The obtained results permit to conclude that in order to reduce the magnitude of surface residual stresses, the cutting speed should be increased, the uncut chip thickness (or feed) should be reduced and machining with honed tools having large cutting edge radii produce better results than chamfered tools. Moreover, increasing tool wear increases the magnitude of surface residual stresses.

  4. Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Hyeon Kang; Kim, Kyu Bo; Chie, Eui Kyu; Ha, Sung W. [Seoul National University College of Medicine, Seoul (Korea, Republic of); Park, Hae Jin [Dept. of Radiation Oncology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2012-12-15

    To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and {beta}-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and {beta}-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and {beta}-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

  5. Molecular biomarkers in extrahepatic bile duct cancer patients undergoing chemoradiotherapy for gross residual disease after surgery

    International Nuclear Information System (INIS)

    Koh, Hyeon Kang; Kim, Kyu Bo; Chie, Eui Kyu; Ha, Sung W.; Park, Hae Jin

    2012-01-01

    To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers. Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and β-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated. At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and β-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes. There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and β-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

  6. Modeling coding-sequence evolution within the context of residue solvent accessibility.

    Science.gov (United States)

    Scherrer, Michael P; Meyer, Austin G; Wilke, Claus O

    2012-09-12

    Protein structure mediates site-specific patterns of sequence divergence. In particular, residues in the core of a protein (solvent-inaccessible residues) tend to be more evolutionarily conserved than residues on the surface (solvent-accessible residues). Here, we present a model of sequence evolution that explicitly accounts for the relative solvent accessibility of each residue in a protein. Our model is a variant of the Goldman-Yang 1994 (GY94) model in which all model parameters can be functions of the relative solvent accessibility (RSA) of a residue. We apply this model to a data set comprised of nearly 600 yeast genes, and find that an evolutionary-rate ratio ω that varies linearly with RSA provides a better model fit than an RSA-independent ω or an ω that is estimated separately in individual RSA bins. We further show that the branch length t and the transition-transverion ratio κ also vary with RSA. The RSA-dependent GY94 model performs better than an RSA-dependent Muse-Gaut 1994 (MG94) model in which the synonymous and non-synonymous rates individually are linear functions of RSA. Finally, protein core size affects the slope of the linear relationship between ω and RSA, and gene expression level affects both the intercept and the slope. Structure-aware models of sequence evolution provide a significantly better fit than traditional models that neglect structure. The linear relationship between ω and RSA implies that genes are better characterized by their ω slope and intercept than by just their mean ω.

  7. Modeling coding-sequence evolution within the context of residue solvent accessibility

    Directory of Open Access Journals (Sweden)

    Scherrer Michael P

    2012-09-01

    Full Text Available Abstract Background Protein structure mediates site-specific patterns of sequence divergence. In particular, residues in the core of a protein (solvent-inaccessible residues tend to be more evolutionarily conserved than residues on the surface (solvent-accessible residues. Results Here, we present a model of sequence evolution that explicitly accounts for the relative solvent accessibility of each residue in a protein. Our model is a variant of the Goldman-Yang 1994 (GY94 model in which all model parameters can be functions of the relative solvent accessibility (RSA of a residue. We apply this model to a data set comprised of nearly 600 yeast genes, and find that an evolutionary-rate ratio ω that varies linearly with RSA provides a better model fit than an RSA-independent ω or an ω that is estimated separately in individual RSA bins. We further show that the branch length t and the transition-transverion ratio κ also vary with RSA. The RSA-dependent GY94 model performs better than an RSA-dependent Muse-Gaut 1994 (MG94 model in which the synonymous and non-synonymous rates individually are linear functions of RSA. Finally, protein core size affects the slope of the linear relationship between ω and RSA, and gene expression level affects both the intercept and the slope. Conclusions Structure-aware models of sequence evolution provide a significantly better fit than traditional models that neglect structure. The linear relationship between ω and RSA implies that genes are better characterized by their ω slope and intercept than by just their mean ω.

  8. Approaches for Modelling the Residual Service Life of Marine Concrete Structures

    Directory of Open Access Journals (Sweden)

    Amir Rahimi

    2014-01-01

    Full Text Available This paper deals with the service life design of existing reinforced concrete structures in a marine environment. The general procedure of condition assessment for estimating the residual service life of structures before a repair measure is illustrated. For assessment of the residual service life of structures which have undergone a repair measure a simplified mathematical model of chloride diffusion in a 2-layer system is presented. Preliminary probabilistic calculations demonstrate the effect of various conditions on the residual service life. First studies of the chloride diffusion in a 2-layer system have been conducted using the finite element method. Results of a long-term exposure test are presented to illustrate the performance of two different repair materials. The distribution of residual chlorides after application of a repair material is being studied in laboratory investigations. The residual chlorides migrate from the concrete layer into the new layer immediately after the repair material has been applied to the concrete member. The content and gradient of residual chlorides, along with the thickness and the chloride ingress resistance of both the remaining and the new layer of cover, will determine the residual service life of the repaired structures.

  9. Thermal oxidative degradation kinetics of agricultural residues using distributed activation energy model and global kinetic model.

    Science.gov (United States)

    Ren, Xiu'e; Chen, Jianbiao; Li, Gang; Wang, Yanhong; Lang, Xuemei; Fan, Shuanshi

    2018-08-01

    The study concerned the thermal oxidative degradation kinetics of agricultural residues, peanut shell (PS) and sunflower shell (SS). The thermal behaviors were evaluated via thermogravimetric analysis and the kinetic parameters were determined by using distributed activation energy model (DAEM) and global kinetic model (GKM). Results showed that thermal oxidative decomposition of two samples processed in three zones; the ignition, burnout, and comprehensive combustibility between two agricultural residues were of great difference; and the combustion performance could be improved by boosting heating rate. The activation energy ranges calculated by the DAEM for the thermal oxidative degradation of PS and SS were 88.94-145.30 kJ mol -1 and 94.86-169.18 kJ mol -1 , respectively. The activation energy obtained by the GKM for the oxidative decomposition of hemicellulose and cellulose was obviously lower than that for the lignin oxidation at identical heating rate. To some degree, the determined kinetic parameters could acceptably simulate experimental data. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution.

    Directory of Open Access Journals (Sweden)

    Amanda Tse

    Full Text Available Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib and promiscuous (Bosutinib, Dasatinib kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations

  11. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    Science.gov (United States)

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  12. Modeling ion sensing in molecular electronics

    International Nuclear Information System (INIS)

    Chen, Caroline J.; Smeu, Manuel; Ratner, Mark A.

    2014-01-01

    We examine the ability of molecules to sense ions by measuring the change in molecular conductance in the presence of such charged species. The detection of protons (H + ), alkali metal cations (M + ), calcium ions (Ca 2+ ), and hydronium ions (H 3 O + ) is considered. Density functional theory (DFT) is used within the Keldysh non-equilibrium Green's function framework (NEGF) to model electron transport properties of quinolinedithiol (QDT, C 9 H 7 NS 2 ), bridging Al electrodes. The geometry of the transport region is relaxed with DFT. The transport properties of the device are modeled with NEGF-DFT to determine if this device can distinguish among the M + + QDT species containing monovalent cations, where M + = H + , Li + , Na + , or K + . Because of the asymmetry of QDT in between the two electrodes, both positive and negative biases are considered. The electron transmission function and conductance properties are simulated for electrode biases in the range from −0.5 V to 0.5 V at increments of 0.1 V. Scattering state analysis is used to determine the molecular orbitals that are the main contributors to the peaks in the transmission function near the Fermi level of the electrodes, and current-voltage relationships are obtained. The results show that QDT can be used as a proton detector by measuring transport through it and can conceivably act as a pH sensor in solutions. In addition, QDT may be able to distinguish among different monovalent species. This work suggests an approach to design modern molecular electronic conductance sensors with high sensitivity and specificity using well-established quantum chemistry

  13. Molecular Basis for Enzymatic Sulfite Oxidation -- HOW THREE CONSERVED ACTIVE SITE RESIDUES SHAPE ENZYME ACTIVITY

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Susan; Rapson, Trevor; Johnson-Winters, Kayunta; Astashkin, Andrei; Enemark, John; Kappler, Ulrike

    2008-11-10

    Sulfite dehydrogenases (SDHs) catalyze the oxidation and detoxification of sulfite to sulfate, a reaction critical to all forms of life. Sulfite-oxidizing enzymes contain three conserved active site amino acids (Arg-55, His-57, and Tyr-236) that are crucial for catalytic competency. Here we have studied the kinetic and structural effects of two novel and one previously reported substitution (R55M, H57A, Y236F) in these residues on SDH catalysis. Both Arg-55 and His-57 were found to have key roles in substrate binding. An R55M substitution increased Km(sulfite)(app) by 2-3 orders of magnitude, whereas His-57 was required for maintaining a high substrate affinity at low pH when the imidazole ring is fully protonated. This effect may be mediated by interactions of His-57 with Arg-55 that stabilize the position of the Arg-55 side chain or, alternatively, may reflect changes in the protonation state of sulfite. Unlike what is seen for SDHWT and SDHY236F, the catalytic turnover rates of SDHR55M and SDHH57A are relatively insensitive to pH (~;;60 and 200 s-1, respectively). On the structural level, striking kinetic effects appeared to correlate with disorder (in SDHH57A and SDHY236F) or absence of Arg-55 (SDHR55M), suggesting that Arg-55 and the hydrogen bonding interactions it engages in are crucial for substrate binding and catalysis. The structure of SDHR55M has sulfate bound at the active site, a fact that coincides with a significant increase in the inhibitory effect of sulfate in SDHR55M. Thus, Arg-55 also appears to be involved in enabling discrimination between the substrate and product in SDH.

  14. Modelling of a downdraft gasifier fed by agricultural residues

    International Nuclear Information System (INIS)

    Antonopoulos, I.-S.; Karagiannidis, A.; Gkouletsos, A.; Perkoulidis, G.

    2012-01-01

    Highlights: ► Development of software for downdraft gasification simulation. ► Prediction of the syngas concentration. ► Prediction of the syngas heating value. ► Investigation of the temperature effect in reduction zone in syngas concentration. - Abstract: A non-stoichiometric model for a downdraft gasifier was developed in order to simulate the overall gasification process. Mass and energy balances of the gasifier were calculated and the composition of produced syngas was predicted. The capacity of the modeled gasifier was assumed to be 0.5 MW, with an Equivalence Ratio (EQ) of 0.45. The model incorporates the chemical reactions and species involved, while it starts by selecting all species containing C, H, and O, or any other dominant elements. Olive wood, miscanthus and cardoon were tested in the formulated model for a temperature range of 800–1200 °C, in order to examine the syngas composition and the moisture impact on the supplied fuel. Model results were then used in order to design an olive wood gasification reactor.

  15. Molecular Modeling: A Powerful Tool for Drug Design and Molecular ...

    Indian Academy of Sciences (India)

    eling studies is generally a two-dimensional drawing of a re- quired molecule. ... The most active area of theoretical research using molecular orbi tal theory has been in ... minimum energy structure for example, by using conjugated gradient algorithm .... QSARwas applied to understand how the structure might be modified ...

  16. Noise Residual Learning for Noise Modeling in Distributed Video Coding

    DEFF Research Database (Denmark)

    Luong, Huynh Van; Forchhammer, Søren

    2012-01-01

    Distributed video coding (DVC) is a coding paradigm which exploits the source statistics at the decoder side to reduce the complexity at the encoder. The noise model is one of the inherently difficult challenges in DVC. This paper considers Transform Domain Wyner-Ziv (TDWZ) coding and proposes...

  17. Residual circulation and freshwater transport in the Dutch Wadden Sea: a numerical modelling study

    NARCIS (Netherlands)

    Duran-Matute, M.; Gerkema, T.; de Boer, G.J.; Nauw, J.; Grawe, U.

    2014-01-01

    The Dutch Wadden Sea is a region of intertidal flats located between the chain of Wadden Islands and the Dutch mainland. We present numerical model results on the tidal prisms and residual flows through the tidal inlets and across one of the main watersheds. The model also provides insight into the

  18. A residual life prediction model based on the generalized σ -N curved surface

    Directory of Open Access Journals (Sweden)

    Zongwen AN

    2016-06-01

    Full Text Available In order to investigate change rule of the residual life of structure under random repeated load, firstly, starting from the statistic meaning of random repeated load, the joint probability density function of maximum stress and minimum stress is derived based on the characteristics of order statistic (maximum order statistic and minimum order statistic; then, based on the equation of generalized σ -N curved surface, considering the influence of load cycles number on fatigue life, a relationship among minimum stress, maximum stress and residual life, that is the σmin(n- σmax(n-Nr(n curved surface model, is established; finally, the validity of the proposed model is demonstrated by a practical case. The result shows that the proposed model can reflect the influence of maximum stress and minimum stress on residual life of structure under random repeated load, which can provide a theoretical basis for life prediction and reliability assessment of structure.

  19. Residual stress behaviors induced by laser peening along the edge of curved models

    International Nuclear Information System (INIS)

    Im, Jong Bin; Grandhi, Ramana V.; Ro, Young Hee

    2012-01-01

    Laser peening (LP) induces high magnitude compressive residual stresses in a small region of a component. The compressive residual stresses cause plastic deformation that is resistant to fatigue fracture. Fatigue cracks are generally nucleated at critical areas, and LP is applied for those regions so as to delay the crack initiation. Many critical regions are located on the edge of the curved portion of structures because of stress concentration effects. Several investigations that are available for straight components may not give meaningful guidelines for peening curved components. Therefore, in this paper, we investigate residual stress behaviors induced by LP along the edge of curved models. Three curved models that have different curvatures are investigated for peening performance. Two types of peening configurations, which are simultaneous corner shot and sequential corner shots, are considered in order to obtain compressive residual stresses along an edge. LP simulations of multiple shots are performed to identify overlapping effects on the edge portion of a curved model. In addition, the uncertainty calculation of residual stress induced by LP considering laser pulse duration is performed

  20. Identification of key residues for protein conformational transition using elastic network model.

    Science.gov (United States)

    Su, Ji Guo; Xu, Xian Jin; Li, Chun Hua; Chen, Wei Zu; Wang, Cun Xin

    2011-11-07

    Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase β, are used as case studies to identify the critical residues responsible for their open-closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions.

  1. Failure Analysis of Nonvolatile Residue (NVR) Analyzer Model SP-1000

    Science.gov (United States)

    Potter, Joseph C.

    2011-01-01

    National Aeronautics and Space Administration (NASA) subcontractor Wiltech contacted the NASA Electrical Lab (NE-L) and requested a failure analysis of a Solvent Purity Meter; model SP-IOOO produced by the VerTis Instrument Company. The meter, used to measure the contaminate in a solvent to determine the relative contamination on spacecraft flight hardware and ground servicing equipment, had been inoperable and in storage for an unknown amount of time. NE-L was asked to troubleshoot the unit and make a determination on what may be required to make the unit operational. Through the use of general troubleshooting processes and the review of a unit in service at the time of analysis, the unit was found to be repairable but would need the replacement of multiple components.

  2. 14C Carbofuran residue in rice-fish ecosystem model

    International Nuclear Information System (INIS)

    Sumatra, M.; Soekarna, D.; Suhanda; Kuswadi, A.N.

    1988-01-01

    14-C-carbofuran in the form of 14-C-Furada 3G was applied with doses of 0, 2, and 4 g/m2 to a rice-fish ecosystem model consisting of water, soil, rice, plant, and fish (Cyprinus carpio) in tanks of the size 1 m length, 1 m width, and 0.5 m depth. 14-C-carbofuran was released from 14-C-Furadan 3G, entered into the water, absorbed by plant root, and then distributed into the whole plant. A part of the 14-C-carbofuran was absorbed and retained by soil. In both doses of 4 and 2 g/m2, the 14-C-Furadan 3G was toxic to Cyprinus carpio under this experiment condition. (author). 5 refs, 5 figs, 6 tabs

  3. Microwave-assisted RAFT polymerization of well-constructed magnetic surface molecularly imprinted polymers for specific recognition of benzimidazole residues

    Science.gov (United States)

    Chen, Fangfang; Wang, Jiayu; Chen, Huiru; Lu, Ruicong; Xie, Xiaoyu

    2018-03-01

    Magnetic nanoparticles have been widely used as support core for fast separation, which could be directly separated from complicated matrices using an external magnet in few minutes. Surface imprinting based on magnetic core has shown favorable adsorption and separation performance, including good adsorption capacity, fast adsorption kinetics and special selectivity adsorption. Reversible addition-fragmentation chain transfer (RAFT) is an ideal choice for producing well-defined complex architecture with mild reaction conditions. We herein describe the preparation of well-constructed magnetic molecularly imprinted polymers (MMIPs) for the recognition of benzimidazole (BMZ) residues via the microwave-assisted RAFT polymerization. The merits of RAFT polymerization assisting with microwave heating allowed successful and more efficient preparation of well-constructed imprinted coats. Moreover, the polymerization time dramatically shortened and was just 1/24th of the time taken by conventional heating. The results indicated that a uniform nanoscale imprinted layer was formed on the Fe3O4 core successfully, and enough saturation magnetization of MMIPs (16.53 emu g-1) was got for magnetic separation. The desirable adsorption capacity (30.18 μmol g-1) and high selectivity toward template molecule with a selectivity coefficient (k) of 13.85 of MMIPs were exhibited by the adsorption isothermal assay and competitive binding assay, respectively. A solid phase extraction enrichment approach was successfully established for the determination of four BMZ residues from apple samples using MMIPs coupled to HPLC. Overall, this study provides a versatile approach for highly efficient fabrication of well-constructed MMIPs for enrichment and determination of target molecules from complicated samples.

  4. Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

    Science.gov (United States)

    Singer, M S; Shepherd, G M

    1994-06-02

    Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

  5. Surfactant-enhanced solubilization of residual dodecane in soil columns. 2. Mathematical modeling

    International Nuclear Information System (INIS)

    Abriola, L.M.; Dekker, T.J.; Pennell, K.D.

    1993-01-01

    A mathematical model is developed to describe surfactant-enhanced solubilization of nonaqueous-phase liquids (NAPLs) in porous media. The model incorporates aqueous-phase transport equations for organic and surfactant components as well as a mass balance for the organic phase. Rate-limited solubilization and surfactant sorption are represented by a linear driving force expression and a Langmuir isotherm, respectively. The model is implemented in a one-dimensional Galerkin finite element simulator which idealizes the entrapped residual organic as a collection of spherical globules. Soil column data for the solubilization of residual dodecane by an aqueous solution of polyoxyethylene (20) sorbitan monooleate are used to evaluate the conceptual model. Input parameters were obtained, where possible, from independent batch experiments. Calibrated model simulations exhibit good agreement with measured effluent concentrations, supporting the utility of the conceptual modeling approach. Sensitivity analyses explore the influence of surfactant concentration and flushing strategy on NAPL recovery. 45 refs., 6 figs., 3 tabs

  6. Molecular characterization of two Arabidopsis thaliana glycosyltransferase mutants, rra1 and rra2, which have a reduced residual arabinose content in a polymer tightly associated with the cellulosic wall residue

    DEFF Research Database (Denmark)

    Egelund, Jack; Obel, Nicolai; Ulvskov, Peter

    2007-01-01

    identified and characterized at the molecular and biochemical level. Monosaccharide compositional analyses of cell wall material isolated from the meristematic region showed a ca. 20% reduction in the arabinose content in the insoluble/undigested cell wall residue after enzymatic removal of xyloglucan...... and pectic polysaccharides. These data indicate that both RRA-1 and -2 play a role in the arabinosylation of cell wall component(s)....

  7. On the residual stress modeling of shot-peened AISI 4340 steel: finite element and response surface methods

    Science.gov (United States)

    Asgari, Ali; Dehestani, Pouya; Poruraminaie, Iman

    2018-02-01

    Shot peening is a well-known process in applying the residual stress on the surface of industrial parts. The induced residual stress improves fatigue life. In this study, the effects of shot peening parameters such as shot diameter, shot speed, friction coefficient, and the number of impacts on the applied residual stress will be evaluated. To assess these parameters effect, firstly the shot peening process has been simulated by finite element method. Then, effects of the process parameters on the residual stress have been evaluated by response surface method as a statistical approach. Finally, a strong model is presented to predict the maximum residual stress induced by shot peening process in AISI 4340 steel. Also, the optimum parameters for the maximum residual stress are achieved. The results indicate that effect of shot diameter on the induced residual stress is increased by increasing the shot speed. Also, enhancing the friction coefficient magnitude always cannot lead to increase in the residual stress.

  8. Feedback between residual circulations and sediment distribution in highly turbid estuaries: an analytical model

    NARCIS (Netherlands)

    Talke, S.A.|info:eu-repo/dai/nl/304823554; de Swart, H.E.|info:eu-repo/dai/nl/073449725; Schuttelaars, H.|info:eu-repo/dai/nl/164035656

    2009-01-01

    Motivated by field studies of the Ems estuary which show longitudinal gradients in bottom sediment concentration as high as O(0.01 kg/m4), we develop an analytical model for estuarine residual circulation based on currents from salinity gradients, turbidity gradients, and freshwater discharge.

  9. Molecular scale modeling of polymer imprint nanolithography.

    Science.gov (United States)

    Chandross, Michael; Grest, Gary S

    2012-01-10

    We present the results of large-scale molecular dynamics simulations of two different nanolithographic processes, step-flash imprint lithography (SFIL), and hot embossing. We insert rigid stamps into an entangled bead-spring polymer melt above the glass transition temperature. After equilibration, the polymer is then hardened in one of two ways, depending on the specific process to be modeled. For SFIL, we cross-link the polymer chains by introducing bonds between neighboring beads. To model hot embossing, we instead cool the melt to below the glass transition temperature. We then study the ability of these methods to retain features by removing the stamps, both with a zero-stress removal process in which stamp atoms are instantaneously deleted from the system as well as a more physical process in which the stamp is pulled from the hardened polymer at fixed velocity. We find that it is necessary to coat the stamp with an antifriction coating to achieve clean removal of the stamp. We further find that a high density of cross-links is necessary for good feature retention in the SFIL process. The hot embossing process results in good feature retention at all length scales studied as long as coated, low surface energy stamps are used.

  10. The independent molecular interaction sites model. Pt. 1

    International Nuclear Information System (INIS)

    Naumann, K.H.; Lippert, E.

    1981-01-01

    A new reference system for the treatment of molecular fluids within the framework of thermodynamic perturbation theory is presented. The basic ingredient of our approach is a potential transformation which allows us to view molecular liquids and gases as mixtures of formally independent molecular interaction sites (IMIS model). Some relations between out method and the RAM theory are discussed. (orig.)

  11. Hanford Site Tank 241-C-108 Residual Waste Contaminant Release Models and Supporting Data

    Energy Technology Data Exchange (ETDEWEB)

    Cantrell, Kirk J.; Krupka, Kenneth M.; Geiszler, Keith N.; Arey, Bruce W.; Schaef, Herbert T.

    2010-06-18

    This report presents the results of laboratory characterization, testing, and analysis for a composite sample (designated 20578) of residual waste collected from single-shell tank C-108 during the waste retrieval process after modified sluicing. These studies were completed to characterize concentration and form of contaminant of interest in the residual waste; assess the leachability of contaminants from the solids; and develop release models for contaminants of interest. Because modified sluicing did not achieve 99% removal of the waste, it is expected that additional retrieval processing will take place. As a result, the sample analyzed here is not expected to represent final retrieval sample.

  12. Modeling of Residual Stress and Machining Distortion in Aerospace Components (PREPRINT)

    Science.gov (United States)

    2010-03-01

    John Gayda, “The Effect of Heat Treatment on Residual Stress and Machining Distortions in Advanced Nickel Base Disk Alloys,” NASA/TM-2001-210717. 2...Wei-Tsu Wu, Guoji Li, Juipeng Tang, Shesh Srivatsa, Ravi Shankar, Ron Wallis, Padu Ramasundaram and John Gayda, “A process modeling system for heat...Materials Processing Technology 98 (2000) 189-195. 6. M.A. Rist, S. Tin, B.A. Roder, J.A. James, and M.R. Daymond , “Residual Stresses in a

  13. A Thermodamage Strength Theoretical Model of Ceramic Materials Taking into Account the Effect of Residual Stress

    Directory of Open Access Journals (Sweden)

    Weiguo Li

    2012-01-01

    Full Text Available A thermodamage strength theoretical model taking into account the effect of residual stress was established and applied to each temperature phase based on the study of effects of various physical mechanisms on the fracture strength of ultrahigh-temperature ceramics. The effects of SiC particle size, crack size, and SiC particle volume fraction on strength corresponding to different temperatures were studied in detail. This study showed that when flaw size is not large, the bigger SiC particle size results in the greater effect of tensile residual stress in the matrix grains on strength reduction, and this prediction coincides with experimental results; and the residual stress and the combined effort of particle size and crack size play important roles in controlling material strength.

  14. MODEL FOR THE CORRECTION OF THE SPECIFIC GRAVITY OF BIODIESEL FROM RESIDUAL OIL

    Directory of Open Access Journals (Sweden)

    Tatiana Aparecida Rosa da Silva

    2013-06-01

    Full Text Available Biodiesel is a important fuel with economic benefits, social and environmental. The production cost of the biodiesel can be significantly lowered if the raw material is replaced by a alternative material as residual oil. In this study, the variation of specific gravity with temperature increase for diesel and biodiesel from residual oil obtained by homogeneous basic catalysis. All properties analyzed for biodiesel are within specification Brazil. The determination of the correction algorithm for the specific gravity function of temperature is also presented, and the slope of the line to diesel fuel, methylic biodiesel (BMR and ethylic biodiesel (BER from residual oil were respectively the values -0.7089, -0.7290 and -0.7277. This demonstrates the existence of difference of the model when compared chemically different fuels, like diesel and biodiesel from different sources, indicating the importance of determining the specific algorithm for the operations of conversion of volume to the reference temperature.

  15. Validation of Weld Residual Stress Modeling in the NRC International Round Robin Study

    International Nuclear Information System (INIS)

    Mullins, Jonathan; Gunnars, Jens

    2013-01-01

    Weld residual stresses (WRS) have a large influence on the behavior of cracks growing under normal operation loads and on the leakage flow from a through-wall crack. Accurate prediction on weld residual stresses is important to make proper decisions when cracks in weld joints are detected. During the latest years, there has been a strong development in both analytical procedures to numerically determine WRS and experimental measurements of WRS. The USNRC (United States Nuclear Regulatory Commission) has formed a program for validation of WRS predictions through comparison of numerically calculated residual stress fields in dissimilar welds measured by different methods. The present report describes the results of the project with special focus on the contribution from Inspecta Technology. Objectives: The principal objective of the project is to compare different WRS predictions for a dissimilar pipe weld with careful measurements on a mock-up weld. The results of the project will make it possible to make recommendations on computational procedures for WRS in dissimilar metal welds. Results: It is concluded that numerical analysis of weld residual stresses using the finite element method is very useful for the estimation of weld residual stresses in complex geometries and dissimilar metal welds. The validation study increases the understanding of uncertainties associated with different modeling approaches and helps to identify the most sensitive parameters

  16. An analytical model to predict and minimize the residual stress of laser cladding process

    Science.gov (United States)

    Tamanna, N.; Crouch, R.; Kabir, I. R.; Naher, S.

    2018-02-01

    Laser cladding is one of the advanced thermal techniques used to repair or modify the surface properties of high-value components such as tools, military and aerospace parts. Unfortunately, tensile residual stresses generate in the thermally treated area of this process. This work focuses on to investigate the key factors for the formation of tensile residual stress and how to minimize it in the clad when using dissimilar substrate and clad materials. To predict the tensile residual stress, a one-dimensional analytical model has been adopted. Four cladding materials (Al2O3, TiC, TiO2, ZrO2) on the H13 tool steel substrate and a range of preheating temperatures of the substrate, from 300 to 1200 K, have been investigated. Thermal strain and Young's modulus are found to be the key factors of formation of tensile residual stresses. Additionally, it is found that using a preheating temperature of the substrate immediately before laser cladding showed the reduction of residual stress.

  17. Greenhouse crop residues: Energy potential and models for the prediction of their higher heating value

    Energy Technology Data Exchange (ETDEWEB)

    Callejon-Ferre, A.J.; Lopez-Martinez, J.A.; Manzano-Agugliaro, F. [Departamento de Ingenieria Rural, Universidad de Almeria, Ctra. Sacramento s/n, La Canada de San Urbano, 04120 Almeria (Spain); Velazquez-Marti, B. [Departamento de Ingenieria Rural y Agroalimentaria, Universidad Politecnica de Valencia, Camino de Vera s/n, 46022 Valencia (Spain)

    2011-02-15

    Almeria, in southeastern Spain, generates some 1,086,261 t year{sup -1} (fresh weight) of greenhouse crop (Cucurbita pepo L., Cucumis sativus L., Solanum melongena L., Solanum lycopersicum L., Phaseoulus vulgaris L., Capsicum annuum L., Citrillus vulgaris Schrad. and Cucumis melo L.) residues. The energy potential of this biomass is unclear. The aim of the present work was to accurately quantify this variable, differentiating between crop species while taking into consideration the area they each occupy. This, however, required the direct analysis of the higher heating value (HHV) of these residues, involving very expensive and therefore not commonly available equipment. Thus, a further aim was to develop models for predicting the HHV of these residues, taking into account variables measured by elemental and/or proximate analysis, thus providing an economically attractive alternative to direct analysis. All the analyses in this work involved the use of worldwide-recognised standards and methods. The total energy potential for these plant residues, as determined by direct analysis, was 1,003,497.49 MW h year{sup -1}. Twenty univariate and multivariate equations were developed to predict the HHV. The R{sup 2} and adjusted R{sup 2} values obtained for the univariate and multivariate models were 0.909 and 0.946 or above respectively. In all cases, the mean absolute percentage error varied between 0.344 and 2.533. These results show that any of these 20 equations could be used to accurately predict the HHV of crop residues. The residues produced by the Almeria greenhouse industry would appear to be an interesting source of renewable energy. (author)

  18. Statistical modeling to management and treatment of scrap with low and very low residual activity

    International Nuclear Information System (INIS)

    Garcia-Bermejo Fernandez, R.; Anaya Lazaro, M.

    2011-01-01

    The experience of recent years on the management of scrap metal containing residual activity have allowed the development of a simple statistical model for the management of these materials. This statistical model includes a breakdown of the various processing operations to which these materials undergo and the effects in the process of radiological controls associated to the control of declassification that defines disposal (recycled by smelting, reclamation, temporary storage the plant or sent to final storage of radioactive waste.

  19. Molecular modeling and multiscaling issues for electronic material applications

    CERN Document Server

    Iwamoto, Nancy; Yuen, Matthew; Fan, Haibo

    Volume 1 : Molecular Modeling and Multiscaling Issues for Electronic Material Applications provides a snapshot on the progression of molecular modeling in the electronics industry and how molecular modeling is currently being used to understand material performance to solve relevant issues in this field. This book is intended to introduce the reader to the evolving role of molecular modeling, especially seen through the eyes of the IEEE community involved in material modeling for electronic applications.  Part I presents  the role that quantum mechanics can play in performance prediction, such as properties dependent upon electronic structure, but also shows examples how molecular models may be used in performance diagnostics, especially when chemistry is part of the performance issue.  Part II gives examples of large-scale atomistic methods in material failure and shows several examples of transitioning between grain boundary simulations (on the atomistic level)and large-scale models including an example ...

  20. On the extension of multi-phase models to sub-residual saturations

    International Nuclear Information System (INIS)

    Lingineni, S.; Chen, Y.T.; Boehm, R.F.

    1995-01-01

    This paper focuses on the limitations of applying multi-phase flow and transport models to simulate the hydrothermal processes occurring when the liquid saturation falls below residual levels. A typical scenario of a heat-generating high-level waste package emplaced in a backfilled drift of a waste repository is presented. The hydrothermal conditions in the vicinity of the waste package as well as in the far-field are determined using multi-phase, non-isothermal codes such as TOUGH2 and FEHM. As the waste package temperature increases, heat-pipe effects are created and water is driven away from the package into colder regions where it condenses. The variations in the liquid saturations close to the waste package are determined using these models with extended capillary pressure-saturations relationships to sub-residual regime. The predictions indicate even at elevated temperatures, waste package surroundings are not completely dry. However, if transport based modeling is used to represent liquid saturation variations in the sub-residual regime, then complete dry conditions are predicted within the backfill for extended periods of time. The relative humidity conditions near the waste package are also found to be sensitive to the representation of capillary pressure-saturation relationship used for sub-residual regime. An experimental investigation is carried out to study the variations in liquid saturations and relative humidity conditions in sub-residual regimes. Experimental results indicated that extended multi-phase models without interphase transport can not predict dry-out conditions and the simulations underpredict the humidity conditions near the waste package

  1. Improving probabilistic prediction of daily streamflow by identifying Pareto optimal approaches for modelling heteroscedastic residual errors

    Science.gov (United States)

    David, McInerney; Mark, Thyer; Dmitri, Kavetski; George, Kuczera

    2017-04-01

    This study provides guidance to hydrological researchers which enables them to provide probabilistic predictions of daily streamflow with the best reliability and precision for different catchment types (e.g. high/low degree of ephemerality). Reliable and precise probabilistic prediction of daily catchment-scale streamflow requires statistical characterization of residual errors of hydrological models. It is commonly known that hydrological model residual errors are heteroscedastic, i.e. there is a pattern of larger errors in higher streamflow predictions. Although multiple approaches exist for representing this heteroscedasticity, few studies have undertaken a comprehensive evaluation and comparison of these approaches. This study fills this research gap by evaluating 8 common residual error schemes, including standard and weighted least squares, the Box-Cox transformation (with fixed and calibrated power parameter, lambda) and the log-sinh transformation. Case studies include 17 perennial and 6 ephemeral catchments in Australia and USA, and two lumped hydrological models. We find the choice of heteroscedastic error modelling approach significantly impacts on predictive performance, though no single scheme simultaneously optimizes all performance metrics. The set of Pareto optimal schemes, reflecting performance trade-offs, comprises Box-Cox schemes with lambda of 0.2 and 0.5, and the log scheme (lambda=0, perennial catchments only). These schemes significantly outperform even the average-performing remaining schemes (e.g., across ephemeral catchments, median precision tightens from 105% to 40% of observed streamflow, and median biases decrease from 25% to 4%). Theoretical interpretations of empirical results highlight the importance of capturing the skew/kurtosis of raw residuals and reproducing zero flows. Recommendations for researchers and practitioners seeking robust residual error schemes for practical work are provided.

  2. Modeling shockwave deformation via molecular dynamics

    International Nuclear Information System (INIS)

    Holian, B.L.

    1987-01-01

    Molecular dynamics (MD), where the equations of motion of up to thousands of interacting atoms are solved on the computer, has proven to be a powerful tool for investigating a wide variety of nonequilibrium processes from the atomistic viewpoint. Simulations of shock waves in three-dimensional (3D) solids and fluids have shown conclusively that shear-stress relaxation is achieved through atomic rearrangement. In the case of fluids, the transverse motion is viscous, and the constitutive model of Navier-Stokes hydrodynamics has been shown to be accurate - even on the time and distance scales of MD experiments. For strong shocks in solids, the plastic flow that leads to shear-stress relaxation in MD is highly localized near the shock front, involving a slippage along close-packed planes. For shocks of intermediate strength, MD calculations exhibit an elastic precursor running out in front of the steady plastic wave, where slippage similar in character to that in the very strong shocks leads to shear-stress relaxation. An interesting correlation between the maximum shear stress and the Hugoniot pressure jump is observed for both 3D and fluid shockwave calculations, which may have some utility in modeling applications. At low shock strengths, the MD simulations show only elastic compression, with no permanent transverse atomic strains. The result for perfect 3D crystals is also seen in calculations for 1D chains. It is speculated that, if it were practical, a very large MD system containing dislocations could be expected to exhibit more realistic plastic flow for weak shock waves, too

  3. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  4. Polycrystalline models for the calculation of residual stresses in zirconium alloys tubes

    International Nuclear Information System (INIS)

    Signorelli, J.W.; Turner, P.A.; Lebensohn, R.A.; Pochettino, A.A.

    1995-01-01

    Tubes made of different Zirconium alloys are used in various types of reactors. The final texture of tubes as well as the distribution of residual stresses depend on the mechanical treatments done during their manufacturing process. The knowledge and prediction of both the final texture and the distribution of residual stresses in a tube for nuclear applications are of outstanding importance in relation with in-reactor performance of the tube, especially in what concerns to its irradiation creep and growth behaviour. The viscoplastic and the elastoplastic self consistent polycrystal models are used to investigate the influence of different mechanical treatments, performed during rolling processes on the final distribution of intergranular residual stresses of zirconium alloys tubes. The residual strains predictions with both formulations show a non linear dependence with the orientation, but they are qualitatively different. This discrepancy could be explain in terms of the relative plastic activity between the -type and -type deformation modes predicted with the viscoplastic and elastoplastic models. (author). 10 refs., 4 figs., 1 tab

  5. A consistent transported PDF model for treating differential molecular diffusion

    Science.gov (United States)

    Wang, Haifeng; Zhang, Pei

    2016-11-01

    Differential molecular diffusion is a fundamentally significant phenomenon in all multi-component turbulent reacting or non-reacting flows caused by the different rates of molecular diffusion of energy and species concentrations. In the transported probability density function (PDF) method, the differential molecular diffusion can be treated by using a mean drift model developed by McDermott and Pope. This model correctly accounts for the differential molecular diffusion in the scalar mean transport and yields a correct DNS limit of the scalar variance production. The model, however, misses the molecular diffusion term in the scalar variance transport equation, which yields an inconsistent prediction of the scalar variance in the transported PDF method. In this work, a new model is introduced to remedy this problem that can yield a consistent scalar variance prediction. The model formulation along with its numerical implementation is discussed, and the model validation is conducted in a turbulent mixing layer problem.

  6. Modeling the residual effects and threshold saturation of training: a case study of Olympic swimmers.

    Science.gov (United States)

    Hellard, Philippe; Avalos, Marta; Millet, Gregoire; Lacoste, Lucien; Barale, Frederic; Chatard, Jean-Claude

    2005-02-01

    The aim of this study was to model the residual effects of training on the swimming performance and to compare a model that includes threshold saturation (MM) with the Banister model (BM). Seven Olympic swimmers were studied over a period of 4 +/- 2 years. For 3 training loads (low-intensity w(LIT), high-intensity w(HIT), and strength training w(ST)), 3 residual training effects were determined: short-term (STE) during the taper phase (i.e., 3 weeks before the performance [weeks 0, 1, and 2]), intermediate-term (ITE) during the intensity phase (weeks 3, 4, and 5), and long-term (LTE) during the volume phase (weeks 6, 7, and 8). ITE and LTE were positive for w(HIT) and w(LIT), respectively (p measures indicated that MM compares favorably with BM. Identifying individual training thresholds may help individualize the distribution of training loads.

  7. Study on grey theoretical model of passive residual heat removal system

    International Nuclear Information System (INIS)

    Zhou Tao; Yang Ruichang; Su, G.H.; Jia Dounan; Sugiyama, K.

    2004-01-01

    Natural Circulation Passive Residual Heat Removal System is treated as a Grey System by taking into account of its complexity and uncertainty of effect for factors each other. The magnitude and degree of some factors are confirmed by grey incidence analysis method; The one-one relationship of some variables is built by GM (1, 1) model; The relationship between key factor and other effect factors is built (1, 4) model. Grey model shows its more advantage of precision through comparing with multivariate model. (author)

  8. Biomass supply from alternative cellulosic crops and crop residues: A spatially explicit bioeconomic modeling approach

    International Nuclear Information System (INIS)

    Egbendewe-Mondzozo, Aklesso; Swinton, Scott M.; Izaurralde, César R.; Manowitz, David H.; Zhang, Xuesong

    2011-01-01

    This paper introduces a spatially-explicit bioeconomic model for the study of potential cellulosic biomass supply. For biomass crops to begin to replace current crops, farmers must earn more from them than from current crops. Using weather, topographic and soil data, the terrestrial ecosystem model, EPIC, dynamically simulates multiple cropping systems that vary by crop rotation, tillage, fertilization and residue removal rate. EPIC generates predicted crop yield and environmental outcomes over multiple watersheds. These EPIC results are used to parameterize a regional profit-maximization mathematical programming model that identifies profitable cropping system choices. The bioeconomic model is calibrated to 2007–09 crop production in a 9-county region of southwest Michigan. A simulation of biomass supply in response to rising biomass prices shows that cellulosic residues from corn stover and wheat straw begin to be supplied at minimum delivered biomass:corn grain price ratios of 0.15 and 0.18, respectively. At the mean corn price of $162.6/Mg ($4.13 per bushel) at commercial moisture content during 2007–2009, these ratios correspond to stover and straw prices of $24 and $29 per dry Mg. Perennial bioenergy crops begin to be supplied at price levels 2–3 times higher. Average biomass transport costs to the biorefinery plant range from $6 to $20/Mg compared to conventional crop production practices in the area, biomass supply from annual crop residues increased greenhouse gas emissions and reduced water quality through increased nutrient loss. By contrast, perennial cellulosic biomass crop production reduced greenhouse gas emissions and improved water quality. -- Highlights: ► A new bioeconomic model predicts biomass supply and its environmental impacts. ► The model captures the opportunity cost of switching to new cellulosic crops. ► Biomass from crop residues is supplied at lower biomass price than cellulosic crops. ► Biomass from cellulosic crops has

  9. Extended Lipkin-type models with residual proton-neutron interaction

    International Nuclear Information System (INIS)

    Stoica, S.

    1999-01-01

    Extended Lipkin-Meshkov-Glick (LMG) models for testing the Random Phase Approximation (RPA) and proton-neutron Random Phase Approximation (pnRPA) methods are developed taking into account explicitly the proton and neutron degrees of freedom. First, an extended LMG model for testing RPA is developed. The proton and neutron Hamiltonians are taken to be of the LMG form and, in addition, a residual proton-neutron interaction is included. Exact solutions in a SU(2) x SU(2) basis as well as the RPA solutions for the energy spectrum of the model Hamiltonian are obtained. Then, the behaviour of the first collective excited state is studied as a function of the interaction parameters of the model using the exact and RPA methods. Secondly, an extended LMG model for testing pnRPA method is developed. Besides the proton and neutron single particle terms two types of residual proton-neutron interactions, one simulating a particle-particle and the other a particle-hole interaction, are included in the model Hamiltonian, so that the model is exactly solvable in an isospin SU(2) x SU(2) basis. The exact and pnRPA spectra of the model Hamiltonian are calculated as a function of the model parameters and compared to each other. Furthermore, charge-changing operators simulating a nuclear beta decay and their action on eigenfunctions of the model Hamiltonian are defined, and transition amplitude of them are calculated using exact and pnRPA wave functions. The best agreement between the exact RPA-type calculations for spectra and transitions, was obtained when the correlated RPA ground state, instead of the uncorrelated HF ground state was employed and when both kinds of residual interactions (i.e. like- and unlike-particle two-body interactions) are included in the model Hamiltonians. (author)

  10. Molecular Dynamic Modeling and Simulation for Polymers

    National Research Council Canada - National Science Library

    Harrell, Anthony

    2003-01-01

    ... the mechanical properties of polymers. In particular, the goal was to develop insights as to how a molecular level structure is connected to the bulk properties of materials assuming homogeneity...

  11. Viscoelasticity in Polymers: Phenomenological to Molecular Mathematical Modelling

    National Research Council Canada - National Science Library

    Banks, H. T; Luke, N. S

    2006-01-01

    We report on two recent advances in the modelling of viscoelastic polymers: (i) a new constitutive model which combines the virtual stick-slip continuum "molecular-based" ideas of Johnson and Stacer with the Rouse bead chain ideas; (ii...

  12. Modeling Complex Workflow in Molecular Diagnostics

    Science.gov (United States)

    Gomah, Mohamed E.; Turley, James P.; Lu, Huimin; Jones, Dan

    2010-01-01

    One of the hurdles to achieving personalized medicine has been implementing the laboratory processes for performing and reporting complex molecular tests. The rapidly changing test rosters and complex analysis platforms in molecular diagnostics have meant that many clinical laboratories still use labor-intensive manual processing and testing without the level of automation seen in high-volume chemistry and hematology testing. We provide here a discussion of design requirements and the results of implementation of a suite of lab management tools that incorporate the many elements required for use of molecular diagnostics in personalized medicine, particularly in cancer. These applications provide the functionality required for sample accessioning and tracking, material generation, and testing that are particular to the evolving needs of individualized molecular diagnostics. On implementation, the applications described here resulted in improvements in the turn-around time for reporting of more complex molecular test sets, and significant changes in the workflow. Therefore, careful mapping of workflow can permit design of software applications that simplify even the complex demands of specialized molecular testing. By incorporating design features for order review, software tools can permit a more personalized approach to sample handling and test selection without compromising efficiency. PMID:20007844

  13. Modelling and experimental characterisation of a residual stress field in a ferritic compact tension specimen

    International Nuclear Information System (INIS)

    Wenman, M.R.; Price, A.J.; Steuwer, A.; Chard-Tuckey, P.R.; Crocombe, A.

    2009-01-01

    The aim of the work is to elucidate the influence of plasticity behaviour on the residual stress field in a ferritic reactor pressure vessel steel. To this end, we investigate two compressively pre-loaded compact tension (CT) specimens to generate a mechanical residual stress field. One specimen was subsequently pre-cracked by fatigue before both specimens were measured using high-energy synchrotron X-ray diffraction. A fine grain size microstructure (∼5-10 μm grain size) allowed a small X-ray beam slit size and therefore gauge volume. The results provide an excellent data set for validation of finite element (FE) modelling predictions against which they have been compared. The results of both mechanical testing and modelling suggest that the use of a combined hardening model is needed to accurately predict the residual stress field present in the specimen after pre-loading. Some discrepancy between the modelled crack tip stress values and those found by X-ray diffraction remain which can be partly explained by volume averaging effects in the presence of very high stress/strain gradients.

  14. Modeling Emissions and Vertical Plume Transport of Crop Residue Burning Experiments in the Pacific Northwest

    Science.gov (United States)

    Zhou, L.; Baker, K. R.; Napelenok, S. L.; Pouliot, G.; Elleman, R. A.; ONeill, S. M.; Urbanski, S. P.; Wong, D. C.

    2017-12-01

    Crop residue burning has long been a common practice in agriculture with the smoke emissions from the burning linked to negative health impacts. A field study in eastern Washington and northern Idaho in August 2013 consisted of multiple burns of well characterized fuels with nearby surface and aerial measurements including trace species concentrations, plume rise height and boundary layer structure. The chemical transport model CMAQ (Community Multiscale Air Quality Model) was used to assess the fire emissions and subsequent vertical plume transport. The study first compared assumptions made by the 2014 National Emission Inventory approach for crop residue burning with the fuel and emissions information obtained from the field study and then investigated the sensitivity of modeled carbon monoxide (CO) and PM2.5 concentrations to these different emission estimates and plume rise treatment with CMAQ. The study suggests that improvements to the current parameterizations are needed in order for CMAQ to reliably reproduce smoke plumes from burning. In addition, there is enough variability in the smoke emissions, stemming from variable field-specific information such as field size, that attempts to model crop residue burning should use field-specific information whenever possible.

  15. Modelling and experimental characterisation of a residual stress field in a ferritic compact tension specimen

    Energy Technology Data Exchange (ETDEWEB)

    Wenman, M.R., E-mail: m.wenman@imperial.ac.u [Department of Materials, Imperial College London, London SW7 2AZ (United Kingdom); Price, A.J. [Faculty of Engineering and Physical Sciences (J5), University of Surrey, Guildford GU2 7XH (United Kingdom); Steuwer, A. [ESS Scandinavia, Stora Algatan 4, 22350 Lund (Sweden) and Nelson Mandela Metropolitan University, Port Elizabeth 6031 (South Africa); Chard-Tuckey, P.R. [Nuclear Department, Defence College of Management and Technology, HMS Sultan, Gosport, Hants PO12 3BY (United Kingdom); Crocombe, A. [Faculty of Engineering and Physical Sciences (J5), University of Surrey, Guildford GU2 7XH (United Kingdom)

    2009-12-15

    The aim of the work is to elucidate the influence of plasticity behaviour on the residual stress field in a ferritic reactor pressure vessel steel. To this end, we investigate two compressively pre-loaded compact tension (CT) specimens to generate a mechanical residual stress field. One specimen was subsequently pre-cracked by fatigue before both specimens were measured using high-energy synchrotron X-ray diffraction. A fine grain size microstructure (approx5-10 mum grain size) allowed a small X-ray beam slit size and therefore gauge volume. The results provide an excellent data set for validation of finite element (FE) modelling predictions against which they have been compared. The results of both mechanical testing and modelling suggest that the use of a combined hardening model is needed to accurately predict the residual stress field present in the specimen after pre-loading. Some discrepancy between the modelled crack tip stress values and those found by X-ray diffraction remain which can be partly explained by volume averaging effects in the presence of very high stress/strain gradients.

  16. Characterization of Flame Cut Heavy Steel: Modeling of Temperature History and Residual Stress Formation

    Science.gov (United States)

    Jokiaho, T.; Laitinen, A.; Santa-aho, S.; Isakov, M.; Peura, P.; Saarinen, T.; Lehtovaara, A.; Vippola, M.

    2017-12-01

    Heavy steel plates are used in demanding applications that require both high strength and hardness. An important step in the production of such components is cutting the plates with a cost-effective thermal cutting method such as flame cutting. Flame cutting is performed with a controlled flame and oxygen jet, which burns the steel and forms a cutting edge. However, the thermal cutting of heavy steel plates causes several problems. A heat-affected zone (HAZ) is generated at the cut edge due to the steep temperature gradient. Consequently, volume changes, hardness variations, and microstructural changes occur in the HAZ. In addition, residual stresses are formed at the cut edge during the process. In the worst case, unsuitable flame cutting practices generate cracks at the cut edge. The flame cutting of thick steel plate was modeled using the commercial finite element software ABAQUS. The results of modeling were verified by X-ray diffraction-based residual stress measurements and microstructural analysis. The model provides several outcomes, such as obtaining more information related to the formation of residual stresses and the temperature history during the flame cutting process. In addition, an extensive series of flame cut samples was designed with the assistance of the model.

  17. Electrostatics of cysteine residues in proteins: Parameterization and validation of a simple model

    Science.gov (United States)

    Salsbury, Freddie R.; Poole, Leslie B.; Fetrow, Jacquelyn S.

    2013-01-01

    One of the most popular and simple models for the calculation of pKas from a protein structure is the semi-macroscopic electrostatic model MEAD. This model requires empirical parameters for each residue to calculate pKas. Analysis of current, widely used empirical parameters for cysteine residues showed that they did not reproduce expected cysteine pKas; thus, we set out to identify parameters consistent with the CHARMM27 force field that capture both the behavior of typical cysteines in proteins and the behavior of cysteines which have perturbed pKas. The new parameters were validated in three ways: (1) calculation across a large set of typical cysteines in proteins (where the calculations are expected to reproduce expected ensemble behavior); (2) calculation across a set of perturbed cysteines in proteins (where the calculations are expected to reproduce the shifted ensemble behavior); and (3) comparison to experimentally determined pKa values (where the calculation should reproduce the pKa within experimental error). Both the general behavior of cysteines in proteins and the perturbed pKa in some proteins can be predicted reasonably well using the newly determined empirical parameters within the MEAD model for protein electrostatics. This study provides the first general analysis of the electrostatics of cysteines in proteins, with specific attention paid to capturing both the behavior of typical cysteines in a protein and the behavior of cysteines whose pKa should be shifted, and validation of force field parameters for cysteine residues. PMID:22777874

  18. Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

    Directory of Open Access Journals (Sweden)

    Persson Bengt

    2010-10-01

    Full Text Available Abstract Background We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R and its ligand the tuberoinfundibular peptide of 39 residues (TIP39 by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH and parathyroid hormone related protein (PTHrP are compared with the complex to examine their interactions. Findings In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation. Conclusions A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.

  19. Hanford Tank 241-C-106: Residual Waste Contaminant Release Model and Supporting Data

    International Nuclear Information System (INIS)

    Deutsch, William J.; Krupka, Kenneth M.; Lindberg, Michael J.; Cantrell, Kirk J.; Brown, Christopher F.; Schaef, Herbert T.

    2005-01-01

    CH2M HILL is producing risk/performance assessments to support the closure of single-shell tanks at the DOE's Hanford Site. As part of this effort, staff at PNNL were asked to develop release models for contaminants of concern that are present in residual sludge remaining in tank 241-C-106 (C-106) after final retrieval of waste from the tank. This report provides the information developed by PNNL

  20. Using a consensus approach based on the conservation of inter-residue contacts to rank CAPRI models

    KAUST Repository

    Vangone, Anna; Cavallo, Luigi; Oliva, Romina M.

    2013-01-01

    Herein we propose the use of a consensus approach, CONSRANK, for ranking CAPRI models. CONSRANK relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. Models are ranked according to their ability to match the most

  1. A study of the influence of charged residues on β-hairpin formation by nuclear magnetic resonance and molecular dynamics.

    Science.gov (United States)

    Makowska, Joanna; Zmudzińska, Wioletta; Uber, Dorota; Chmurzyński, Lech

    2014-12-01

    Chain reversals are often nucleation sites in protein folding. The β-hairpins of FBP28 WW domain and IgG are stable and have been proved to initiate the folding and are, therefore, suitable for studying the influence of charged residues on β-hairpin conformation. In this paper, we carried out NMR examination of the conformations in solution of two fragments from the FPB28 protein (PDB code: 1E0L) (N-terminal part) namely KTADGKT-NH2 (1E0L 12-18, D7) and YKTADGKTY-NH2 (1E0L 11-19, D9), one from the B3 domain of the protein G (PDB code: 1IGD), namely DDATKT-NH2 (1IGD 51-56) (Dag1), and three variants of Dag1 peptide: DVATKT-NH2 (Dag2), OVATKT-NH2 (Dag3) and KVATKT-NH2 (Dag4), respectively, in which the original charged residue were replaced with non-polar residues or modified charged residues. It was found that both the D7 and D9 peptides form a large fraction bent conformations. However, no hydrophobic contacts between the terminal Tyr residues of D9 occur, which suggests that the presence of a pair of like-charged residues stabilizes chain reversal. Conversely, only the Dag1 and Dag2 peptides exhibit some chain reversal; replacing the second aspartic-acid residue with a valine and the first one with a basic residue results in a nearly extended conformation. These results suggest that basic residues farther away in sequence can result in stabilization of chain reversal owing to screening of the non-polar core. Conversely, smaller distance in sequence prohibits this screening, while the presence oppositely-charged residues can stabilize a turn because of salt-bridge formation.

  2. Calibration and validation of models for short-term decomposition and N mineralization of plant residues in the tropics

    Directory of Open Access Journals (Sweden)

    Alexandre Ferreira do Nascimento

    2012-12-01

    Full Text Available Insight of nutrient release patterns associated with the decomposition of plant residues is important for their effective use as a green manure in food production systems. Thus, this study aimed to evaluate the ability of the Century, APSIM and NDICEA simulation models for predicting the decomposition and N mineralization of crop residues in the tropical Atlantic forest biome, Brazil. The simulation models were calibrated based on actual decomposition and N mineralization rates of three types of crop residues with different chemical and biochemical composition. The models were also validated for different pedo-climatic conditions and crop residues conditions. In general, the accuracy of decomposition and N mineralization improved after calibration. Overall RMSE values for the decomposition and N mineralization of the crop materials varied from 7.4 to 64.6% before models calibration compared to 3.7 to 16.3 % after calibration. Therefore, adequate calibration of the models is indispensable for use them under humid tropical conditions. The NDICEA model generally outperformed the other models. However, the decomposition and N mineralization was not very accurate during the first 30 days of incubation, especially for easily decomposable crop residues. An additional model variable may be required to capture initial microbiological growth as affected by the moisture dynamics of the residues, as is the case in surface residues decomposition models.

  3. Nonlinear Model of Pseudoelastic Shape Memory Alloy Damper Considering Residual Martensite Strain Effect

    Directory of Open Access Journals (Sweden)

    Y. M. Parulekar

    2012-01-01

    Full Text Available Recently, there has been increasing interest in using superelastic shape memory alloys for applications in seismic resistant-design. Shape memory alloys (SMAs have a unique property by which they can recover their original shape after experiencing large strains up to 8% either by heating (shape memory effect or removing stress (pseudoelastic effect. Many simplified shape memory alloy models are suggested in the past literature for capturing the pseudoelastic response of SMAs in passive vibration control of structures. Most of these models do not consider the cyclic effects of SMA's and resulting residual martensite deformation. Therefore, a suitable constitutive model of shape memory alloy damper which represents the nonlinear hysterical dynamic system appropriately is essential. In this paper a multilinear hysteretic model incorporating residual martensite strain effect of pseudoelastic shape memory alloy damper is developed and experimentally validated using SMA wire, based damper device. A sensitivity analysis is done using the proposed model along with three other simplified SMA models. The models are implemented on a steel frame representing an SDOF system and the comparison of seismic response of structure with all the models is made in the numerical study.

  4. Computation of a Reference Model for Robust Fault Detection and Isolation Residual Generation

    Directory of Open Access Journals (Sweden)

    Emmanuel Mazars

    2008-01-01

    Full Text Available This paper considers matrix inequality procedures to address the robust fault detection and isolation (FDI problem for linear time-invariant systems subject to disturbances, faults, and polytopic or norm-bounded uncertainties. We propose a design procedure for an FDI filter that aims to minimize a weighted combination of the sensitivity of the residual signal to disturbances and modeling errors, and the deviation of the faults to residual dynamics from a fault to residual reference model, using the ℋ∞-norm as a measure. A key step in our procedure is the design of an optimal fault reference model. We show that the optimal design requires the solution of a quadratic matrix inequality (QMI optimization problem. Since the solution of the optimal problem is intractable, we propose a linearization technique to derive a numerically tractable suboptimal design procedure that requires the solution of a linear matrix inequality (LMI optimization. A jet engine example is employed to demonstrate the effectiveness of the proposed approach.

  5. Residual stress distribution analysis of heat treated APS TBC using image based modelling.

    Science.gov (United States)

    Li, Chun; Zhang, Xun; Chen, Ying; Carr, James; Jacques, Simon; Behnsen, Julia; di Michiel, Marco; Xiao, Ping; Cernik, Robert

    2017-08-01

    We carried out a residual stress distribution analysis in a APS TBC throughout the depth of the coatings. The samples were heat treated at 1150 °C for 190 h and the data analysis used image based modelling based on the real 3D images measured by Computed Tomography (CT). The stress distribution in several 2D slices from the 3D model is included in this paper as well as the stress distribution along several paths shown on the slices. Our analysis can explain the occurrence of the "jump" features near the interface between the top coat and the bond coat. These features in the residual stress distribution trend were measured (as a function of depth) by high-energy synchrotron XRD (as shown in our related research article entitled 'Understanding the Residual Stress Distribution through the Thickness of Atmosphere Plasma Sprayed (APS) Thermal Barrier Coatings (TBCs) by high energy Synchrotron XRD; Digital Image Correlation (DIC) and Image Based Modelling') (Li et al., 2017) [1].

  6. On Atomistic Models for Molecular Oxygen

    DEFF Research Database (Denmark)

    Javanainen, Matti; Vattulainen, Ilpo; Monticelli, Luca

    2017-01-01

    Molecular oxygen (O2) is key to all life on earth, as it is constantly cycled via photosynthesis and cellular respiration. Substantial scientific effort has been devoted to understanding every part of this cycle. Classical molecular dynamics (MD) simulations have been used to study some of the key...... processes involved in cellular respiration: O2 permeation through alveolar monolayers and cellular membranes, its binding to hemoglobin during transport in the bloodstream, as well as its transport along optimal pathways toward its reduction sites in proteins. Moreover, MD simulations can help interpret...

  7. The VSEPR model of molecular geometry

    CERN Document Server

    Gillespie, Ronald J

    2012-01-01

    Valence Shell Electron Pair Repulsion (VSEPR) theory is a simple technique for predicting the geometry of atomic centers in small molecules and molecular ions. This authoritative reference was written by Istvan Hartiggai and the developer of VSEPR theory, Ronald J. Gillespie. In addition to its value as a text for courses in molecular geometry and chemistry, it constitutes a classic reference for professionals.Starting with coverage of the broader aspects of VSEPR, this volume narrows its focus to a succinct survey of the methods of structural determination. Additional topics include the appli

  8. Improving probabilistic prediction of daily streamflow by identifying Pareto optimal approaches for modeling heteroscedastic residual errors

    Science.gov (United States)

    McInerney, David; Thyer, Mark; Kavetski, Dmitri; Lerat, Julien; Kuczera, George

    2017-03-01

    Reliable and precise probabilistic prediction of daily catchment-scale streamflow requires statistical characterization of residual errors of hydrological models. This study focuses on approaches for representing error heteroscedasticity with respect to simulated streamflow, i.e., the pattern of larger errors in higher streamflow predictions. We evaluate eight common residual error schemes, including standard and weighted least squares, the Box-Cox transformation (with fixed and calibrated power parameter λ) and the log-sinh transformation. Case studies include 17 perennial and 6 ephemeral catchments in Australia and the United States, and two lumped hydrological models. Performance is quantified using predictive reliability, precision, and volumetric bias metrics. We find the choice of heteroscedastic error modeling approach significantly impacts on predictive performance, though no single scheme simultaneously optimizes all performance metrics. The set of Pareto optimal schemes, reflecting performance trade-offs, comprises Box-Cox schemes with λ of 0.2 and 0.5, and the log scheme (λ = 0, perennial catchments only). These schemes significantly outperform even the average-performing remaining schemes (e.g., across ephemeral catchments, median precision tightens from 105% to 40% of observed streamflow, and median biases decrease from 25% to 4%). Theoretical interpretations of empirical results highlight the importance of capturing the skew/kurtosis of raw residuals and reproducing zero flows. Paradoxically, calibration of λ is often counterproductive: in perennial catchments, it tends to overfit low flows at the expense of abysmal precision in high flows. The log-sinh transformation is dominated by the simpler Pareto optimal schemes listed above. Recommendations for researchers and practitioners seeking robust residual error schemes for practical work are provided.

  9. A coupled creep plasticity model for residual stress relaxation of a shot-peened nickel-based superalloy

    Science.gov (United States)

    Buchanan, Dennis J.; John, Reji; Brockman, Robert A.; Rosenberger, Andrew H.

    2010-01-01

    Shot peening is a commonly used surface treatment process that imparts compressive residual stresses into the surface of metal components. Compressive residual stresses retard initiation and growth of fatigue cracks. During component loading history, shot-peened residual stresses may change due to thermal exposure, creep, and cyclic loading. In these instances, taking full credit for compressive residual stresses would result in a nonconservative life prediction. This article describes a methodical approach for characterizing and modeling residual stress relaxation under elevated temperature loading, near and above the monotonic yield strength of INI 00. The model incorporates the dominant creep deformation mechanism, coupling between the creep and plasticity models, and effects of prior plastic strain to simulate surface treatment deformation.

  10. A Simplified Model for the Effect of Weld-Induced Residual Stresses on the Axial Ultimate Strength of Stiffened Plates

    Science.gov (United States)

    Chen, Bai-Qiao; Guedes Soares, C.

    2018-03-01

    The present work investigates the compressive axial ultimate strength of fillet-welded steel-plated ship structures subjected to uniaxial compression, in which the residual stresses in the welded plates are calculated by a thermo-elasto-plastic finite element analysis that is used to fit an idealized model of residual stress distribution. The numerical results of ultimate strength based on the simplified model of residual stress show good agreement with those of various methods including the International Association of Classification Societies (IACS) Common Structural Rules (CSR), leading to the conclusion that the simplified model can be effectively used to represent the distribution of residual stresses in steel-plated structures in a wide range of engineering applications. It is concluded that the widths of the tension zones in the welded plates have a quasi-linear behavior with respect to the plate slenderness. The effect of residual stress on the axial strength of the stiffened plate is analyzed and discussed.

  11. Modeling of residual stress mitigation in austenitic stainless steel pipe girth weldment

    International Nuclear Information System (INIS)

    Li, M.; Atteridge, D.G.; Anderson, W.E.; West, S.L.

    1994-01-01

    This study provides numerical procedures to model 40-cm-diameter, schedule 40, Type 304L stainless steel pipe girth welding and a newly proposed post-weld treatment. The treatment can be used to accomplish the goal of imparting compressive residual stresses at the inner surface of a pipe girth weldment to prevent/retard the intergranular stress corrosion cracking (IGSCC) of the piping system in nuclear reactors. This new post-weld treatment for mitigating residual stresses is cooling stress improvement (CSI). The concept of CSI is to establish and maintain a certain temperature gradient across the pipe wall thickness to change the final stress state. Thus, this process involves sub-zero low temperature cooling of the inner pipe surface of a completed girth weldment, while simultaneously keeping the outer pipe surface at a slightly elevated temperature with the help of a certain heating method. Analyses to obtain quantitative results on pipe girth welding and CSI by using a thermo-elastic-plastic finite element model are described in this paper. Results demonstrate the potential effectiveness of CSI for introducing compressive residual stresses to prevent/retard IGSCC. Because of the symmetric nature of CSI, it shows great potential for industrial application

  12. Modeling and experimental study of residual stresses in NOREM hardfacing coatings used in valve parts

    International Nuclear Information System (INIS)

    Beaurin, G.

    2012-01-01

    Hardfacing coatings are widely used on the surfaces of parts subjected to drastic loadings. Norem02 alloy, Fe-based, is used in PWR nuclear power plants on valves seating surfaces. Its microstructure consists of a dendritic austenite structure with ferrite islets and carbides. This work tends to demonstrate that for this alloy, metallurgical evolution during the welding process has very little influence on mechanical properties. Tensile behavior was characterized and completed by dilatometry tests in welding process temperature range until 1000 Celsius degrees, in order to identify an elastoplastic model with non linear kinematic hardening rule. Temperature, displacements, distortions and residual stresses were measured during the PTAW (Plasma Transferred Arc Welding) process and used to identify an equivalent thermal loading by solving an inverse problem. Finally, the numerical simulation of the whole process using the EDF FEM software Code-Aster is presented. Predicted temperatures are consistent with experimental ones. In the same way, predicted displacements, residual distortions and residual stresses at the end of the cooling phase are close to experimental measures, validating the modeling strategy presented in this work. (author)

  13. Residual Stresses in DC cast Aluminum Billet: Neutron Diffraction Measurements and Thermomechanical Modeling

    International Nuclear Information System (INIS)

    Drezet, J.-M.; Evans, A.; Pirling, T.

    2011-01-01

    Thermally-induced residual stresses, generated during the industrial Direct Chill casting process of aluminum alloys, can cause both significant safety concerns as well as the formation of defects during down-stream processing. Although these thermally induced strains can be partially relieved by permanent deformation, cracks will be generated either during solidification (hot tears) or post-solidification cooling (cold cracks) when stresses exceed the deformation limit of the alloy. Furthermore, the thermally induced strains result in the presence of large internal stresses within the billet before further processing steps. Although numerical models have been previously developed to compute these residual stresses, most of the computations have been validated only against measured surface distortions. In the present work, the variation in residual elastic strains and stresses in the steady state regime of casting has been measured as a function of radial position using neutron diffraction in an AA6063 grain-refined cylindrical billet. These measurements have been carried out on the same billet section at Poldi at PSI-Villigen and at Salsa at ILL-Grenoble and compare favorably. The results are used to validate a thermo-mechanical finite element casting model and to assess the level of stored elastic energy within the billet.

  14. Measurement and modeling of residual stress in a welded Haynes[reg] 25 cylinder

    International Nuclear Information System (INIS)

    Larsson, C.; Holden, T.M.; Bourke, M.A.M.; Stout, M.; Teague, J.; Lindgren, L.-E.

    2005-01-01

    An experimental and simulation study of residual stresses was made in the vicinity of a gas tungsten arc weld, used to join a hemispherical end cap to a cylinder. The capped cylinder is used in a satellite application and was fabricated from a Co-based Haynes[reg] 25 alloy. The cylinder was 34.7 mm in outer diameter and 3.3 mm in thickness. The experimental measurements were made by neutron diffraction and the simulation used the implicit Marc finite element code. The experimental resolution was limited to approximately 3 mm parallel to the axis of the cylinder (the weld was 6 mm in the same direction) and comparison over the same volume of the finite element prediction showed general agreement. Subject to the limited spatial resolution, the largest experimentally measured tensile residual stress was 180 MPa, located at the middle of the weld. However, the predictions suggest that there are regions in the weld where average tensile residual stresses as much as 400 MPa exist. One qualitative disparity between the model and the experiments was that the measurement included a larger degree of asymmetry on either side of the weld than predicted by the model

  15. Measurement and modeling of residual stress in a welded Haynes[reg] 25 cylinder

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, C. [Div. of Eng. Mat., Department of Mech. Eng., Linkoeping University, 58183 Linkoeping (Sweden)]. E-mail: clarsson@cfl.rr.com; Holden, T.M. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Bourke, M.A.M. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Stout, M. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Teague, J. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Lindgren, L.-E. [Div. Comp. Aided Design, Lulea University of Technology and Dalarna University, 97187 Lulea (Sweden)

    2005-06-15

    An experimental and simulation study of residual stresses was made in the vicinity of a gas tungsten arc weld, used to join a hemispherical end cap to a cylinder. The capped cylinder is used in a satellite application and was fabricated from a Co-based Haynes[reg] 25 alloy. The cylinder was 34.7 mm in outer diameter and 3.3 mm in thickness. The experimental measurements were made by neutron diffraction and the simulation used the implicit Marc finite element code. The experimental resolution was limited to approximately 3 mm parallel to the axis of the cylinder (the weld was 6 mm in the same direction) and comparison over the same volume of the finite element prediction showed general agreement. Subject to the limited spatial resolution, the largest experimentally measured tensile residual stress was 180 MPa, located at the middle of the weld. However, the predictions suggest that there are regions in the weld where average tensile residual stresses as much as 400 MPa exist. One qualitative disparity between the model and the experiments was that the measurement included a larger degree of asymmetry on either side of the weld than predicted by the model.

  16. GOODNESS-OF-FIT TEST FOR THE ACCELERATED FAILURE TIME MODEL BASED ON MARTINGALE RESIDUALS

    Czech Academy of Sciences Publication Activity Database

    Novák, Petr

    2013-01-01

    Roč. 49, č. 1 (2013), s. 40-59 ISSN 0023-5954 R&D Projects: GA MŠk(CZ) 1M06047 Grant - others:GA MŠk(CZ) SVV 261315/2011 Keywords : accelerated failure time model * survival analysis * goodness-of-fit Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.563, year: 2013 http://library.utia.cas.cz/separaty/2013/SI/novak-goodness-of-fit test for the aft model based on martingale residuals.pdf

  17. Light Path Model of Fiber Optic Liquid Level Sensor Considering Residual Liquid Film on the Wall

    Directory of Open Access Journals (Sweden)

    Zhijun Zhang

    2015-01-01

    Full Text Available The working principle of the refractive-type fiber optic liquid level sensor is analyzed in detail based on the light refraction principle. The optic path models are developed in consideration of common simplification and the residual liquid film on the glass tube wall. The calculating formulae for the model are derived, constraint conditions are obtained, influencing factors are discussed, and the scopes and skills of application are analyzed through instance simulations. The research results are useful in directing the correct usage of the fiber optic liquid level sensor, especially in special cases, such as those involving viscous liquid in the glass tube monitoring.

  18. Computational Analysis of Residue Interaction Networks and Coevolutionary Relationships in the Hsp70 Chaperones: A Community-Hopping Model of Allosteric Regulation and Communication.

    Directory of Open Access Journals (Sweden)

    Gabrielle Stetz

    2017-01-01

    allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms.

  19. [Joint application of mathematic models in assessing the residual risk of hepatitis C virus transmitted through blood transfusion].

    Science.gov (United States)

    Wang, Xun; Jia, Yao; Xie, Yun-zheng; Li, Xiu-mei; Liu, Xiao-ying; Wu, Xiao-fei

    2011-09-01

    The practicable and effective methods for residual risk assessment on transfusion-transmitted disease was to establish the mathematic models. Based on the characteristics of the repeat donors which donated their blood on a regular base, a model of sero-conversion during the interval of donations was established to assess the incidence of the repeat donors. Based on the characteristics of the prevalence in the population, a model of 'prevalence increased with the age of the donor' was established to assess the incidence of those first-time donors. And based on the impact of the windows period through blood screening program, a model of residual risk associated with the incidence and the length of the windows period was established to assess the residual risk of blood transfusion. In this paper, above said 3 kinds of mathematic models were jointly applied to assess the residual risk of hepatitis C virus (HCV) which was transmitted through blood transfusion in Shanghai, based on data from the routine blood collection and screening program. All the anti-HCV unqualified blood donations were confirmed before assessment. Results showed that the residual risk of HCV transmitted through blood transfusion during Jan. 1(st), 2007 to Dec. 31(st), 2008 in Shanghai was 1:101 000. Data showed that the results of residual risk assessment with mathematic models was valuable. The residual risk of transfusion-transmitted HCV in Shanghai was at a safe level, according to the results in this paper.

  20. Developing an Integrated Model Framework for the Assessment of Sustainable Agricultural Residue Removal Limits for Bioenergy Systems

    Energy Technology Data Exchange (ETDEWEB)

    David Muth, Jr.; Jared Abodeely; Richard Nelson; Douglas McCorkle; Joshua Koch; Kenneth Bryden

    2011-08-01

    Agricultural residues have significant potential as a feedstock for bioenergy production, but removing these residues can have negative impacts on soil health. Models and datasets that can support decisions about sustainable agricultural residue removal are available; however, no tools currently exist capable of simultaneously addressing all environmental factors that can limit availability of residue. The VE-Suite model integration framework has been used to couple a set of environmental process models to support agricultural residue removal decisions. The RUSLE2, WEPS, and Soil Conditioning Index models have been integrated. A disparate set of databases providing the soils, climate, and management practice data required to run these models have also been integrated. The integrated system has been demonstrated for two example cases. First, an assessment using high spatial fidelity crop yield data has been run for a single farm. This analysis shows the significant variance in sustainably accessible residue across a single farm and crop year. A second example is an aggregate assessment of agricultural residues available in the state of Iowa. This implementation of the integrated systems model demonstrates the capability to run a vast range of scenarios required to represent a large geographic region.

  1. Polynomic nonlinear dynamical systems - A residual sensitivity method for model reduction

    Science.gov (United States)

    Yurkovich, S.; Bugajski, D.; Sain, M.

    1985-01-01

    The motivation for using polynomic combinations of system states and inputs to model nonlinear dynamics systems is founded upon the classical theories of analysis and function representation. A feature of such representations is the need to make available all possible monomials in these variables, up to the degree specified, so as to provide for the description of widely varying functions within a broad class. For a particular application, however, certain monomials may be quite superfluous. This paper examines the possibility of removing monomials from the model in accordance with the level of sensitivity displayed by the residuals to their absence. Critical in these studies is the effect of system input excitation, and the effect of discarding monomial terms, upon the model parameter set. Therefore, model reduction is approached iteratively, with inputs redesigned at each iteration to ensure sufficient excitation of remaining monomials for parameter approximation. Examples are reported to illustrate the performance of such model reduction approaches.

  2. Molecular models of zinc phthalocyanines: semi-empirical molecular orbital computations and physicochemical properties studied by molecular mechanics simulations

    International Nuclear Information System (INIS)

    Gantchev, Tsvetan G.; van Lier, Johan E.; Hunting, Darel J.

    2005-01-01

    To build 3D-molecular models of Zinc-phthalocyanines (ZnPc) and to study their diverse chemical and photosensitization properties, we performed quantum mechanical molecular orbital (MO) semi-empirical (AM1) computations of the ground, excited singlet and triplet states as well as free radical (ionic) species. RHF and UHF (open shell) geometry optimizations led to near-perfect symmetrical ZnPc. Predicted ionization potentials (IP), electron affinities (EA) and lowest electronic transitions of ZnPc are in good agreement with the published experimental and theoretical data. The computation-derived D 4h /D 2h -symmetry 3D-structures of ground and excited states and free radicals of ZnPc, together with the frontier orbital energies and Mulliken electron population analysis enabled us to build robust molecular models. These models were used to predict important chemical-reactivity entities such as global electronegativity (χ), hardness (η) and local softness based on Fukui-functions analysis. Examples of molecular mechanics (MM) applications of the 3D-molecular models are presented as approaches to evaluate solvation free energy (ΔG 0 ) solv and to estimate ground- and excited- state oxidation/reduction potentials as well as intermolecular interactions and stability of ground and excited state dimers (exciplexes) and radical ion-pairs

  3. Roles of the β 146 histidyl residue in the molecular basis of the Bohr Effect of hemoglobin: A proton nuclear magnetic resonance study

    International Nuclear Information System (INIS)

    Busch, M.R.; Mace, J.E.; Ho, N.T.; Ho, Chien

    1991-01-01

    Assessment of the roles of the carboxyl-terminal β146 histidyl residues in the alkaline Bohr effect in human and normal adult hemoglobin by high-resolution proton nuclear magnetic resonance spectroscopy requires assignment of the resonances corresponding to these residues. By a careful spectroscopic study of human normal adult hemoglobin, enzymatically prepared des(His146β)-hemoglobin, and the mutant hemoglobins Cowtown (β146His → Leu) and York (β146His → Pro), the authors have resolved some of these conflicting results. By a close incremental variation of pH over a wide range in chloride-free 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer, a single resonance has been found to be consistently missing in the proton nuclear magnetic resonance spectra of these hemoglobin variants. The results indicate that the contribution of the β146 histidyl residues is 0.52 H + /hemoglobin tetramer at pH 7.6, markedly less than 0.8 H + /hemoglobin tetramer estimated by study of the mutant hemoglobin Cowtown (β146His → Leu) by Shih and Perutz. They have found that at least two histidyl residues in the carbonmonoxy form of this mutant have pK values that are perturbed, and they suggest that these pK differences may in part account for this discrepancy. The results show that the pK values of β146 histidyl residues in the carbonmonoxy form of hemoglobin are substantially affected by the presence of chloride and other anions in the solvent, and thus, the contribution of this amino acid residue to the alkaline Bohr effect can be shown to vary widely in magnitude, depending on the solvent composition. These results demonstrate that the detailed molecular mechanisms of the alkaline Bohr effect are not unique but are affected both by the hemoglobin structure and by the interactions with the solvent components in which the hemoglobin molecule resides

  4. Modeling the Influence of Diffusion-Controlled Reactions and Residual Termination and Deactivation on the Rate and Control of Bulk ATRP at High Conversions

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Rabea

    2015-04-01

    Full Text Available In high-conversion atom transfer radical polymerization (ATRP, all the reactions, such as radical termination, radical deactivation, dormant chain activation, monomer propagation, etc. could become diffusion controlled sooner or later, depending on relative diffusivities of the involved reacting species. These diffusion-controlled reactions directly affect the rate of polymerization and the control of polymer molecular weight. A model is developed to investigate the influence of diffusion-controlled reactions on the high conversion ATRP kinetics. Model simulation reveals that diffusion-controlled termination slightly increases the rate, but it is the diffusion-controlled deactivation that causes auto-acceleration in the rate (“gel effect” and loss of control. At high conversions, radical chains are “trapped” because of high molecular weight. However, radical centers can still migrate through (1 radical deactivation–activation cycles and (2 monomer propagation, which introduce “residual termination” reactions. It is found that the “residual termination” does not have much influence on the polymerization kinetics. The migration of radical centers through propagation can however facilitate catalytic deactivation of radicals, which improves the control of polymer molecular weight to some extent. Dormant chain activation and monomer propagation also become diffusion controlled and finally stop the polymerization when the system approaches its glass state.

  5. Electrostatics of cysteine residues in proteins: parameterization and validation of a simple model.

    Science.gov (United States)

    Salsbury, Freddie R; Poole, Leslie B; Fetrow, Jacquelyn S

    2012-11-01

    One of the most popular and simple models for the calculation of pK(a) s from a protein structure is the semi-macroscopic electrostatic model MEAD. This model requires empirical parameters for each residue to calculate pK(a) s. Analysis of current, widely used empirical parameters for cysteine residues showed that they did not reproduce expected cysteine pK(a) s; thus, we set out to identify parameters consistent with the CHARMM27 force field that capture both the behavior of typical cysteines in proteins and the behavior of cysteines which have perturbed pK(a) s. The new parameters were validated in three ways: (1) calculation across a large set of typical cysteines in proteins (where the calculations are expected to reproduce expected ensemble behavior); (2) calculation across a set of perturbed cysteines in proteins (where the calculations are expected to reproduce the shifted ensemble behavior); and (3) comparison to experimentally determined pK(a) values (where the calculation should reproduce the pK(a) within experimental error). Both the general behavior of cysteines in proteins and the perturbed pK(a) in some proteins can be predicted reasonably well using the newly determined empirical parameters within the MEAD model for protein electrostatics. This study provides the first general analysis of the electrostatics of cysteines in proteins, with specific attention paid to capturing both the behavior of typical cysteines in a protein and the behavior of cysteines whose pK(a) should be shifted, and validation of force field parameters for cysteine residues. Copyright © 2012 Wiley Periodicals, Inc.

  6. Molecular modelling of a chemodosimeter for the selective detection ...

    Indian Academy of Sciences (India)

    Wintec

    Molecular modelling of a chemodosimeter for the selective detection of. As(III) ion in water. † ... high levels of arsenic cause severe skin diseases in- cluding skin cancer ..... Special Attention to Groundwater in SE Asia (eds) D. Chakraborti, A ...

  7. Geochemical modeling of leaching from MSVI air-pollution-control residues

    DEFF Research Database (Denmark)

    Astrup, Thomas; Dijkstra, J.J.; Comans, R.N.J.

    2006-01-01

    This paper provides an improved understanding of the leaching behavior of waste incineration air-pollution-control (APC) residues in a long-term perspective. Leaching was investigated by a series of batch experiments reflecting leaching conditions after initial washout of highly soluble salts from...... residues. Leaching experiments were performed at a range of pH-values using carbonated and noncarbonated versions of two APC residues. The leaching data were evaluated by geochemical speciation modeling and discussed with respect to possible solubility control. The leaching of major elements as well...... of Al, Ba, Ca, Cr, Pb, S, Si, V, and Zn was found influenced by solubility control from Al2O3, Al(OH)3, Ba(S,Cr)O4 solid solutions, BaSO4, Ca6Al2(SO4)3(OH)12â26H2O, CaAl2Si4O12â2H2O, Ca-(OH)2, CaSiO3, CaSO4â2H2O, CaZn2(OH)6â2H2O, KAlSi2O6, PbCO3, PbCrO4, Pb2O3, Pb2V2O7, Pb3(VO4)2, ZnO, Zn2SiO4, and Zn...

  8. Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

    Directory of Open Access Journals (Sweden)

    Kones R

    2013-10-01

    Full Text Available Richard KonesCardiometabolic Research Institute, Houston, TX, USAAbstract: Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL cholesterol

  9. Constructing Molecular Models with Low-Cost Toy Beads

    Science.gov (United States)

    Ng, Pun-hon; Wong, Siu-ling; Mak, Se-yuen

    2012-01-01

    In teaching the science of the nano world, ball-and-stick molecular models are frequently used as 3D representations of molecules. Unlike a chemical formula, a molecular model allows us to visualise the 3D shape of the molecule and the relative positions of its atoms, the bonds between atoms and why a pair of mirror isomers with the same atoms,…

  10. Modelling of different enzyme productions by solid-state fermentation on several agro-industrial residues.

    Science.gov (United States)

    Diaz, Ana Belen; Blandino, Ana; Webb, Colin; Caro, Ildefonso

    2016-11-01

    A simple kinetic model, with only three fitting parameters, for several enzyme productions in Petri dishes by solid-state fermentation is proposed in this paper, which may be a valuable tool for simulation of this type of processes. Basically, the model is able to predict temporal fungal enzyme production by solid-state fermentation on complex substrates, maximum enzyme activity expected and time at which these maxima are reached. In this work, several fermentations in solid state were performed in Petri dishes, using four filamentous fungi grown on different agro-industrial residues, measuring xylanase, exo-polygalacturonase, cellulose and laccase activities over time. Regression coefficients after fitting experimental data to the proposed model turned out to be quite high in all cases. In fact, these results are very interesting considering, on the one hand, the simplicity of the model and, on the other hand, that enzyme activities correspond to different enzymes, produced by different fungi on different substrates.

  11. Solution to the spectral filter problem of residual terrain modelling (RTM)

    Science.gov (United States)

    Rexer, Moritz; Hirt, Christian; Bucha, Blažej; Holmes, Simon

    2018-06-01

    In physical geodesy, the residual terrain modelling (RTM) technique is frequently used for high-frequency gravity forward modelling. In the RTM technique, a detailed elevation model is high-pass-filtered in the topography domain, which is not equivalent to filtering in the gravity domain. This in-equivalence, denoted as spectral filter problem of the RTM technique, gives rise to two imperfections (errors). The first imperfection is unwanted low-frequency (LF) gravity signals, and the second imperfection is missing high-frequency (HF) signals in the forward-modelled RTM gravity signal. This paper presents new solutions to the RTM spectral filter problem. Our solutions are based on explicit modelling of the two imperfections via corrections. The HF correction is computed using spectral domain gravity forward modelling that delivers the HF gravity signal generated by the long-wavelength RTM reference topography. The LF correction is obtained from pre-computed global RTM gravity grids that are low-pass-filtered using surface or solid spherical harmonics. A numerical case study reveals maximum absolute signal strengths of ˜ 44 mGal (0.5 mGal RMS) for the HF correction and ˜ 33 mGal (0.6 mGal RMS) for the LF correction w.r.t. a degree-2160 reference topography within the data coverage of the SRTM topography model (56°S ≤ φ ≤ 60°N). Application of the LF and HF corrections to pre-computed global gravity models (here the GGMplus gravity maps) demonstrates the efficiency of the new corrections over topographically rugged terrain. Over Switzerland, consideration of the HF and LF corrections reduced the RMS of the residuals between GGMplus and ground-truth gravity from 4.41 to 3.27 mGal, which translates into ˜ 26% improvement. Over a second test area (Canada), our corrections reduced the RMS of the residuals between GGMplus and ground-truth gravity from 5.65 to 5.30 mGal (˜ 6% improvement). Particularly over Switzerland, geophysical signals (associated, e.g. with

  12. Modeling the residual effects and threshold saturation of training: a case study of Olympic swimmers

    Science.gov (United States)

    Hellard, Philippe; Avalos, Marta; Millet, Grégoire; Lacoste, Lucien; Barale, Frédéric; Chatard, Jean-Claude

    2005-01-01

    The aim of this study was to model the residual effects of training on the swimming performance and to compare a model including threshold saturation (MM) to the Banister model (BM). Seven Olympic swimmers were studied over a period of 4 ± 2 years. For three training loads (low-intensity wLIT, high-intensity wHIT and strength training wST), three residual training effects were determined: short-term (STE) during the taper phase, i.e. three weeks before the performance (weeks 0, −1, −2), intermediate-term (ITE) during the intensity phase (weeks −3, −4 and −5) and long-term (LTE) during the volume phase (weeks −6, −7, −8). ITE and LTE were positive for wHIT and wLIT, respectively (P < 0.05). wLIT during taper was related to performances by a parabolic relationship (P < 0.05). Different quality measures indicated that MM compares favorably with BM. Identifying individual training thresholds may help individualizing the distribution of training loads. PMID:15705048

  13. Molecular Models of Genetic and Organismic Structures

    CERN Document Server

    Baianu, I C

    2004-01-01

    In recent studies we showed that the earlier relational theories of organismic sets (Rashevsky,1967), Metabolic-Replication (M,R)-systems (Rosen,1958)and molecular sets (Bartholomay,1968) share a joint foundation that can be studied within a unified categorical framework of functional organismic structures (Baianu,1980. This is possible because all relational theories have a biomolecular basis, that is, complex structures such as genomes, cells,organs and biological organisms are mathematically represented in terms of biomolecular properties and entities,(that are often implicit in their representation axioms. The definition of organismic sets, for example, requires that certain essential quantities be determined from experiment: these are specified by special sets of values of general observables that are derived from physicochemical measurements(Baianu,1970; Baianu,1980; Baianu et al, 2004a.)Such observables are context-dependent and lead directly to natural transformations in categories and Topoi, that are...

  14. Diamond-like nanoparticles influence on flavonoids transport: molecular modelling

    Science.gov (United States)

    Plastun, Inna L.; Agandeeva, Ksenia E.; Bokarev, Andrey N.; Zenkin, Nikita S.

    2017-03-01

    Intermolecular interaction of diamond-like nanoparticles and flavonoids is investigated by numerical simulation. Using molecular modelling by the density functional theory method, we analyze hydrogen bonds formation and their influence on IR - spectra and structure of molecular complex which is formed due to interaction between flavonoids and nanodiamonds surrounded with carboxylic groups. Enriched adamantane (1,3,5,7 - adamantanetetracarboxylic acid) is used as an example of diamond-like nanoparticles. Intermolecular forces and structure of hydrogen bonds are investigated. IR - spectra and structure parameters of quercetin - adamantanetetracarboxylic acid molecular complex are obtained by numerical simulation using the Gaussian software complex. Received data coincide well with experimental results. Intermolecular interactions and hydrogen bonding structure in the obtained molecular complex are examined. Possibilities of flavonoids interaction with DNA at the molecular level are also considered.

  15. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

    Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

  16. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

    DEFF Research Database (Denmark)

    Salleh, M. S.; Mazzoni, G.; Höglund, J. K.

    2017-01-01

    -throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate...... genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency....... On average, 57 million reads (short reads or short mRNA sequences ...

  17. Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

    Science.gov (United States)

    Warnock, Rachel C M; Yang, Ziheng; Donoghue, Philip C J

    2017-06-28

    Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. © 2017 The Authors.

  18. Molecular Dynamics Simulations of Kinetic Models for Chiral Dominance in Soft Condensed Matter

    DEFF Research Database (Denmark)

    Toxvaerd, Søren

    2001-01-01

    Molecular dynamics simulation, models for isomerization kinetics, origin of biomolecular chirality......Molecular dynamics simulation, models for isomerization kinetics, origin of biomolecular chirality...

  19. Molecular Modeling of Myrosinase from Brassica oleracea: A Structural Investigation of Sinigrin Interaction

    Directory of Open Access Journals (Sweden)

    Sathishkumar Natarajan

    2015-12-01

    Full Text Available Myrosinase, which is present in cruciferous plant species, plays an important role in the hydrolysis of glycosides such as glucosinolates and is involved in plant defense. Brassicaceae myrosinases are diverse although they share common ancestry, and structural knowledge about myrosinases from cabbage (Brassica oleracea was needed. To address this, we constructed a three-dimensional model structure of myrosinase based on Sinapis alba structures using Iterative Threading ASSEmbly Refinement server (I-TASSER webserver, and refined model coordinates were evaluated with ProQ and Verify3D. The resulting model was predicted with β/α fold, ten conserved N-glycosylation sites, and three disulfide bridges. In addition, this model shared features with the known Sinapis alba myrosinase structure. To obtain a better understanding of myrosinase–sinigrin interaction, the refined model was docked using Autodock Vina with crucial key amino acids. The key nucleophile residues GLN207 and GLU427 were found to interact with sinigrin to form a hydrogen bond. Further, 20-ns molecular dynamics simulation was performed to examine myrosinase–sinigrin complex stability, revealing that residue GLU207 maintained its hydrogen bond stability throughout the entire simulation and structural orientation was similar to that of the docked state. This conceptual model should be useful for understanding the structural features of myrosinase and their binding orientation with sinigrin.

  20. Modeling the Influence of Process Parameters and Additional Heat Sources on Residual Stresses in Laser Cladding

    Science.gov (United States)

    Brückner, F.; Lepski, D.; Beyer, E.

    2007-09-01

    In laser cladding thermal contraction of the initially liquid coating during cooling causes residual stresses and possibly cracks. Preweld or postweld heating using inductors can reduce the thermal strain difference between coating and substrate and thus reduce the resulting stress. The aim of this work is to better understand the influence of various thermometallurgical and mechanical phenomena on stress evolution and to optimize the induction-assisted laser cladding process to get crack-free coatings of hard materials at high feed rates. First, an analytical one-dimensional model is used to visualize the most important features of stress evolution for a Stellite coating on a steel substrate. For more accurate studies, laser cladding is simulated including the powder-beam interaction, the powder catchment by the melt pool, and the self-consistent calculation of temperature field and bead shape. A three-dimensional finite element model and the required equivalent heat sources are derived from the results and used for the transient thermomechanical analysis, taking into account phase transformations and the elastic-plastic material behavior with strain hardening. Results are presented for the influence of process parameters such as feed rate, heat input, and inductor size on the residual stresses at a single bead of Stellite coatings on steel.

  1. Modeling of ultrafast THz interactions in molecular crystals

    DEFF Research Database (Denmark)

    Pedersen, Pernille Klarskov; Clark, Stewart J.; Jepsen, Peter Uhd

    2014-01-01

    In this paper we present a numerical study of terahertz pulses interacting with crystals of cesium iodide. We model the molecular dynamics of the cesium iodide crystals with the Density Functional Theory software CASTEP, where ultrafast terahertz pulses are implemented to the CASTEP software...... to interact with molecular crystals. We investigate the molecular dynamics of cesium iodide crystals when interacting with realistic terahertz pulses of field strengths from 0 to 50 MV/cm. We find nonlinearities in the response of the CsI crystals at field strengths higher than 10 MV/cm....

  2. ESTIMATION MODEL OF RESIDUAL LIFE-TIME OF LOCOMOTIVE FRAME BOGIE WITH ALLOWANCE FOR CREEP

    Directory of Open Access Journals (Sweden)

    V. R. Skalskyi

    2014-12-01

    Full Text Available Purpose. The problem of determining the residual life of frame bogie elements of locomotives is a great importance for predicting their work safely and avoidance potential failures on the track. This especially concern cases when such elements have creep-fatigue cracks which grow under action of cyclic loading with excerpts T1 in the cycle and reach their critical size. Here the question of the propagation of such defects (cracks arises, their kinetics and about the period of subcritical cracks growth. The aim is to develop a calculation model for determination the period of subcritical creep-fatigue cracks growth in the bogies frames of electric locomotive. The model takes into account the basic parameters of load, geometry of the construction element and cracks. Methodology. The calculation model for determination the period of subcritical creep-fatigue cracks growth in structural elements of frame under conditions of variable load time has been formulated. It is based on the first law of thermodynamics concerning to mechanics of solids slow fracture at low temperature creep and variable loadings. It is assumed that the period of unsteady creep dominates here (the first section of the creep curve. Low-temperature creep is creep of materials at temperatures T0 < 0,5Tmp, where Tmp − the melting point of the material. Findings. The analytical formula for the determination of the stress intensity factor of truck bolster with technological hole has been obtained. It is shown that by experimentally established constants of the material using the proposed analytical relations can easily determine residual resource of the bogie frame elements. Originality. The new mathematical model for describing the kinetics of creep-fatigue cracks growth in the frames bogies of electric locomotive under variable in time loadings with various time excerpts and on this base the period determination of subcritical crack growth has been proposed. Practical value

  3. Two-Dimensional Model of Scrolled Packings of Molecular Nanoribbons

    Science.gov (United States)

    Savin, A. V.; Mazo, M. A.

    2018-04-01

    A simplified model of the in-plane molecular chain, allowing the description of folded and scrolled packings of molecular nanoribbons of different structures, is proposed. Using this model, possible steady states of single-layer nanoribbons scrolls of graphene, graphane, fluorographene, and fluorographane (graphene hydrogenated on the one side and fluorinated on the other side) are obtained. Their stability is demonstrated and their energy is calculated as a function of the nanoribbon length. It is shown that the scrolled packing is the most energetically favorable nanoribbon conformation at long lengths. The existences of scrolled packings for fluorographene nanoribbons and the existence of two different scroll types corresponding to left- and right-hand Archimedean spirals for fluorographane nanoribbons in the chain model are shown for the first time. The simplicity of the proposed model makes it possible to consider the dynamics of scrolls of rather long molecular nanoribbons at long enough time intervals.

  4. Adjust of the residuals of the Arima model by means of the analysis of the residuals of the explanatory variables by means of the analysis of main components

    International Nuclear Information System (INIS)

    Bernal Suarez, Nestor Ricardo; Montealegre Bocanegra, Jose Edgar

    2000-01-01

    Based on the previous knowledge and understanding of the causality relationships between the fields of surface temperature of the Pacific and North and South tropical Atlantic oceans and rainfall behaviour in Colombia, we purport to model those relations with a (statistical) transfer model. This work is aimed at improving the adjustment of the model for the monthly mean rainfall registered in Funza (nearby the Capital Bogota). The residues of ARIMA models with six explanatory variables may contribute some percentage to the explanation of the total variability of rainfall as a consequence of their interrelationship. Such effect can be represented as a summary of the six variables, which can be achieved with principal components, taking into account that they are not mutually dependent, since they are white noise time series

  5. Molecular models for DNA damaged by photoreaction

    International Nuclear Information System (INIS)

    Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.H.; Kim, S.H.

    1985-01-01

    Structural models of a DNA molecule containing a radiation-induced psoralen cross-link and of a DNA containing a thymine photodimer were constructed by applying energy-minimization techniques and model-building procedures to data from x-ray crystallographic studies. The helical axes of the models show substantial kinking and unwinding at the sites of the damage, which may have long-range as well as local effects arising from the concomitant changes in the supercoiling and overall structure of the DNA. The damaged areas may also serve as recognition sites for repair enzymes. These results should help in understanding the biologic effects of radiation-induced damage on cells

  6. Computational models for residual creep life prediction of power plant components

    International Nuclear Information System (INIS)

    Grewal, G.S.; Singh, A.K.; Ramamoortry, M.

    2006-01-01

    All high temperature - high pressure power plant components are prone to irreversible visco-plastic deformation by the phenomenon of creep. The steady state creep response as well as the total creep life of a material is related to the operational component temperature through, respectively, the exponential and inverse exponential relationships. Minor increases in the component temperature can thus have serious consequences as far as the creep life and dimensional stability of a plant component are concerned. In high temperature steam tubing in power plants, one mechanism by which a significant temperature rise can occur is by the growth of a thermally insulating oxide film on its steam side surface. In the present paper, an elegantly simple and computationally efficient technique is presented for predicting the residual creep life of steel components subjected to continual steam side oxide film growth. Similarly, fabrication of high temperature power plant components involves extensive use of welding as the fabrication process of choice. Naturally, issues related to the creep life of weldments have to be seriously addressed for safe and continual operation of the welded plant component. Unfortunately, a typical weldment in an engineering structure is a zone of complex microstructural gradation comprising of a number of distinct sub-zones with distinct meso-scale and micro-scale morphology of the phases and (even) chemistry and its creep life prediction presents considerable challenges. The present paper presents a stochastic algorithm, which can be' used for developing experimental creep-cavitation intensity versus residual life correlations for welded structures. Apart from estimates of the residual life in a mean field sense, the model can be used for predicting the reliability of the plant component in a rigorous probabilistic setting. (author)

  7. Worst-case residual clipping noise power model for bit loading in LACO-OFDM

    KAUST Repository

    Zhang, Zhenyu

    2018-03-19

    Layered ACO-OFDM enjoys better spectral efficiency than ACO-OFDM, but its performance is challenged by residual clipping noise (RCN). In this paper, the power of RCN of LACO-OFDM is analyzed and modeled. As RCN is data-dependent, the worst-case situation is considered. A worst-case indicator is defined for relating the power of RCN and the power of noise at the receiver, wherein a linear relation is shown to be a practical approximation. An LACO-OFDM bit-loading experiment is performed to examine the proposed RCN power model for data rates of 6 to 7 Gbps. The experiment\\'s results show that accounting for RCN has two advantages. First, it leads to better bit loading and achieves up to 59% lower overall bit-error rate (BER) than when the RCN is ignored. Second, it balances the BER across layers, which is a desired property from a channel coding perspective.

  8. Worst-case residual clipping noise power model for bit loading in LACO-OFDM

    KAUST Repository

    Zhang, Zhenyu; Chaaban, Anas; Shen, Chao; Elgala, Hany; Ng, Tien Khee; Ooi, Boon S.; Alouini, Mohamed-Slim

    2018-01-01

    Layered ACO-OFDM enjoys better spectral efficiency than ACO-OFDM, but its performance is challenged by residual clipping noise (RCN). In this paper, the power of RCN of LACO-OFDM is analyzed and modeled. As RCN is data-dependent, the worst-case situation is considered. A worst-case indicator is defined for relating the power of RCN and the power of noise at the receiver, wherein a linear relation is shown to be a practical approximation. An LACO-OFDM bit-loading experiment is performed to examine the proposed RCN power model for data rates of 6 to 7 Gbps. The experiment's results show that accounting for RCN has two advantages. First, it leads to better bit loading and achieves up to 59% lower overall bit-error rate (BER) than when the RCN is ignored. Second, it balances the BER across layers, which is a desired property from a channel coding perspective.

  9. Neoclassical versus Frontier Production Models ? Testing for the Skewness of Regression Residuals

    DEFF Research Database (Denmark)

    Kuosmanen, T; Fosgerau, Mogens

    2009-01-01

    The empirical literature on production and cost functions is divided into two strands. The neoclassical approach concentrates on model parameters, while the frontier approach decomposes the disturbance term to a symmetric noise term and a positively skewed inefficiency term. We propose a theoreti......The empirical literature on production and cost functions is divided into two strands. The neoclassical approach concentrates on model parameters, while the frontier approach decomposes the disturbance term to a symmetric noise term and a positively skewed inefficiency term. We propose...... a theoretical justification for the skewness of the inefficiency term, arguing that this skewness is the key testable hypothesis of the frontier approach. We propose to test the regression residuals for skewness in order to distinguish the two competing approaches. Our test builds directly upon the asymmetry...

  10. Demonstration of a computer model for residual radioactive material guidelines, RESRAD

    International Nuclear Information System (INIS)

    Yu, C.; Yuan, Y.C.; Zielen, A.J.; Wallo, A. III

    1989-01-01

    A computer model was developed to calculate residual radioactive material guidelines for the US Department of Energy (DOE). This model, called RESRAD, can be run on IBM or IBM-compatible microcomputer. Seven potential exposure pathways from contaminated soil are analyzed, including external radiation exposure and internal radiation exposure from inhalation and food digestion. The RESRAD code has been applied to several DOE sites to derive soil cleanup guidelines. The experience gained indicates that a comprehensive set of site-specific hydrogeologic and geochemical input parameters must be used for a realistic pathway analysis. The RESRAD code is a useful tool; it is easy to run and very user-friendly. 6 refs., 12 figs

  11. Toluene model for molecular dynamics simulations in the ranges 298

    NARCIS (Netherlands)

    Fioroni, M.; Vogt, D.

    2004-01-01

    An all-atom model for toluene is presented in the framework of classical molecular dynamics (MD). The model has been parametrized under the GROMOS96 force field to reproduce the physicochemical properties of the neat liquid. Four new atom types have been introduced, distinguishing between carbons

  12. Thermodynamic Models from Fluctuation Solution Theory Analysis of Molecular Simulations

    DEFF Research Database (Denmark)

    Christensen, Steen; Peters, Günther H.j.; Hansen, Flemming Yssing

    2007-01-01

    Fluctuation solution theory (FST) is employed to analyze results of molecular dynamics (MD) simulations of liquid mixtures. The objective is to generate parameters for macroscopic GE-models, here the modified Margules model. We present a strategy for choosing the number of parameters included...

  13. Molecular modeling of nucleic Acid structure: electrostatics and solvation.

    Science.gov (United States)

    Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

    2014-12-19

    This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit. Copyright © 2014 John Wiley & Sons, Inc.

  14. Corn Storage Protein - A Molecular Genetic Model

    Energy Technology Data Exchange (ETDEWEB)

    Messing, Joachim [Rutgers Univ., Piscataway, NJ (United States)

    2013-05-31

    Corn is the highest yielding crop on earth and probably the most valuable agricultural product of the United States. Because it converts sun energy through photosynthesis into starch and proteins, we addressed energy savings by focusing on protein quality. People and animals require essential amino acids derived from the digestion of proteins. If proteins are relatively low in certain essential amino acids, the crop becomes nutritionally defective and has to be supplemented. Such deficiency affects meat and fish production and countries where corn is a staple. Because corn seed proteins have relatively low levels of lysine and methionine, a diet has to be supplemented with soybeans for the missing lysine and with chemically synthesized methionine. We therefore have studied genes expressed during maize seed development and their chromosomal organization. A critical technical requirement for the understanding of the molecular structure of genes and their positional information was DNA sequencing. Because of the length of sequences, DNA sequencing methods themselves were insufficient for this type of analysis. We therefore developed the so-called “DNA shotgun sequencing” strategy, where overlapping DNA fragments were sequenced in parallel and used to reconstruct large DNA molecules via overlaps. Our publications became the most frequently cited ones during the decade of 1981-1990 and former Associate Director of Science for the Office of Basic Energy Sciences Patricia M. Dehmer presented our work as one of the great successes of this program. A major component of the sequencing strategy was the development of bacterial strains and vectors, which were also used to develop the first biotechnology crops. These crops possessed new traits thanks to the expression of foreign genes in plants. To enable such expression, chimeric genes had to be constructed using our materials and methods by the industry. Because we made our materials and methods freely available to

  15. Molecular modeling: An open invitation for applied mathematics

    Science.gov (United States)

    Mezey, Paul G.

    2013-10-01

    Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

  16. Solution structure of tRNA{sup Val} from refinement of homology model against residual dipolar coupling and SAXS data

    Energy Technology Data Exchange (ETDEWEB)

    Grishaev, Alexander, E-mail: AlexanderG@intra.niddk.nih.gov; Ying, Jinfa [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Canny, Marella D.; Pardi, Arthur [University of Colorado, Boulder, Department of Chemistry and Biochemistry, 215 UCB (United States)], E-mail: Arthur.Pardi@Colorado.edu; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: bax@nih.gov

    2008-10-15

    A procedure is presented for refinement of a homology model of E. coli tRNA{sup Val}, originally based on the X-ray structure of yeast tRNA{sup Phe}, using experimental residual dipolar coupling (RDC) and small angle X-ray scattering (SAXS) data. A spherical sampling algorithm is described for refinement against SAXS data that does not require a globbic approximation, which is particularly important for nucleic acids where such approximations are less appropriate. Substantially higher speed of the algorithm also makes its application favorable for proteins. In addition to the SAXS data, the structure refinement employed a sparse set of NMR data consisting of 24 imino N-H{sup N} RDCs measured with Pf1 phage alignment, and 20 imino N-H{sup N} RDCs obtained from magnetic field dependent alignment of tRNA{sup Val}. The refinement strategy aims to largely retain the local geometry of the 58% identical tRNA{sup Phe} by ensuring that the atomic coordinates for short, overlapping segments of the ribose-phosphate backbone and the conserved base pairs remain close to those of the starting model. Local coordinate restraints are enforced using the non-crystallographic symmetry (NCS) term in the XPLOR-NIH or CNS software package, while still permitting modest movements of adjacent segments. The RDCs mainly drive the relative orientation of the helical arms, whereas the SAXS restraints ensure an overall molecular shape compatible with experimental scattering data. The resulting structure exhibits good cross-validation statistics (jack-knifed Q{sub free} = 14% for the Pf1 RDCs, compared to 25% for the starting model) and exhibits a larger angle between the two helical arms than observed in the X-ray structure of tRNA{sup Phe}, in agreement with previous NMR-based tRNA{sup Val} models.

  17. Identification of key amino acid residues in the hTGR5-nomilin interaction and construction of its binding model.

    Science.gov (United States)

    Sasaki, Takashi; Mita, Moeko; Ikari, Naho; Kuboyama, Ayane; Hashimoto, Shuzo; Kaneko, Tatsuya; Ishiguro, Masaji; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2017-01-01

    TGR5, a member of the G protein-coupled receptor (GPCR) family, is activated by bile acids. Because TGR5 promotes energy expenditure and improves glucose homeostasis, it is recognized as a key target in treating metabolic diseases. We previously showed that nomilin, a citrus limonoid, activates TGR5 and confers anti-obesity and anti-hyperglycemic effects in mice. Information on the TGR5-nomilin interaction regarding molecular structure, however, has not been reported. In the present study, we found that human TGR5 (hTGR5) shows higher nomilin responsiveness than does mouse TGR5 (mTGR5). Using mouse-human chimeric TGR5, we also found that three amino acid residues (Q77ECL1, R80ECL1, and Y893.29) are important in the hTGR5-nomilin interaction. Based on these results, an hTGR5-nomilin binding model was constructed using in silico docking simulation, demonstrating that four hydrophilic hydrogen-bonding interactions occur between nomilin and hTGR5. The binding mode of hTGR5-nomilin is vastly different from those of other TGR5 agonists previously reported, suggesting that TGR5 forms various binding patterns depending on the type of agonist. Our study promotes a better understanding of the structure of TGR5, and it may be useful in developing and screening new TGR5 agonists.

  18. Molecular modeling studies of 1,4-dihydro-4-oxoquinoline ribonucleosides with anti-HSV-1 activity

    Science.gov (United States)

    Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Seidl, Peter Rudolf; de Alencastro, Ricardo Bicca

    2011-12-01

    Eight human herpes viruses ( e.g., herpes simplex, varicella-zoster, Epstein-Barr, cytomegalovirus, Kaposi's sarcoma) are responsible for several diseases from sub-clinic manifestations to fatal infections, mostly in immunocompromised patients. The major limitations of the currently available antiviral drug therapy are drug resistance, host toxicity, and narrow spectrum of activity. However, some non-nucleoside 1,4-dihydro-4-oxoquinoline derivatives ( e.g., PNU-183792) [4] shows broad spectrum antiviral activity. We have developed molecular modeling studies, including molecular docking and molecular dynamics simulations, based on a model proposed by Liu and co-workers [14] in order to understand the mechanism of action of a 6-chloro substituted 1,4-dihydro-4-oxoquinoline ribonucleoside, synthesized by the synthetic group, which showed anti-HSV-1 activity [9]. The molecular docking simulations confirmed the Liu's model showing that the ligand needs to dislocate template residues from the active site in order to interact with the viral DNA polymerase enzyme, reinforcing that the interaction with the Val823 residue is pivotal for the inhibitory activity of non-nucleoside 1,4-dihydro-4-oxoquinoline derivatives, such as PNU-183792, with the HSV-1. The molecular dynamics simulations showed that the 6-chloro-benzyl group of PNU-183792 maintains its interaction with residues of the HSV-1 DNA polymerase hydrophobic pocket, considered important according to the Liu's model, and also showed that the methyl group bounded to the nitrogen atom from PNU-183792 is probably contributing to a push-pull effect with the carbonyl group.

  19. Structural Characterization and Antioxidative Activity of Low-Molecular-Weights Beta-1,3-Glucan from the Residue of Extracted Ganoderma lucidum Fruiting Bodies

    Directory of Open Access Journals (Sweden)

    Pai-Feng Kao

    2012-01-01

    Full Text Available The major cell wall constituent of Ganoderma lucidum (G. lucidum is β-1,3-glucan. This study examined the polysaccharide from the residues of alkaline-extracted fruiting bodies using high-performance anion-exchange chromatography (HPAEC, and it employed nuclear magnetic resonance (NMR and mass spectrometry (MS to confirm the structures. We have successfully isolated low-molecular-weight β-1,3-glucan (LMG, in high yields, from the waste residue of extracted fruiting bodies of G. lucidum. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay evaluated the capability of LMG to suppress H2O2-induced cell death in RAW264.7 cells, identifying that LMG protected cells from H2O2-induced damage. LMG treatment decreased H2O2-induced intracellular reactive oxygen species (ROS production. LMG also influenced sphingomyelinase (SMase activity, stimulated by cell death to induce ceramide formation, and then increase cell ROS production. Estimation of the activities of neutral and acid SMases in vitro showed that LMG suppressed the activities of both neutral and acid SMases in a concentration-dependent manner. These results suggest that LMG, a water-soluble β-1,3-glucan recycled from extracted residue of G. lucidum, possesses antioxidant capability against H2O2-induced cell death by attenuating intracellular ROS and inhibiting SMase activity.

  20. Identification of the hot spot residues for pyridine derivative inhibitor CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by molecular dynamic simulation.

    Science.gov (United States)

    Chen, Kai; Duan, Wenxiu; Han, Qianqian; Sun, Xuan; Li, Wenqian; Hu, Shuangyun; Wan, Jiajia; Wu, Jiang; Ge, Yushu; Liu, Dan

    2018-03-08

    Protein kinase monopolar spindle 1 plays an important role in spindle assembly checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a wide range of human tumors makes it an attractive target for finding an effective and specific inhibitor. In this work, we performed molecular dynamics simulations of protein MPS1 itself as well as protein bound systems with the inhibitor and natural substrate based on crystal structures. The reported orally bioavailable 1 h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the catalytic site, while natural substrate ATP could not stay. Comparative study of stability and flexibility of three systems reveals position shifting of β-sheet region within the catalytic site, which indicates inhibition mechanism was through stabilizing the β-sheet region. Binding free energies calculated with MM-GB/PBSA method shows different binding affinity for inhibitor and ATP. Finally, interactions between protein and inhibitor during molecular dynamic simulations were measured and counted. Residue Gly605 and Leu654 were suggested as important hot spots for stable binding of inhibitor by molecular dynamic simulation. Our results reveal an important position shifting within catalytic site for non-inhibited proteins. Together with hot spots found by molecular dynamic simulation, the results provide important information of inhibition mechanism and will be referenced for designing novel inhibitors.

  1. Two-stage residual inclusion estimation: addressing endogeneity in health econometric modeling.

    Science.gov (United States)

    Terza, Joseph V; Basu, Anirban; Rathouz, Paul J

    2008-05-01

    The paper focuses on two estimation methods that have been widely used to address endogeneity in empirical research in health economics and health services research-two-stage predictor substitution (2SPS) and two-stage residual inclusion (2SRI). 2SPS is the rote extension (to nonlinear models) of the popular linear two-stage least squares estimator. The 2SRI estimator is similar except that in the second-stage regression, the endogenous variables are not replaced by first-stage predictors. Instead, first-stage residuals are included as additional regressors. In a generic parametric framework, we show that 2SRI is consistent and 2SPS is not. Results from a simulation study and an illustrative example also recommend against 2SPS and favor 2SRI. Our findings are important given that there are many prominent examples of the application of inconsistent 2SPS in the recent literature. This study can be used as a guide by future researchers in health economics who are confronted with endogeneity in their empirical work.

  2. Automatic transfer function generation using contour tree controlled residue flow model and color harmonics.

    Science.gov (United States)

    Zhou, Jianlong; Takatsuka, Masahiro

    2009-01-01

    Transfer functions facilitate the volumetric data visualization by assigning optical properties to various data features and scalar values. Automation of transfer function specifications still remains a challenge in volume rendering. This paper presents an approach for automating transfer function generations by utilizing topological attributes derived from the contour tree of a volume. The contour tree acts as a visual index to volume segments, and captures associated topological attributes involved in volumetric data. A residue flow model based on Darcy's Law is employed to control distributions of opacity between branches of the contour tree. Topological attributes are also used to control color selection in a perceptual color space and create harmonic color transfer functions. The generated transfer functions can depict inclusion relationship between structures and maximize opacity and color differences between them. The proposed approach allows efficient automation of transfer function generations, and exploration on the data to be carried out based on controlling of opacity residue flow rate instead of complex low-level transfer function parameter adjustments. Experiments on various data sets demonstrate the practical use of our approach in transfer function generations.

  3. Anelastic Models of Fully-Convective Stars: Differential Rotation, Meridional Circulation and Residual Entropy

    Science.gov (United States)

    Sainsbury-Martinez, Felix; Browning, Matthew; Miesch, Mark; Featherstone, Nicholas A.

    2018-01-01

    Low-Mass stars are typically fully convective, and as such their dynamics may differ significantly from sun-like stars. Here we present a series of 3D anelastic HD and MHD simulations of fully convective stars, designed to investigate how the meridional circulation, the differential rotation, and residual entropy are affected by both varying stellar parameters, such as the luminosity or the rotation rate, and by the presence of a magnetic field. We also investigate, more specifically, a theoretical model in which isorotation contours and residual entropy (σ‧ = σ ‑ σ(r)) are intrinsically linked via the thermal wind equation (as proposed in the Solar context by Balbus in 2009). We have selected our simulation parameters in such as way as to span the transition between Solar-like differential rotation (fast equator + slow poles) and ‘anti-Solar’ differential rotation (slow equator + fast poles), as characterised by the convective Rossby number and △Ω. We illustrate the transition from single-celled to multi-celled MC profiles, and from positive to negative latitudinal entropy gradients. We show that an extrapolation involving both TWB and the σ‧/Ω link provides a reasonable estimate for the interior profile of our fully convective stars. Finally, we also present a selection of MHD simulations which exhibit an almost unsuppressed differential rotation profile, with energy balances remaining dominated by kinetic components.

  4. Long-term leaching from MSWI air-pollution-control residues: Leaching characterization and modeling

    DEFF Research Database (Denmark)

    Hyks, Jiri; Astrup, Thomas; Christensen, Thomas Højlund

    2009-01-01

    Long-term leaching of Ca, Fe, Mg, K, Na, S, Al, As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Zn, Mo, Sb, Si, Sri, Sr, Ti, V, P, Cl, and dissolved organic carbon from two different municipal solid waste incineration (MSWI) air-pollution-control residues was monitored during 24 months of column percolat......Long-term leaching of Ca, Fe, Mg, K, Na, S, Al, As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Zn, Mo, Sb, Si, Sri, Sr, Ti, V, P, Cl, and dissolved organic carbon from two different municipal solid waste incineration (MSWI) air-pollution-control residues was monitored during 24 months of column...... percolation experiments; liquid-to-solid (L/S) ratios of 200-250 L/kg corresponding to more than 10,000 years in a conventional landfill were reached. Less than 2% of the initially present As, Cu, Pb, Zn, Cr, and Sb had leached during the Course of the experiments. Concentrations of Cd, Fe, Mg, Hg, Mn, Ni, Co......, Sn, Ti, and P were generally bellow 1 mu g/L; overall less than 1% of their mass leached. Column leaching data were further used in a two-step geochemical modeling in PHREEQC in order to (i) identify solubility controlling minerals and (ii) evaluate their interactions in a water-percolated column...

  5. A fermionic molecular dynamics technique to model nuclear matter

    International Nuclear Information System (INIS)

    Vantournhout, K.; Jachowicz, N.; Ryckebusch, J.

    2009-01-01

    Full text: At sub-nuclear densities of about 10 14 g/cm 3 , nuclear matter arranges itself in a variety of complex shapes. This can be the case in the crust of neutron stars and in core-collapse supernovae. These slab like and rod like structures, designated as nuclear pasta, have been modelled with classical molecular dynamics techniques. We present a technique, based on fermionic molecular dynamics, to model nuclear matter at sub-nuclear densities in a semi classical framework. The dynamical evolution of an antisymmetric ground state is described making the assumption of periodic boundary conditions. Adding the concepts of antisymmetry, spin and probability distributions to classical molecular dynamics, brings the dynamical description of nuclear matter to a quantum mechanical level. Applications of this model vary from investigation of macroscopic observables and the equation of state to the study of fundamental interactions on the microscopic structure of the matter. (author)

  6. The emerging role of cloud computing in molecular modelling.

    Science.gov (United States)

    Ebejer, Jean-Paul; Fulle, Simone; Morris, Garrett M; Finn, Paul W

    2013-07-01

    There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Multiphysics modelling and experimental validation of an air-coupled array of PMUTs with residual stresses

    Science.gov (United States)

    Massimino, G.; Colombo, A.; D'Alessandro, L.; Procopio, F.; Ardito, R.; Ferrera, M.; Corigliano, A.

    2018-05-01

    In this paper a complete multiphysics modelling via the finite element method (FEM) of an air-coupled array of piezoelectric micromachined ultrasonic transducers (PMUT) and its experimental validation are presented. Two numerical models are described for the single transducer, axisymmetric and 3D, with the following features: the presence of fabrication induced residual stresses, which determine a non-linear initial deformed configuration of the diaphragm and a substantial fundamental mode frequency shift; the multiple coupling between different physics, namely electro-mechanical coupling for the piezo-electric model, thermo-acoustic-structural interaction and thermo-acoustic-pressure interaction for the waves propagation in the surrounding fluid. The model for the single transducer is enhanced considering the full set of PMUTs belonging to the silicon dye in a 4 × 4 array configuration. The results of the numerical multiphysics models are compared with experimental ones in terms of the initial static pre-deflection, of the diaphragm central point spectrum and of the sound intensity at 3.5 cm on the vertical direction along the axis of the diaphragm.

  8. Calibration of the century, apsim and ndicea models of decomposition and n mineralization of plant residues in the humid tropics

    Directory of Open Access Journals (Sweden)

    Alexandre Ferreira do Nascimento

    2011-06-01

    Full Text Available The aim of this study was to calibrate the CENTURY, APSIM and NDICEA simulation models for estimating decomposition and N mineralization rates of plant organic materials (Arachis pintoi, Calopogonium mucunoides, Stizolobium aterrimum, Stylosanthes guyanensis for 360 days in the Atlantic rainforest bioma of Brazil. The models´ default settings overestimated the decomposition and N-mineralization of plant residues, underlining the fact that the models must be calibrated for use under tropical conditions. For example, the APSIM model simulated the decomposition of the Stizolobium aterrimum and Calopogonium mucunoides residues with an error rate of 37.62 and 48.23 %, respectively, by comparison with the observed data, and was the least accurate model in the absence of calibration. At the default settings, the NDICEA model produced an error rate of 10.46 and 14.46 % and the CENTURY model, 21.42 and 31.84 %, respectively, for Stizolobium aterrimum and Calopogonium mucunoides residue decomposition. After calibration, the models showed a high level of accuracy in estimating decomposition and N- mineralization, with an error rate of less than 20 %. The calibrated NDICEA model showed the highest level of accuracy, followed by the APSIM and CENTURY. All models performed poorly in the first few months of decomposition and N-mineralization, indicating the need of an additional parameter for initial microorganism growth on the residues that would take the effect of leaching due to rainfall into account.

  9. Models and algorithms for biomolecules and molecular networks

    CERN Document Server

    DasGupta, Bhaskar

    2016-01-01

    By providing expositions to modeling principles, theories, computational solutions, and open problems, this reference presents a full scope on relevant biological phenomena, modeling frameworks, technical challenges, and algorithms. * Up-to-date developments of structures of biomolecules, systems biology, advanced models, and algorithms * Sampling techniques for estimating evolutionary rates and generating molecular structures * Accurate computation of probability landscape of stochastic networks, solving discrete chemical master equations * End-of-chapter exercises

  10. Model of molecular structure of the insoluble organic matter isolated from Murchison meteorite

    Science.gov (United States)

    Derenne, Sylvie; Robert, François

    2010-09-01

    The molecular structure of the insoluble organic matter (IOM) from Murchison meteorite has been investigated by our group for several years using a large set of analytical methods including various spectroscopies (Fourier transform infrared spectroscopy, nuclear magnetic resonance, electron paramagnetic resonance, X-ray absorption near-edge spectroscopy), high resolution electron microscopy, and thermal (pyrolyses in the presence or not of tetramethylammonium hydroxide) and chemical (RuO4 oxidation) degradations. Taken together, these techniques provided a wealth of qualitative and quantitative information, from which we derived 11 elemental and molecular parameters on the same IOM residue. In addition to the basic elemental composition, these parameters describe the distribution of the different types of carbon, nitrogen, and sulfur atoms as well as the size of the polyaromatic units. For this molecular structure, we therefore propose a model which fits with these 11 molecular quantitative parameters. Several cosmochemical implications are derived from this structure. Based on the fact that aromatic moieties are highly substituted and aliphatic chains highly branched, it can be anticipated that the synthesis of this IOM occurred through successive additions of single carbon units in the gas-phase ending by a spontaneous cyclization for chain length ≥7 C. As a whole, these observations favor an organosynthesis in the solar T-Tauri disk.

  11. Molecular Modeling of Prion Transmission to Humans

    Directory of Open Access Journals (Sweden)

    Etienne Levavasseur

    2014-10-01

    Full Text Available Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.

  12. Modelling residual stresses in friction stir welding of Al alloys - a review of possibilities and future trends

    DEFF Research Database (Denmark)

    Hattel, Jesper Henri; Sonne, Mads Rostgaard; Tutum, Cem C.

    2015-01-01

    Residual stresses are very important in any joining process of materials since they act as pre-stresses in the loading situation of the joint, thereby affecting the final mechanical performance of the component. This is also the case for friction stir welding (FSW) which is a complex solid-state ......, numerical framework and application as well as putting them into proper context with respect to some of the new trends in the field, e.g. coupling with subsequent load analyses of the in-service situation or applying residual stress models of FSWin numerical optimization.......Residual stresses are very important in any joining process of materials since they act as pre-stresses in the loading situation of the joint, thereby affecting the final mechanical performance of the component. This is also the case for friction stir welding (FSW) which is a complex solid......-state joining process characterized by a pronounced multiphysical behaviour involving phenomena such as change of temperature, material flow, change of microstructures and formation of residual stresses. Thus, models of FSWare typically divided into thermal models, flow models, residual stress models...

  13. Multilevel models for multiple-baseline data: modeling across-participant variation in autocorrelation and residual variance.

    Science.gov (United States)

    Baek, Eun Kyeng; Ferron, John M

    2013-03-01

    Multilevel models (MLM) have been used as a method for analyzing multiple-baseline single-case data. However, some concerns can be raised because the models that have been used assume that the Level-1 error covariance matrix is the same for all participants. The purpose of this study was to extend the application of MLM of single-case data in order to accommodate across-participant variation in the Level-1 residual variance and autocorrelation. This more general model was then used in the analysis of single-case data sets to illustrate the method, to estimate the degree to which the autocorrelation and residual variances differed across participants, and to examine whether inferences about treatment effects were sensitive to whether or not the Level-1 error covariance matrix was allowed to vary across participants. The results from the analyses of five published studies showed that when the Level-1 error covariance matrix was allowed to vary across participants, some relatively large differences in autocorrelation estimates and error variance estimates emerged. The changes in modeling the variance structure did not change the conclusions about which fixed effects were statistically significant in most of the studies, but there was one exception. The fit indices did not consistently support selecting either the more complex covariance structure, which allowed the covariance parameters to vary across participants, or the simpler covariance structure. Given the uncertainty in model specification that may arise when modeling single-case data, researchers should consider conducting sensitivity analyses to examine the degree to which their conclusions are sensitive to modeling choices.

  14. Radiological Modeling for Determination of Derived Concentration Levels of an Area with Uranium Residual Material - 13533

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Sanchez, Danyl [CIEMAT, Avenida Complutense 40, 28040, Madrid (Spain)

    2013-07-01

    As a result of a pilot project developed at the old Spanish 'Junta de Energia Nuclear' to extract uranium from ores, tailings materials were generated. Most of these residual materials were sent back to different uranium mines, but a small amount of it was mixed with conventional building materials and deposited near the old plant until the surrounding ground was flattened. The affected land is included in an area under institutional control and used as recreational area. At the time of processing, uranium isotopes were separated but other radionuclides of the uranium decay series as Th-230, Ra-226 and daughters remain in the residue. Recently, the analyses of samples taken at different ground's depths confirmed their presence. This paper presents the methodology used to calculate the derived concentration level to ensure that the reference dose level of 0.1 mSv y-1 used as radiological criteria. In this study, a radiological impact assessment was performed modeling the area as recreational scenario. The modelization study was carried out with the code RESRAD considering as exposure pathways, external irradiation, inadvertent ingestion of soil, inhalation of resuspended particles, and inhalation of radon (Rn-222). As result was concluded that, if the concentration of Ra-226 in the first 15 cm of soil is lower than, 0.34 Bq g{sup -1}, the dose would not exceed the reference dose. Applying this value as a derived concentration level and comparing with the results of measurements on the ground, some areas with a concentration of activity slightly higher than latter were found. In these zones the remediation proposal has been to cover with a layer of 15 cm of clean material. This action represents a reduction of 85% of the dose and ensures compliance with the reference dose. (authors)

  15. Molecular-level removal of proteinaceous contamination from model surfaces and biomedical device materials by air plasma treatment.

    Science.gov (United States)

    Banerjee, K K; Kumar, S; Bremmell, K E; Griesser, H J

    2010-11-01

    Established methods for cleaning and sterilising biomedical devices may achieve removal of bioburden only at the macroscopic level while leaving behind molecular levels of contamination (mainly proteinaceous). This is of particular concern if the residue might contain prions. We investigated at the molecular level the removal of model and real-life proteinaceous contamination from model and practical surfaces by air plasma (ionised air) treatment. The surface-sensitive technique of X-ray photoelectron spectroscopy (XPS) was used to assess the removal of proteinaceous contamination, with the nitrogen (N1s) photoelectron signal as its marker. Model proteinaceous contamination (bovine serum albumin) adsorbed on to a model surface (silicon wafer) and the residual proteinaceous contamination resulting from incubating surgical stainless steel (a practical biomaterial) in whole human blood exhibited strong N1s signals [16.8 and 18.5 atomic percent (at.%), respectively] after thorough washing. After 5min air plasma treatment, XPS detected no nitrogen on the sample surfaces, indicating complete removal of proteinaceous contamination, down to the estimated XPS detection limit 10ng/cm(2). Applying the same plasma treatment, the 7.7at.% nitrogen observed on a clinically cleaned dental bur was reduced to a level reflective of new, as-received burs. Contact angle measurements and atomic force microscopy also indicated complete molecular-level removal of the proteinaceous contamination upon air plasma treatment. This study demonstrates the effectiveness of air plasma treatment for removing proteinaceous contamination from both model and practical surfaces and offers a method for ensuring that no molecular residual contamination such as prions is transferred upon re-use of surgical and dental instruments. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  16. Molecular modeling of protein materials: case study of elastin

    International Nuclear Information System (INIS)

    Tarakanova, Anna; Buehler, Markus J

    2013-01-01

    Molecular modeling of protein materials is a quickly growing area of research that has produced numerous contributions in fields ranging from structural engineering to medicine and biology. We review here the history and methods commonly employed in molecular modeling of protein materials, emphasizing the advantages for using modeling as a complement to experimental work. We then consider a case study of the protein elastin, a critically important ‘mechanical protein’ to exemplify the approach in an area where molecular modeling has made a significant impact. We outline the progression of computational modeling studies that have considerably enhanced our understanding of this important protein which endows elasticity and recoil to the tissues it is found in, including the skin, lungs, arteries and the heart. A vast collection of literature has been directed at studying the structure and function of this protein for over half a century, the first molecular dynamics study of elastin being reported in the 1980s. We review the pivotal computational works that have considerably enhanced our fundamental understanding of elastin's atomistic structure and its extraordinary qualities—focusing on two in particular: elastin's superb elasticity and the inverse temperature transition—the remarkable ability of elastin to take on a more structured conformation at higher temperatures, suggesting its effectiveness as a biomolecular switch. Our hope is to showcase these methods as both complementary and enriching to experimental approaches that have thus far dominated the study of most protein-based materials. (topical review)

  17. Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking

    Directory of Open Access Journals (Sweden)

    N. Harathi

    2016-01-01

    Full Text Available The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb. In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA, the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis.

  18. Computational modeling on the recognition of the HRE motif by HIF-1: molecular docking and molecular dynamics studies.

    Science.gov (United States)

    Sokkar, Pandian; Sathis, Vani; Ramachandran, Murugesan

    2012-05-01

    Hypoxia inducible factor-1 (HIF-1) is a bHLH-family transcription factor that controls genes involved in glycolysis, angiogenesis, migration, as well as invasion factors that are important for tumor progression and metastasis. HIF-1, a heterodimer of HIF-1α and HIF-1β, binds to the hypoxia responsive element (HRE) present in the promoter regions of hypoxia responsive genes, such as vascular endothelial growth factor (VEGF). Neither the structure of free HIF-1 nor that of its complex with HRE is available. Computational modeling of the transcription factor-DNA complex has always been challenging due to their inherent flexibility and large conformational space. The present study aims to model the interaction between the DNA-binding domain of HIF-1 and HRE. Experiments showed that rigid macromolecular docking programs (HEX and GRAMM-X) failed to predict the optimal dimerization of individually modeled HIF-1 subunits. Hence, the HIF-1 heterodimer was modeled based on the phosphate system positive regulatory protein (PHO4) homodimer. The duplex VEGF-DNA segment containing HRE with flanking nucleotides was modeled in the B form and equilibrated via molecular dynamics (MD) simulation. A rigid docking approach was used to predict the crude binding mode of HIF-1 dimer with HRE, in which the putative contacts were found to be present. An MD simulation (5 ns) of the HIF-1-HRE complex in explicit water was performed to account for its flexibility and to optimize its interactions. All of the conserved amino acid residues were found to play roles in the recognition of HRE. The present work, which sheds light on the recognition of HRE by HIF-1, could be beneficial in the design of peptide or small molecule therapeutics that can mimic HIF-1 and bind with the HRE sequence.

  19. Molecular dynamics and binary collisions modeling of the primary damage state of collision cascades

    International Nuclear Information System (INIS)

    Heinisch, H.L.; Singh, B.N.

    1992-01-01

    The objective of this work is to determine the spectral dependence of defect production and microstructure evolution for the development of fission-fusion correlations. Quantitative information on defect production in cascades in copper obtained from recent molecular dynamics (MD) simulations is compared to defect production information determined earlier with a model based on the binary collision approximation (BCA). The total numbers of residual defects, the fractions of them that are mobile, and the sizes of immobile clusters compare favorably, especially when the termination conditions of the two simulations are taken into account. A strategy is laid out for integrating the details of the cascade quenching phase determined by MD into a BCA-based model that is practical for simulating much higher energies and longer times than MD alone can achieve. The extraction of collisional phase information from MD simulations and the correspondence of MD and BCA versions of the collisional phase demonstrated at low energy

  20. Molecular dynamics and binary collision modeling of the primary damage state of collision cascades

    DEFF Research Database (Denmark)

    Heinisch, H.L.; Singh, B.N.

    1992-01-01

    Quantitative information on defect production in cascades in copper obtained from recent molecular dynamics simulations is compared to defect production information determined earlier with a model based on the binary collision approximation (BCA). The total numbers of residual defects......, the fractions of them that are mobile, and the sizes of immobile clusters compare favorably, especially when the termination conditions of the two simulations are taken into account. A strategy is laid out for integrating the details of the cascade quenching phase determined by MD into a BCA-based model...... that is practical for simulating much higher energies and longer times than MD alone can achieve. The extraction of collisional phase information from MD simulations and the correspondence of MD and BCA versions of the collisional phase is demonstrated at low energy....

  1. Modeling and simulation of stamp deflections in nanoimprint lithography: Exploiting backside grooves to enhance residual layer thickness uniformity

    DEFF Research Database (Denmark)

    Taylor, Hayden; Smistrup, Kristian; Boning, Duane

    2011-01-01

    We describe a model for the compliance of a nanoimprint stamp etched with a grid of backside grooves. We integrate the model with a fast simulation technique that we have previously demonstrated, to show how etched grooves help reduce the systematic residual layer thickness (RLT) variations...

  2. Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Pawan Kaushik

    2014-01-01

    Full Text Available The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β, dipeptidyl peptidase-IV (DPP-IV, aldose reductase (AR, and insulin receptor (IR with help of docking software Molegro virtual docker (MVD. From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

  3. Novel thrombopoietin mimetic peptides bind c-Mpl receptor: Synthesis, biological evaluation and molecular modeling.

    Science.gov (United States)

    Liu, Yaquan; Tian, Fang; Zhi, Dejuan; Wang, Haiqing; Zhao, Chunyan; Li, Hongyu

    2017-02-01

    Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor. The results presented that three of four mimetic peptides showed significant activities. In addition, the molecular modeling approaches proved hydrophobic interactions were the driven positive forces for binding behavior between peptides and c-Mpl receptor. TPO peptide residues in P7, P13 and P7' positions were identified by the analysis of hydrogen bonds and energy decompositions as the key ones for benefiting better biological activities. Our data suggested the synthesized peptides have considerable potential for the future development of stable and highly active TPO mimetic peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.

    Science.gov (United States)

    Harrold, Marc W.

    1992-01-01

    This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)

  5. Metal cluster fission: jellium model and Molecular dynamics simulations

    DEFF Research Database (Denmark)

    Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Ilia

    2004-01-01

    Fission of doubly charged sodium clusters is studied using the open-shell two-center deformed jellium model approximation and it ab initio molecular dynamic approach accounting for all electrons in the system. Results of calculations of fission reactions Na_10^2+ --> Na_7^+ + Na_3^+ and Na_18...

  6. Modeling the Thiophene HDS reaction on a molecular level

    NARCIS (Netherlands)

    Diemann, E.; Weber, T.; Müller, A.

    1994-01-01

    The structure of MoS2/Al2O3 catalyst and the initial step of the hydrodesulfurization (HDS) reaction using an experimental model have been studied by in situ Raman-, infrared emission (IRE)-, inelastic electron tunneling (IET)-spectroscopy and thermal desorption measurements accompanied by molecular

  7. Structure-function relationship of a plant NCS1 member - Homology modeling and mutagenesis identified residues critical for substrate specificity of PLUTO, a nucleobase transporter from arabidopsis

    KAUST Repository

    Witz, Sandra

    2014-03-12

    Plastidic uracil salvage is essential for plant growth and development. So far, PLUTO, the plastidic nucleobase transporter from Arabidopsis thaliana is the only known uracil importer at the inner plastidic membrane which represents the permeability barrier of this organelle. We present the first homology model of PLUTO, the sole plant NCS1 member from Arabidopsis based on the crystal structure of the benzyl hydantoin transporter MHP1 from Microbacterium liquefaciens and validated by molecular dynamics simulations. Polar side chains of residues Glu-227 and backbones of Val-145, Gly-147 and Thr-425 are proposed to form the binding site for the three PLUTO substrates uracil, adenine and guanine. Mutational analysis and competition studies identified Glu-227 as an important residue for uracil and to a lesser extent for guanine transport. A differential response in substrate transport was apparent with PLUTO double mutants E227Q G147Q and E227Q T425A, both of which most strongly affected adenine transport, and in V145A G147Q, which markedly affected guanine transport. These differences could be explained by docking studies, showing that uracil and guanine exhibit a similar binding mode whereas adenine binds deep into the catalytic pocket of PLUTO. Furthermore, competition studies confirmed these results. The present study defines the molecular determinants for PLUTO substrate binding and demonstrates key differences in structure-function relations between PLUTO and other NCS1 family members. 2014 Witz et al.

  8. Development of risk-based computer models for deriving criteria on residual radioactivity and recycling

    International Nuclear Information System (INIS)

    Chen, Shih-Yew

    1995-01-01

    Argonne National Laboratory (ANL) is developing multimedia environmental pathway and health risk computer models to assess radiological risks to human health and to derive cleanup guidelines for environmental restoration, decommissioning, and recycling activities. These models are based on the existing RESRAD code, although each has a separate design and serves different objectives. Two such codes are RESRAD-BUILD and RESRAD-PROBABILISTIC. The RESRAD code was originally developed to implement the U.S. Department of Energy's (DOE's) residual radioactive materials guidelines for contaminated soils. RESRAD has been successfully used by DOE and its contractors to assess health risks and develop cleanup criteria for several sites selected for cleanup or restoration programs. RESRAD-BUILD analyzes human health risks from radioactive releases during decommissioning or rehabilitation of contaminated buildings. Risks to workers are assessed for dismantling activities; risks to the public are assessed for occupancy. RESRAD-BUILD is based on a room compartmental model analyzing the effects on room air quality of contaminant emission and resuspension (as well as radon emanation), the external radiation pathway, and other exposure pathways. RESRAD-PROBABILISTIC, currently under development, is intended to perform uncertainty analysis for RESRAD by using the Monte Carlo approach based on the Latin-Hypercube sampling scheme. The codes being developed at ANL are tailored to meet a specific objective of human health risk assessment and require specific parameter definition and data gathering. The combined capabilities of these codes satisfy various risk assessment requirements in environmental restoration and remediation activities. (author)

  9. Development of risk-based computer models for deriving criteria on residual radioactivity and recycling

    International Nuclear Information System (INIS)

    Chen, S.Y.

    1994-01-01

    Argonne National Laboratory (ANL) is developing multimedia environmental pathway and health risk computer models to assess radiological risks to human health and to derive cleanup guidelines for environmental restoration, decommissioning, and recycling activities. These models are based on the existing RESRAD code, although each has a separate design and serves different objectives. Two such codes are RESRAD-BUILD and RESRAD-PROBABILISTIC. The RESRAD code was originally developed to implement the US Department of Energy's (DOE's) residual radioactive materials guidelines for contaminated soils. RESRAD has been successfully used by DOE and its contractors to assess health risks and develop cleanup criteria for several sites selected for cleanup or restoration programs. RESRAD-BUILD analyzes human health risks from radioactive releases during decommissioning or rehabilitation of contaminated buildings. Risks to workers are assessed for dismantling activities; risks to the public are assessed for occupancy. RESRAD-BUILD is based on a room compartmental model analyzing the effects on room air quality of contaminant emission and resuspension (as well as radon emanation), the external radiation pathway, and other exposure pathways. RESRAD-PROBABILISTIC, currently under development, is intended to perform uncertainty analysis for RESRAD by using the Monte Carlo approach based on the Latin-Hypercube sampling scheme. The codes being developed at ANL are tailored to meet a specific objective of human health risk assessment and require specific parameter definition and data gathering. The combined capabilities of these codes satisfy various risk assessment requirements in environmental restoration and remediation activities

  10. Modelling of residual stresses in valves Norem hard-facing alloys: a material characterization issue

    International Nuclear Information System (INIS)

    Mathieu, J.P.; Arnoldi, F.; Gauthier, E.; Beaurin, G.

    2011-01-01

    Replacement of cobalt-based hard-facing alloys (Stellite) is of high interest within the topic of reduction of human radiation exposure during field-work. Iron-based hard-facing alloys, such as Norem, are considered as good replacement candidates. Their wear characteristics are known to be quite equivalent to Stellite but are counter-balanced by lack of feedback in the field, especially about their resistance/toughness to brutal thermal shocks (60 C - 280 C for primary water). Norem alloys show a solid-solution strengthened austenitic dendrites matrix with a continuous network of eutectic and non-eutectic carbides at the grain boundaries. Toughness evaluation also requires information about residual stresses due to the welding (deposition) process: this work aims at furnishing tools for this purpose. First part of the work involved a microstructural study in order to compare the as-received material to other Norem samples previously observed in EDF's works and literature. A characterization of the different phase evolutions after heating and fast cooling of Norem is then made, in order to characterize whether metallurgical aspects have to be considered in the mechanical part during welding modelling: it appears that no strong solid-solid phase transformation may occur in welding situation. Tensile characterization is then performed on bulk PTAW (Plasma Transferred Arc Welding) specimens. A simplified welding simulation is eventually conducted on different axis-symmetric geometry and on real valve geometry in order to define a representative sample that will be used for further investigation on residual stresses. (authors)

  11. Energetics and efficiency of a molecular motor model

    DEFF Research Database (Denmark)

    C. Fogedby, Hans; Svane, Axel

    2013-01-01

    The energetics and efficiency of a linear molecular motor model proposed by Mogilner et al. (Phys. Lett. 237, 297 (1998)) is analyzed from an analytical point of view. The model which is based on protein friction with a track is described by coupled Langevin equations for the motion in combination...... when incorporating the full motor dynamics, owing to the strong dissipation associated with the motor action....

  12. Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities.

    Science.gov (United States)

    Bardhan, Jaydeep P

    2013-12-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

  13. Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities

    Science.gov (United States)

    Bardhan, Jaydeep P.

    2014-01-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics. PMID:25505358

  14. Gradient models in molecular biophysics: progress, challenges, opportunities

    Science.gov (United States)

    Bardhan, Jaydeep P.

    2013-12-01

    In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g., molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding nonlocal dielectric response. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain, and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost 40 years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The review concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

  15. Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations.

    Science.gov (United States)

    Itteboina, Ramesh; Ballu, Srilata; Sivan, Sree Kanth; Manga, Vijjulatha

    2017-10-01

    Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r 2 ncv and q 2 loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r 2 Pred ) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.

  16. Understanding the structural and energetic basis of PD-1 and monoclonal antibodies bound to PD-L1: A molecular modeling perspective.

    Science.gov (United States)

    Shi, Danfeng; Zhou, Shuangyan; Liu, Xuewei; Zhao, Chenxi; Liu, Huanxiang; Yao, Xiaojun

    2018-03-01

    The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated. Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L1 and different protein ligands. The results of virtual alanine scanning mutagenesis suggest that Y56, Q66, M115, D122, Y123, R125 are the hotspot residues on PD-L1. The residue-residue contact analysis further shows that PD-1 interacts with PD-L1 mainly by F and G strands while monoclonal antibodies like avelumab and BMS-936559 mainly interact with PD-L1 by CDR2 and CDR3 loops of the heavy chain. A structurally similar β-hairpin peptide with 13 or 14 residues was extracted from each protein ligand and these β-hairpin peptides were found tightly binding to the putative hotspot residues on PD-L1. This study recognizes the hotspot residues on PD-L1 and uncovers the common structural and energetic basis of different protein ligands binding to PD-L1. These results will be valuable for the design of small molecule or peptide inhibitors targeting on PD-L1. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Hydrophobic ampersand hydrophilic: Theoretical models of solvation for molecular biophysics

    International Nuclear Information System (INIS)

    Pratt, L.R.; Tawa, G.J.; Hummer, G.; Garcia, A.E.; Corcelli, S.A.

    1996-01-01

    Molecular statistical thermodynamic models of hydration for chemistry and biophysics have advanced abruptly in recent years. With liquid water as solvent, salvation phenomena are classified as either hydrophobic or hydrophilic effects. Recent progress in treatment of hydrophilic effects have been motivated by continuum dielectric models interpreted as a modelistic implementation of second order perturbation theory. New results testing that perturbation theory of hydrophilic effects are presented and discussed. Recent progress in treatment of hydrophobic effects has been achieved by applying information theory to discover models of packing effects in dense liquids. The simplest models to which those ideas lead are presented and discussed

  18. Modeling molecular boiling points using computed interaction energies.

    Science.gov (United States)

    Peterangelo, Stephen C; Seybold, Paul G

    2017-12-20

    The noncovalent van der Waals interactions between molecules in liquids are typically described in textbooks as occurring between the total molecular dipoles (permanent, induced, or transient) of the molecules. This notion was tested by examining the boiling points of 67 halogenated hydrocarbon liquids using quantum chemically calculated molecular dipole moments, ionization potentials, and polarizabilities obtained from semi-empirical (AM1 and PM3) and ab initio Hartree-Fock [HF 6-31G(d), HF 6-311G(d,p)], and density functional theory [B3LYP/6-311G(d,p)] methods. The calculated interaction energies and an empirical measure of hydrogen bonding were employed to model the boiling points of the halocarbons. It was found that only terms related to London dispersion energies and hydrogen bonding proved significant in the regression analyses, and the performances of the models generally improved at higher levels of quantum chemical computation. An empirical estimate for the molecular polarizabilities was also tested, and the best models for the boiling points were obtained using either this empirical polarizability itself or the polarizabilities calculated at the B3LYP/6-311G(d,p) level, along with the hydrogen-bonding parameter. The results suggest that the cohesive forces are more appropriately described as resulting from highly localized interactions rather than interactions between the global molecular dipoles.

  19. Multi-level molecular modelling for plasma medicine

    International Nuclear Information System (INIS)

    Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C W; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C

    2016-01-01

    Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma–biomolecule interactions. (paper)

  20. Model reduction and frequency residuals for a robust estimation of nonlinearities in subspace identification

    Science.gov (United States)

    De Filippis, G.; Noël, J. P.; Kerschen, G.; Soria, L.; Stephan, C.

    2017-09-01

    The introduction of the frequency-domain nonlinear subspace identification (FNSI) method in 2013 constitutes one in a series of recent attempts toward developing a realistic, first-generation framework applicable to complex structures. If this method showed promising capabilities when applied to academic structures, it is still confronted with a number of limitations which needs to be addressed. In particular, the removal of nonphysical poles in the identified nonlinear models is a distinct challenge. In the present paper, it is proposed as a first contribution to operate directly on the identified state-space matrices to carry out spurious pole removal. A modal-space decomposition of the state and output matrices is examined to discriminate genuine from numerical poles, prior to estimating the extended input and feedthrough matrices. The final state-space model thus contains physical information only and naturally leads to nonlinear coefficients free of spurious variations. Besides spurious variations due to nonphysical poles, vibration modes lying outside the frequency band of interest may also produce drifts of the nonlinear coefficients. The second contribution of the paper is to include residual terms, accounting for the existence of these modes. The proposed improved FNSI methodology is validated numerically and experimentally using a full-scale structure, the Morane-Saulnier Paris aircraft.

  1. Rural electrification for isolated consumers: Sustainable management model based on residue biomass

    International Nuclear Information System (INIS)

    Pinheiro, Giorgiana; Rendeiro, Goncalo; Pinho, Joao; Macedo, Emanuel

    2011-01-01

    This paper presents a case study of the electrification of a riparian community in the State of Para, Brazil, within the scope of the Program for Electric Power Service Universalization in Brazil. The community is located in a remote area; approximately 100 km from the municipal district, there is no regular transport to access the community, and adequate communication service. The community is provided with electrification facilities through a small biomass-based power plant, directly firing residues produced by the local economic activity. The objective of the paper is to propose a sustainable management model that is suitable for community's isolation conditions, considering the high costs with operation and maintenance related to the supply of isolated consumers in small locations. A simulation is conducted for the operation of the small biomass-based power plant, the generation costs are determined, the legal aspects are analyzed, and a suggestion for the management model is presented. - Highlights: → Electrification of isolated consumers is a great challenge for utilities. → Using local labor and resources allows lower energy costs for electrification. → Creation of a specific legislation for utilities is required. → Should also be implemented social activities together with electrification.

  2. Simulation of distortion and residual stress in high pressure die casting – modelling and experiments

    International Nuclear Information System (INIS)

    Hofer, P; Kaschnitz, E; Schumacher, P

    2012-01-01

    Two individual high-pressure die-casting geometries were developed in order to study the influence of process parameters and different alloys on the distortion behaviour of castings. These geometries were a stress lattice and a V-shaped sample tending to form residual stress due to different wall thickness respectively by a deliberate massive gating system. In the experimental castings the influence of the most important process parameters such as die temperature and die opening time and the cooling regime was examined. The time evolution of process temperatures was measured using thermal imaging. The heat transfer coefficients were adapted to the observed temperature distributions. Castings were produced from the two alloys AlSi12 and AlSi10MnMg. The distortion of the castings was measured by means of a tactile measuring device. For the alloy AlSi10MnMg thermo-physical and thermo-mechanical data were obtained using differential scanning calorimetry, laser flash technique, dilatometry and tensile testing at elevated temperatures. These data were used for modelling the material behaviour of the AlSi10MnMg alloy in the numerical model while for the alloy AlSi12(Fe) literature data were used. Process and stress simulation were conducted using the commercial FEM software ANSYS Workbench. A survey on the results of the comparison between simulation and experiment is given for both alloys.

  3. Quantum Mechanics/Molecular Mechanics Modeling of Drug Metabolism

    DEFF Research Database (Denmark)

    Lonsdale, Richard; Fort, Rachel M; Rydberg, Patrik

    2016-01-01

    )-mexiletine in CYP1A2 with hybrid quantum mechanics/molecular mechanics (QM/MM) methods, providing a more detailed and realistic model. Multiple reaction barriers have been calculated at the QM(B3LYP-D)/MM(CHARMM27) level for the direct N-oxidation and H-abstraction/rebound mechanisms. Our calculated barriers......The mechanism of cytochrome P450(CYP)-catalyzed hydroxylation of primary amines is currently unclear and is relevant to drug metabolism; previous small model calculations have suggested two possible mechanisms: direct N-oxidation and H-abstraction/rebound. We have modeled the N-hydroxylation of (R...... indicate that the direct N-oxidation mechanism is preferred and proceeds via the doublet spin state of Compound I. Molecular dynamics simulations indicate that the presence of an ordered water molecule in the active site assists in the binding of mexiletine in the active site...

  4. MOLECULAR VALIDATED MODEL FOR ADSORPTION OF PROTONATED DYE ON LDH

    Directory of Open Access Journals (Sweden)

    B. M. Braga

    Full Text Available Abstract Hydrotalcite-like compounds are anionic clays of scientific and technological interest for their use as ion exchange materials, catalysts and modified electrodes. Surface phenomenon are important for all these applications. Although conventional analytical methods have enabled progress in understanding the behavior of anionic clays in solution, an evaluation at the atomic scale of the dynamics of their ionic interactions has never been performed. Molecular simulation has become an extremely useful tool to provide this perspective. Our purpose is to validate a simplified model for the adsorption of 5-benzoyl-4-hydroxy-2-methoxy-benzenesulfonic acid (MBSA, a prototype molecule of anionic dyes, onto a hydrotalcite surface. Monte Carlo simulations were performed in the canonical ensemble with MBSA ions and a pore model of hydrotalcite using UFF and ClayFF force fields. The proposed molecular model has allowed us to reproduce experimental data of atomic force microscopy. Influences of protonation during the adsorption process are also presented.

  5. Hierarchical modeling of molecular energies using a deep neural network

    Science.gov (United States)

    Lubbers, Nicholas; Smith, Justin S.; Barros, Kipton

    2018-06-01

    We introduce the Hierarchically Interacting Particle Neural Network (HIP-NN) to model molecular properties from datasets of quantum calculations. Inspired by a many-body expansion, HIP-NN decomposes properties, such as energy, as a sum over hierarchical terms. These terms are generated from a neural network—a composition of many nonlinear transformations—acting on a representation of the molecule. HIP-NN achieves the state-of-the-art performance on a dataset of 131k ground state organic molecules and predicts energies with 0.26 kcal/mol mean absolute error. With minimal tuning, our model is also competitive on a dataset of molecular dynamics trajectories. In addition to enabling accurate energy predictions, the hierarchical structure of HIP-NN helps to identify regions of model uncertainty.

  6. Spherical convolutions and their application in molecular modelling

    DEFF Research Database (Denmark)

    Boomsma, Wouter; Frellsen, Jes

    2017-01-01

    Convolutional neural networks are increasingly used outside the domain of image analysis, in particular in various areas of the natural sciences concerned with spatial data. Such networks often work out-of-the box, and in some cases entire model architectures from image analysis can be carried over...... to other problem domains almost unaltered. Unfortunately, this convenience does not trivially extend to data in non-euclidean spaces, such as spherical data. In this paper, we introduce two strategies for conducting convolutions on the sphere, using either a spherical-polar grid or a grid based...... of spherical convolutions in the context of molecular modelling, by considering structural environments within proteins. We show that the models are capable of learning non-trivial functions in these molecular environments, and that our spherical convolutions generally outperform standard 3D convolutions...

  7. Modeling of nanotoxicity molecular interactions of nanomaterials with bionanomachines

    CERN Document Server

    Zhou, Ruhong

    2015-01-01

    This book provides a comprehensive overview of the fundamentals of nanotoxicity modeling and its implications for the development of novel nanomedicines. It lays out the fundamentals of nanotoxicity modeling for an array of nanomaterial systems, ranging from carbon-based nanoparticles to noble metals, metal oxides, and quantum dots. The author illustrates how molecular (classical mechanics) and atomic (quantum mechanics) modeling approaches can be applied to bolster our understanding of many important aspects of this critical nanotoxicity issue. Each chapter is organized by types of nanomaterials for practicality, making this an ideal book for senior undergraduate students, graduate students, and researchers in nanotechnology, chemistry, physics, molecular biology, and computer science. It is also of interest to academic and industry professionals who work on nanodrug delivery and related biomedical applications, and aids readers in their biocompatibility assessment efforts in the coming age of nanotechnology...

  8. Analyzing key constraints to biogas production from crop residues and manure in the EU—A spatially explicit model

    Science.gov (United States)

    Persson, U. Martin

    2017-01-01

    This paper presents a spatially explicit method for making regional estimates of the potential for biogas production from crop residues and manure, accounting for key technical, biochemical, environmental and economic constraints. Methods for making such estimates are important as biofuels from agricultural residues are receiving increasing policy support from the EU and major biogas producers, such as Germany and Italy, in response to concerns over unintended negative environmental and social impacts of conventional biofuels. This analysis comprises a spatially explicit estimate of crop residue and manure production for the EU at 250 m resolution, and a biogas production model accounting for local constraints such as the sustainable removal of residues, transportation of substrates, and the substrates’ biochemical suitability for anaerobic digestion. In our base scenario, the EU biogas production potential from crop residues and manure is about 0.7 EJ/year, nearly double the current EU production of biogas from agricultural substrates, most of which does not come from residues or manure. An extensive sensitivity analysis of the model shows that the potential could easily be 50% higher or lower, depending on the stringency of economic, technical and biochemical constraints. We find that the potential is particularly sensitive to constraints on the substrate mixtures’ carbon-to-nitrogen ratio and dry matter concentration. Hence, the potential to produce biogas from crop residues and manure in the EU depends to large extent on the possibility to overcome the challenges associated with these substrates, either by complementing them with suitable co-substrates (e.g. household waste and energy crops), or through further development of biogas technology (e.g. pretreatment of substrates and recirculation of effluent). PMID:28141827

  9. Analyzing key constraints to biogas production from crop residues and manure in the EU-A spatially explicit model.

    Science.gov (United States)

    Einarsson, Rasmus; Persson, U Martin

    2017-01-01

    This paper presents a spatially explicit method for making regional estimates of the potential for biogas production from crop residues and manure, accounting for key technical, biochemical, environmental and economic constraints. Methods for making such estimates are important as biofuels from agricultural residues are receiving increasing policy support from the EU and major biogas producers, such as Germany and Italy, in response to concerns over unintended negative environmental and social impacts of conventional biofuels. This analysis comprises a spatially explicit estimate of crop residue and manure production for the EU at 250 m resolution, and a biogas production model accounting for local constraints such as the sustainable removal of residues, transportation of substrates, and the substrates' biochemical suitability for anaerobic digestion. In our base scenario, the EU biogas production potential from crop residues and manure is about 0.7 EJ/year, nearly double the current EU production of biogas from agricultural substrates, most of which does not come from residues or manure. An extensive sensitivity analysis of the model shows that the potential could easily be 50% higher or lower, depending on the stringency of economic, technical and biochemical constraints. We find that the potential is particularly sensitive to constraints on the substrate mixtures' carbon-to-nitrogen ratio and dry matter concentration. Hence, the potential to produce biogas from crop residues and manure in the EU depends to large extent on the possibility to overcome the challenges associated with these substrates, either by complementing them with suitable co-substrates (e.g. household waste and energy crops), or through further development of biogas technology (e.g. pretreatment of substrates and recirculation of effluent).

  10. Analyzing key constraints to biogas production from crop residues and manure in the EU-A spatially explicit model.

    Directory of Open Access Journals (Sweden)

    Rasmus Einarsson

    Full Text Available This paper presents a spatially explicit method for making regional estimates of the potential for biogas production from crop residues and manure, accounting for key technical, biochemical, environmental and economic constraints. Methods for making such estimates are important as biofuels from agricultural residues are receiving increasing policy support from the EU and major biogas producers, such as Germany and Italy, in response to concerns over unintended negative environmental and social impacts of conventional biofuels. This analysis comprises a spatially explicit estimate of crop residue and manure production for the EU at 250 m resolution, and a biogas production model accounting for local constraints such as the sustainable removal of residues, transportation of substrates, and the substrates' biochemical suitability for anaerobic digestion. In our base scenario, the EU biogas production potential from crop residues and manure is about 0.7 EJ/year, nearly double the current EU production of biogas from agricultural substrates, most of which does not come from residues or manure. An extensive sensitivity analysis of the model shows that the potential could easily be 50% higher or lower, depending on the stringency of economic, technical and biochemical constraints. We find that the potential is particularly sensitive to constraints on the substrate mixtures' carbon-to-nitrogen ratio and dry matter concentration. Hence, the potential to produce biogas from crop residues and manure in the EU depends to large extent on the possibility to overcome the challenges associated with these substrates, either by complementing them with suitable co-substrates (e.g. household waste and energy crops, or through further development of biogas technology (e.g. pretreatment of substrates and recirculation of effluent.

  11. Moisture removal of paddy by agricultural residues: basic physical parameters and drying kinetics modeling

    Directory of Open Access Journals (Sweden)

    Saniso, E.

    2007-05-01

    Full Text Available The objectives of this research were to study basic physical parameters of three agricultural residues that could be used for prediction of paddy drying kinetics using desiccants, to investigate a suitable methodfor moisture reduction of fresh paddy using 3 absorbents, and to modify the drying model of Inoue et al. for determining the evolution of moisture transfer during the drying period. Rice husk, sago palm rachis andcoconut husk were used as moisture desiccants in these experiments. From the results, it was concluded that the apparent density of all adsorbents was a linear function of moisture content whilst an equilibriummoisture content equation following Hendersonís model gave the best fit to the experimental results. From studying the relationship between moisture ratio and drying time under the condition of drying temperaturesof 30, 50 and 70oC, air flow rate of 1.6 m/s and initial moisture content of absorbents of 15, 20 and 27% dry-basis, it was shown that the moisture ratio decreased when drying time increased. In addition, thethin-layer desiccant drying equation following of the Page model can appropriately explain the evolution of moisture content of paddy over the drying time. The diffusion coefficient of all absorbents, which was in therange of 1x10-8 to 6x10-8 m2/h, was relatively dependent on drying temperature and inversely related to drying time. The diffusivity of coconut husk had the highest value compared to the other absorbents.The simulating modified mathematical model to determine drying kinetics of paddy using absorption technique and the simulated results had good relation to the experimental results for all adsorbents.

  12. A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.

    Directory of Open Access Journals (Sweden)

    Hui-Hui Cao

    Full Text Available Esophageal squamous cell carcinoma (ESCC has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR, phosphorylated Specificity protein 1 (p-Sp1, and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset and validated using an independent cohort of 185 specimens (validation dataset.The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001. Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset. Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

  13. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site

    Directory of Open Access Journals (Sweden)

    Marlet Martinez-Archundia

    2012-01-01

    Full Text Available The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS. Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand.

  14. Improvement of a Robotic Manipulator Model Based on Multivariate Residual Modeling

    Directory of Open Access Journals (Sweden)

    Serge Gale

    2017-07-01

    Full Text Available A new method is presented for extending a dynamic model of a six degrees of freedom robotic manipulator. A non-linear multivariate calibration of input–output training data from several typical motion trajectories is carried out with the aim of predicting the model systematic output error at time (t + 1 from known input reference up till and including time (t. A new partial least squares regression (PLSR based method, nominal PLSR with interactions was developed and used to handle, unmodelled non-linearities. The performance of the new method is compared with least squares (LS. Different cross-validation schemes were compared in order to assess the sampling of the state space based on conventional trajectories. The method developed in the paper can be used as fault monitoring mechanism and early warning system for sensor failure. The results show that the suggested methods improves trajectory tracking performance of the robotic manipulator by extending the initial dynamic model of the manipulator.

  15. Molecular level biodegradation of phenol and its derivatives through dmp operon of Pseudomonas putida: A bio-molecular modeling and docking analysis.

    Science.gov (United States)

    Ray, Sujay; Banerjee, Arundhati

    2015-10-01

    Participation of Pseudomonas putida-derived methyl phenol (dmp) operon and DmpR protein in the biodegradation of phenol or other harmful, organic, toxic pollutants was investigated at a molecular level. Documentation documents that P. putida has DmpR protein which positively regulates dmp operon in the presence of inducers; like phenols. From the operon, phenol hydroxylase encoded by dmpN gene, participates in degrading phenols after dmp operon is expressed. For the purpose, the 3-D models of the four domains from DmpR protein and of the DNA sequences from the two Upstream Activation Sequences (UAS) present at the promoter region of the operon were demonstrated using discrete molecular modeling techniques. The best modeled structures satisfying their stereo-chemical properties were selected in each of the cases. To stabilize the individual structures, energy optimization was performed. In the presence of inducers, probable interactions among domains and then the two independent DNA structures with the fourth domain were perused by manifold molecular docking simulations. The complex structures were made to be stable by minimizing their overall energy. Responsible amino acid residues, nucleotide bases and binding patterns for the biodegradation, were examined. In the presence of the inducers, the biodegradation process is initiated by the interaction of phe50 from the first protein domain with the inducers. Only after the interaction of the last domain with the DNA sequences individually, the operon is expressed. This novel residue level study is paramount for initiating transcription in the operon; thereby leading to expression of phenol hydroxylase followed by phenol biodegradation. Copyright © 2015. Published by Elsevier B.V.

  16. SCRINING IN SILICO ACTIVE COMPOUND OF Pachyrrhizus erosus AS ANTITIROSINASE ON Aspergillus oryzae (COMPUTATTIONAL STUDY WITH HOMOLOGY MODELING AND MOLECULAR DOCKING

    Directory of Open Access Journals (Sweden)

    Endang Lukitaningsih

    2015-11-01

    Full Text Available Bengkoang telah banyak digunakan dalam industri kosmetika sebagai whitening agent. Berdasarkan penelitian Lukitaningsih (2009, bengkoang mengandung 6 senyawa aktif yang mampu berperan sebagai whitening agent dengan menghambat aktivitas enzim tirosinase dari jamur Aspergillus oryzae (TyrAo. Namun interaksi senyawa aktif bengkoang dalam menghambat enzim tirosinase belum dapat diketahui. Interaksi senyawa-senyawa aktif bengkoang dengan enzim TyrAo dapat diketahui dengan studi komputasional (in silico. Pemodelan interaksi senyawa aktif bengkoang dengan enzim TyrAo dilakukan dengan metode homology modeling dan molecular docking. Homology modeling dilakukan untuk memodelkan struktur tiga dimensi (3D enzim tirosinase Aspergillus oryzae (TyrAo melalui template berupa protein homolog yang sudah diketahui struktur 3D-nya yaitu enzim TyrAb (PDBID: 2Y9X. Model TyrAo digunakan sebagai target makromolekul dalam metode molecular docking. Metode molecular docking merupakan metode untuk menggambarkan posisi ligan (senyawa-senyawa aktif bengkoang pada sisi aktif reseptor (model TyrAo. Berdasarkan docking yang dilakukan diketahui bahwa residu-residu yang banyak berpengaruh pada interaksi ligan pada sisi aktif adalah residu Thr275 yang berinteraksi secara ikatan hidrogen dengan ligan dan residu His294 yang berinteraksi secara hidrofobik pada cincin aromatik ligan. Penelitian in silico dan in vitro yang telah dilakukan memiliki korelasi (R2 sebesar -0,8366. Korelasi ini menandakan bahwa aktivitas senyawa-senyawa aktif pada bengkoang dalam menghambat enzim TyrAo memiliki hasil yang serupa pada penelitian yang  dilakukan secara in silico dan in vitro.

  17. Molecular Models for DSMC Simulations of Metal Vapor Deposition

    OpenAIRE

    Venkattraman, A; Alexeenko, Alina A

    2010-01-01

    The direct simulation Monte Carlo (DSMC) method is applied here to model the electron‐beam (e‐beam) physical vapor deposition of copper thin films. A suitable molecular model for copper‐copper interactions have been determined based on comparisons with experiments for a 2D slit source. The model for atomic copper vapor is then used in axi‐symmetric DSMC simulations for analysis of a typical e‐beam metal deposition system with a cup crucible. The dimensional and non‐dimensional mass fluxes obt...

  18. Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors

    Directory of Open Access Journals (Sweden)

    Sri Devi Sukumaran

    2016-07-01

    Full Text Available A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE. The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40–85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.

  19. Molecular modeling and anticholinesterasic activity of novel 2-arylaminocyclohexyl N,N-dimethylcarbamates

    International Nuclear Information System (INIS)

    Bagatin, Mariane C.; Candido, Augusto A.; Basso, Ernani A.; Gauze, Gisele F.; Pinheiro, Glaucia M. S.; Hoeehr, Nelci F.; Machinski Junior, Miguel; Mossini, Simone A.G.

    2013-01-01

    This work reports a detailed theoretical and experimental study of the novel isomer series cis- and trans-2-arylaminocyclohexyl N,N-dimethylcarbamates as potential inhibitors of cholinesterases. In vitro inhibition assay by Ellman's method with human blood samples showed that the new carbamates are selective to the inhibition of enzyme butyrylcholinesterase (BuChE) with maximum inhibition of 90% and IC 50 of 6 and 8 mmol L -1 for the more actives compounds of the series. Molecular modeling studies point to significant differences for the conformations of the compounds in the active sites of enzymes BuChE and acetylcholinesterase (AChE). The results show that the compounds interact more effectively with the active site of enzyme BuChE since the carbamate group is close to the key residues of the catalytic triad. (author)

  20. Molecular modeling and anticholinesterasic activity of novel 2-arylaminocyclohexyl N,N-dimethylcarbamates

    Energy Technology Data Exchange (ETDEWEB)

    Bagatin, Mariane C.; Candido, Augusto A.; Basso, Ernani A.; Gauze, Gisele F., E-mail: gfgbandoch@uem.br [Universidade Estadual de Maringa (UEM), PR (Brazil). Departamento de Quimica; Pinheiro, Glaucia M. S.; Hoeehr, Nelci F. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Departamento de Patologia Clinica; Machinski Junior, Miguel; Mossini, Simone A.G. [Universidade Estadual de Maringa (UEM), PR (Brazil). Departamento de Ciencias Basicas da Saude

    2013-11-15

    This work reports a detailed theoretical and experimental study of the novel isomer series cis- and trans-2-arylaminocyclohexyl N,N-dimethylcarbamates as potential inhibitors of cholinesterases. In vitro inhibition assay by Ellman's method with human blood samples showed that the new carbamates are selective to the inhibition of enzyme butyrylcholinesterase (BuChE) with maximum inhibition of 90% and IC{sub 50} of 6 and 8 mmol L{sup -1} for the more actives compounds of the series. Molecular modeling studies point to significant differences for the conformations of the compounds in the active sites of enzymes BuChE and acetylcholinesterase (AChE). The results show that the compounds interact more effectively with the active site of enzyme BuChE since the carbamate group is close to the key residues of the catalytic triad. (author)

  1. Modeling of molecular weight and molecular weight distribution in slurry polymerization of propylene by Ziegler-Natta catalysts

    International Nuclear Information System (INIS)

    Khorasani, R.; Pourmahdian, S.

    2007-01-01

    The Precise prediction of polypropylene synthesized by heterogeneous Ziegler-Natta catalysts needs good knowledge of parameters affecting on polymerization. molecular weight and molecular weight distribution are among important characteristics of a polymer determining physical-mechanical properties. broadening of molecular weight distribution is an important and well known characteristic of polypropylene synthesized by heterogeneous Ziegler-Natta catalysts, So it is important to understand the origin of broad molecular weight. Two main factors in broadening molecular weight, namely mass transfer resistances and multiplicity of active sites, are discussed in this paper and a model including these factors is presented. Then we calculate molecular weight and molecular weight distribution by the model and compare our results with

  2. Pesticide nonextractable residue formation in soil: insights from inverse modeling of degradation time series.

    Science.gov (United States)

    Loos, Martin; Krauss, Martin; Fenner, Kathrin

    2012-09-18

    Formation of soil nonextractable residues (NER) is central to the fate and persistence of pesticides. To investigate pools and extent of NER formation, an established inverse modeling approach for pesticide soil degradation time series was evaluated with a Monte Carlo Markov Chain (MCMC) sampling procedure. It was found that only half of 73 pesticide degradation time series from a homogeneous soil source allowed for well-behaved identification of kinetic parameters with a four-pool model containing a parent compound, a metabolite, a volatile, and a NER pool. A subsequent simulation indeed confirmed distinct parameter combinations of low identifiability. Taking the resulting uncertainties into account, several conclusions regarding NER formation and its impact on persistence assessment could nonetheless be drawn. First, rate constants for transformation of parent compounds to metabolites were correlated to those for transformation of parent compounds to NER, leading to degradation half-lives (DegT50) typically not being larger than disappearance half-lives (DT50) by more than a factor of 2. Second, estimated rate constants were used to evaluate NER formation over time. This showed that NER formation, particularly through the metabolite pool, may be grossly underestimated when using standard incubation periods. It further showed that amounts and uncertainties in (i) total NER, (ii) NER formed from the parent pool, and (iii) NER formed from the metabolite pool vary considerably among data sets at t→∞, with no clear dominance between (ii) and (iii). However, compounds containing aromatic amine moieties were found to form significantly more total NER when extrapolating to t→∞ than the other compounds studied. Overall, our study stresses the general need for assessing uncertainties, identifiability issues, and resulting biases when using inverse modeling of degradation time series for evaluating persistence and NER formation.

  3. Calibration and validation of models for short-term decomposition and N mineralization of plant residues in the tropics

    NARCIS (Netherlands)

    Nascimento, do A.F.; Mendona, E.D.; Leite, L.F.C.; Scholberg, J.M.S.; Neves, J.C.L.

    2012-01-01

    Insight of nutrient release patterns associated with the decomposition of plant residues is important for their effective use as a green manure in food production systems. Thus, this study aimed to evaluate the ability of the Century, APSIM and NDICEA simulation models for predicting the

  4. CONSRANK: a server for the analysis, comparison and ranking of docking models based on inter-residue contacts

    KAUST Repository

    Chermak, Edrisse; Petta, A.; Serra, L.; Vangone, A.; Scarano, V.; Cavallo, Luigi; Oliva, R.

    2014-01-01

    Summary: Herein, we present CONSRANK, a web tool for analyzing, comparing and ranking protein–protein and protein–nucleic acid docking models, based on the conservation of inter-residue contacts and its visualization in 2D and 3D interactive contact maps.

  5. The effect of hardening laws and thermal softening on modeling residual stresses in FSW of aluminum alloy 2024-T3

    DEFF Research Database (Denmark)

    Sonne, Mads Rostgaard; Tutum, Cem Celal; Hattel, Jesper Henri

    2013-01-01

    or kinematic hardening together with the metallurgical softening model were applied in order to give a first impression of the tendencies in residual stresses in friction stir welds when choosing different hardening and softening behaviors. Secondly, real friction stir butt welding of aluminum alloy 2024-T3...

  6. Numerical Methods for the Optimization of Nonlinear Residual-Based Sungrid-Scale Models Using the Variational Germano Identity

    NARCIS (Netherlands)

    Maher, G.D.; Hulshoff, S.J.

    2014-01-01

    The Variational Germano Identity [1, 2] is used to optimize the coefficients of residual-based subgrid-scale models that arise from the application of a Variational Multiscale Method [3, 4]. It is demonstrated that numerical iterative methods can be used to solve the Germano relations to obtain

  7. CONSRANK: a server for the analysis, comparison and ranking of docking models based on inter-residue contacts

    KAUST Repository

    Chermak, Edrisse

    2014-12-21

    Summary: Herein, we present CONSRANK, a web tool for analyzing, comparing and ranking protein–protein and protein–nucleic acid docking models, based on the conservation of inter-residue contacts and its visualization in 2D and 3D interactive contact maps.

  8. A Search Technique for Weak and Long-Duration Gamma-Ray Bursts from Background Model Residuals

    Science.gov (United States)

    Skelton, R. T.; Mahoney, W. A.

    1993-01-01

    We report on a planned search technique for Gamma-Ray Bursts too weak to trigger the on-board threshold. The technique is to search residuals from a physically based background model used for analysis of point sources by the Earth occultation method.

  9. A simulation model for the prediction of tissue:plasma partition coefficients for drug residues in natural casings.

    NARCIS (Netherlands)

    Haritova, A.M.; Fink-Gremmels, J.

    2010-01-01

    Tissue residues arise from the exposure of animals to undesirable substances in animal feed materials and drinking water and to the therapeutic or zootechnical use of veterinary medicinal products. In the framework of this study, an advanced toxicokinetic model was developed to predict the

  10. Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir.

    Science.gov (United States)

    Walsh, Ann W; Langley, David R; Colonno, Richard J; Tenney, Daniel J

    2010-02-12

    Entecavir (ETV) is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV) polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr) is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT) domain involve lamivudine-resistance (LVDr) substitutions in the conserved YMDD motif (M204V/I +/- L180M), plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M) and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i)) for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat)) in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP) binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of comprehensive substitutions of each ETVr position

  11. Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir.

    Directory of Open Access Journals (Sweden)

    Ann W Walsh

    Full Text Available BACKGROUND: Entecavir (ETV is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT domain involve lamivudine-resistance (LVDr substitutions in the conserved YMDD motif (M204V/I +/- L180M, plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. METHODS/PRINCIPAL FINDINGS: To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of

  12. Prediction of beta-turns from amino acid sequences using the residue-coupled model.

    Science.gov (United States)

    Guruprasad, K; Shukla, S

    2003-04-01

    We evaluated the prediction of beta-turns from amino acid sequences using the residue-coupled model with an enlarged representative protein data set selected from the Protein Data Bank. Our results show that the probability values derived from a data set comprising 425 protein chains yielded an overall beta-turn prediction accuracy 68.74%, compared with 94.7% reported earlier on a data set of 30 proteins using the same method. However, we noted that the overall beta-turn prediction accuracy using probability values derived from the 30-protein data set reduces to 40.74% when tested on the data set comprising 425 protein chains. In contrast, using probability values derived from the 425 data set used in this analysis, the overall beta-turn prediction accuracy yielded consistent results when tested on either the 30-protein data set (64.62%) used earlier or a more recent representative data set comprising 619 protein chains (64.66%) or on a jackknife data set comprising 476 representative protein chains (63.38%). We therefore recommend the use of probability values derived from the 425 representative protein chains data set reported here, which gives more realistic and consistent predictions of beta-turns from amino acid sequences.

  13. Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles.

    Science.gov (United States)

    Uzun, Lokman; Uzek, Recep; Senel, Serap; Say, Ridvan; Denizli, Adil

    2013-08-01

    In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Molecular modeling of polycarbonate materials: Glass transition and mechanical properties

    Science.gov (United States)

    Palczynski, Karol; Wilke, Andreas; Paeschke, Manfred; Dzubiella, Joachim

    2017-09-01

    Linking the experimentally accessible macroscopic properties of thermoplastic polymers to their microscopic static and dynamic properties is a key requirement for targeted material design. Classical molecular dynamics simulations enable us to study the structural and dynamic behavior of molecules on microscopic scales, and statistical physics provides a framework for relating these properties to the macroscopic properties. We take a first step toward creating an automated workflow for the theoretical prediction of thermoplastic material properties by developing an expeditious method for parameterizing a simple yet surprisingly powerful coarse-grained bisphenol-A polycarbonate model which goes beyond previous coarse-grained models and successfully reproduces the thermal expansion behavior, the glass transition temperature as a function of the molecular weight, and several elastic properties.

  15. Jacobian elliptic wave solutions in an anharmonic molecular crystal model

    International Nuclear Information System (INIS)

    Teh, C.G.R.; Lee, B.S.; Koo, W.K.

    1997-07-01

    Explicit Jacobian elliptic wave solutions are found in the anharmonic molecular crystal model for both the continuum limit and discrete modes. This class of wave solutions include the famous pulse-like and kink-like solitary modes. We would also like to report on the existence of some highly discrete staggered solitary wave modes not found in the continuum limit. (author). 9 refs, 1 fig

  16. Development of Circular Disk Model for Polymeric Nanocomposites and Micromechanical Analysis of Residual Stresses in Reinforced Fibers with Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    A. R. Ghasemi

    2017-02-01

    Full Text Available In this study, Circular Disk Model (CDM has been developed to determine the residual stresses in twophase and three- phase unit cell. The two-phase unit cell is consisting of carbon fiber and matrix. The three-phase unit cell is consisting of carbon fiber, carbon nanotubes and matrix in which the carbon fiber is reinforced with the carbon nanotube using electrophoresis method. For different volume fractions of carbon nanotubes, thermal properties of the carbon fiber and carbon nanotube in different linear and lateral directions and also different placement conditions of carbon nanotubes have been considered. Also, residual stresses distribution in two and three phases has been studied, separately. Results of micromechanical analysis of residual stresses obtained from Finite Element Method and CDM, confirms the evaluation and development of three dimensional CDM.

  17. Composite Cure Process Modeling and Simulations using COMPRO(Registered Trademark) and Validation of Residual Strains using Fiber Optics Sensors

    Science.gov (United States)

    Sreekantamurthy, Thammaiah; Hudson, Tyler B.; Hou, Tan-Hung; Grimsley, Brian W.

    2016-01-01

    Composite cure process induced residual strains and warping deformations in composite components present significant challenges in the manufacturing of advanced composite structure. As a part of the Manufacturing Process and Simulation initiative of the NASA Advanced Composite Project (ACP), research is being conducted on the composite cure process by developing an understanding of the fundamental mechanisms by which the process induced factors influence the residual responses. In this regard, analytical studies have been conducted on the cure process modeling of composite structural parts with varied physical, thermal, and resin flow process characteristics. The cure process simulation results were analyzed to interpret the cure response predictions based on the underlying physics incorporated into the modeling tool. In the cure-kinetic analysis, the model predictions on the degree of cure, resin viscosity and modulus were interpreted with reference to the temperature distribution in the composite panel part and tool setup during autoclave or hot-press curing cycles. In the fiber-bed compaction simulation, the pore pressure and resin flow velocity in the porous media models, and the compaction strain responses under applied pressure were studied to interpret the fiber volume fraction distribution predictions. In the structural simulation, the effect of temperature on the resin and ply modulus, and thermal coefficient changes during curing on predicted mechanical strains and chemical cure shrinkage strains were studied to understand the residual strains and stress response predictions. In addition to computational analysis, experimental studies were conducted to measure strains during the curing of laminated panels by means of optical fiber Bragg grating sensors (FBGs) embedded in the resin impregnated panels. The residual strain measurements from laboratory tests were then compared with the analytical model predictions. The paper describes the cure process

  18. Evaluation of gastrointestinal solubilization of petroleum hydrocarbon residues in soil using an in vitro physiologically based model.

    Science.gov (United States)

    Holman, Hoi-Ying N; Goth-Goldstein, Regine; Aston, David; Yun, Mao; Kengsoontra, Jenny

    2002-03-15

    Petroleum hydrocarbon residues in weathered soils may pose risks to humans through the ingestion pathway. To understand the factors controlling their gastrointestinal (GI) absorption, a newly developed experimental extraction protocol was used to model the GI solubility of total petroleum hydrocarbon (TPH) residues in highly weathered soils from different sites. The GI solubility of TPH residues was significantly higher for soil contaminated with diesel than with crude oil. Compared to the solubility of TPH residues during fasted state,the solubility of TPH residues during fat digestion was much greater. Diesel solubility increased from an average of 8% during the "gallbladder empty" phase of fasting (and less than 0.2% during the otherfasting phase) to an average of 16% during fat digestion. For crude oil, the solubility increased from an average of 1.2% during the gallbladder empty phase of fasting (and undetectable during the other fasting phase) to an average of 4.5% during fat digestion. Increasing the concentration of bile salts also increased GI solubility. GI solubility was reduced by soil organic carbon but enhanced by the TPH content.

  19. Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles

    International Nuclear Information System (INIS)

    Uzun, Lokman; Uzek, Recep; Şenel, Serap; Say, Ridvan; Denizli, Adil

    2013-01-01

    In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes. Highlights: • Lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles • Direct incorporation of the fluorescent complex into polymeric backbone. • Imprinting by assistance of cupric ion coordination into nanoparticles • Evaluation of the chiral biorecognition ability of nanoparticles • Simultaneous selective separation and fluorescent monitoring

  20. Chiral recognition of proteins having L-histidine residues on the surface with lanthanide ion complex incorporated-molecularly imprinted fluorescent nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Uzun, Lokman, E-mail: lokman@hacettepe.edu.tr [Hacettepe University, Department of Chemistry, 06381, Ankara (Turkey); Uzek, Recep; Şenel, Serap [Hacettepe University, Department of Chemistry, 06381, Ankara (Turkey); Say, Ridvan [Anadolu University, Department of Chemistry, 26470, Eskisehir (Turkey); Denizli, Adil [Hacettepe University, Department of Chemistry, 06381, Ankara (Turkey)

    2013-08-01

    In this study, lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles were synthesized. A combination of three novel approaches was applied for the purpose. First, lanthanide ions [Terbium(III)] were complexed with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine amino acid, in order to incorporate the complex directly into the polymeric backbone. At the second stage, L-histidine molecules imprinted nanoparticles were utilized instead of whole protein imprinting in order to avoid whole drawbacks such as fragility, complexity, denaturation tendency, and conformation dependency. At the third stage following the first two steps mentioned above, imprinted L-histidine was coordinated with cupric ions [Cu(II)] to conduct the study under mild conditions. Then, molecularly imprinted fluorescent nanoparticles synthesized were used for L-histidine adsorption from aqueous solution to optimize conditions for adsorption and fluorimetric detection. Finally, usability of nanoparticles was investigated for chiral biorecognition using stereoisomer, D-histidine, racemic mixture, D,L-histidine, proteins with surface L-histidine residue, lysozyme, cytochrome C, or without ribonuclease A. The results revealed that the proposed polymerization strategy could make significant contribution to the solution of chronic problems of fluorescent component introduction into polymers. Additionally, the fluorescent nanoparticles reported here could be used for selective separation and fluorescent monitoring purposes. Highlights: • Lanthanide ion complex incorporated molecularly imprinted fluorescent nanoparticles • Direct incorporation of the fluorescent complex into polymeric backbone. • Imprinting by assistance of cupric ion coordination into nanoparticles • Evaluation of the chiral biorecognition ability of nanoparticles • Simultaneous selective separation and fluorescent monitoring.

  1. Development of a prediction model for residual disease in newly diagnosed advanced ovarian cancer.

    Science.gov (United States)

    Janco, Jo Marie Tran; Glaser, Gretchen; Kim, Bohyun; McGree, Michaela E; Weaver, Amy L; Cliby, William A; Dowdy, Sean C; Bakkum-Gamez, Jamie N

    2015-07-01

    To construct a tool, using computed tomography (CT) imaging and preoperative clinical variables, to estimate successful primary cytoreduction for advanced epithelial ovarian cancer (EOC). Women who underwent primary cytoreductive surgery for stage IIIC/IV EOC at Mayo Clinic between 1/2/2003 and 12/30/2011 and had preoperative CT images of the abdomen and pelvis within 90days prior to their surgery available for review were included. CT images were reviewed for large-volume ascites, diffuse peritoneal thickening (DPT), omental cake, lymphadenopathy (LP), and spleen or liver involvement. Preoperative factors included age, body mass index (BMI), Eastern Cooperative Oncology Group performance status (ECOG PS), American Society of Anesthesiologists (ASA) score, albumin, CA-125, and thrombocytosis. Two prediction models were developed to estimate the probability of (i) complete and (ii) suboptimal cytoreduction (residual disease (RD) >1cm) using multivariable logistic analysis with backward and stepwise variable selection methods. Internal validation was assessed using bootstrap resampling to derive an optimism-corrected estimate of the c-index. 279 patients met inclusion criteria: 143 had complete cytoreduction, 26 had suboptimal cytoreduction (RD>1cm), and 110 had measurable RD ≤1cm. On multivariable analysis, age, absence of ascites, omental cake, and DPT on CT imaging independently predicted complete cytoreduction (c-index=0.748). Conversely, predictors of suboptimal cytoreduction were ECOG PS, DPT, and LP on preoperative CT imaging (c-index=0.685). The generated models serve as preoperative evaluation tools that may improve counseling and selection for primary surgery, but need to be externally validated. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. A stochastic phase-field model determined from molecular dynamics

    KAUST Repository

    von Schwerin, Erik; Szepessy, Anders

    2010-01-01

    The dynamics of dendritic growth of a crystal in an undercooled melt is determined by macroscopic diffusion-convection of heat and by capillary forces acting on the nanometer scale of the solid-liquid interface width. Its modelling is useful for instance in processing techniques based on casting. The phase-field method is widely used to study evolution of such microstructural phase transformations on a continuum level; it couples the energy equation to a phenomenological Allen-Cahn/Ginzburg-Landau equation modelling the dynamics of an order parameter determining the solid and liquid phases, including also stochastic fluctuations to obtain the qualitatively correct result of dendritic side branching. This work presents a method to determine stochastic phase-field models from atomistic formulations by coarse-graining molecular dynamics. It has three steps: (1) a precise quantitative atomistic definition of the phase-field variable, based on the local potential energy; (2) derivation of its coarse-grained dynamics model, from microscopic Smoluchowski molecular dynamics (that is Brownian or over damped Langevin dynamics); and (3) numerical computation of the coarse-grained model functions. The coarse-grained model approximates Gibbs ensemble averages of the atomistic phase-field, by choosing coarse-grained drift and diffusion functions that minimize the approximation error of observables in this ensemble average. © EDP Sciences, SMAI, 2010.

  3. A stochastic phase-field model determined from molecular dynamics

    KAUST Repository

    von Schwerin, Erik

    2010-03-17

    The dynamics of dendritic growth of a crystal in an undercooled melt is determined by macroscopic diffusion-convection of heat and by capillary forces acting on the nanometer scale of the solid-liquid interface width. Its modelling is useful for instance in processing techniques based on casting. The phase-field method is widely used to study evolution of such microstructural phase transformations on a continuum level; it couples the energy equation to a phenomenological Allen-Cahn/Ginzburg-Landau equation modelling the dynamics of an order parameter determining the solid and liquid phases, including also stochastic fluctuations to obtain the qualitatively correct result of dendritic side branching. This work presents a method to determine stochastic phase-field models from atomistic formulations by coarse-graining molecular dynamics. It has three steps: (1) a precise quantitative atomistic definition of the phase-field variable, based on the local potential energy; (2) derivation of its coarse-grained dynamics model, from microscopic Smoluchowski molecular dynamics (that is Brownian or over damped Langevin dynamics); and (3) numerical computation of the coarse-grained model functions. The coarse-grained model approximates Gibbs ensemble averages of the atomistic phase-field, by choosing coarse-grained drift and diffusion functions that minimize the approximation error of observables in this ensemble average. © EDP Sciences, SMAI, 2010.

  4. Molecular modeling in the development of metal radiopharmaceuticals

    International Nuclear Information System (INIS)

    Green, M.A.

    1993-10-01

    We began this project with a compilation of a structural library to serve as a data base containing descriptions of the molecular features of metal-labeled radiopharmaceuticals known to efficiently cross the blood-brain barrier. Such a data base is needed in order to identify structural features (size, shape, molecular surface areas and volumes) that are critical in allowing blood-brain barrier penetration. Nine metal complexes have been added to this structural library. We have completed a detailed comparison of four molecular mechanics computer programs QUANTA, SYBYL, BOYD, and MM2DREW to assess their applicability to modeling the structures of low molecular weight metal complexes. We tested the ability of each program to reproduce the crystallographic structures of 38 complexes between nickel(II) and saturated N-donor ligands. The programs were evaluated in terns of their ability to reproduce structural features such as bond lengths, bond angles, and torsion angles. Recently, we investigated the synthesis and characterization of lipophilic cationic gallium complexes with hexadentate bis(salicylaldimine) ligands. This work identified the first gallium-68 radiopharrnaceuticals that can be injected intravenously and that subsequently exhibit significant myocardial uptake followed by prolonged myocardial retention of 68 Ga radioactivity. Tracers of this type remain under investigation as agents for evaluation of myocardial perfusion with positron emission tomography

  5. Two Models of Magnetic Support for Photoevaporated Molecular Clouds

    International Nuclear Information System (INIS)

    Ryutov, D; Kane, J; Mizuta, A; Pound, M; Remington, B

    2004-01-01

    The thermal pressure inside molecular clouds is insufficient for maintaining the pressure balance at an ablation front at the cloud surface illuminated by nearby UV stars. Most probably, the required stiffness is provided by the magnetic pressure. After surveying existing models of this type, we concentrate on two of them: the model of a quasi-homogeneous magnetic field and the recently proposed model of a ''magnetostatic turbulence''. We discuss observational consequences of the two models, in particular, the structure and the strength of the magnetic field inside the cloud and in the ionized outflow. We comment on the possible role of reconnection events and their observational signatures. We mention laboratory experiments where the most significant features of the models can be tested

  6. Molecular model for solubility of gases in flexible polymers

    DEFF Research Database (Denmark)

    Neergaard, Jesper; Hassager, Ole; Szabo, Peter

    1999-01-01

    We propose a model for a priori prediction of the solubility of gases in flexible polymers. The model is based on the concept of ideal solubility of gases in liquids. According to this concept, the mole fraction of gases in liquids is given by Raoult's law with the total pressure and the vapor...... pressure of the gas, where the latter may have to be extrapolated. However, instead of considering each polymer molecule as a rigid structure, we estimate the effective number of degrees of freedom from an equivalent freely jointed bead-rod model for the flexible polymer. In this model, we associate...... the length of the rods with the molecular weight corresponding to a Kuhn step. The model provides a tool for crude estimation of the gas solubility on the basis of only the monomer unit of the polymer and properties of the gas. A comparison with the solubility data for several gases in poly...

  7. A restraint molecular dynamics and simulated annealing approach for protein homology modeling utilizing mean angles

    Directory of Open Access Journals (Sweden)

    Maurer Till

    2005-04-01

    Full Text Available Abstract Background We have developed the program PERMOL for semi-automated homology modeling of proteins. It is based on restrained molecular dynamics using a simulated annealing protocol in torsion angle space. As main restraints defining the optimal local geometry of the structure weighted mean dihedral angles and their standard deviations are used which are calculated with an algorithm described earlier by Döker et al. (1999, BBRC, 257, 348–350. The overall long-range contacts are established via a small number of distance restraints between atoms involved in hydrogen bonds and backbone atoms of conserved residues. Employing the restraints generated by PERMOL three-dimensional structures are obtained using standard molecular dynamics programs such as DYANA or CNS. Results To test this modeling approach it has been used for predicting the structure of the histidine-containing phosphocarrier protein HPr from E. coli and the structure of the human peroxisome proliferator activated receptor γ (Ppar γ. The divergence between the modeled HPr and the previously determined X-ray structure was comparable to the divergence between the X-ray structure and the published NMR structure. The modeled structure of Ppar γ was also very close to the previously solved X-ray structure with an RMSD of 0.262 nm for the backbone atoms. Conclusion In summary, we present a new method for homology modeling capable of producing high-quality structure models. An advantage of the method is that it can be used in combination with incomplete NMR data to obtain reasonable structure models in accordance with the experimental data.

  8. MULTI: a shared memory approach to cooperative molecular modeling.

    Science.gov (United States)

    Darden, T; Johnson, P; Smith, H

    1991-03-01

    A general purpose molecular modeling system, MULTI, based on the UNIX shared memory and semaphore facilities for interprocess communication is described. In addition to the normal querying or monitoring of geometric data, MULTI also provides processes for manipulating conformations, and for displaying peptide or nucleic acid ribbons, Connolly surfaces, close nonbonded contacts, crystal-symmetry related images, least-squares superpositions, and so forth. This paper outlines the basic techniques used in MULTI to ensure cooperation among these specialized processes, and then describes how they can work together to provide a flexible modeling environment.

  9. Molecular level in silico studies for oncology. Direct models review

    Science.gov (United States)

    Psakhie, S. G.; Tsukanov, A. A.

    2017-09-01

    The combination of therapy and diagnostics in one process "theranostics" is a trend in a modern medicine, especially in oncology. Such an approach requires development and usage of multifunctional hybrid nanoparticles with a hierarchical structure. Numerical methods and mathematical models play a significant role in the design of the hierarchical nanoparticles and allow looking inside the nanoscale mechanisms of agent-cell interactions. The current position of in silico approach in biomedicine and oncology is discussed. The review of the molecular level in silico studies in oncology, which are using the direct models, is presented.

  10. Can molecular dynamics simulations help in discriminating correct from erroneous protein 3D models?

    Directory of Open Access Journals (Sweden)

    Gibrat Jean-François

    2008-01-01

    Full Text Available Abstract Background Recent approaches for predicting the three-dimensional (3D structure of proteins such as de novo or fold recognition methods mostly rely on simplified energy potential functions and a reduced representation of the polypeptide chain. These simplifications facilitate the exploration of the protein conformational space but do not permit to capture entirely the subtle relationship that exists between the amino acid sequence and its native structure. It has been proposed that physics-based energy functions together with techniques for sampling the conformational space, e.g., Monte Carlo or molecular dynamics (MD simulations, are better suited to the task of modelling proteins at higher resolutions than those of models obtained with the former type of methods. In this study we monitor different protein structural properties along MD trajectories to discriminate correct from erroneous models. These models are based on the sequence-structure alignments provided by our fold recognition method, FROST. We define correct models as being built from alignments of sequences with structures similar to their native structures and erroneous models from alignments of sequences with structures unrelated to their native structures. Results For three test sequences whose native structures belong to the all-α, all-β and αβ classes we built a set of models intended to cover the whole spectrum: from a perfect model, i.e., the native structure, to a very poor model, i.e., a random alignment of the test sequence with a structure belonging to another structural class, including several intermediate models based on fold recognition alignments. We submitted these models to 11 ns of MD simulations at three different temperatures. We monitored along the corresponding trajectories the mean of the Root-Mean-Square deviations (RMSd with respect to the initial conformation, the RMSd fluctuations, the number of conformation clusters, the evolution of

  11. Bayesian semiparametric regression models to characterize molecular evolution

    Directory of Open Access Journals (Sweden)

    Datta Saheli

    2012-10-01

    Full Text Available Abstract Background Statistical models and methods that associate changes in the physicochemical properties of amino acids with natural selection at the molecular level typically do not take into account the correlations between such properties. We propose a Bayesian hierarchical regression model with a generalization of the Dirichlet process prior on the distribution of the regression coefficients that describes the relationship between the changes in amino acid distances and natural selection in protein-coding DNA sequence alignments. Results The Bayesian semiparametric approach is illustrated with simulated data and the abalone lysin sperm data. Our method identifies groups of properties which, for this particular dataset, have a similar effect on evolution. The model also provides nonparametric site-specific estimates for the strength of conservation of these properties. Conclusions The model described here is distinguished by its ability to handle a large number of amino acid properties simultaneously, while taking into account that such data can be correlated. The multi-level clustering ability of the model allows for appealing interpretations of the results in terms of properties that are roughly equivalent from the standpoint of molecular evolution.

  12. Effect of the spray volume adjustment model on the efficiency of fungicides and residues in processing tomato

    Energy Technology Data Exchange (ETDEWEB)

    Ratajkiewicz, H.; Kierzek, R.; Raczkowski, M.; Hołodyńska-Kulas, A.; Łacka, A.; Wójtowicz, A.; Wachowiak, M.

    2016-11-01

    This study compared the effects of a proportionate spray volume (PSV) adjustment model and a fixed model (300 L/ha) on the infestation of processing tomato with potato late blight (Phytophthora infestans (Mont.) de Bary) (PLB) and azoxystrobin and chlorothalonil residues in fruits in three consecutive seasons. The fungicides were applied in alternating system with or without two spreader adjuvants. The proportionate spray volume adjustment model was based on the number of leaves on plants and spray volume index. The modified Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method was optimized and validated for extraction of azoxystrobin and chlorothalonil residue. Gas chromatography with a nitrogen and phosphorus detector and an electron capture detector were used for the analysis of fungicides. The results showed that higher fungicidal residues were connected with lower infestation of tomato with PLB. PSV adjustment model resulted in lower infestation of tomato than the fixed model (300 L/ha) when fungicides were applied at half the dose without adjuvants. Higher expected spray interception into the tomato canopy with the PSV system was recognized as the reasons of better control of PLB. The spreader adjuvants did not have positive effect on the biological efficacy of spray volume application systems. The results suggest that PSV adjustment model can be used to determine the spray volume for fungicide application for processing tomato crop. (Author)

  13. Effect of the spray volume adjustment model on the efficiency of fungicides and residues in processing tomato

    Directory of Open Access Journals (Sweden)

    Henryk Ratajkiewicz

    2016-08-01

    Full Text Available This study compared the effects of a proportionate spray volume (PSV adjustment model and a fixed model (300 L/ha on the infestation of processing tomato with potato late blight (Phytophthora infestans (Mont. de Bary (PLB and azoxystrobin and chlorothalonil residues in fruits in three consecutive seasons. The fungicides were applied in alternating system with or without two spreader adjuvants. The proportionate spray volume adjustment model was based on the number of leaves on plants and spray volume index. The modified Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS method was optimized and validated for extraction of azoxystrobin and chlorothalonil residue. Gas chromatography with a nitrogen and phosphorus detector and an electron capture detector were used for the analysis of fungicides. The results showed that higher fungicidal residues were connected with lower infestation of tomato with PLB. PSV adjustment model resulted in lower infestation of tomato than the fixed model (300 L/ha when fungicides were applied at half the dose without adjuvants. Higher expected spray interception into the tomato canopy with the PSV system was recognized as the reasons of better control of PLB. The spreader adjuvants did not have positive effect on the biological efficacy of spray volume application systems. The results suggest that PSV adjustment model can be used to determine the spray volume for fungicide application for processing tomato crop.

  14. Theoretical model for calculation of molecular stopping power

    International Nuclear Information System (INIS)

    Xu, Y.J.

    1984-01-01

    A modified local plasma model based on the work of Linhard-Winther, Bethe, Brown, and Walske is established. The Gordon-Kim's molecular charged density model is employed to obtain a formula to evaluate the stopping power of many useful molecular systems. The stopping power of H 2 and He gas was calculated for incident proton energy ranging from 100 KeV to 2.5 MeV. The stopping power of O 2 , N 2 , and water vapor was also calculated for incident proton energy ranging from 40 keV to 2.5 MeV. Good agreement with experimental data was obtained. A discussion of molecular effects leading to departure from Bragg's rule is presented. The equipartition rule and the effect of nuclear momentum recoiling in stopping power are also discussed in the appendix. The calculation procedure presented hopefully can easily be extended to include the most useful organic systems such as the molecules composed of carbon, nitrogen, hydrogen and oxygen which are useful in radiation protection field

  15. Molecular modeling of the microstructure evolution during carbon fiber processing

    Science.gov (United States)

    Desai, Saaketh; Li, Chunyu; Shen, Tongtong; Strachan, Alejandro

    2017-12-01

    The rational design of carbon fibers with desired properties requires quantitative relationships between the processing conditions, microstructure, and resulting properties. We developed a molecular model that combines kinetic Monte Carlo and molecular dynamics techniques to predict the microstructure evolution during the processes of carbonization and graphitization of polyacrylonitrile (PAN)-based carbon fibers. The model accurately predicts the cross-sectional microstructure of the fibers with the molecular structure of the stabilized PAN fibers and physics-based chemical reaction rates as the only inputs. The resulting structures exhibit key features observed in electron microcopy studies such as curved graphitic sheets and hairpin structures. In addition, computed X-ray diffraction patterns are in good agreement with experiments. We predict the transverse moduli of the resulting fibers between 1 GPa and 5 GPa, in good agreement with experimental results for high modulus fibers and slightly lower than those of high-strength fibers. The transverse modulus is governed by sliding between graphitic sheets, and the relatively low value for the predicted microstructures can be attributed to their perfect longitudinal texture. Finally, the simulations provide insight into the relationships between chemical kinetics and the final microstructure; we observe that high reaction rates result in porous structures with lower moduli.

  16. Naumovozyma castellii: an alternative model for budding yeast molecular biology.

    Science.gov (United States)

    Karademir Andersson, Ahu; Cohn, Marita

    2017-03-01

    Naumovozyma castellii (Saccharomyces castellii) is a member of the budding yeast family Saccharomycetaceae. It has been extensively used as a model organism for telomere biology research and has gained increasing interest as a budding yeast model for functional analyses owing to its amenability to genetic modifications. Owing to the suitable phylogenetic distance to S. cerevisiae, the whole genome sequence of N. castellii has provided unique data for comparative genomic studies, and it played a key role in the establishment of the timing of the whole genome duplication and the evolutionary events that took place in the subsequent genomic evolution of the Saccharomyces lineage. Here we summarize the historical background of its establishment as a laboratory yeast species, and the development of genetic and molecular tools and strains. We review the research performed on N. castellii, focusing on areas where it has significantly contributed to the discovery of new features of molecular biology and to the advancement of our understanding of molecular evolution. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. A comparative modeling and molecular docking study on Mycobacterium tuberculosis targets involved in peptidoglycan biosynthesis.

    Science.gov (United States)

    Fakhar, Zeynab; Naiker, Suhashni; Alves, Claudio N; Govender, Thavendran; Maguire, Glenn E M; Lameira, Jeronimo; Lamichhane, Gyanu; Kruger, Hendrik G; Honarparvar, Bahareh

    2016-11-01

    An alarming rise of multidrug-resistant Mycobacterium tuberculosis strains and the continuous high global morbidity of tuberculosis have reinvigorated the need to identify novel targets to combat the disease. The enzymes that catalyze the biosynthesis of peptidoglycan in M. tuberculosis are essential and noteworthy therapeutic targets. In this study, the biochemical function and homology modeling of MurI, MurG, MraY, DapE, DapA, Alr, and Ddl enzymes of the CDC1551 M. tuberculosis strain involved in the biosynthesis of peptidoglycan cell wall are reported. Generation of the 3D structures was achieved with Modeller 9.13. To assess the structural quality of the obtained homology modeled targets, the models were validated using PROCHECK, PDBsum, QMEAN, and ERRAT scores. Molecular dynamics simulations were performed to calculate root mean square deviation (RMSD) and radius of gyration (Rg) of MurI and MurG target proteins and their corresponding templates. For further model validation, RMSD and Rg for selected targets/templates were investigated to compare the close proximity of their dynamic behavior in terms of protein stability and average distances. To identify the potential binding mode required for molecular docking, binding site information of all modeled targets was obtained using two prediction algorithms. A docking study was performed for MurI to determine the potential mode of interaction between the inhibitor and the active site residues. This study presents the first accounts of the 3D structural information for the selected M. tuberculosis targets involved in peptidoglycan biosynthesis.

  18. Use of Residual Biomass from the Textile Industry as Carbon Source for Production of a Low-Molecular-Weight Xylanase from Aspergillus oryzae

    Directory of Open Access Journals (Sweden)

    Gilvan Caetano Duarte

    2012-10-01

    Full Text Available Pretreated dirty cotton residue (PDCR from the textile industry was used as an alternative carbon source for the submerged cultivation of Aspergillus oryzae and the production of xylanases. The filtered culture supernatant was fractionated by ultrafiltration followed by three chromatographic steps, which resulted in the isolation of a homogeneous low-molecular-weight xylanase (Xyl-O1 with a mass of 21.5 kDa as determined by sodium dodecyl sulfate-polyacrilamide gel electrophoresis (SDS-PAGE co-polymerized with 0.1% oat spelt xylan. Enzyme catalysis was the most efficient at 50 °C and pH 6.0. The Km values (mg·mL−1 for the soluble fraction of oat spelt and birchwood xylans were 10.05 and 3.34, respectively. Xyl-O1 was more stable in the presence of 5,5-dithio-bis-(2-nitrobenzoic acid (DTNB, 1,4-dithiothreitol (DTT, l-cysteine or β-mercaptoethanol, which increased the rate of catalysis by 40%, 14%, 40% or 37%, respectively. The enzyme stability was improved at pH 7.0 in the presence of 20 mM l-cysteine, with the retention of nearly 100% of the activity after 6 h at 50 °C. Xyl-O1 catalyzed the cleavage of internal β-1,4 linkages of the soluble substrates containing d-xylose residues, with a maximum efficiency of 33% for the hydrolysis of birchwood xylan after 12 h of incubation. Identification of the hydrolysis products by high-performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD indicated the predominance of the hydrolysis products X2-X6 during the first 12 h of incubation and the accumulation of higher xylooligomers after the elution of the last xylooligomer standard, xylohexaose.

  19. Homology modeling, molecular docking and DNA binding studies of nucleotide excision repair UvrC protein from M. tuberculosis.

    Science.gov (United States)

    Parulekar, Rishikesh S; Barage, Sagar H; Jalkute, Chidambar B; Dhanavade, Maruti J; Fandilolu, Prayagraj M; Sonawane, Kailas D

    2013-08-01

    Mycobacterium tuberculosis is a Gram positive, acid-fast bacteria belonging to genus Mycobacterium, is the leading causative agent of most cases of tuberculosis. The pathogenicity of the bacteria is enhanced by its developed DNA repair mechanism which consists of machineries such as nucleotide excision repair. Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. UvrC protein is a part of this complex and thus helps to repair the damaged DNA of M. tuberculosis. Hence, structural bioinformatics study of UvrC protein from M. tuberculosis was carried out using homology modeling and molecular docking techniques. Assessment of the reliability of the homology model was carried out by predicting its secondary structure along with its model validation. The predicted structure was docked with the ATP and the interacting amino acid residues of UvrC protein with the ATP were found to be TRP539, PHE89, GLU536, ILE402 and ARG575. The binding of UvrC protein with the DNA showed two different domains. The residues from domain I of the protein VAL526, THR524 and LEU521 interact with the DNA whereas, amino acids interacting from the domain II of the UvrC protein included ARG597, GLU595, GLY594 and GLY592 residues. This predicted model could be useful to design new inhibitors of UvrC enzyme to prevent pathogenesis of Mycobacterium and so the tuberculosis.

  20. Advances in molecular modeling of human cytochrome P450 polymorphism.

    Science.gov (United States)

    Martiny, Virginie Y; Miteva, Maria A

    2013-11-01

    Cytochrome P450 (CYP) is a supergene family of metabolizing enzymes involved in the phase I metabolism of drugs and endogenous compounds. CYP oxidation often leads to inactive drug metabolites or to highly toxic or carcinogenic metabolites involved in adverse drug reactions (ADR). During the last decade, the impact of CYP polymorphism in various drug responses and ADR has been demonstrated. Of the drugs involved in ADR, 56% are metabolized by polymorphic phase I metabolizing enzymes, 86% among them being CYP. Here, we review the major CYP polymorphic forms, their impact for drug response and current advances in molecular modeling of CYP polymorphism. We focus on recent studies exploring CYP polymorphism performed by the use of sequence-based and/or protein-structure-based computational approaches. The importance of understanding the molecular mechanisms related to CYP polymorphism and drug response at the atomic level is outlined. © 2013.

  1. Towards structural models of molecular recognition in olfactory receptors.

    Science.gov (United States)

    Afshar, M; Hubbard, R E; Demaille, J

    1998-02-01

    The G protein coupled receptors (GPCR) are an important class of proteins that act as signal transducers through the cytoplasmic membrane. Understanding the structure and activation mechanism of these proteins is crucial for understanding many different aspects of cellular signalling. The olfactory receptors correspond to the largest family of GPCRs. Very little is known about how the structures of the receptors govern the specificity of interaction which enables identification of particular odorant molecules. In this paper, we review recent developments in two areas of molecular modelling: methods for modelling the configuration of trans-membrane helices and methods for automatic docking of ligands into receptor structures. We then show how a subset of these methods can be combined to construct a model of a rat odorant receptor interacting with lyral for which experimental data are available. This modelling can help us make progress towards elucidating the specificity of interactions between receptors and odorant molecules.

  2. Effects of glass composition on the residual rate of alteration and modelling parameters

    International Nuclear Information System (INIS)

    Fleury, Benjamin

    2013-01-01

    This PhD thesis deals with the long-term behavior of the French nuclear glasses R7T7. An experiment plan (based on 27 glass compositions) is developed for studying the effect of glass composition on the residual rate of alteration. The impact of Mg-phase precipitation on glass alteration is also studied and several modelling exercises are performed. There is one order of magnitude between the different measurements (rate or pH...) associated with the different glass compositions. The statistical treatment of these measurements results in predictive equations and several observable trends are valid for all materials with a composition complying with the experiment plan conditions. The effect of Si, Na, B and Al on alteration (.i.e, gel and secondary phase's formation, pH) is confirmed, the influence of Zn, Zr and Ni-Co is evidenced. The role of Cr has to be clarified. Experiments show that glass alteration rate in underground water, which contains high level of Ca and Mg, is one order of magnitude higher than in the case of pure water. The glass composition plays the same role for the alteration in the two types of solution. During alteration, the late addition of Mg introduces a time lag in the resumption response because silicon is first provided from partial dissolution of the previously-formed alteration gel. The nucleation process does not limit Mg-silicate precipitation whereas a pH above 8-8.5 is necessary for Mg-silicate precipitation. The glass alteration rate can be a limiting factor if the quantity of Mg supplied to the reaction is enough. The Mg silicate phase seems to have systematically a molar ratio Mg/Si between 0.2 and 0.4. It is also shown that the air tightness of the reactor influences the rate of dissolution of CO 2 in the solution leading to a decrease of pH. Finally, modelling exercises with GRAAL show promising results. Such modelling is required in order to extend the prediction of the long-term alteration behavior to different glass

  3. Application of grey model on analyzing the passive natural circulation residual heat removal system of HTR-10

    Institute of Scientific and Technical Information of China (English)

    ZHOU Tao; PENG Changhong; WANG Zenghui; WANG Ruosu

    2008-01-01

    Using the grey correlation analysis, it can be concluded that the reactor pressure vessel wall temperature has the strongest effect on the passive residual heat removal system in HTR (High Temperature gas-cooled Reactor),the chimney height takes the second place, and the influence of inlet air temperature of the chimney is the least. This conclusion is the same as that analyzed by the traditional method. According to the grey model theory, the GM(1,1) and GM(1, 3) model are built based on the inlet air temperature of chimney, pressure vessel temperature and the chimney height. Then the effect of three factors on the heat removal power is studied in this paper. The model plays an important role on data prediction, and is a new method for studying the heat removal power. The method can provide a new theoretical analysis to the passive residual heat removal system of HTR.

  4. Learning Probabilistic Models of Hydrogen Bond Stability from Molecular Dynamics Simulation Trajectories

    KAUST Repository

    Chikalov, Igor

    2011-04-02

    Hydrogen bonds (H-bonds) play a key role in both the formation and stabilization of protein structures. H-bonds involving atoms from residues that are close to each other in the main-chain sequence stabilize secondary structure elements. H-bonds between atoms from distant residues stabilize a protein’s tertiary structure. However, H-bonds greatly vary in stability. They form and break while a protein deforms. For instance, the transition of a protein from a nonfunctional to a functional state may require some H-bonds to break and others to form. The intrinsic strength of an individual H-bond has been studied from an energetic viewpoint, but energy alone may not be a very good predictor. Other local interactions may reinforce (or weaken) an H-bond. This paper describes inductive learning methods to train a protein-independent probabilistic model of H-bond stability from molecular dynamics (MD) simulation trajectories. The training data describes H-bond occurrences at successive times along these trajectories by the values of attributes called predictors. A trained model is constructed in the form of a regression tree in which each non-leaf node is a Boolean test (split) on a predictor. Each occurrence of an H-bond maps to a path in this tree from the root to a leaf node. Its predicted stability is associated with the leaf node. Experimental results demonstrate that such models can predict H-bond stability quite well. In particular, their performance is roughly 20% better than that of models based on H-bond energy alone. In addition, they can accurately identify a large fraction of the least stable H-bonds in a given conformation. The paper discusses several extensions that may yield further improvements.

  5. The numerical high cycle fatigue damage model of fillet weld joint under weld-induced residual stresses

    Science.gov (United States)

    Nguyen Van Do, Vuong

    2018-04-01

    In this study, a development of nonlinear continuum damage mechanics (CDM) model for multiaxial high cycle fatigue is proposed in which the cyclic plasticity constitutive model has been incorporated in the finite element (FE) framework. T-joint FE simulation of fillet welding is implemented to characterize sequentially coupled three-dimensional (3-D) of thermo-mechanical FE formulation and simulate the welding residual stresses. The high cycle fatigue damage model is then taken account into the fillet weld joints under the various cyclic fatigue load types to calculate the fatigue life considering the residual stresses. The fatigue crack initiation and the propagation in the present model estimated for the total fatigue is compared with the experimental results. The FE results illustrated that the proposed high cycle fatigue damage model in this study could become a powerful tool to effectively predict the fatigue life of the welds. Parametric studies in this work are also demonstrated that the welding residual stresses cannot be ignored in the computation of the fatigue life of welded structures.

  6. Exploring a model of human chemokine receptor CCR2 in presence of TAK779: A membrane based molecular dynamics study

    Science.gov (United States)

    Balupuri, Anand; Sobhia, M. Elizabeth

    2014-04-01

    Chemokine receptor 2 (CCR2) is a G-protein coupled receptor (GPCR) and a crucial target for various inflammation-driven diseases. In the present study, molecular docking and molecular dynamics simulations were performed on a CCR2 homology model. This work includes the comparative MD simulations of uncomplexed and ‘antagonist-complexed’ CCR2 models. These simulations yield insights into the binding mechanism of antagonist TAK779 and improve the understanding of various structural changes induced by the ligand in the CCR2 protein. Here, one 20 ns MD simulation was carried out on the uncomplexed CCR2 model in lipid bilayer to explore the effects of lipid membrane on the protein. Another 20 ns MD simulation was performed under the similar conditions on the docked CCR2-TAK779 complex. An alteration in the position and orientation of the ligand in binding site was observed after the simulation. Examination of protein-ligand complex suggested that TAK779 produced a greater structural change on the TM-III, TM-IV, TM-V and TM-VI than TM-I, TM-II and TM-VII. Interaction networks involving the conserved residues of uncomplexed and ‘antagonist-complexed’ CCR2 models were also examined. The major difference was observed to be the role of conserved residues of the DRY motif of TM-III and the NPxxY motif of TM-VII of CCR2.

  7. Validating clustering of molecular dynamics simulations using polymer models

    Directory of Open Access Journals (Sweden)

    Phillips Joshua L

    2011-11-01

    Full Text Available Abstract Background Molecular dynamics (MD simulation is a powerful technique for sampling the meta-stable and transitional conformations of proteins and other biomolecules. Computational data clustering has emerged as a useful, automated technique for extracting conformational states from MD simulation data. Despite extensive application, relatively little work has been done to determine if the clustering algorithms are actually extracting useful information. A primary goal of this paper therefore is to provide such an understanding through a detailed analysis of data clustering applied to a series of increasingly complex biopolymer models. Results We develop a novel series of models using basic polymer theory that have intuitive, clearly-defined dynamics and exhibit the essential properties that we are seeking to identify in MD simulations of real biomolecules. We then apply spectral clustering, an algorithm particularly well-suited for clustering polymer structures, to our models and MD simulations of several intrinsically disordered proteins. Clustering results for the polymer models provide clear evidence that the meta-stable and transitional conformations are detected by the algorithm. The results for the polymer models also help guide the analysis of the disordered protein simulations by comparing and contrasting the statistical properties of the extracted clusters. Conclusions We have developed a framework for validating the performance and utility of clustering algorithms for studying molecular biopolymer simulations that utilizes several analytic and dynamic polymer models which exhibit well-behaved dynamics including: meta-stable states, transition states, helical structures, and stochastic dynamics. We show that spectral clustering is robust to anomalies introduced by structural alignment and that different structural classes of intrinsically disordered proteins can be reliably discriminated from the clustering results. To our

  8. Chemical modelling of trace elements in pore water from PFBC residues containing ammonia

    International Nuclear Information System (INIS)

    Karlsson, L.G.; Brandberg, F.

    1993-01-01

    Ammonia is added to the PFBC process with the purpose to reduce the emissions of NO x in the stack gases. The design of the system for cleaning the stack gases will lead to an increased adsorption of ammonia and an accumulation of soluble ammonium salts in the cyclone ash from PFBC processes. This can be an environmental problem since the amounts will increase over the coming years and there will be a need to dispose the residues. When infiltrating rainwater penetrates the disposed residues ammonia and ammonium salts result in a contamination of the pore water with ammonia in the disposed residues. This entail the solubility of several trace elements in the residues that form soluble complexes with ammonia will increase and cause an increased contamination of groundwater and surface water. In this study the increased solubilities is calculated for the trace elements cadmium, cobalt, copper, mercury, nickel, silver and zinc in the residues using thermodynamical data. The calculations have been performed with probable solid phases of the trace elements at oxidizing and reducing conditions as a function of pH and at varying concentration of ammonia in the pore water. The thermodynamic calculations have been performed with the geochemical code EQ3NR. The results from the calculations show that as a concentration of 17 mg NH 3 /l in the pore water of the residues increases the solubilities for copper and silver. If the concentration of ammonia increases to 170 mg NH 3 /l will the solubilities increase also for cadmium, nickel and zinc. (12 refs., 39 figs.)

  9. FAO/IAEA model protocol for the determination of bound residues in soil

    International Nuclear Information System (INIS)

    1986-01-01

    A protocol for determining bound pesticide residue content in soils was developed and collaboratively tested by 11 members of the FAO/IAEA Research Co-ordination Committee. The method assumes prior incubation of soil with a radioactive pesticide or related organic compound. The major process steps of the protocol include: (a) Soxhlet extraction of air-dry soil with methanol for 24 h; (b) determination of radioactivity in unextracted soil, in methanol-extracted soil (yielding bound residue content), and in the methanol extract (yielding extractable residue content); and (c) use of triplicate samples per analysis. The participants received lysimeter soils treated six to seven years earlier with 14 C-allyl alcohol (Soil A) or 14 C-hexachloro-benzene (Soil H). The inter-laboratory results first indicated non-homogeneity of Soil A sub-samples, since the initial and bound radioactivity for four laboratories was about half of that found by the remaining seven laboratories. Intra-laboratory (in one laboratory) analyses of sub-subsamples from six 'high-group' laboratories, two 'low-group' laboratories and two additional laboratories confirmed the homogeneity of Soil A and implicated error in the combustion methods at 'low-group' laboratories. The intra- and inter-laboratory coefficients of variation for initial 14 C-content were 4.7% and 7.0%, respectively. Of the residual 14 C in Soil A, 95% was bound; in contrast, only 15% of 14 C in Soil H was bound. The coefficients of variation among ten laboratories, for Soil H, were 8.4% and 18.1% for percentage extractable residue and percentage bound residue, respectively. Some limited testing of alternative protocols, using other solvents or batch extraction, confirmed that the IAEA protocol was most efficient in the extraction of non-bound radioactivity; pre-wetting Soil A may, however, improve extraction. (author)

  10. A kinetic model of trp-cage folding from multiple biased molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Fabrizio Marinelli

    2009-08-01

    Full Text Available Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, its folding mechanism is not yet fully understood. Indeed, some experiments suggest a two-state behavior, while others point to the presence of intermediates. In this work we show that the results of a bias-exchange metadynamics simulation can be used for constructing a detailed thermodynamic and kinetic model of the system. The model, although constructed from a biased simulation, has a quality similar to those extracted from the analysis of long unbiased molecular dynamics trajectories. This is demonstrated by a careful benchmark of the approach on a smaller system, the solvated Ace-Ala3-Nme peptide. For theTrp-cage folding, the model predicts that the relaxation time of 3100 ns observed experimentally is due to the presence of a compact molten globule-like conformation. This state has an occupancy of only 3% at 300 K, but acts as a kinetic trap.Instead, non-compact structures relax to the folded state on the sub-microsecond timescale. The model also predicts the presence of a state at Calpha-RMSD of 4.4 A from the NMR structure in which the Trp strongly interacts with Pro12. This state can explain the abnormal temperature dependence of the Pro12-delta3 and Gly11-alpha3 chemical shifts. The structures of the two most stable misfolded intermediates are in agreement with NMR experiments on the unfolded protein. Our work shows that, using biased molecular dynamics trajectories, it is possible to construct a model describing in detail the Trp-cage folding kinetics and thermodynamics in agreement with experimental data.

  11. Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    2017-09-01

    Full Text Available Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1 hyperinsulinemia may be due to the drastically reduced activity (and binding affinity of the mutant insulins. 2 Y26BS and Y26BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

  12. A molecular-thermodynamic model for polyelectrolyte solutions

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, J.; Liu, H.; Hu, Y. [Thermodynamics Research Laboratory, East China University of Science and Technology, Shanghai 200237 (China); Prausnitz, J.M. [Department of Chemical Engineering, University of California, Berkeley, and Chemical Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley, California 94720 (United States)

    1998-01-01

    Polyelectrolyte solutions are modeled as freely tangent-jointed, charged hard-sphere chains and corresponding counterions in a continuum medium with permitivity {var_epsilon}. By adopting the sticky-point model, the Helmholtz function for polyelectrolyte solutions is derived through the r-particle cavity-correlation function (CCF) for chains of sticky, charged hard spheres. The r-CCF is approximated by a product of effective nearest-neighbor two-particle CCFs; these are determined from the hypernetted-chain and mean-spherical closures (HNC/MSA) inside and outside the hard core, respectively, for the integral equation theory for electrolytes. The colligative properties are given as explicit functions of a scaling parameter {Gamma} that can be estimated by a simple iteration procedure. Osmotic pressures, osmotic coefficients, and activity coefficients are calculated for model solutions with various chain lengths. They are in good agreement with molecular simulation and experimental results. {copyright} {ital 1998 American Institute of Physics.}

  13. Structural and Molecular Modeling Features of P2X Receptors

    Directory of Open Access Journals (Sweden)

    Luiz Anastacio Alves

    2014-03-01

    Full Text Available Currently, adenosine 5'-triphosphate (ATP is recognized as the extracellular messenger that acts through P2 receptors. P2 receptors are divided into two subtypes: P2Y metabotropic receptors and P2X ionotropic receptors, both of which are found in virtually all mammalian cell types studied. Due to the difficulty in studying membrane protein structures by X-ray crystallography or NMR techniques, there is little information about these structures available in the literature. Two structures of the P2X4 receptor in truncated form have been solved by crystallography. Molecular modeling has proven to be an excellent tool for studying ionotropic receptors. Recently, modeling studies carried out on P2X receptors have advanced our knowledge of the P2X receptor structure-function relationships. This review presents a brief history of ion channel structural studies and shows how modeling approaches can be used to address relevant questions about P2X receptors.

  14. Analysis and radiological assessment of residues containing NORM materials resulting from earlier activities including modelling of typical industrial residues. Pt. 1. Historical investigation of the radiological relevance of NORM residues and concepts for site identification

    International Nuclear Information System (INIS)

    Reichelt, Andreas; Niedermayer, Matthias; Sitte, Beate; Hamel, Peter Michael

    2007-01-01

    Natural radionuclides are part of the human environment and of the raw materials used. Technical processes may cause their accumulation in residues, and the result will be so-called NORM materials (Naturally occurring radioactive material). The amended Radiation Protection Ordinance (StrlSchV 2001) specifies how the public should be protected, but there are also residues dating back before the issuing of the StrlSchV 2001, the so-called NORM residues. The project intended to assess the risks resulting from these residues. It comprises four parts. Part 1 was for clarification of the radiological relevance of NORM residues and for the development of concepts to detect them. The criterion for their radiological relevance was their activity per mass unit and the material volume accumulated through the centuries. The former was calculated from a wide bibliographic search in the relevant literature on radiation protection, while the mass volume was obtained by a detailed historical search of the consumption of materials that may leave NORM residues. These are, in particular, residues from coal and ore mining and processing. To identify concrete sites, relevant data sources were identified, and a concept for identification of concrete NORM residues was developed on this basis. (orig.) [de

  15. Application of Molecular Modeling to Urokinase Inhibitors Development

    Directory of Open Access Journals (Sweden)

    V. B. Sulimov

    2014-01-01

    Full Text Available Urokinase-type plasminogen activator (uPA plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program, postprocessing (DISCORE program, direct generalized docking (FLM program, and the application of the quantum chemical calculations (MOPAC package, search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM.

  16. Cross-link guided molecular modeling with ROSETTA.

    Directory of Open Access Journals (Sweden)

    Abdullah Kahraman

    Full Text Available Chemical cross-links identified by mass spectrometry generate distance restraints that reveal low-resolution structural information on proteins and protein complexes. The technology to reliably generate such data has become mature and robust enough to shift the focus to the question of how these distance restraints can be best integrated into molecular modeling calculations. Here, we introduce three workflows for incorporating distance restraints generated by chemical cross-linking and mass spectrometry into ROSETTA protocols for comparative and de novo modeling and protein-protein docking. We demonstrate that the cross-link validation and visualization software Xwalk facilitates successful cross-link data integration. Besides the protocols we introduce XLdb, a database of chemical cross-links from 14 different publications with 506 intra-protein and 62 inter-protein cross-links, where each cross-link can be mapped on an experimental structure from the Protein Data Bank. Finally, we demonstrate on a protein-protein docking reference data set the impact of virtual cross-links on protein docking calculations and show that an inter-protein cross-link can reduce on average the RMSD of a docking prediction by 5.0 Å. The methods and results presented here provide guidelines for the effective integration of chemical cross-link data in molecular modeling calculations and should advance the structural analysis of particularly large and transient protein complexes via hybrid structural biology methods.

  17. 4D-PET reconstruction using a spline-residue model with spatial and temporal roughness penalties

    Science.gov (United States)

    Ralli, George P.; Chappell, Michael A.; McGowan, Daniel R.; Sharma, Ricky A.; Higgins, Geoff S.; Fenwick, John D.

    2018-05-01

    4D reconstruction of dynamic positron emission tomography (dPET) data can improve the signal-to-noise ratio in reconstructed image sequences by fitting smooth temporal functions to the voxel time-activity-curves (TACs) during the reconstruction, though the optimal choice of function remains an open question. We propose a spline-residue model, which describes TACs as weighted sums of convolutions of the arterial input function with cubic B-spline basis functions. Convolution with the input function constrains the spline-residue model at early time-points, potentially enhancing noise suppression in early time-frames, while still allowing a wide range of TAC descriptions over the entire imaged time-course, thus limiting bias. Spline-residue based 4D-reconstruction is compared to that of a conventional (non-4D) maximum a posteriori (MAP) algorithm, and to 4D-reconstructions based on adaptive-knot cubic B-splines, the spectral model and an irreversible two-tissue compartment (‘2C3K’) model. 4D reconstructions were carried out using a nested-MAP algorithm including spatial and temporal roughness penalties. The algorithms were tested using Monte-Carlo simulated scanner data, generated for a digital thoracic phantom with uptake kinetics based on a dynamic [18F]-Fluromisonidazole scan of a non-small cell lung cancer patient. For every algorithm, parametric maps were calculated by fitting each voxel TAC within a sub-region of the reconstructed images with the 2C3K model. Compared to conventional MAP reconstruction, spline-residue-based 4D reconstruction achieved  >50% improvements for five of the eight combinations of the four kinetics parameters for which parametric maps were created with the bias and noise measures used to analyse them, and produced better results for 5/8 combinations than any of the other reconstruction algorithms studied, while spectral model-based 4D reconstruction produced the best results for 2/8. 2C3K model-based 4D reconstruction generated

  18. New models and molecular markers in evaluation of developmental toxicity

    International Nuclear Information System (INIS)

    Huuskonen, Hannele

    2005-01-01

    Mammalian and non-mammalian embryos and embryonic stem cells may be used as models in mechanistic studies and in testing embryotoxicity of compounds. In addition to conventional culture methods, genetic modifications and use of molecular markers offer significant advantages in mechanistic studies as well as in developing new test methods for embryotoxicity. Zebrafish model has been used for a long time and at present several applications are available. It is an easy vertebral non-mammalian model, whose genome is largely known and several genetic modifications are easily constructed to study gene expression or knocked down genes. Fluorescent marker proteins can be used also in zebrafish to indicate gene activation in transgenic models. Chemical genetics approach has been developed using zebrafish model. This is a new approach to screen small molecules that regulate signaling pathways. Embryonic stem cells have been used in mechanistic studies and mouse embryonic stem cell test has been validated to study embryotoxicity in vitro. This method has been improved using quantitative measurements of molecular endpoints by real-time RT-PCR or fluorescent activated cell sorting methods (FACS). Methods facilitating differentiation to several different cell types are available. We have studied preimplantation mouse embryos as a possible model for in vitro testing. In this method, superovulated and in vivo fertilized preimplantation embryos were collected at morula stage and cultured up to blastocysts. The mouse preimplantation culture test was improved by quantitative gene expression measurement using two-step real-time RT-PCR methods. New endpoints improve the tests of in vitro embryotoxicity because subjective assessments are replaced by objective measurements. In addition, automation is possible and less time is needed for analysis. Thus, high throughput screening will come possible to test large numbers of compounds

  19. Molecular Simulation towards Efficient and Representative Subsurface Reservoirs Modeling

    KAUST Repository

    Kadoura, Ahmad

    2016-09-01

    This dissertation focuses on the application of Monte Carlo (MC) molecular simulation and Molecular Dynamics (MD) in modeling thermodynamics and flow of subsurface reservoir fluids. At first, MC molecular simulation is proposed as a promising method to replace correlations and equations of state in subsurface flow simulators. In order to accelerate MC simulations, a set of early rejection schemes (conservative, hybrid, and non-conservative) in addition to extrapolation methods through reweighting and reconstruction of pre-generated MC Markov chains were developed. Furthermore, an extensive study was conducted to investigate sorption and transport processes of methane, carbon dioxide, water, and their mixtures in the inorganic part of shale using both MC and MD simulations. These simulations covered a wide range of thermodynamic conditions, pore sizes, and fluid compositions shedding light on several interesting findings. For example, the possibility to have more carbon dioxide adsorbed with more preadsorbed water concentrations at relatively large basal spaces. The dissertation is divided into four chapters. The first chapter corresponds to the introductory part where a brief background about molecular simulation and motivations are given. The second chapter is devoted to discuss the theoretical aspects and methodology of the proposed MC speeding up techniques in addition to the corresponding results leading to the successful multi-scale simulation of the compressible single-phase flow scenario. In chapter 3, the results regarding our extensive study on shale gas at laboratory conditions are reported. At the fourth and last chapter, we end the dissertation with few concluding remarks highlighting the key findings and summarizing the future directions.

  20. Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin

    International Nuclear Information System (INIS)

    Xiong, Wei; Liu, Liang; Wang, Wen-Quan; Tang, Zhao-You; Ren, Zheng-Gang; Qiu, Shuang-Jian; Sun, Hui-Chuan; Wang, Lu; Liu, Bin-Bin; Li, Qi-Song; Zhang, Wei; Zhu, Xiao-Dong

    2010-01-01

    The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC

  1. A Refined Model for the Structure of Acireductone Dioxygenase from Klebsiella ATCC 8724 Incorporating Residual Dipolar Couplings

    Energy Technology Data Exchange (ETDEWEB)

    Pochapsky, Thomas C., E-mail: pochapsk@brandeis.edu; Pochapsky, Susan S.; Ju Tingting [Brandeis University, Department of Chemistry (United States); Hoefler, Chris [Brandeis University, Department of Biochemistry (United States); Liang Jue [Brandeis University, Department of Chemistry (United States)

    2006-02-15

    Acireductone dioxygenase (ARD) from Klebsiella ATCC 8724 is a metalloenzyme that is capable of catalyzing different reactions with the same substrates (acireductone and O{sub 2}) depending upon the metal bound in the active site. A model for the solution structure of the paramagnetic Ni{sup 2+}-containing ARD has been refined using residual dipolar couplings (RDCs) measured in two media. Additional dihedral restraints based on chemical shift (TALOS) were included in the refinement, and backbone structure in the vicinity of the active site was modeled from a crystallographic structure of the mouse homolog of ARD. The incorporation of residual dipolar couplings into the structural refinement alters the relative orientations of several structural features significantly, and improves local secondary structure determination. Comparisons between the solution structures obtained with and without RDCs are made, and structural similarities and differences between mouse and bacterial enzymes are described. Finally, the biological significance of these differences is considered.

  2. Residual water transport in the Marsdiep tidal inlet inferred from observations and a numerical model

    NARCIS (Netherlands)

    Sassi, M.G.; Gerkema, T.; Duran-Matute, M.; Nauw, J.J.

    2016-01-01

    At tidal inlets, large amounts of water are exchanged with the adjacent sea during the tidal cycle.The residual flows, the net effect of ebb and flood, are generally small compared with the gross flux;they vary in magnitude and sign from one tidal period to the other; and their long-term mean

  3. Residual water transport in the Marsdiep tidal inlet inferred from observations and a numerical model

    NARCIS (Netherlands)

    Sassi, M.G.; Gerkema, T.; Duran-Matute, M.; Nauw, J.J.

    At tidal inlets, large amounts of water are exchanged with the adjacent sea during the tidal cycle. The residual flows, the net effect of ebb and flood, are generally small compared with the gross flux; they vary in magnitude and sign from one tidal period to the other; and their long-term mean

  4. Geochemical modeling of leaching from MSWI air-pollution control residues

    NARCIS (Netherlands)

    Astrup, T.; Dijkstra, J.J.; Comans, R.N.J.; Sloot, van der H.A.; Christensen, T.H.

    2006-01-01

    This paper provides an improved understanding of the leaching behavior of waste incineration air-pollution-control (APC) residues in a long-term perspective. Leaching was investigated by a series of batch experiments reflecting leaching conditions after initial washout of highly soluble salts from

  5. POPULATION DIVERSITY IN MODEL DRINKING WATER BIOFILMS RECEIVING CHLORINE OR MONOCHLORAMINE RESIDUAL

    Science.gov (United States)

    Most water utilities add monochloramine or chlorine as a residual disinfectant in potable water distribution systems (WDS) to control bacterial regrowth. While monochloramine is considered more stable than chlorine, little is known about the fate of this disinfectant or the effec...

  6. Optical modeling of a corneal inlay in real eyes to increase depth of focus: optimum centration and residual defocus.

    Science.gov (United States)

    Tabernero, Juan; Artal, Pablo

    2012-02-01

    To determine the optimum position to center a small-aperture corneal inlay and the effect of residual defocus in the surgical eye to maximize depth of focus. Laboratorio de Óptica, Universidad de Murcia, Murcia, Spain. Cohort study. Personalized eye models were built using actual data (corneal topography, eye length, ocular aberrations, and eye alignment). A small aperture 1.6 mm in diameter was placed at the corneal plane in each model. The monochromatic and polychromatic Strehl ratios were calculated as a function of the pinhole position. Different residual defocus values were also incorporated into the models, and the through-focus Strehl ratios were calculated. Sixteen eye models were built. For most subjects, the optimum location of the aperture for distance vision was close to the corneal reflex position. For a given optimized centration of the aperture, the best compromise of depth of focus was obtained when the eyes had some residual myopic defocus (range -0.75 to -1.00 diopter [D]). Strehl ratio values were over 0.1 for far distance, which led to visual acuities better than 20/20. The depth of focus was 2.50 D with a mean near visual acuity of Jaeger 1 or better. In eyes with little astigmatism and aberrations, the optimum centration of the small aperture was near the corneal reflex position. To improve optical outcomes with the inlay, some small residual myopia and correction of corneal astigmatism might be required. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  7. Tyrosine residues modification studied by MALDI-TOF mass spectrometry

    International Nuclear Information System (INIS)

    Santrucek, Jiri; Strohalm, Martin; Kadlcik, Vojtech; Hynek, Radovan; Kodicek, Milan

    2004-01-01

    Amino acid residue-specific reactivity in proteins is of great current interest in structural biology as it provides information about solvent accessibility and reactivity of the residue and, consequently, about protein structure and possible interactions. In the work presented tyrosine residues of three model proteins with known spatial structure are modified with two tyrosine-specific reagents: tetranitromethane and iodine. Modified proteins were specifically digested by proteases and the mass of resulting peptide fragments was determined using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. Our results show that there are only small differences in the extent of tyrosine residues modification by tetranitromethane and iodine. However, data dealing with accessibility of reactive residues obtained by chemical modifications are not completely identical with those obtained by nuclear magnetic resonance and X-ray crystallography. These interesting discrepancies can be caused by local molecular dynamics and/or by specific chemical structure of the residues surrounding

  8. Validity and reliability of a novel 3D scanner for assessment of the shape and volume of amputees' residual limb models.

    Directory of Open Access Journals (Sweden)

    Elena Seminati

    Full Text Available Objective assessment methods to monitor residual limb volume following lower-limb amputation are required to enhance practitioner-led prosthetic fitting. Computer aided systems, including 3D scanners, present numerous advantages and the recent Artec Eva scanner, based on laser free technology, could potentially be an effective solution for monitoring residual limb volumes.The aim of this study was to assess the validity and reliability of the Artec Eva scanner (practical measurement against a high precision laser 3D scanner (criterion measurement for the determination of residual limb model shape and volume.Three observers completed three repeat assessments of ten residual limb models, using both the scanners. Validity of the Artec Eva scanner was assessed (mean percentage error <2% and Bland-Altman statistics were adopted to assess the agreement between the two scanners. Intra and inter-rater reliability (repeatability coefficient <5% of the Artec Eva scanner was calculated for measuring indices of residual limb model volume and shape (i.e. residual limb cross sectional areas and perimeters.Residual limb model volumes ranged from 885 to 4399 ml. Mean percentage error of the Artec Eva scanner (validity was 1.4% of the criterion volumes. Correlation coefficients between the Artec Eva and the Romer determined variables were higher than 0.9. Volume intra-rater and inter-rater reliability coefficients were 0.5% and 0.7%, respectively. Shape percentage maximal error was 2% at the distal end of the residual limb, with intra-rater reliability coefficients presenting the lowest errors (0.2%, both for cross sectional areas and perimeters of the residual limb models.The Artec Eva scanner is a valid and reliable method for assessing residual limb model shapes and volumes. While the method needs to be tested on human residual limbs and the results compared with the current system used in clinical practice, it has the potential to quantify shape and volume

  9. Structural modeling and molecular simulation analysis of HvAP2/EREBP from barley.

    Science.gov (United States)

    Pandey, Bharati; Sharma, Pradeep; Tyagi, Chetna; Goyal, Sukriti; Grover, Abhinav; Sharma, Indu

    2016-06-01

    AP2/ERF transcription factors play a critical role in plant development and stress adaptation. This study reports the three-dimensional ab initio-based model of AP2/EREBP protein of barley and its interaction with DNA. Full-length coding sequence of HvAP2/EREBP gene isolated from two Indian barley cultivars, RD 2503 and RD 31, was used to model the protein. Of five protein models obtained, the one with lowest C-score was chosen for further analysis. The N- and C-terminal regions of HvAP2 protein were found to be highly disordered. The dynamic properties of AP2/EREBP and its interaction with DNA were investigated by molecular dynamics simulation. Analysis of trajectories from simulation yielded the equilibrated conformation between 2-10ns for protein and 7-15ns for protein-DNA complex. We established relationship between DNA having GCC box and DNA-binding domain of HvAP2/EREBP was established by modeling 11-base-pair-long nucleotide sequence and HvAP2/EREBP protein using ab initio method. Analysis of protein-DNA interaction showed that a β-sheet motif constituting amino acid residues THR105, ARG100, ARG93, and ARG83 seems to play important role in stabilizing the complex as they form strong hydrogen bond interactions with the DNA motif. Taken together, this study provides first-hand comprehensive information detailing structural conformation and interactions of HvAP2/EREBP proteins in barley. The study intensifies the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information. It also provides molecular insight into protein-DNA binding for understanding and enhancing abiotic stress resistance for improving the water use efficiency in crop plants.

  10. Regression models for the restricted residual mean life for right-censored and left-truncated data

    DEFF Research Database (Denmark)

    Cortese, Giuliana; Holmboe, Stine A.; Scheike, Thomas H.

    2017-01-01

    The hazard ratios resulting from a Cox's regression hazards model are hard to interpret and to be converted into prolonged survival time. As the main goal is often to study survival functions, there is increasing interest in summary measures based on the survival function that are easier to inter......The hazard ratios resulting from a Cox's regression hazards model are hard to interpret and to be converted into prolonged survival time. As the main goal is often to study survival functions, there is increasing interest in summary measures based on the survival function that are easier...... to interpret than the hazard ratio; the residual mean time is an important example of those measures. However, because of the presence of right censoring, the tail of the survival distribution is often difficult to estimate correctly. Therefore, we consider the restricted residual mean time, which represents...... a partial area under the survival function, given any time horizon τ, and is interpreted as the residual life expectancy up to τ of a subject surviving up to time t. We present a class of regression models for this measure, based on weighted estimating equations and inverse probability of censoring weighted...

  11. Statistical molecular design of balanced compound libraries for QSAR modeling.

    Science.gov (United States)

    Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

    2010-01-01

    A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

  12. Multiscale Molecular Dynamics Model for Heterogeneous Charged Systems

    Science.gov (United States)

    Stanton, L. G.; Glosli, J. N.; Murillo, M. S.

    2018-04-01

    Modeling matter across large length scales and timescales using molecular dynamics simulations poses significant challenges. These challenges are typically addressed through the use of precomputed pair potentials that depend on thermodynamic properties like temperature and density; however, many scenarios of interest involve spatiotemporal variations in these properties, and such variations can violate assumptions made in constructing these potentials, thus precluding their use. In particular, when a system is strongly heterogeneous, most of the usual simplifying assumptions (e.g., spherical potentials) do not apply. Here, we present a multiscale approach to orbital-free density functional theory molecular dynamics (OFDFT-MD) simulations that bridges atomic, interionic, and continuum length scales to allow for variations in hydrodynamic quantities in a consistent way. Our multiscale approach enables simulations on the order of micron length scales and 10's of picosecond timescales, which exceeds current OFDFT-MD simulations by many orders of magnitude. This new capability is then used to study the heterogeneous, nonequilibrium dynamics of a heated interface characteristic of an inertial-confinement-fusion capsule containing a plastic ablator near a fuel layer composed of deuterium-tritium ice. At these scales, fundamental assumptions of continuum models are explored; features such as the separation of the momentum fields among the species and strong hydrogen jetting from the plastic into the fuel region are observed, which had previously not been seen in hydrodynamic simulations.

  13. Molecular Modeling Studies of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Haiyan Qian

    2016-09-01

    Full Text Available 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11β-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11β-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11β-HSD1 inhibitors.

  14. Molecular Modeling Studies of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations.

    Science.gov (United States)

    Qian, Haiyan; Chen, Jiongjiong; Pan, Youlu; Chen, Jianzhong

    2016-09-19

    11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11β-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11β-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11β-HSD1 inhibitors.

  15. Interactive display of molecular models using a microcomputer system

    Science.gov (United States)

    Egan, J. T.; Macelroy, R. D.

    1980-01-01

    A simple, microcomputer-based, interactive graphics display system has been developed for the presentation of perspective views of wire frame molecular models. The display system is based on a TERAK 8510a graphics computer system with a display unit consisting of microprocessor, television display and keyboard subsystems. The operating system includes a screen editor, file manager, PASCAL and BASIC compilers and command options for linking and executing programs. The graphics program, written in USCD PASCAL, involves the centering of the coordinate system, the transformation of centered model coordinates into homogeneous coordinates, the construction of a viewing transformation matrix to operate on the coordinates, clipping invisible points, perspective transformation and scaling to screen coordinates; commands available include ZOOM, ROTATE, RESET, and CHANGEVIEW. Data file structure was chosen to minimize the amount of disk storage space. Despite the inherent slowness of the system, its low cost and flexibility suggests general applicability.

  16. Energetics and efficiency of a molecular motor model

    International Nuclear Information System (INIS)

    Fogedby, Hans C; Svane, Axel

    2013-01-01

    The energetics and efficiency of a linear molecular motor model proposed by Mogilner et al are analyzed from an analytical point of view. The model, which is based on protein friction with a track, is described by coupled Langevin equations for the motion in combination with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor are addressed using a many body scheme with focus on the efficiency at maximum power (EMP). It is found that the EMP is reduced from about 10% in a heuristic description of the motor to about 1 per mille when incorporating the full motor dynamics, owing to the strong dissipation associated with the motor action. (paper)

  17. A review of molecular modelling of electric double layer capacitors.

    Science.gov (United States)

    Burt, Ryan; Birkett, Greg; Zhao, X S

    2014-04-14

    Electric double-layer capacitors are a family of electrochemical energy storage devices that offer a number of advantages, such as high power density and long cyclability. In recent years, research and development of electric double-layer capacitor technology has been growing rapidly, in response to the increasing demand for energy storage devices from emerging industries, such as hybrid and electric vehicles, renewable energy, and smart grid management. The past few years have witnessed a number of significant research breakthroughs in terms of novel electrodes, new electrolytes, and fabrication of devices, thanks to the discovery of innovative materials (e.g. graphene, carbide-derived carbon, and templated carbon) and the availability of advanced experimental and computational tools. However, some experimental observations could not be clearly understood and interpreted due to limitations of traditional theories, some of which were developed more than one hundred years ago. This has led to significant research efforts in computational simulation and modelling, aimed at developing new theories, or improving the existing ones to help interpret experimental results. This review article provides a summary of research progress in molecular modelling of the physical phenomena taking place in electric double-layer capacitors. An introduction to electric double-layer capacitors and their applications, alongside a brief description of electric double layer theories, is presented first. Second, molecular modelling of ion behaviours of various electrolytes interacting with electrodes under different conditions is reviewed. Finally, key conclusions and outlooks are given. Simulations on comparing electric double-layer structure at planar and porous electrode surfaces under equilibrium conditions have revealed significant structural differences between the two electrode types, and porous electrodes have been shown to store charge more efficiently. Accurate electrolyte and

  18. A n-vector model for charge transport in molecular semiconductors.

    Science.gov (United States)

    Jackson, Nicholas E; Kohlstedt, Kevin L; Chen, Lin X; Ratner, Mark A

    2016-11-28

    We develop a lattice model utilizing coarse-grained molecular sites to study charge transport in molecular semiconducting materials. The model bridges atomistic descriptions and structureless lattice models by mapping molecular structure onto sets of spatial vectors isomorphic with spin vectors in a classical n-vector Heisenberg model. Specifically, this model incorporates molecular topology-dependent orientational and intermolecular coupling preferences, including the direct inclusion of spatially correlated transfer integrals and site energy disorder. This model contains the essential physics required to explicitly simulate the interplay of molecular topology and correlated structural disorder, and their effect on charge transport. As a demonstration of its utility, we apply this model to analyze the effects of long-range orientational correlations, molecular topology, and intermolecular interaction strength on charge motion in bulk molecular semiconductors.

  19. The influence of a residual group in low-molecular-weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE- and IgG-binding properties.

    Science.gov (United States)

    Cirković, T; Gavrović-Jankulović, M; Prisić, S; Jankov, R M; Burazer, L; Vucković, O; Sporcić, Z; Paranos, S

    2002-11-01

    Reaction of epsilon-amino groups of lysine with potassium cyanate, maleic, or succinic anhydride leads to allergoids of low molecular weight. No study has been performed to compare their properties and investigate the influence of a residual group on allergenicity and human IgE- and IgG-binding of these derivatives. Allergoids of a pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, and succinic and maleic anhydride. Biochemical properties were investigated by determination of amino groups, enzyme activity, isoelectric focusing IEF and SDS-PAGE. IgE- and IgG-binding was determined using immunoblots and ELISA inhibition. Allergenicity was investigated by skin prick tests (SPT) on a group of 52 patients, of which 6 were control subjects, 30 were patients with no previous immunotherapy (IT), and 16 were patients undergoing immunotherapy. The same degree of amino-group modification (more than 85%), residual enzyme activity (less then 15%), IEF, and SDS-PAGE pattern were noted. In the immunoblots of IgE-binding, there was more pronounced reduction in the succinyl and maleyl derivatives than in the carbamyl one. IgG-binding was less affected by carbamylation than by acid anhydride modification. The SPT showed that the succinylated derivative had the most reduced allergenicity (98% showed a reduced wheal diameter when tested with the succinyl derivative, 87% with the maleyl allergoid, and 83% with the carbamyl allergoid). The most significant difference among allergoids could be seen in the group of patients with high skin reactivity (83% of patients showed no reaction to the succinyl derivative when compared to the value of 28% for the carbamyl derivative or 22% for the maleyl derivative). According to our results, all three modification procedures yielded allergoids with a similar extent of modification. No single biochemical parameter investigated in the study could predict the degree of reduced allergenicity in vivo. The most reduced

  20. A residual life prediction model based on the generalized σ -N curved surface

    OpenAIRE

    Zongwen AN; Xuezong BAI; Jianxiong GAO

    2016-01-01

    In order to investigate change rule of the residual life of structure under random repeated load, firstly, starting from the statistic meaning of random repeated load, the joint probability density function of maximum stress and minimum stress is derived based on the characteristics of order statistic (maximum order statistic and minimum order statistic); then, based on the equation of generalized σ -N curved surface, considering the influence of load cycles number on fatigue life, a relation...

  1. Modeling long-term carbon residue in the ocean-atmosphere system following large CO2 emissions

    Science.gov (United States)

    Towles, N. J.; Olson, P.; Gnanadesikan, A.

    2013-12-01

    We use the LOSCAR carbon cycle model (Zeebe et al., 2009; Zeebe, 2012) to calculate the residual carbon in the ocean and atmosphere following large CO2 emissions. We consider the system response to CO2 emissions ranging from 100 to 20000 PgC, and emission durations from 100 yr to 100 kyr, subject to a wide range of system parameters such as the strengths of silicate weathering and the oceanic biological carbon pump. We define the carbon gain factor as the ratio of residual carbon in the ocean-atmosphere to the total emitted carbon. For moderate sized emissions shorter than about 50 kyr, we find that the carbon gain factor grows during the emission and peaks at about 1.7, primarily due to the erosion of carbonate marine sediments. In contrast, for longer emissions, the carbon gain factor peaks at a smaller value, and for very large emissions (more than 5000 PgC), the gain factor decreases with emission size due to carbonate sediment exhaustion. This gain factor is sensitive to model parameters such as low latitude efficiency of the biological pump. The timescale for removal of the residual carbon (reducing the carbon gain factor to zero) depends strongly on the assumed sensitivity of silicate weathering to atmospheric pCO2, and ranges from less than one million years to several million years.

  2. Modeling and Parameter Optimization for Surface Roughness and Residual Stress in Dry Turning Process

    Directory of Open Access Journals (Sweden)

    M. H. El-Axir

    2017-10-01

    Full Text Available The influence of some turning variables and tool overhang on surface roughness parameters and residual stress induced due to machining 6061-T6 aluminum alloy is investigated in this paper. Four input parameters (cutting speed, feed rate, depth of cut and tool overhang are considered. Tests are carried out by precision turning operation on a lathe. Design of experiment techniques, i.e. response surface methodology (RSM and Taguchi's technique have been used to accomplish the objective of the experimental study. Surface roughness parameters are measured using a portable surface roughness device while residual stresses are measured employing deflection-etching technique using electrochemical analysis. The results obtained reveal that feed and rotational speed play significant role in determining the average surface roughness. Furthermore, the depth of cut and tool overhang are less significant parameters, whereas tool overhang interacts with feed rate. The best result of surface roughness was obtained using low or medium values of overhang with low speed and /or feed rate. Minimum maximum tensile residual stress can be obtained with a combination of tool overhang of 37 mm with very low depth of cut, low rotational speed and feed rate of 0.188 mm/rev.

  3. Creep Modeling in a Composite Rotating Disc with Thickness Variation in Presence of Residual Stress

    Directory of Open Access Journals (Sweden)

    Vandana Gupta

    2012-01-01

    Full Text Available Steady-state creep response in a rotating disc made of Al-SiC (particle composite having linearly varying thickness has been carried out using isotropic/anisotropic Hoffman yield criterion and results are compared with those using von Mises yield criterion/Hill's criterion ignoring difference in yield stresses. The steady-state creep behavior has been described by Sherby's creep law. The material parameters characterizing difference in yield stresses have been used from the available experimental results in literature. Stress and strain rate distributions developed due to rotation have been calculated. It is concluded that the stress and strain distributions got affected from the thermal residual stress in an isotropic/anisotropic rotating disc, although the effect of residual stress on creep behavior in an anisotropic rotating disc is observed to be lower than those observed in an isotropic disc. Thus, the presence of residual stress in composite rotating disc with varying thickness needs attention for designing a disc.

  4. Finite element modelling of shot peening process: Prediction of the compressive residual stresses, the plastic deformations and the surface integrity

    International Nuclear Information System (INIS)

    Frija, M.; Hassine, T.; Fathallah, R.; Bouraoui, C.; Dogui, A.

    2006-01-01

    This paper presents a numerical simulation of the shot peening process using finite element method. The majority of the controlling parameters of the process have been taken into account. The shot peening loading has been characterised by using energy equivalence between the dynamic impact and a static indentation of a peening shot in the treated surface. The behaviour of the subjected material is supposed to be elastic plastic with damage. An integrated law of the damage proposed by Lemaitre and Chaboche has been used. The proposed model leads to obtain the residual stress, the plastic deformation profiles and the surface damage. An application on a shot peened Ni-based super alloy Waspaloy has been carried out. The comparison of the residual stresses, obtained by X-ray diffraction method and by finite element calculation, shows a good correlation. The in-depth profile of the plastic deformations and the superficial damage values are in good agreement with the experimental observations

  5. Numerical weld modeling - a method for calculating weld-induced residual stresses

    International Nuclear Information System (INIS)

    Fricke, S.; Keim, E.; Schmidt, J.

    2001-01-01

    In the past, weld-induced residual stresses caused damage to numerous (power) plant parts, components and systems (Erve, M., Wesseling, U., Kilian, R., Hardt, R., Bruemmer, G., Maier, V., Ilg, U., 1994. Cracking in Stabilized Austenitic Stainless Steel Piping of German Boiling Water Reactors - Characteristic Features and Root Causes. 20. MPA-Seminar 1994, vol. 2, paper 29, pp.29.1-29.21). In the case of BWR nuclear power plants, this damage can be caused by the mechanism of intergranular stress corrosion cracking in austenitic piping or the core shroud in the reactor pressure vessel and is triggered chiefly by weld-induced residual stresses. One solution of this problem that has been used in the past involves experimental measurements of residual stresses in conjunction with weld optimization testing. However, the experimental analysis of all relevant parameters is an extremely tedious process. Numerical simulation using the finite element method (FEM) not only supplements this method but, in view of modern computer capacities, is also an equally valid alternative in its own right. This paper will demonstrate that the technique developed for numerical simulation of the welding process has not only been properly verified and validated on austenitic pipe welds, but that it also permits making selective statements on improvements to the welding process. For instance, numerical simulation can provide information on the starting point of welding for every weld bead, the effect of interpass cooling as far as a possible sensitization of the heat affected zone (HAZ) is concerned, the effect of gap width on the resultant weld residual stresses, or the effect of the 'last pass heat sink welding' (welding of the final passes while simultaneously cooling the inner surface with water) producing compressive stresses in the root area of a circumferential weld in an austenitic pipe. The computer program FERESA (finite element residual stress analysis) was based on a commercially

  6. Fracture of Carbon Nanotube - Amorphous Carbon Composites: Molecular Modeling

    Science.gov (United States)

    Jensen, Benjamin D.; Wise, Kristopher E.; Odegard, Gregory M.

    2015-01-01

    Carbon nanotubes (CNTs) are promising candidates for use as reinforcements in next generation structural composite materials because of their extremely high specific stiffness and strength. They cannot, however, be viewed as simple replacements for carbon fibers because there are key differences between these materials in areas such as handling, processing, and matrix design. It is impossible to know for certain that CNT composites will represent a significant advance over carbon fiber composites before these various factors have been optimized, which is an extremely costly and time intensive process. This work attempts to place an upper bound on CNT composite mechanical properties by performing molecular dynamics simulations on idealized model systems with a reactive forcefield that permits modeling of both elastic deformations and fracture. Amorphous carbon (AC) was chosen for the matrix material in this work because of its structural simplicity and physical compatibility with the CNT fillers. It is also much stiffer and stronger than typical engineering polymer matrices. Three different arrangements of CNTs in the simulation cell have been investigated: a single-wall nanotube (SWNT) array, a multi-wall nanotube (MWNT) array, and a SWNT bundle system. The SWNT and MWNT array systems are clearly idealizations, but the SWNT bundle system is a step closer to real systems in which individual tubes aggregate into large assemblies. The effect of chemical crosslinking on composite properties is modeled by adding bonds between the CNTs and AC. The balance between weakening the CNTs and improving fiber-matrix load transfer is explored by systematically varying the extent of crosslinking. It is, of course, impossible to capture the full range of deformation and fracture processes that occur in real materials with even the largest atomistic molecular dynamics simulations. With this limitation in mind, the simulation results reported here provide a plausible upper limit on

  7. Molecular modeling used to evaluate CYP2C9-dependent metabolism: homology modeling, molecular dynamics and docking simulations.

    Science.gov (United States)

    Mendieta-Wejebe, Jessica E; Correa-Basurto, José; García-Segovia, Erika M; Ceballos-Cancino, Gisela; Rosales-Hernández, Martha C

    2011-07-01

    Cytochrome P450 (CYP) 2C9 is the principal isoform of the CYP2C subfamily in the human liver and is involved in the oxidation of several endogenous and xenobiotic compounds, including many therapeutic drugs. The metabolism of drugs by CYP2C9 can yield either safe or toxic products, which may be related to the recognition and binding modes of the substrates to this isoform. These interactions can be studied using in silico methods such as quantum chemistry, molecular dynamics and docking simulations, which can also be useful for predicting the structure of metabolites. In these types of studies, the ligand and the protein must be tridimensional models; thus, the protein can be built by homology modeling or retrieved from the Protein Data Bank. Therefore, the current review emphasizes the importance of using in silico methods to predict the metabolism of CYP2C9 because these computational tools have allowed the description of the principal characteristics of the active site of this isoform at the molecular level and the chemical properties of its ligands.

  8. Combined cycle power plants: A comparison between two different dynamic models to evaluate transient behaviour and residual life

    International Nuclear Information System (INIS)

    Benato, Alberto; Stoppato, Anna; Bracco, Stefano

    2014-01-01

    Highlights: • Two procedures aimed at simulating the dynamic behaviour of power plants are compared. • They both are aimed at predicting the residual life of plant devices. • A single pressure gas-steam combined plant has been modelled. • A good correspondence has been found despite the different approaches used. - Abstract: The deregulated energy market and the increasing quota of electrical capacity covered by non-predictable renewable sources require strongly irregular and discontinuous operation of thermoelectric plants to satisfy users demand and compensate the variability of renewable sources. As a consequence, due to thermo-mechanical fatigue, creep and corrosion, a lifetime reduction of the most critical components occurs. The availability of a procedure able to predict the residual life of plant devices is necessary to assist the management decisions about power plants’ operation and maintenance scheduling. The first step of this procedure is the capability of simulating the plant behaviour versus time by evaluating the trends of the main thermodynamic parameters that describe the plant operation during different transient periods. In this context, the main contribution of the present paper is to propose a complete procedure able to simulate the plant dynamic behaviour and estimate the residual life reduction of some components. Indeed, two different models, developed by two different research groups, of the same single pressure heat recovery steam generator unit are presented and utilized to characterize the dynamic behaviour of the above mentioned power plant. The main thermodynamic variables during different transient operation conditions are predicted and good correspondence between the two methods is obtained. It can be also noted that, when the geometry and size of the devices are considered, the thermal inertia related to heat exchangers tubes, pipes and other physical masses causes a delay in the system response. Moreover, a residual life

  9. Exploring the boundaries of molecular modeling : a study of nanochannels and transmembrane proteins

    NARCIS (Netherlands)

    Spijker, P.

    2009-01-01

    Many interesting physical and biological phenomena can be investigated using molecular modeling techniques, either theoretically or by using computer simulation methods, such as molecular dynamics and Monte Carlo simulations. Due to the increasing power of computer processing units, these simulation

  10. Delineating residues for haemolytic activities of snake venom cardiotoxin 1 from Naja naja as probed by molecular dynamics simulations and in vitro validations.

    Science.gov (United States)

    Gorai, Biswajit; Sivaraman, Thirunavukkarasu

    2017-02-01

    Cardiotoxins (CTXs) are single polypeptide chain consisting of 59-62 amino acids with four disulfide bridges and globular proteins of simple β-sheet folds. The CTXs are one of principal toxic components causing haemolysis and damaging various cells and belong to three-finger toxin (TFT) superfamily of snake venoms. However, there is no natural or synthetic small molecular inhibitor to the protein toxins to date. In the present study, modes of interaction of cardiotoxin 1 (CTX1) from Indian cobra (Naja naja) with heterogeneous erythrocyte membrane (EM) model system have been extensively examined by using all-atom molecular dynamics (MD) simulations in near physiological conditions and comprehensive analyses of the MD data revealed two distinct principal regions ('head groove' and 'loop groove') of the protein toxin for establishing structural interactions with the EM system. Moreover, combined analyses of data from high-throughput virtual screening of NCI small molecular database, in vitro haemolytic assays for top-hits of the chemical compounds against crude venom of Naja naja and as well CTXs purified from the venom and pharmacokinetic examinations on the chemical compounds retarding haemolytic activities of CTXs suggested that Etidronic acid and Zoledronic acid are promising prototypic chemical inhibitors to CTXs of snake venoms. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. A stochastic logical system approach to model and optimal control of cyclic variation of residual gas fraction in combustion engines

    International Nuclear Information System (INIS)

    Wu, Yuhu; Kumar, Madan; Shen, Tielong

    2016-01-01

    Highlights: • An in-cylinder pressure based measuring method for the RGF is derived. • A stochastic logical dynamical model is proposed to represent the transient behavior of the RGF. • The receding horizon controller is designed to reduce the variance of the RGF. • The effectiveness of the proposed model and control approach is validated by the experimental evidence. - Abstract: In four stroke internal combustion engines, residual gas from the previous cycle is an important factor influencing the combustion quality of the current cycle, and the residual gas fraction (RGF) is a popular index to monitor the influence of residual gas. This paper investigates the cycle-to-cycle transient behavior of the RGF in the view of systems theory and proposes a multi-valued logic-based control strategy for attenuation of RGF fluctuation. First, an in-cylinder pressure sensor-based method for measuring the RGF is provided by following the physics of the in-cylinder transient state of four-stroke internal combustion engines. Then, the stochastic property of the RGF is examined based on statistical data obtained by conducting experiments on a full-scale gasoline engine test bench. Based on the observation of the examination, a stochastic logical transient model is proposed to represent the cycle-to-cycle transient behavior of the RGF, and with the model an optimal feedback control law, which targets on rejection of the RGF fluctuation, is derived in the framework of stochastic logical system theory. Finally, experimental results are demonstrated to show the effectiveness of the proposed model and the control strategy.

  12. Bayesian molecular design with a chemical language model

    Science.gov (United States)

    Ikebata, Hisaki; Hongo, Kenta; Isomura, Tetsu; Maezono, Ryo; Yoshida, Ryo

    2017-04-01

    The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes' law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository.

  13. Insights into channel dysfunction from modelling and molecular dynamics simulations.

    Science.gov (United States)

    Musgaard, Maria; Paramo, Teresa; Domicevica, Laura; Andersen, Ole Juul; Biggin, Philip C

    2018-04-01

    Developments in structural biology mean that the number of different ion channel structures has increased significantly in recent years. Structures of ion channels enable us to rationalize how mutations may lead to channelopathies. However, determining the structures of ion channels is still not trivial, especially as they necessarily exist in many distinct functional states. Therefore, the use of computational modelling can provide complementary information that can refine working hypotheses of both wild type and mutant ion channels. The simplest but still powerful tool is homology modelling. Many structures are available now that can provide suitable templates for many different types of ion channels, allowing a full three-dimensional interpretation of mutational effects. These structural models, and indeed the structures themselves obtained by X-ray crystallography, and more recently cryo-electron microscopy, can be subjected to molecular dynamics simulations, either as a tool to help explore the conformational dynamics in detail or simply as a means to refine the models further. Here we review how these approaches have been used to improve our understanding of how diseases might be linked to specific mutations in ion channel proteins. This article is part of the Special Issue entitled 'Channelopathies.' Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Development and Evaluation of Amino Acid Molecular Models

    Directory of Open Access Journals (Sweden)

    Aparecido R. Silva

    2007-05-01

    Full Text Available The comprehension of structure and function of proteins has a tight relationshipwith the development of structural biology. However, biochemistry students usuallyfind difficulty to visualize the structures when they use only schematic drawings ofdidactic books. The representation of three-dimensional structures of somebiomolecules with ludic models, built with representative units, have supplied tothe students and teachers a successfully experience to better visualize andcorrelate the structures to the real molecules. The present work shows thedeveloped models and the process to produce the representative units of the mainamino acids in industrial scale. The design and applicability of the representativeunits were discussed with many teachers and some suggestions wereimplemented to the models. The preliminary evaluation and perspective ofutilization by researchers show that the work is in the right direction. At the actualstage, the models are defined, prototypes were made and will be presented in thismeeting. The moulds for the units are at the final stage of construction and trial inspecialized tool facilities. The last term will consist of an effective evaluation of thedidactic tool for the teaching/learning process in Structural Molecular Biology. Theevaluation protocol is being elaborated containing simple and objective questions,similar to those used in research on science teaching.

  15. Mechanical Properties of Nanostructured Materials Determined Through Molecular Modeling Techniques

    Science.gov (United States)

    Clancy, Thomas C.; Gates, Thomas S.

    2005-01-01

    The potential for gains in material properties over conventional materials has motivated an effort to develop novel nanostructured materials for aerospace applications. These novel materials typically consist of a polymer matrix reinforced with particles on the nanometer length scale. In this study, molecular modeling is used to construct fully atomistic models of a carbon nanotube embedded in an epoxy polymer matrix. Functionalization of the nanotube which consists of the introduction of direct chemical bonding between the polymer matrix and the nanotube, hence providing a load transfer mechanism, is systematically varied. The relative effectiveness of functionalization in a nanostructured material may depend on a variety of factors related to the details of the chemical bonding and the polymer structure at the nanotube-polymer interface. The objective of this modeling is to determine what influence the details of functionalization of the carbon nanotube with the polymer matrix has on the resulting mechanical properties. By considering a range of degree of functionalization, the structure-property relationships of these materials is examined and mechanical properties of these models are calculated using standard techniques.

  16. Spin models for the single molecular magnet Mn12-AC

    Science.gov (United States)

    Al-Saqer, Mohamad A.

    2005-11-01

    The single molecular magnet (SMM) Mn12-AC attracted the attention of scientists since the discovery of its magnetic hystereses which are accompanied by sudden jumps in magnetic moments at low temperature. Unlike conventional bulk magnets, hysteresis in SMMs is of molecular origin. This qualifies them as candidates for next generation of high density storage media where a molecule which is at most few nanometers in size can be used to store a bit of information. However, the jumps in these hystereses, due to spin tunneling, can lead to undesired loss of information. Mn12-AC molecule contains twelve magnetic ions antiferromagnetically coupled by exchanges leading to S = 10 ground state manifold. The magnetic ions are surrounded by ligands which isolate them magnetically from neighboring molecules. The lowest state of S = 9 manifold is believed to lie at about 40 K above the ground state. Therefore, at low temperatures, the molecule is considered as a single uncoupled moment of spin S = 10. Such model has been used widely to understand phenomena exhibited by the molecule at low temperatures including the tunneling of its spin, while a little attention has been paid for the multi-spin nature of the molecule. Using the 8-spin model, we demonstrate that in order to understand the phenomena of tunneling, a full spin description of the molecule is required. We utilized a calculation scheme where a fraction of energy levels are used in the calculations and the influence of levels having higher energy is neglected. From the dependence of tunnel splittings on the number of states include, we conclude that models based on restricting the number of energy levels (single-spin and 8-spin models) lead to unreliable results of tunnel splitting calculations. To attack the full 12-spin model, we employed the Davidson algorithm to calculated lowest energy levels produced by exchange interactions and single ion anisotropies. The model reproduces the anisotropy properties at low

  17. Multi-scale modelling of supercapacitors: From molecular simulations to a transmission line model

    Science.gov (United States)

    Pean, C.; Rotenberg, B.; Simon, P.; Salanne, M.

    2016-09-01

    We perform molecular dynamics simulations of a typical nanoporous-carbon based supercapacitor. The organic electrolyte consists in 1-ethyl-3-methylimidazolium and hexafluorophosphate ions dissolved in acetonitrile. We simulate systems at equilibrium, for various applied voltages. This allows us to determine the relevant thermodynamic (capacitance) and transport (in-pore resistivities) properties. These quantities are then injected in a transmission line model for testing its ability to predict the charging properties of the device. The results from this macroscopic model are in good agreement with non-equilibrium molecular dynamics simulations, which validates its use for interpreting electrochemical impedance experiments.

  18. Prediction of residual stress for dissimilar metals welding at nuclear power plants using fuzzy neural network models

    International Nuclear Information System (INIS)

    Na, Man Gyun; Kim, Jin Weon; Lim, Dong Hyuk

    2007-01-01

    A fuzzy neural network model is presented to predict residual stress for dissimilar metal welding under various welding conditions. The fuzzy neural network model, which consists of a fuzzy inference system and a neuronal training system, is optimized by a hybrid learning method that combines a genetic algorithm to optimize the membership function parameters and a least squares method to solve the consequent parameters. The data of finite element analysis are divided into four data groups, which are split according to two end-section constraints and two prediction paths. Four fuzzy neural network models were therefore applied to the numerical data obtained from the finite element analysis for the two end-section constraints and the two prediction paths. The fuzzy neural network models were trained with the aid of a data set prepared for training (training data), optimized by means of an optimization data set and verified by means of a test data set that was different (independent) from the training data and the optimization data. The accuracy of fuzzy neural network models is known to be sufficiently accurate for use in an integrity evaluation by predicting the residual stress of dissimilar metal welding zones

  19. Aging impacts of low molecular weight organic acids (LMWOAs) on furfural production residue-derived biochars: Porosity, functional properties, and inorganic minerals.

    Science.gov (United States)

    Liu, Guocheng; Chen, Lei; Jiang, Zhixiang; Zheng, Hao; Dai, Yanhui; Luo, Xianxiang; Wang, Zhenyu

    2017-12-31

    The aging of biochar by low molecular weight organic acids (LMWOAs), which are typical root-derived exudates, is not well understood. Three LMWOAs (ethanoic, malic, and citric acids) were employed to investigate their aging impacts on the biochars from furfural production residues at 300-600°C (BC300-600). The LMWOAs created abundant macropores in BC300, whereas they significantly increased the mesoporosity and surface area of BC600 by 13.5-27.0% and 44.6-61.5%, respectively. After LMWOA aging, the content of C and H of the biochars increased from 51.3-60.2% and 1.87-3.45% to 56.8-69.9% and 2.06-4.45%, respectively, but the O content decreased from 13.8-24.8% to 7.82-19.4% (except BC300). For carbon fraction in the biochars, the LMWOAs barely altered the bulk and surface functional properties during short-term aging. The LMWOAs facilitated the dissolution of minerals (e.g., K 2 Mg(PO 3 ) 4 , AlPO 4 , and Pb 2 P 2 O 7 ) and correspondingly promoted the release of not only plant nutrients (K + , Ca 2+ , Mg 2+ , Fe 3+ , PO 4 3- , and SO 4 2- ) but also toxic metals (Al 3+ and Pb 2+ ). This research provided systematic insights on the responses of biochar properties to LMWOAs and presented direct evidence for acid activation of inorganic minerals in the biochars by LMWOAs, which could enhance the understanding of environmental behaviors of biochars in rhizosphere soils. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Combining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding.

    Science.gov (United States)

    Shi, Jiye; Anderson, Dina; Lynch, Berkley A; Castaigne, Jean-Gabriel; Foerch, Patrik; Lebon, Florence

    2011-10-01

    LEV (levetiracetam), an antiepileptic drug which possesses a unique profile in animal models of seizure and epilepsy, has as its unique binding site in brain, SV2A (synaptic vesicle protein 2A). Previous studies have used a chimaeric and site-specific mutagenesis approach to identify three residues in the putative tenth transmembrane helix of SV2A that, when mutated, alter binding of LEV and related racetam derivatives to SV2A. In the present paper, we report a combined modelling and mutagenesis study that successfully identifies another 11 residues in SV2A that appear to be involved in ligand binding. Sequence analysis and modelling of SV2A suggested residues equivalent to critical functional residues of other MFS (major facilitator superfamily) transporters. Alanine scanning of these and other SV2A residues resulted in the identification of residues affecting racetam binding, including Ile273 which differentiated between racetam analogues, when mutated to alanine. Integrating mutagenesis results with docking analysis led to the construction of a mutant in which six SV2A residues were replaced with corresponding SV2B residues. This mutant showed racetam ligand-binding affinity intermediate to the affinities observed for SV2A and SV2B.

  1. First Principles Modelling of Shape Memory Alloys Molecular Dynamics Simulations

    CERN Document Server

    Kastner, Oliver

    2012-01-01

    Materials sciences relate the macroscopic properties of materials to their microscopic structure and postulate the need for holistic multiscale research. The investigation of shape memory alloys is a prime example in this regard. This particular class of materials exhibits strong coupling of temperature, strain and stress, determined by solid state phase transformations of their metallic lattices. The present book presents a collection of simulation studies of this behaviour. Employing conceptually simple but comprehensive models, the fundamental material properties of shape memory alloys are qualitatively explained from first principles. Using contemporary methods of molecular dynamics simulation experiments, it is shown how microscale dynamics may produce characteristic macroscopic material properties. The work is rooted in the materials sciences of shape memory alloys and  covers  thermodynamical, micro-mechanical  and crystallographical aspects. It addresses scientists in these research fields and thei...

  2. A simplified tether model for molecular motor transporting cargo

    International Nuclear Information System (INIS)

    Fang-Zhen, Li; Li-Chun, Jiang

    2010-01-01

    Molecular motors are proteins or protein complexes which function as transporting engines in biological cells. This paper models the tether between motor and its cargo as a symmetric linear potential. Different from Elston and Peskin's work for which performance of the system was discussed only in some limiting cases, this study produces analytic solutions of the problem for general cases by simplifying the transport system into two physical states, which makes it possible to discuss the dynamics of the motor–cargo system in detail. It turns out that the tether strength between motor and cargo should be greater than a threshold or the motor will fail to transport the cargo, which was not discussed by former researchers yet. Value of the threshold depends on the diffusion coefficients of cargo and motor and also on the strength of the Brownian ratchets dragging the system. The threshold approaches a finite constant when the strength of the ratchet tends to infinity. (general)

  3. Probing ligand binding modes of Mycobacterium tuberculosis MurC ligase by molecular modeling, dynamics simulation and docking.

    Science.gov (United States)

    Anuradha, C M; Mulakayala, Chaitanya; Babajan, Banaganapalli; Naveen, M; Rajasekhar, Chikati; Kumar, Chitta Suresh

    2010-01-01

    Multi drug resistance capacity for Mycobacterium tuberculosis (MDR-Mtb) demands the profound need for developing new anti-tuberculosis drugs. The present work is on Mtb-MurC ligase, which is an enzyme involved in biosynthesis of peptidoglycan, a component of Mtb cell wall. In this paper the 3-D structure of Mtb-MurC has been constructed using the templates 1GQQ and 1P31. Structural refinement and energy minimization of the predicted Mtb-MurC ligase model has been carried out by molecular dynamics. The streochemical check failures in the energy minimized model have been evaluated through Procheck, Whatif ProSA, and Verify 3D. Further torsion angles for the side chains of amino acid residues of the developed model were determined using Predictor. Docking analysis of Mtb-MurC model with ligands and natural substrates enabled us to identify specific residues viz. Gly125, Lys126, Arg331, and Arg332, within the Mtb-MurC binding pocket to play an important role in ligand and substrate binding affinity and selectivity. The availability of Mtb-MurC ligase built model, together with insights gained from docking analysis will promote the rational design of potent and selective Mtb-MurC ligase inhibitors as antituberculosis therapeutics.

  4. Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase.

    Science.gov (United States)

    Iman, Maryam; Khansefid, Zeynab; Davood, Asghar

    2016-01-01

    Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme.

  5. Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited.

    Science.gov (United States)

    Khoshnood, Atefeh; Lukanov, Boris; Firoozabadi, Abbas

    2016-03-08

    Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces.

  6. Computer aided molecular design with combined molecular modeling and group contribution

    DEFF Research Database (Denmark)

    Harper, Peter Mathias; Gani, Rafiqul; Kolar, Petr

    1999-01-01

    Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures and on th......Computer-aided molecular design (CAMD) provides a means for determining molecules or mixtures of molecules (CAMMD) having a desirable set of physicochemical properties. The application range of CAMD is restricted due to limitations on the complexity of the generated molecular structures...

  7. Site-directed mutagenesis and molecular modelling studies show the role of Asp82 and cysteines in rat acylase 1, a member of the M20 family

    International Nuclear Information System (INIS)

    Herga, Sameh; Brutus, Alexandre; Vitale, Rosa Maria; Miche, Helene; Perrier, Josette; Puigserver, Antoine; Scaloni, Andrea; Giardina, Thierry

    2005-01-01

    Acylase 1 from rat kidney catalyzes the hydrolysis of acyl-amino acids. Sequence alignment has shown that this enzyme belongs to the metalloprotein family M20. Site-directed mutagenesis experiments led to the identification of one functionally important amino acid residue located near one of the zinc coordinating residues, which play a critical role in the enzymatic activity. The D82N- and D82E-substituted forms showed no significant activity and very low activity, respectively, along with a loss of zinc coordination. Molecular modelling investigations indicated a putative role of D82 in ensuring a proper protonation of catalytic histidine. In addition, none of the five cysteine residues present in the rat kidney acylase 1 sequence seemed involved in the catalytic process: the loss of activity induced by the C294A substitution was probably due to a conformational change in the 3D structure

  8. Nonlinear Fatigue Damage Model Based on the Residual Strength Degradation Law

    Science.gov (United States)

    Yongyi, Gao; Zhixiao, Su

    In this paper, a logarithmic expression to describe the residual strength degradation process is developed in order to fatigue test results for normalized carbon steel. The definition and expression of fatigue damage due to symmetrical stress with a constant amplitude are also given. The expression of fatigue damage can also explain the nonlinear properties of fatigue damage. Furthermore, the fatigue damage of structures under random stress is analyzed, and an iterative formula to describe the fatigue damage process is deduced. Finally, an approximate method for evaluating the fatigue life of structures under repeated random stress blocking is presented through various calculation examples.

  9. Reliability analysis on passive residual heat removal of AP1000 based on Grey model

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Shi; Zhou, Tao; Shahzad, Muhammad Ali; Li, Yu [North China Electric Power Univ., Beijing (China). School of Nuclear Science and Engineering; Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, Beijing (China); Jiang, Guangming [Nuclear Power Institute of China, Chengdu (China). Science and Technology on Reactor System Design Technology Laboratory

    2017-06-15

    It is common to base the design of passive systems on the natural laws of physics, such as gravity, heat conduction, inertia. For AP1000, a generation-III reactor, such systems have an inherent safety associated with them due to the simplicity of their structures. However, there is a fairly large amount of uncertainty in the operating conditions of these passive safety systems. In some cases, a small deviation in the design or operating conditions can affect the function of the system. The reliability of the passive residual heat removal is analysed.

  10. MOLECULAR MODELING INDICATES THAT HOMOCYSTEINE INDUCES CONFORMATIONAL CHANGES IN THE STRUCTURE OF PUTATIVE TARGET PROTEINS

    Directory of Open Access Journals (Sweden)

    Yumnam Silla

    2015-09-01

    Full Text Available An elevated level of homocysteine, a reactive thiol containing amino acid is associated with a multitude of complex diseases. A majority (>80% of homocysteine in circulation is bound to protein cysteine residues. Although, till date only 21 proteins have been experimentally shown to bind with homocysteine, using an insilico approach we had earlier identified several potential target proteins that could bind with homocysteine. Shomocysteinylation of proteins could potentially alter the structure and/or function of the protein. Earlier studies have shown that binding of homocysteine to protein alters its function. However, the effect of homocysteine on the target protein structure has not yet been documented. In the present work, we assess conformational or structural changes if any due to protein homocysteinylation using two proteins, granzyme B (GRAB and junctional adhesion molecule 1 (JAM1, which could potentially bind to homocysteine. We, for the first time, constructed computational models of homocysteine bound to target proteins and monitored their structural changes using explicit solvent molecular dynamic (MD simulation. Analysis of homocysteine bound trajectories revealed higher flexibility of the active site residues and local structural perturbations compared to the unbound native structure’s simulation, which could affect the stability of the protein. In addition, secondary structure analysis of homocysteine bound trajectories also revealed disappearance of â-helix within the G-helix and linker region that connects between the domain regions (as defined in the crystal structure. Our study thus captures the conformational transitions induced by homocysteine and we suggest these structural alterations might have implications for hyperhomocysteinemia induced pathologies.

  11. Molecular cloning, sequence analysis and homology modeling of the first caudata amphibian antifreeze-like protein in axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Zhang, Songyan; Gao, Jiuxiang; Lu, Yiling; Cai, Shasha; Qiao, Xue; Wang, Yipeng; Yu, Haining

    2013-08-01

    Antifreeze proteins (AFPs) refer to a class of polypeptides that are produced by certain vertebrates, plants, fungi, and bacteria and which permit their survival in subzero environments. In this study, we report the molecular cloning, sequence analysis and three-dimensional structure of the axolotl antifreeze-like protein (AFLP) by homology modeling of the first caudate amphibian AFLP. We constructed a full-length spleen cDNA library of axolotl (Ambystoma mexicanum). An EST having highest similarity (∼42%) with freeze-responsive liver protein Li16 from Rana sylvatica was identified, and the full-length cDNA was subsequently obtained by RACE-PCR. The axolotl antifreeze-like protein sequence represents an open reading frame for a putative signal peptide and the mature protein composed of 93 amino acids. The calculated molecular mass and the theoretical isoelectric point (pl) of this mature protein were 10128.6 Da and 8.97, respectively. The molecular characterization of this gene and its deduced protein were further performed by detailed bioinformatics analysis. The three-dimensional structure of current AFLP was predicted by homology modeling, and the conserved residues required for functionality were identified. The homology model constructed could be of use for effective drug design. This is the first report of an antifreeze-like protein identified from a caudate amphibian.

  12. Molecular Physiology of Root System Architecture in Model Grasses

    Science.gov (United States)

    Hixson, K.; Ahkami, A. H.; Anderton, C.; Veličković, D.; Myers, G. L.; Chrisler, W.; Lindenmaier, R.; Fang, Y.; Yabusaki, S.; Rosnow, J. J.; Farris, Y.; Khan, N. E.; Bernstein, H. C.; Jansson, C.

    2017-12-01

    Unraveling the molecular and physiological mechanisms involved in responses of Root System Architecture (RSA) to abiotic stresses and shifts in microbiome structure is critical to understand and engineer plant-microbe-soil interactions in the rhizosphere. In this study, accessions of Brachypodium distachyon Bd21 (C3 model grass) and Setaria viridis A10.1 (C4 model grass) were grown in phytotron chambers under current and elevated CO2 levels. Detailed growth stage-based phenotypic analysis revealed different above- and below-ground morphological and physiological responses in C3 and C4 grasses to enhanced CO2 levels. Based on our preliminary results and by screening values of total biomass, water use efficiency, root to shoot ratio, RSA parameters and net assimilation rates, we postulated a three-phase physiological mechanism, i.e. RootPlus, BiomassPlus and YieldPlus phases, for grass growth under elevated CO2 conditions. Moreover, this comprehensive set of morphological and process-based observations are currently in use to develop, test, and calibrate biophysical whole-plant models and in particular to simulate leaf-level photosynthesis at various developmental stages of C3 and C4 using the model BioCro. To further link the observed phenotypic traits at the organismal level to tissue and molecular levels, and to spatially resolve the origin and fate of key metabolites involved in primary carbohydrate metabolism in different root sections, we complement root phenotypic observations with spatial metabolomics data using mass spectrometry imaging (MSI) methods. Focusing on plant-microbe interactions in the rhizosphere, six bacterial strains with plant growth promoting features are currently in use in both gel-based and soil systems to screen root growth and development in Brachypodium. Using confocal microscopy, GFP-tagged bacterial systems are utilized to study the initiation of different root types of RSA, including primary root (PR), coleoptile node axile root (CNR

  13. Large-scale evaluation of dynamically important residues in proteins predicted by the perturbation analysis of a coarse-grained elastic model

    Directory of Open Access Journals (Sweden)

    Tekpinar Mustafa

    2009-07-01

    Full Text Available Abstract Backgrounds It is increasingly recognized that protein functions often require intricate conformational dynamics, which involves a network of key amino acid residues that couple spatially separated functional sites. Tremendous efforts have been made to identify these key residues by experimental and computational means. Results We have performed a large-scale evaluation of the predictions of dynamically important residues by a variety of computational protocols including three based on the perturbation and correlation analysis of a coarse-grained elastic model. This study is performed for two lists of test cases with >500 pairs of protein structures. The dynamically important residues predicted by the perturbation and correlation analysis are found to be strongly or moderately conserved in >67% of test cases. They form a sparse network of residues which are clustered both in 3D space and along protein sequence. Their overall conservation is attributed to their dynamic role rather than ligand binding or high network connectivity. Conclusion By modeling how the protein structural fluctuations respond to residue-position-specific perturbations, our highly efficient perturbation and correlation analysis can be used to dissect the functional conformational changes in various proteins with a residue level of detail. The predictions of dynamically important residues serve as promising targets for mutational and functional studies.

  14. Diffusion-bonded 16MND5-Inconel 690-316LN junction: elaboration and process residual stresses modeling

    International Nuclear Information System (INIS)

    Martinez, Michael

    1999-01-01

    The objective of this research thesis is, on the one hand, to elaborate and to characterise a bonded junction of 16MND5 and 316LN steels, and, on the other hand, to develop a simulation tool for the prediction of microstructures after bonding, as well as residual stresses related to this process. The author first reports the study of the use of diffusion bonding by hot isostatic pressing (HIP diffusion bonding) for the bonding of 16MND5 (steel used in French PWR vessel) and 316LN (austenitic stainless steel used in piping), in order to obtain junctions adapted to a use within PWRs. In this case, the use of an Inconel insert material appeared to be necessary to avoid stainless steel carburization. Thus, inserts in Inconel 600 and 690 have been tested. The objective has then been to develop a realistic calculation of residual stresses in this assembly. These stresses are stimulated by quenching. The author notably studied the simulation of temperature dependent phase transformations, and stress induced phase transformations. An existing model is validated and applied to HIP and quenching cycles. The last part reports the calculation of residual stresses by simulation of the mechanical response of the three-component material cooled from 900 C to room temperature and thus submitted to a loading of thermal origin (dilatation) and metallurgical origin (phase transformations in the 16MND5). The effect of carbon diffusion on mechanical properties has also been taken into account. The author discusses problems faced by existing models, and explains the choice of conventional macro-mechanical models. The three materials are supposed to have a plastic-viscoplastic behaviour with isotropic and kinematic strain hardening, and this behaviour is identified between 20 and 900 C [fr

  15. A tight-binding model of the transmission probability through a molecular junction; a single molecule vs. a molecular layer

    International Nuclear Information System (INIS)

    Landau, A.; Nitzan, A.

    2006-01-01

    Full Text: Molecular electronics, one of the major fields of the current effort in nano-science, may be de ed as the study of electronic behaviors, devices and applications that depend on the properties of matter at the molecular scale. If the miniaturization trend of microelectronic devices is to continue, elements such as transistors and contacts will soon shrink to single molecules. The promise of these new technological breakthroughs has been major driving force in this ld. Moreover, the consideration of molecular systems as electronic devices has raised new fundamental questions. In particular, while traditional quantum chemistry deals with electronically closed systems, we now face problems involving molecular systems that are open to their electronic environment, moreover, function in far from equilibrium situations. A generic molecular junction is made of two electrodes connected by a molecular spacer that takes the form of a molecular chain of varying length or a molecular layer of varying thickness. We use a simple nearest-neighbors tight-biding model with the non-equilibrium Green's function (NEGF) method to investigate and compare between a self-assembled monolayer (SAM), finite molecular layer (FML), and single molecule (SM) chemisorption to a surface of a metal substrate. In addition, we examine the difference in the transmission probability through a SAM, FML and SM sandwiched between two metallic electrodes. Dramatic differences are observed between the SM, FML and SAM density of electronic states and transmission functions. In addition, we analyze the effects of changing different physical parameters such as molecule-substrate interaction, molecule-molecule interactions, etc; interesting effects that pertain to the conduction properties of single molecules and molecular layers are observed. Intriguing results are attained when we investigate the commensurability of the SAM with the metallic surface

  16. A Study of Residual Amplitude Modulation Suppression in Injection Locked Quantum Cascade Lasers Based on a Simplified Rate Equation Model

    International Nuclear Information System (INIS)

    Webb, J F; Yong, K S C; Haldar, M K

    2015-01-01

    Using results that come out of a simplified rate equation model, the suppression of residual amplitude modulation in injection locked quantum cascade lasers with the master laser modulated by its drive current is investigated. Quasi-static and dynamic expressions for intensity modulation are used. The suppression peaks at a specific value of the injection ratio for a given detuning and linewidth enhancement factor. The intensity modulation suppression remains constant over a range of frequencies. The effects of injection ratio, detuning, coupling efficiency and linewidth enhancement factor are considered. (paper)

  17. Modelling the Molecular Transportation of Subcutaneously Injected Salubrinal

    Directory of Open Access Journals (Sweden)

    Andy Chen

    2011-01-01

    Full Text Available For the subcutaneous administration of a chemical agent (salubrinal, we constructed a mathematical model of molecule transportation and subsequently evaluated the kinetics of diffusion, convection, and molecular turnover. Salubrinal is a potential therapeutic agent that can reduce cellular damage and death. The understanding of its temporal profiles in local tissue as well as in a whole body is important to develop a proper strategy for its administration. Here, the diffusion and convection kinetics was formulated using partial and ordinary differential equations in one- and three-dimensional (semi-spherical coordinates. Several key parameters including an injection velocity, a diffusion coefficient, thickness of subcutaneous tissue, and a permeability factor at the tissue-blood boundary were estimated from experimental data in rats. With reference to analytical solutions in a simplified model without convection, numerical solutions revealed that the diffusion coefficient and thickness of subcutaneous tissue determined the timing of the peak concentration in the plasma, and its magnitude was dictated by the permeability factor. Furthermore, the initial velocity, induced by needle injection, elevated an immediate transport of salubrinal at t < 1h. The described analysis with a combination of partial and ordinary differential equations contributes to the prediction of local and systemic effects and the understanding of the transportation mechanism of salubrinal and other agents.

  18. Residual stresses

    International Nuclear Information System (INIS)

    Sahotra, I.M.

    2006-01-01

    The principal effect of unloading a material strained into the plastic range is to create a permanent set (plastic deformation), which if restricted somehow, gives rise to a system of self-balancing within the same member or reaction balanced by other members of the structure., known as residual stresses. These stresses stay there as locked-in stresses, in the body or a part of it in the absence of any external loading. Residual stresses are induced during hot-rolling and welding differential cooling, cold-forming and extruding: cold straightening and spot heating, fabrication and forced fitting of components constraining the structure to a particular geometry. The areas which cool more quickly develop residual compressive stresses, while the slower cooling areas develop residual tensile stresses, and a self-balancing or reaction balanced system of residual stresses is formed. The phenomenon of residual stresses is the most challenging in its application in surface modification techniques determining endurance mechanism against fracture and fatigue failures. This paper discusses the mechanism of residual stresses, that how the residual stresses are fanned and what their behavior is under the action of external forces. Such as in the case of a circular bar under limit torque, rectangular beam under limt moment, reclaiming of shafts welds and peening etc. (author)

  19. Conceptual model and procedures to assimilate production technologies of bioenergetics of residual biomass

    International Nuclear Information System (INIS)

    Muto Lubota, David; González Suárez, Erenio; Hernández Pérez, Gilberto; Miño Valdés, Juan Esteban

    2016-01-01

    The present work expose the conceptual pattern for a process of assimilation of technologies with the purpose of creating obtaining capacities of bio energy with the objective of achieving an energy insurance of the recycle of Urban Solid Residuals (RSU) in the municipality of Cabinda, Angola. The conceptual pattern is novel because it considers the south-south collaboration, and it is supported by a general procedure of assimilation of the technologies that includes in one of its steps a specify procedure for the step concerning the insurance of the chain supply that contains as additional aspect, in a novel way, the determination of the initial’s investors capacities assisting to the demand of final products as well as to the readiness of the raw materials, based in the problems of uncertainty to the future changes. Finally conclusions are elaborated with projections for the future work. (author)

  20. Modeling seasonal redox dynamics and the corresponding fate of the pharmaceutical residue phenazone during artificial recharge of groundwater.

    Science.gov (United States)

    Greskowiak, Janek; Prommer, Henning; Massmann, Gudrun; Nützmann, Gunnar

    2006-11-01

    Reactive multicomponent transport modeling was used to investigate and quantify the factors that affect redox zonation and the fate of the pharmaceutical residue phenazone during artificial recharge of groundwater at an infiltration site in Berlin, Germany. The calibrated model and the corresponding sensitivity analysis demonstrated thattemporal and spatial redox zonation at the study site was driven by seasonally changing, temperature-dependent organic matter degradation rates. Breakthrough of phenazone at monitoring wells occurred primarily during the warmer summer months, when anaerobic conditions developed. Assuming a redox-sensitive phenazone degradation behavior the model results provided an excellent agreement between simulated and measured phenazone concentrations. Therefore, the fate of phenazone was shown to be indirectly controlled by the infiltration water temperature through its effect on the aquifer's redox conditions. Other factors such as variable residence times appeared to be of less importance.

  1. Optimization of a Nucleic Acids united-RESidue 2-Point model (NARES-2P) with a maximum-likelihood approach

    International Nuclear Information System (INIS)

    He, Yi; Scheraga, Harold A.; Liwo, Adam

    2015-01-01

    Coarse-grained models are useful tools to investigate the structural and thermodynamic properties of biomolecules. They are obtained by merging several atoms into one interaction site. Such simplified models try to capture as much as possible information of the original biomolecular system in all-atom representation but the resulting parameters of these coarse-grained force fields still need further optimization. In this paper, a force field optimization method, which is based on maximum-likelihood fitting of the simulated to the experimental conformational ensembles and least-squares fitting of the simulated to the experimental heat-capacity curves, is applied to optimize the Nucleic Acid united-RESidue 2-point (NARES-2P) model for coarse-grained simulations of nucleic acids recently developed in our laboratory. The optimized NARES-2P force field reproduces the structural and thermodynamic data of small DNA molecules much better than the original force field

  2. Tangible Models and Haptic Representations Aid Learning of Molecular Biology Concepts

    Science.gov (United States)

    Johannes, Kristen; Powers, Jacklyn; Couper, Lisa; Silberglitt, Matt; Davenport, Jodi

    2016-01-01

    Can novel 3D models help students develop a deeper understanding of core concepts in molecular biology? We adapted 3D molecular models, developed by scientists, for use in high school science classrooms. The models accurately represent the structural and functional properties of complex DNA and Virus molecules, and provide visual and haptic…

  3. Residual oxygen time model for oxygen partial pressure near 130 kPa (1.3 atm).

    Science.gov (United States)

    Shykoff, Barbara E

    2015-01-01

    A two-part residual oxygen time model predicts the probability of detectible pulmonary oxygen toxicity P(P[O2tox]) after dives with oxygen partial pressure (PO2) approximately 130 kPa, and provides a tool to plan dive series with selected risk of P[O2tox]. Data suggest that pulmonary oxygen injury at this PO2 is additive between dives. Recovery begins after a delay and continues during any following dive. A logistic relation expresses P(P[O2tox]) as a function of dive duration (T(dur)) [hours]: P(P[O2tox]) = 100/[1+exp (3.586-0.49 x T(dur))] This expression maps T(dur) to P(P[O2tox]) or, in the linear mid-portion of the curve, P(P[O2tox]) usefully to T(dur). For multiple dives or during recovery, it maps to an equivalent dive duration, T(eq). T(eq) was found after second dives of duration T(dur 2). Residual time from the first dive t(r) = T(eq) - T(dur2). With known t(r), t and T(dur) a recovery model was fitted. t(r) = T(dur) x exp [-k x((t-5)/T(dur)2], where t = t - 5 hours, k = 0.149 for resting, and 0.047 for exercising divers, and t represents time after surfacing. The fits were assessed for 1,352 man-dives. Standard deviations of the residuals were 8.5% and 18.3% probability for resting or exercise dives, respectively.

  4. Statistical modeling to management and treatment of scrap with low and very low residual activity; Hacia la modelizacion estadistica de la gestion y tratamiento de chatarras con baja y muy bajo actividad residual

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Bermejo Fernandez, R.; Anaya Lazaro, M.

    2011-07-01

    The experience of recent years on the management of scrap metal containing residual activity have allowed the development of a simple statistical model for the management of these materials. This statistical model includes a breakdown of the various processing operations to which these materials undergo and the effects in the process of radiological controls associated to the control of declassification that defines disposal (recycled by smelting, reclamation, temporary storage the plant or sent to final storage of radioactive waste).

  5. Discovery of Novel Inhibitors for Nek6 Protein through Homology Model Assisted Structure Based Virtual Screening and Molecular Docking Approaches

    Directory of Open Access Journals (Sweden)

    P. Srinivasan

    2014-01-01

    Full Text Available Nek6 is a member of the NIMA (never in mitosis, gene A-related serine/threonine kinase family that plays an important role in the initiation of mitotic cell cycle progression. This work is an attempt to emphasize the structural and functional relationship of Nek6 protein based on homology modeling and binding pocket analysis. The three-dimensional structure of Nek6 was constructed by molecular modeling studies and the best model was further assessed by PROCHECK, ProSA, and ERRAT plot in order to analyze the quality and consistency of generated model. The overall quality of computed model showed 87.4% amino acid residues under the favored region. A 3 ns molecular dynamics simulation confirmed that the structure was reliable and stable. Two lead compounds (Binding database ID: 15666, 18602 were retrieved through structure-based virtual screening and induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that the potential compounds may act as new leads for Nek6 inhibitors designing.

  6. Modelling of the long-term fate of pesticide residues in agricultural soils and their surface exchange with the atmosphere: Part II. Projected long-term fate of pesticide residues.

    Science.gov (United States)

    Scholtz, M T; Bidleman, T F

    2007-05-01

    In the first part of this paper, a simple coupled dynamic soil-atmosphere model for studying the gaseous exchange of pesticide soil residues with the atmosphere is described and evaluated by comparing model results with published measurements of pesticide concentrations in air and soil. In Part II, the model is used to study the concentration profiles of pesticide residues in both undisturbed and annually tilled agricultural soils. Future trends are estimated for the measured air and soil concentrations of lindane and six highly persistent pesticides (toxaphene, p,p'-DDE, dieldrin, cis- and trans-chlordane and trans-nonachlor) over a twenty-year period due to volatilization and leaching into the deeper soil. Wet deposition and particle associated pesticide deposition (that increase soil residue concentrations) and soil erosion, degradation in the soil (other than for lindane) and run-off in precipitation are not considered in this study. Estimates of the rain deposition fluxes are reported that show that, other than for lindane, net volatilization fluxes greatly exceed rain deposition fluxes. The model shows that the persistent pesticides studied are highly immobile in soil and that loss of these highly persistent residues from the soil is by volatilization rather than leaching into the deeper soil. The soil residue levels of these six pesticides are currently sources of net volatilization to the atmosphere and will remain so for many years. The maximum rate of volatilization from the soil was simulated by setting the atmospheric background concentration to zero; these simulations show that the rates of volatilization will not be significantly increased since soil resistance rather than the atmospheric concentration controls the volatilization rates. Annual tilling of the soils increases the volatilization loss to the atmosphere. Nonetheless, the model predicts that, if only air-soil exchange is considered, more than 76% of current persistent pesticide residues

  7. Computer modeling of properties of complex molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Kulkova, E.Yu. [Moscow State University of Technology “STANKIN”, Vadkovsky per., 1, Moscow 101472 (Russian Federation); Khrenova, M.G.; Polyakov, I.V. [Lomonosov Moscow State University, Chemistry Department, Leninskie Gory 1/3, Moscow 119991 (Russian Federation); Nemukhin, A.V. [Lomonosov Moscow State University, Chemistry Department, Leninskie Gory 1/3, Moscow 119991 (Russian Federation); N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow 119334 (Russian Federation)

    2015-03-10

    Large molecular aggregates present important examples of strongly nonhomogeneous systems. We apply combined quantum mechanics / molecular mechanics approaches that assume treatment of a part of the system by quantum-based methods and the rest of the system with conventional force fields. Herein we illustrate these computational approaches by two different examples: (1) large-scale molecular systems mimicking natural photosynthetic centers, and (2) components of prospective solar cells containing titan dioxide and organic dye molecules. We demonstrate that modern computational tools are capable to predict structures and spectra of such complex molecular aggregates.

  8. Synthesis, antimicrobial, anti-biofilm evaluation, and molecular modelling study of new chalcone linked amines derivatives.

    Science.gov (United States)

    El-Messery, Shahenda M; Habib, El-Sayed E; Al-Rashood, Sarah T A; Hassan, Ghada S

    2018-12-01

    A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques 1 H NMR, 13 C NMR, and ESI-MS. They were screened for in vitro antibacterial activity. Compounds 36, 37, 38, 42, and 44 are the most active among the synthesised series exhibiting MIC value of 2.0-10.0 µg/ml against different bacterial strains. Compound 36 was equipotent to the standard drug Ampicillin displaying MBC value of 2.0 µg/ml against the bacterial strain Staphylococcus aureus. The products were screened for anti-biofilm activity. Compounds 36, 37, and 38 exhibited promising anti-biofilm activity with IC 50 value ranges from 2.4 to 8.6 µg. Molecular modelling was performed suggesting parameters of signalling anti-biofilm mechanism. AspB327 HisB340 (arene-arene interaction) and IleB328 amino acid residues seemed of higher importance to inhibit c-di-GMP. Hydrophobicity may be crucial for activity. ADME calculations suggested that compounds 36, 37, and 38 could be used as good orally absorbed anti-biofilm agents.

  9. Homology modeling, molecular dynamics and inhibitor binding study on MurD ligase of Mycobacterium tuberculosis.

    Science.gov (United States)

    Arvind, Akanksha; Kumar, Vivek; Saravanan, Parameswaran; Mohan, C Gopi

    2012-09-01

    The cell wall of mycobacterium offers well validated targets which can be exploited for discovery of new lead compounds. MurC-MurF ligases catalyze a series of irreversible steps in the biosynthesis of peptidoglycan precursor, i.e. MurD catalyzes the ligation of D-glutamate to the nucleotide precursor UMA. The three dimensional structure of Mtb-MurD is not known and was predicted by us for the first time using comparative homology modeling technique. The accuracy and stability of the predicted Mtb-MurD structure was validated using Procheck and molecular dynamics simulation. Key interactions in Mtb-MurD were studied using docking analysis of available transition state inhibitors of E.coli-MurD. The docking analysis revealed that analogues of both L and D forms of glutamic acid have similar interaction profiles with Mtb-MurD. Further, residues His192, Arg382, Ser463, and Tyr470 are proposed to be important for inhibitor-(Mtb-MurD) interactions. We also identified few pharmacophoric features essential for Mtb-MurD ligase inhibitory activity and which can further been utilized for the discovery of putative antitubercular chemotherapy.

  10. Molecular structure based property modeling: Development/ improvement of property models through a systematic property-data-model analysis

    DEFF Research Database (Denmark)

    Hukkerikar, Amol Shivajirao; Sarup, Bent; Sin, Gürkan

    2013-01-01

    models. To make the property-data-model analysis fast and efficient, an approach based on the “molecular structure similarity criteria” to identify molecules (mono-functional, bi-functional, etc.) containing specified set of structural parameters (that is, groups) is employed. The method has been applied...

  11. Membrane re-modelling by BAR domain superfamily proteins via molecular and non-molecular factors.

    Science.gov (United States)

    Nishimura, Tamako; Morone, Nobuhiro; Suetsugu, Shiro

    2018-04-17

    Lipid membranes are structural components of cell surfaces and intracellular organelles. Alterations in lipid membrane shape are accompanied by numerous cellular functions, including endocytosis, intracellular transport, and cell migration. Proteins containing Bin-Amphiphysin-Rvs (BAR) domains (BAR proteins) are unique, because their structures correspond to the membrane curvature, that is, the shape of the lipid membrane. BAR proteins present at high concentration determine the shape of the membrane, because BAR domain oligomers function as scaffolds that mould the membrane. BAR proteins co-operate with various molecular and non-molecular factors. The molecular factors include cytoskeletal proteins such as the regulators of actin filaments and the membrane scission protein dynamin. Lipid composition, including saturated or unsaturated fatty acid tails of phospholipids, also affects the ability of BAR proteins to mould the membrane. Non-molecular factors include the external physical forces applied to the membrane, such as tension and friction. In this mini-review, we will discuss how the BAR proteins orchestrate membrane dynamics together with various molecular and non-molecular factors. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  12. Peranan Konservatisme Akuntansi dan Faktor Risiko Makro dalam Model Laba Residual: Sebuah Studi di Bursa Efek Indonesia

    Directory of Open Access Journals (Sweden)

    Andry Irwanto

    2015-01-01

    Full Text Available This study examines the association of accounting conservatism, growth and macro-economic risk factors and valuation error of residual income model in Indonesian Stock Exchange. We use beta, book to market ratio, and size as proxies for macro-economic risk. Using sample of 186 companies taken from LQ-45 for the year of 2001 – 2005, we find that accounting conservatism and growth, have no significant influence toward residual income model valuation error. B/M has significant influence toward valuation error and has consistent sign as predicted by theory. Beta and Size has no significant influence toward valuation error. Overall, macro-economic risk factors can explain the valuation error better than accounting-based factors.Future research is expected to find accounting variables that can represent macro-economic risk and test their ability to explain valuation error. Also, future research need to confirm the relevance of accounting conservatism in stock valuation after implementation of IFRS in Indonesia.

  13. Direct methods and residue type specific isotope labeling in NMR structure determination and model-driven sequential assignment

    International Nuclear Information System (INIS)

    Schedlbauer, Andreas; Auer, Renate; Ledolter, Karin; Tollinger, Martin; Kloiber, Karin; Lichtenecker, Roman; Ruedisser, Simon; Hommel, Ulrich; Schmid, Walther; Konrat, Robert; Kontaxis, Georg

    2008-01-01

    Direct methods in NMR based structure determination start from an unassigned ensemble of unconnected gaseous hydrogen atoms. Under favorable conditions they can produce low resolution structures of proteins. Usually a prohibitively large number of NOEs is required, to solve a protein structure ab-initio, but even with a much smaller set of distance restraints low resolution models can be obtained which resemble a protein fold. One problem is that at such low resolution and in the absence of a force field it is impossible to distinguish the correct protein fold from its mirror image. In a hybrid approach these ambiguous models have the potential to aid in the process of sequential backbone chemical shift assignment when 13 C β and 13 C' shifts are not available for sensitivity reasons. Regardless of the overall fold they enhance the information content of the NOE spectra. These, combined with residue specific labeling and minimal triple-resonance data using 13 C α connectivity can provide almost complete sequential assignment. Strategies for residue type specific labeling with customized isotope labeling patterns are of great advantage in this context. Furthermore, this approach is to some extent error-tolerant with respect to data incompleteness, limited precision of the peak picking, and structural errors caused by misassignment of NOEs

  14. Residual stresses

    International Nuclear Information System (INIS)

    Macherauch, E.

    1978-01-01

    Residual stresses are stresses which exist in a material without the influence of external powers and moments. They come into existence when the volume of a material constantly changes its form as a consequence of mechanical, thermal, and/or chemical processes and is hindered by neighbouring volumes. Bodies with residual stress are in mechanical balance. These residual stresses can be manifested by means of all mechanical interventions disturbing this balance. Acoustical, optical, radiological, and magnetical methods involving material changes caused by residual stress can also serve for determining residual stress. Residual stresses have an ambivalent character. In technical practice, they are feared and liked at the same time. They cause trouble because they can be the cause for unexpected behaviour of construction elements. They are feared since they can cause failure, in the worst case with catastrophical consequences. They are appreciated, on the other hand, because, in many cases, they can contribute to improvements of the material behaviour under certain circumstances. But they are especially liked for their giving convenient and (this is most important) mostly uncontrollable explanations. For only in very few cases we have enough knowledge and possibilities for the objective evaluation of residual stresses. (orig.) [de

  15. Integrating molecular diagnostics into histopathology training: the Belfast model.

    Science.gov (United States)

    Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

    2014-07-01

    Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Diffusion in Liquids : Equilibrium Molecular Simulations and Predictive Engineering Models

    NARCIS (Netherlands)

    Liu, X.

    2013-01-01

    The aim of this thesis is to study multicomponent diffusion in liquids using Molecular Dynamics (MD) simulations. Diffusion plays an important role in mass transport processes. In binary systems, mass transfer processes have been studied extensively using both experiments and molecular simulations.

  17. QSAR models based on quantum topological molecular similarity.

    Science.gov (United States)

    Popelier, P L A; Smith, P J

    2006-07-01

    A new method called quantum topological molecular similarity (QTMS) was fairly recently proposed [J. Chem. Inf. Comp. Sc., 41, 2001, 764] to construct a variety of medicinal, ecological and physical organic QSAR/QSPRs. QTMS method uses quantum chemical topology (QCT) to define electronic descriptors drawn from modern ab initio wave functions of geometry-optimised molecules. It was shown that the current abundance of computing power can be utilised to inject realistic descriptors into QSAR/QSPRs. In this article we study seven datasets of medicinal interest : the dissociation constants (pK(a)) for a set of substituted imidazolines , the pK(a) of imidazoles , the ability of a set of indole derivatives to displace [(3)H] flunitrazepam from binding to bovine cortical membranes , the influenza inhibition constants for a set of benzimidazoles , the interaction constants for a set of amides and the enzyme liver alcohol dehydrogenase , the natriuretic activity of sulphonamide carbonic anhydrase inhibitors and the toxicity of a series of benzyl alcohols. A partial least square analysis in conjunction with a genetic algorithm delivered excellent models. They are also able to highlight the active site, of the ligand or the molecule whose structure determines the activity. The advantages and limitations of QTMS are discussed.

  18. Modeling the influence of river discharge on salt intrusion and residual circulation in Danshuei River estuary, Taiwan

    Science.gov (United States)

    Liu, W.-C.; Chen, W.-B.; Cheng, R.T.; Hsu, M.-H.; Kuo, A.Y.

    2007-01-01

    A 3-D, time-dependent, baroclinic, hydrodynamic and salinity model was implemented and applied to the Danshuei River estuarine system and the adjacent coastal sea in Taiwan. The model forcing functions consist of tidal elevations along the open boundaries and freshwater inflows from the main stream and major tributaries in the Danshuei River estuarine system. The bottom friction coefficient was adjusted to achieve model calibration and verification in model simulations of barotropic and baroclinic flows. The turbulent diffusivities were ascertained through comparison of simulated salinity time series with observations. The model simulation results are in qualitative agreement with the available field data. The validated model was then used to investigate the influence of freshwater discharge on residual current and salinity intrusion under different freshwater inflow condition in the Danshuei River estuarine system. The model results reveal that the characteristic two-layered estuarine circulation prevails most of the time at Kuan-Du station near the river mouth. Comparing the estuarine circulation under low- and mean flow conditions, the circulation strengthens during low-flow period and its strength decreases at moderate river discharge. The river discharge is a dominating factor affecting the salinity intrusion in the estuarine system. A correlation between the distance of salt intrusion and freshwater discharge has been established allowing prediction of salt intrusion for different inflow conditions. ?? 2007 Elsevier Ltd. All rights reserved.

  19. Decarboxylation of Δ 9-tetrahydrocannabinol: Kinetics and molecular modeling

    Science.gov (United States)

    Perrotin-Brunel, Helene; Buijs, Wim; van Spronsen, Jaap; van Roosmalen, Maaike J. E.; Peters, Cor J.; Verpoorte, Rob; Witkamp, Geert-Jan

    2011-02-01

    Efficient tetrahydrocannabinol (Δ 9-THC) production from cannabis is important for its medical application and as basis for the development of production routes of other drugs from plants. This work presents one of the steps of Δ 9-THC production from cannabis plant material, the decarboxylation reaction, transforming the Δ 9-THC-acid naturally present in the plant into the psychoactive Δ 9-THC. Results of experiments showed pseudo-first order reaction kinetics, with an activation barrier of 85 kJ mol -1 and a pre-exponential factor of 3.7 × 10 8 s -1. Using molecular modeling, two options were identified for an acid catalyzed β-keto acid type mechanism for the decarboxylation of Δ 9-THC-acid. Each of these mechanisms might play a role, depending on the actual process conditions. Formic acid proved to be a good model for a catalyst of such a reaction. Also, the computational idea of catalysis by water to catalysis by an acid, put forward by Li and Brill, and Churchev and Belbruno was extended, and a new direct keto-enol route was found. A direct keto-enol mechanism catalyzed by formic acid seems to be the best explanation for the observed activation barrier and the pre-exponential factor of the decarboxylation of Δ 9-THC-acid. Evidence for this was found by performing an extraction experiment with Cannabis Flos. It revealed the presence of short chain carboxylic acids supporting this hypothesis. The presented approach is important for the development of a sustainable production of Δ 9-THC from the plant.

  20. Rejuvenation of residual oil hydrotreating catalysts by leaching of foulant metals. Modelling of the metal leaching process

    Energy Technology Data Exchange (ETDEWEB)

    Marafi, M.; Kam, E.K.T.; Stanislaus, A.; Absi-Halabi, M. [Petroleum Technology Department, Petroleum, Petrochemicals and Materials Division, Kuwait Institute for Scientific Research, Safat (Kuwait)

    1996-11-19

    Increasing emphasis has been paid in recent years on the development of processes for the rejuvenation of spent residual oil hydroprocessing catalysts, which are deactivated by deposition of metals (e.g. vanadium) and coke. As part of a research program on this subject, we have investigated selective removal of the major metal foulant from the spent catalyst by chemical leaching. In the present paper, we report the development of a model for foulant metals leaching from the spent catalyst. The leaching process is considered to involve two consecutive operations: (1) removal of metal foulants along the main mass transfer channels connected to the narrow pores until the pore structure begins to develop and (2) removal of metal foulants from the pore structure. Both kinetic and mass transfer aspects were considered in the model development, and a good agreement was noticed between experimental and simulated results

  1. A proposal of parameter determination method in the residual strength degradation model for the prediction of fatigue life (I)

    International Nuclear Information System (INIS)

    Kim, Sang Tae; Jang, Seong Soo

    2001-01-01

    The static and fatigue tests have been carried out to verify the validity of a generalized residual strength degradation model. And a new method of parameter determination in the model is verified experimentally to account for the effect of tension-compression fatigue loading of spheroidal graphite cast iron. It is shown that the correlation between the experimental results and the theoretical prediction on the statistical distribution of fatigue life by using the proposed method is very reasonable. Furthermore, it is found that the correlation between the theoretical prediction and the experimental results of fatigue life in case of tension-tension fatigue data in composite material appears to be reasonable. Therefore, the proposed method is more adjustable in the determination of the parameter than maximum likelihood method and minimization technique

  2. Theoretical modeling of electronic transport in molecular devices

    Science.gov (United States)

    Piccinin, Simone

    In this thesis a novel approach for simulating electronic transport in nanoscale structures is introduced. We consider an open quantum system (the electrons of structure) accelerated by an external electromotive force and dissipating energy through inelastic scattering with a heat bath (phonons) acting on the electrons. This method can be regarded as a quantum-mechanical extension of the semi-classical Boltzmann transport equation. We use periodic boundary conditions and employ Density Functional Theory to recast the many-particle problem in an effective single-particle mean-field problem. By explicitly treating the dissipation in the electrodes, the behavior of the potential is an outcome of our method, at variance with the scattering approaches based on the Landauer formalism. We study the self-consistent steady-state solution, analyzing the out-of-equilibrium electron distribution, the electrical characteristics, the behavior of the self-consistent potential and the density of states of the system. We apply the method to the study of electronic transport in several molecular devices, consisting of small organic molecules or atomic wires sandwiched between gold surfaces. For gold wires we recover the experimental evidence that transport in short wires is ballistic, independent of the length of the wire and with conductance of one quantum. In benzene-1,4-dithiol we find that the delocalization of the frontier orbitals of the molecule is responsible for the high value of conductance and that, by inserting methylene groups to decouple the sulfur atoms from the carbon ring, the current is reduced, in agreement with the experimental measurements. We study the effect a geometrical distortion in a molecular device, namely the relative rotation of the carbon rings in a biphenyl-4,4'-dithiol molecule. We find that the reduced coupling between pi orbitals of the rings induced by the rotation leads to a reduction of the conductance and that this behavior is captured by a

  3. Molecular Dynamics Modeling of PPTA Crystals in Aramid Fibers

    Energy Technology Data Exchange (ETDEWEB)

    Mercer, Brian Scott [Univ. of California, Berkeley, CA (United States)

    2016-05-19

    In this work, molecular dynamics modeling is used to study the mechanical properties of PPTA crystallites, which are the fundamental microstructural building blocks of polymer aramid bers such as Kevlar. Particular focus is given to constant strain rate axial loading simulations of PPTA crystallites, which is motivated by the rate-dependent mechanical properties observed in some experiments with aramid bers. In order to accommodate the covalent bond rupture that occurs in loading a crystallite to failure, the reactive bond order force eld ReaxFF is employed to conduct the simulations. Two major topics are addressed: The rst is the general behavior of PPTA crystallites under strain rate loading. Constant strain rate loading simulations of crystalline PPTA reveal that the crystal failure strain increases with increasing strain rate, while the modulus is not a ected by the strain rate. Increasing temperature lowers both the modulus and the failure strain. The simulations also identify the C N bond connecting the aromatic rings as weakest primary bond along the backbone of the PPTA chain. The e ect of chain-end defects on PPTA micromechanics is explored, and it is found that the presence of a chain-end defect transfers load to the adjacent chains in the hydrogen-bonded sheet in which the defect resides, but does not in uence the behavior of any other chains in the crystal. Chain-end defects are found to lower the strength of the crystal when clustered together, inducing bond failure via stress concentrations arising from the load transfer to bonds in adjacent chains near the defect site. The second topic addressed is the nature of primary and secondary bond failure in crystalline PPTA. Failure of both types of bonds is found to be stochastic in nature and driven by thermal uctuations of the bonds within the crystal. A model is proposed which uses reliability theory to model bonds under constant strain rate loading as components with time-dependent failure rate

  4. Multiscale Modeling of PEEK Using Reactive Molecular Dynamics Modeling and Micromechanics

    Science.gov (United States)

    Pisani, William A.; Radue, Matthew; Chinkanjanarot, Sorayot; Bednarcyk, Brett A.; Pineda, Evan J.; King, Julia A.; Odegard, Gregory M.

    2018-01-01

    Polyether ether ketone (PEEK) is a high-performance, semi-crystalline thermoplastic that is used in a wide range of engineering applications, including some structural components of aircraft. The design of new PEEK-based materials requires a precise understanding of the multiscale structure and behavior of semi-crystalline PEEK. Molecular Dynamics (MD) modeling can efficiently predict bulk-level properties of single phase polymers, and micromechanics can be used to homogenize those phases based on the overall polymer microstructure. In this study, MD modeling was used to predict the mechanical properties of the amorphous and crystalline phases of PEEK. The hierarchical microstructure of PEEK, which combines the aforementioned phases, was modeled using a multiscale modeling approach facilitated by NASA's MSGMC. The bulk mechanical properties of semi-crystalline PEEK predicted using MD modeling and MSGMC agree well with vendor data, thus validating the multiscale modeling approach.

  5. Checking Fine and Gray subdistribution hazards model with cumulative sums of residuals

    DEFF Research Database (Denmark)

    Li, Jianing; Scheike, Thomas; Zhang, Mei Jie

    2015-01-01

    Recently, Fine and Gray (J Am Stat Assoc 94:496–509, 1999) proposed a semi-parametric proportional regression model for the subdistribution hazard function which has been used extensively for analyzing competing risks data. However, failure of model adequacy could lead to severe bias in parameter...... estimation, and only a limited contribution has been made to check the model assumptions. In this paper, we present a class of analytical methods and graphical approaches for checking the assumptions of Fine and Gray’s model. The proposed goodness-of-fit test procedures are based on the cumulative sums...

  6. Spectral Modeling of Residual Stress and Stored Elastic Strain Energy in Thermal Barrier Coatings

    Energy Technology Data Exchange (ETDEWEB)

    Donegan, Sean; Rolett, Anthony

    2013-12-31

    Solutions to the thermoelastic problem are important for characterizing the response under temperature change of refractory systems. This work extends a spectral fast Fourier transform (FFT) technique to analyze the thermoelastic behavior of thermal barrier coatings (TBCs), with the intent of probing the local origins of failure in TBCs. The thermoelastic FFT (teFFT) approach allows for the characterization of local thermal residual stress and strain fields, which constitute the origins of failure in TBC systems. A technique based on statistical extreme value theory known as peaks-over-threshold (POT) is developed to quantify the extreme values ("hot spots") of stored elastic strain energy (i.e., elastic energy density, or EED). The resolution dependence of the teFFT method is assessed through a sensitivity study of the extreme values in EED. The sensitivity study is performed both for the local (point-by-point) eld distributions as well as the grain scale eld distributions. A convergence behavior to a particular distribution shape is demonstrated for the local elds. The grain scale fields are shown to exhibit a possible convergence to a maximum level of EED. To apply the teFFT method to TBC systems, 3D synthetic microstructures are created to approximate actual TBC microstructures. The morphology of the grains in each constituent layer as well as the texture is controlled. A variety of TBC materials, including industry standard materials and potential future materials, are analyzed using the teFFT. The resulting hot spots are quantified using the POT approach. A correlation between hot spots in EED and interface rumpling between constituent layers is demonstrated, particularly for the interface between the bond coat (BC) and the thermally grown oxide (TGO) layer.

  7. Modeling, methodologies and tools for molecular and nano-scale communications modeling, methodologies and tools

    CERN Document Server

    Nakano, Tadashi; Moore, Michael

    2017-01-01

    (Preliminary) The book presents the state of art in the emerging field of molecular and nanoscale communication. It gives special attention to fundamental models, and advanced methodologies and tools used in the field. It covers a wide range of applications, e.g. nanomedicine, nanorobot communication, bioremediation and environmental managements. It addresses advanced graduate students, academics and professionals working at the forefront in their fields and at the interfaces between different areas of research, such as engineering, computer science, biology and nanotechnology.

  8. A Simple Model to Demonstrate the Balance of Forces at Functional Residual Capacity

    Science.gov (United States)

    Kanthakumar, Praghalathan; Oommen, Vinay

    2012-01-01

    Numerous models have been constructed to aid teaching respiratory mechanics. A simple model using a syringe and a water-filled bottle has been described by Thomas Sherman to explain inspiration and expiration. The elastic recoil of the chest wall and lungs has been described using a coat hanger or by using rods and rubber bands. A more complex…

  9. Molecular modeling of protonic acid doping of emeraldine base polyaniline for chemical sensors

    NARCIS (Netherlands)

    Chen, X.; Yuan, C.A.; Wong, C.K.Y.; Ye, H.; Leung, S.Y.Y.; Zhang, G.

    2012-01-01

    We proposed a molecular modeling methodology to study the protonic acid doping of emeraldine base polyaniline which can used in gas detection. The commercial forcefield COMPASS was used for the polymer and protonic acid molecules. The molecular model, which is capable of representing the polyaniline

  10. The identification of new substrates of human DHRS7 by molecular modeling and in vitro testing

    Czech Academy of Sciences Publication Activity Database

    Zemanová, L.; Palani, Kirubakaran; Pato, I. H.; Štambergová, H.; Vondrášek, Jiří

    2017-01-01

    Roč. 105, č. 1 (2017), s. 171-182 ISSN 0141-8130 R&D Projects: GA MŠk(CZ) LM2015047 Institutional support: RVO:61388963 Keywords : DHRS7 * SDR superfamily * SDR34C1 * homology modeling * molecular modeling Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.671, year: 2016

  11. Computer-Based Molecular Modelling: Finnish School Teachers' Experiences and Views

    Science.gov (United States)

    Aksela, Maija; Lundell, Jan

    2008-01-01

    Modern computer-based molecular modelling opens up new possibilities for chemistry teaching at different levels. This article presents a case study seeking insight into Finnish school teachers' use of computer-based molecular modelling in teaching chemistry, into the different working and teaching methods used, and their opinions about necessary…

  12. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    Science.gov (United States)

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

  13. A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

    Science.gov (United States)

    Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

    2011-01-01

    Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

  14. Forcefields based molecular modeling on the mechanical and physical properties of emeraldine base polyaniline

    NARCIS (Netherlands)

    Chen, X.; Yuan, C.A.; Wong, K.Y.; Zhang, G.Q.

    2010-01-01

    Molecular dynamics (MD) and molecular mechanical (MM) analysis are carried out to provide reliable and accurate model for emeraldine base polyaniline. This study validate the forcefields and model with the physical and mechanical properties of the polyaniline. The temperature effects on non-bond

  15. A combined reaction class approach with integrated molecular orbital+molecular orbital (IMOMO) methodology: A practical tool for kinetic modeling

    International Nuclear Information System (INIS)

    Truong, Thanh N.; Maity, Dilip K.; Truong, Thanh-Thai T.

    2000-01-01

    We present a new practical computational methodology for predicting thermal rate constants of reactions involving large molecules or a large number of elementary reactions in the same class. This methodology combines the integrated molecular orbital+molecular orbital (IMOMO) approach with our recently proposed reaction class models for tunneling. With the new methodology, we show that it is possible to significantly reduce the computational cost by several orders of magnitude while compromising the accuracy in the predicted rate constants by less than 40% over a wide range of temperatures. Another important result is that the computational cost increases only slightly as the system size increases. (c) 2000 American Institute of Physics

  16. FROM ATOMISTIC TO SYSTEMATIC COARSE-GRAINED MODELS FOR MOLECULAR SYSTEMS

    KAUST Repository

    Harmandaris, Vagelis; Kalligiannaki, Evangelia; Katsoulakis, Markos; Plechac, Petr

    2017-01-01

    The development of systematic (rigorous) coarse-grained mesoscopic models for complex molecular systems is an intense research area. Here we first give an overview of methods for obtaining optimal parametrized coarse-grained models, starting from

  17. Investigation of the interaction between isomeric derivatives and human serum albumin by fluorescence spectroscopy and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruiyong, E-mail: wangry@zzu.edu.cn; Dou, Huanjing; Yin, Yujing; Xie, Yuanzhe; Sun, Li; Liu, Chunmei; Dong, Jingjing; Huang, Gang; Zhu, Yanyan; Song, Chuanjun, E-mail: chjsong@zzu.edu.cn; Chang, Junbiao, E-mail: changjunbiao@zzu.edu.cn

    2014-10-15

    In this paper, we have synthesized 9H-pyrrolo[1,2-a]indol-9-ones and the isomeric indeno[2,1-b]pyrrol-8-ones. The interactions of human serum albumin with series of isomeric derivatives have been studied by spectrophotometric methods. Results show the intrinsic fluorescence is quenched by the derivatives with a static quenching procedure. The thermodynamics parameters indicate that van der Waals forces and hydrogen bonds play a major role in the interactions. The results of synchronous fluorescence spectra demonstrate that the microenvironments of Trp residue of human serum albumin are disturbed by most derivatives. Thermodynamic results showed that the 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers and bind to human serum albumin with the higher affinity than isomeric indeno[2,1-b]pyrrol-8-ones. The influence of molecular structure on the binding aspects has been investigated. - Highlights: • The interactions between isomeric derivatives and HSA have been investigated. • Results reveal that 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers for HSA. • Hydrogen bonds and van der Waals forces play major role in the binding process. • The influence of molecular structure on the binding aspects has been investigated. • The binding study was also modeled by molecular docking.

  18. Investigation of the interaction between isomeric derivatives and human serum albumin by fluorescence spectroscopy and molecular modeling

    International Nuclear Information System (INIS)

    Wang, Ruiyong; Dou, Huanjing; Yin, Yujing; Xie, Yuanzhe; Sun, Li; Liu, Chunmei; Dong, Jingjing; Huang, Gang; Zhu, Yanyan; Song, Chuanjun; Chang, Junbiao

    2014-01-01

    In this paper, we have synthesized 9H-pyrrolo[1,2-a]indol-9-ones and the isomeric indeno[2,1-b]pyrrol-8-ones. The interactions of human serum albumin with series of isomeric derivatives have been studied by spectrophotometric methods. Results show the intrinsic fluorescence is quenched by the derivatives with a static quenching procedure. The thermodynamics parameters indicate that van der Waals forces and hydrogen bonds play a major role in the interactions. The results of synchronous fluorescence spectra demonstrate that the microenvironments of Trp residue of human serum albumin are disturbed by most derivatives. Thermodynamic results showed that the 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers and bind to human serum albumin with the higher affinity than isomeric indeno[2,1-b]pyrrol-8-ones. The influence of molecular structure on the binding aspects has been investigated. - Highlights: • The interactions between isomeric derivatives and HSA have been investigated. • Results reveal that 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers for HSA. • Hydrogen bonds and van der Waals forces play major role in the binding process. • The influence of molecular structure on the binding aspects has been investigated. • The binding study was also modeled by molecular docking

  19. Assessment of Ex-Vitro Anaerobic Digestion Kinetics of Crop Residues Through First Order Exponential Models: Effect of LAG Phase Period and Curve Factor

    Directory of Open Access Journals (Sweden)

    Abdul Razaque Sahito

    2013-04-01

    Full Text Available Kinetic studies of AD (Anaerobic Digestion process are useful to predict the performance of digesters and design appropriate digesters and also helpful in understanding inhibitory mechanisms of biodegradation. The aim of this study was to assess the anaerobic kinetics of crop residues digestion with buffalo dung. Seven crop residues namely, bagasse, banana plant waste, canola straw, cotton stalks, rice straw, sugarcane trash and wheat straw were selected from the field and were analyzed on MC (Moisture Contents, TS (Total Solids and VS (Volatile Solids with standard methods. In present study, three first order exponential models namely exponential model, exponential lag phase model and exponential curve factor model were used to assess the kinetics of the AD process of crop residues and the effect of lag phase and curve factor was analyzed based on statistical hypothesis testing and on information theory. Assessment of kinetics of the AD of crop residues and buffalo dung follows the first order kinetics. Out of the three models, the simple exponential model was the poorest model, while the first order exponential curve factor model is the best fit model. In addition to statistical hypothesis testing, the exponential curve factor model has least value of AIC (Akaike's Information Criterion and can generate methane production data more accurately. Furthermore, there is an inverse linear relationship between the lag phase period and the curve factor.

  20. Assessment of ex-vitro anaerobic digestion kinetics of crop residues through first order exponential models: effect of lag phase period and curve factor

    International Nuclear Information System (INIS)

    Sahito, A.R.; Brohi, K.M.

    2013-01-01

    Kinetic studies of AD (Anaerobic Digestion) process are useful to predict the performance of digesters and design appropriate digesters and also helpful in understanding inhibitory mechanisms of biodegradation. The aim of this study was to assess the anaerobic kinetics of crop residues digestion with buffalo dung. Seven crop residues namely, bagasse, banana plant waste, canola straw, cotton stalks, rice straw, sugarcane trash and wheat straw were selected from the field and were analyzed on MC (Moisture Contents), TS (Total Solids) and VS (Volatile Solids) with standard methods. In present study, three first order exponential models namely exponential model, exponential lag phase model and exponential curve factor model were used to assess the kinetics of the AD process of crop residues and the effect of lag phase and curve factor was analyzed based on statistical hypothesis testing and on information theory. Assessment of kinetics of the AD of crop residues and buffalo dung follows the first order kinetics. Out of the three models, the simple exponential model was the poorest model, while the first order exponential curve factor model is the best fit model. In addition to statistical hypothesis testing, the exponential curve factor model has least value of AIC (Akaike's Information Criterion) and can generate methane production data more accurately. Furthermore, there is an inverse linear relationship between the lag phase period and the curve factor. (author)

  1. Molecular Line Survey of CRL618 and Complete Modeling

    Science.gov (United States)

    Pardo, J. R.; Cernicharo, J.; Goicoechea, J. R.; Phillips, T. G.

    We present a complete survey and model of the emission from the C-rich protoplanetary nebula CRL 618 at the frequencies accessible with the IRAM-30m telescope (80.25-115.75 GHz, 131.25-179.25 GHz, and 204.25-275.25 GHz) and some results of still on-going observations at the Caltech Submillimeter Observatory (280-360 GHz). Although the number of lines detected is large (several hundreds), the number of chemical species from which they arise is rather small. In fact, lines from cyanopolyynes HC3N and HC5N dominate by far the long-wave spectrum of CRL618, with detection of numerous vibrationally excited states and isotopic substituted species. Most of detected species exhibit P-Cygni profiles at the lowest frequencies (3 mm window), and they evolve to pure emission as frequency increases. This fact can only be explained by the behavior of the continuum emission arising from the inner ultracompact HII region and surrounding dust. The data set itself has been used to characterize the continuum emission by averaging all the continuum measurements during the time span of the survey (~8 years). The physical parameters of the different gas regions have been established by studying the large number of detected cyanopolyynes lines. Using these constraints, the abundances of many other species relative to HC3N could also be determined and a general model, that reproduce the whole data set at a very detailed level of agreement, could be built. 1. Introduction The motivation to perform the complete millimeter line survey presented here with the IRAM-30m telescope has been to gather the most complete information on the molecular content in one particular stage (protoplanetary nebula, PPNe) of stellar evolution from the Asymptotic Giant Branch (AGB) to Planetary Nebulae (PN), of which CRL618 is the best example. Its chemical richness and its complex morphology are now very well known. Detailed chemical models for this object have been developed (Cernicharo 2004) indicating the

  2. Quantum Mechanics/Molecular Mechanics Modeling of Drug Metabolism: Mexiletine N-Hydroxylation by Cytochrome P450 1A2.

    Science.gov (United States)

    Lonsdale, Richard; Fort, Rachel M; Rydberg, Patrik; Harvey, Jeremy N; Mulholland, Adrian J

    2016-06-20

    The mechanism of cytochrome P450(CYP)-catalyzed hydroxylation of primary amines is currently unclear and is relevant to drug metabolism; previous small model calculations have suggested two possible mechanisms: direct N-oxidation and H-abstraction/rebound. We have modeled the N-hydroxylation of (R)-mexiletine in CYP1A2 with hybrid quantum mechanics/molecular mechanics (QM/MM) methods, providing a more detailed and realistic model. Multiple reaction barriers have been calculated at the QM(B3LYP-D)/MM(CHARMM27) level for the direct N-oxidation and H-abstraction/rebound mechanisms. Our calculated barriers indicate that the direct N-oxidation mechanism is preferred and proceeds via the doublet spin state of Compound I. Molecular dynamics simulations indicate that the presence of an ordered water molecule in the active site assists in the binding of mexiletine in the active site, but this is not a prerequisite for reaction via either mechanism. Several active site residues play a role in the binding of mexiletine in the active site, including Thr124 and Phe226. This work reveals key details of the N-hydroxylation of mexiletine and further demonstrates that mechanistic studies using QM/MM methods are useful for understanding drug metabolism.

  3. Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

    Science.gov (United States)

    Hariono, Maywan; Abdullah, Nurshariza; Damodaran, K. V.; Kamarulzaman, Ezatul E.; Mohamed, Nornisah; Hassan, Sharifah Syed; Shamsuddin, Shaharum; Wahab, Habibah A.

    2016-12-01

    We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.

  4. The reactivity of phenolic and non-phenolic residual kraft lignin model compounds with Mn(II)-peroxidase from Lentinula edodes.

    Science.gov (United States)

    Crestini, C; D'Annibale, A; Sermanni, G G; Saladino, R

    2000-02-01

    Three phenolic model compounds representing bonding patterns of residual kraft lignin were incubated with manganese peroxidase from Lentinula edodes. Extensive degradation of all the phenolic models, mainly occurring via side-chain benzylic oxidation, was observed. Among the tested model compounds the diphenylmethane alpha-5 phenolic model was found to be the most reactive, yielding several products showing oxidation and fragmentation at the bridging position. The non-phenolic 5-5' biphenyl and 5-5' diphenylmethane models were found unreactive.

  5. Analysis and Modeling of Process of Residual Deformations Accumulation in Soils and Granular Materials

    Science.gov (United States)

    Aleksandrov, A. S.; Dolgih, G. V.; Kalinin, A. L.

    2017-11-01

    It is established that under the influence of repeated loads the process of plastic deformation in soils and discrete materials is hereditary. To perform the mathematical modeling of plastic deformation, the authors applied the integral equation by solution of which they manage to obtain the power and logarithmic dependencies connecting plastic deformation with the number of repeated loads, the parameters of the material and components of the stress tensor in the principal axes. It is shown that these dependences generalize a number of models proposed earlier in Russia and abroad. Based on the analysis of the experimental data obtained during material testing in the dynamic devices of triaxial compression at different values of the stress deviator, the coefficients in the proposed models of deformation are determined. The authors determined the application domain for logarithmic and degree dependences.

  6. DOE Final Report: A Unified Understanding of Residual Stress in Thin Films: Kinetic Models, Experiments and Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Chason, Eric [Brown Univ., Providence, RI (United States)

    2018-02-01

    Thin films are critical for a wide range of advanced technologies. However, the deposited films often have high levels of residual stress that can limit their performance or lead to failure. The stress is known to depend on many variables, including the processing conditions, type of material, deposition technique and the film’s microstructure. The goal of this DOE program was to develop a fundamental understanding of how the different processes that control thin film growth under different conditions can be related to the development of stress. In the program, systematic experiments were performed or analyzed that related the stress to the processing conditions that were used. Measurements of stress were obtained for films that were grown at different rates, different solutions (for electrodeposition), different particle energies (for sputter deposition) and different microstructures. Based on this data, models were developed to explain the observed dependence on the different parameters. The models were based on considering the balance among different stress-inducing mechanism occurring as the film grows (for both non-energetic and energetic deposition). Comparison of the model predictions with the experiments enabled the kinetic parameters to be determined for different materials. The resulting model equations provide a comprehensive picture of how stress changes with the processing conditions that can be used to optimize the growth of thin films.

  7. Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M

    Directory of Open Access Journals (Sweden)

    Pradeepkiran JA

    2015-03-01

    24934545 and ZINC72319544 – that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex via a hydrogen bonding interaction by aromatic-π contacts, and the ADMET (absorption, distribution, metabolism, and excretion analysis of best leads indicate nontoxic in nature with good potential for drug development. Keywords: brucellosis, rho proteins, transcription inhibitors, SMD simulations, ADMET analysis, therapeutics 

  8. The mechanical properties modeling of nano-scale materials by molecular dynamics

    NARCIS (Netherlands)

    Yuan, C.; Driel, W.D. van; Poelma, R.; Zhang, G.Q.

    2012-01-01

    We propose a molecular modeling strategy which is capable of mod-eling the mechanical properties on nano-scale low-dielectric (low-k) materials. Such modeling strategy has been also validated by the bulking force of carbon nano tube (CNT). This modeling framework consists of model generation method,

  9. Solid residues

    International Nuclear Information System (INIS)

    Mulder, E.; Duin, P.J. van; Grootenboer, G.J.

    1995-01-01

    A summary is presented of the many investigations that have been done on solid residues of atmospheric fluid bed combustion (AFBC). These residues are bed ash, cyclone ash and bag filter ash. Physical and chemical properties are discussed and then the various uses of residues (in fillers, bricks, gravel, and for recovery of aluminium) are summarised. Toxicological properties of fly ash and stack ash are discussed as are risks of pneumoconiosis for workers handling fly ash, and contamination of water by ashes. On the basis of present information it is concluded that risks to public health from exposure to emissions of coal fly ash from AFBC appear small or negligible as are health risk to workers in the coal fly ash processing industry. 35 refs., 5 figs., 12 tabs

  10. A study of probabilistic fatigue crack propagation models in Mg Al Zn alloys under different specimen thickness conditions by using the residual of a random variable

    International Nuclear Information System (INIS)

    Choi, Seon Soon

    2012-01-01

    The primary aim of this paper was to evaluate several probabilistic fatigue crack propagation models using the residual of a random variable, and to present the model fit for probabilistic fatigue behavior in Mg Al Zn alloys. The proposed probabilistic models are the probabilistic Paris Erdogan model, probabilistic Walker model, probabilistic Forman model, and probabilistic modified Forman models. These models were prepared by applying a random variable to the empirical fatigue crack propagation models with these names. The best models for describing fatigue crack propagation models with these names. The best models for describing fatigue crack propagation models with these names. The best models for describing fatigue crack propagation models with these names. The best models vor describing fatigue crack propagation behavior in Mg Al Zn alloys were generally the probabilistic Paris Erdogan and probabilistic Walker models. The probabilistic Forman model was a good model only for a specimen with a thickness of 9.45mm

  11. Stellite failure on a P91 HP valve - failure investigation and modelling of residual stresses

    DEFF Research Database (Denmark)

    Thorborg, Jesper; Hald, John; Hattel, Jesper Henri

    2006-01-01

    , and this provides a tool for process modification in order to minimize the risk for future breakdown. Both classical time independent and time dependent plasticity models have been used to describe the different material behaviours during the different process steps. The description of the materials is highly...

  12. Residual estuarine circulation in the Mandovi, a monsoonal estuary: A three-dimensional model study

    Digital Repository Service at National Institute of Oceanography (India)

    Vijith, V.; Shetye, S.R.; Baetens, K.; Luyten, P.; Michael, G.S.

    -dependence is forced by the Indian Summer Monsoon (ISM) and hence the estuary is referred to as a monsoonal estuary. In this paper, we use a three-dimensional, open source, hydrodynamic, numerical model to reproduce the observed annual salinity field in the Mandovi. We...

  13. Deriving Genomic Breeding Values for Residual Feed Intake from Covariance Functions of Random Regression Models

    DEFF Research Database (Denmark)

    Strathe, Anders B; Mark, Thomas; Nielsen, Bjarne

    2014-01-01

    Random regression models were used to estimate covariance functions between cumulated feed intake (CFI) and body weight (BW) in 8424 Danish Duroc pigs. Random regressions on second order Legendre polynomials of age were used to describe genetic and permanent environmental curves in BW and CFI...

  14. Horizontal Residual Mean Circulation: Evaluation of Spatial Correlations in Coarse Resolution Ocean Models

    Science.gov (United States)

    Li, Y.; McDougall, T. J.

    2016-02-01

    Coarse resolution ocean models lack knowledge of spatial correlations between variables on scales smaller than the grid scale. Some researchers have shown that these spatial correlations play a role in the poleward heat flux. In order to evaluate the poleward transport induced by the spatial correlations at a fixed horizontal position, an equation is obtained to calculate the approximate transport from velocity gradients. The equation involves two terms that can be added to the quasi-Stokes streamfunction (based on temporal correlations) to incorporate the contribution of spatial correlations. Moreover, these new terms do not need to be parameterized and is ready to be evaluated by using model data directly. In this study, data from a high resolution ocean model have been used to estimate the accuracy of this HRM approach for improving the horizontal property fluxes in coarse-resolution ocean models. A coarse grid is formed by sub-sampling and box-car averaging the fine grid scale. The transport calculated on the coarse grid is then compared to the transport on original high resolution grid scale accumulated over a corresponding number of grid boxes. The preliminary results have shown that the estimate on coarse resolution grids roughly match the corresponding transports on high resolution grids.

  15. Complexity in modeling of residual stresses and strains during polymerization of bone cement: effects of conversion, constraint, heat transfer, and viscoelastic property changes.

    Science.gov (United States)

    Gilbert, Jeremy L

    2006-12-15

    Aseptic loosening of cemented joint prostheses remains a significant concern in orthopedic biomaterials. One possible contributor to cement loosening is the development of porosity, residual stresses, and local fracture of the cement that may arise from the in-situ polymerization of the cement. In-situ polymerization of acrylic bone cement is a complex set of interacting processes that involve polymerization reactions, heat generation and transfer, full or partial mechanical constraint, evolution of conversion- and temperature-dependent viscoelastic material properties, and thermal and conversion-driven changes in the density of the cement. Interactions between heat transfer and polymerization can lead to polymerization fronts moving through the material. Density changes during polymerization can, in the presence of mechanical constraint, lead to the development of locally high residual strain energy and residual stresses. This study models the interactions during bone cement polymerization and determines how residual stresses develop in cement and incorporates temperature and conversion-dependent viscoelastic behavior. The results show that the presence of polymerization fronts in bone cement result in locally high residual strain energies. A novel heredity integral approach is presented to track residual stresses incorporating conversion and temperature dependent material property changes. Finally, the relative contribution of thermal- and conversion-dependent strains to residual stresses is evaluated and it is found that the conversion-based strains are the major contributor to the overall behavior. This framework provides the basis for understanding the complex development of residual stresses and can be used as the basis for developing more complex models of cement behavior.

  16. Wastewater disinfection by peracetic acid: assessment of models for tracking residual measurements and inactivation.

    Science.gov (United States)

    Santoro, Domenico; Gehr, Ronald; Bartrand, Timothy A; Liberti, Lorenzo; Notarnicola, Michele; Dell'Erba, Adele; Falsanisi, Dario; Haas, Charles N

    2007-07-01

    With its potential for low (if any) disinfection byproduct formation and easy retrofit for chlorine contactors, peracetic acid (PAA) or use of PAA in combination with other disinfectant technologies may be an attractive alternative to chlorine-based disinfection. Examples of systems that might benefit from use of PAA are water reuse schemes or plants discharging to sensitive receiving water bodies. Though PAA is in use in numerous wastewater treatment plants in Europe, its chemical kinetics, microbial inactivation rates, and mode of action against microorganisms are not thoroughly understood. This paper presents results from experimental studies of PAA demand, PAA decay, and microbial inactivation, with a complementary modeling analysis. Model results are used to evaluate techniques for measurement of PAA concentration and to develop hypotheses regarding the mode of action of PAA in bacterial inactivation. Kinetic and microbial inactivation rate data were collected for typical wastewaters and may be useful for engineers in evaluating whether to convert from chlorine to PAA disinfection.

  17. Molecular modeling study on the allosteric inhibition mechanism of HIV-1 integrase by LEDGF/p75 binding site inhibitors.

    Directory of Open Access Journals (Sweden)

    Weiwei Xue

    Full Text Available HIV-1 integrase (IN is essential for the integration of viral DNA into the host genome and an attractive therapeutic target for developing antiretroviral inhibitors. LEDGINs are a class of allosteric inhibitors targeting LEDGF/p75 binding site of HIV-1 IN. Yet, the detailed binding mode and allosteric inhibition mechanism of LEDGINs to HIV-1 IN is only partially understood, which hinders the structure-based design of more potent anti-HIV agents. A molecular modeling study combining molecular docking, molecular dynamics simulation, and binding free energy calculation were performed to investigate the interaction details of HIV-1 IN catalytic core domain (CCD with two recently discovered LEDGINs BI-1001 and CX14442, as well as the LEDGF/p75 protein. Simulation results demonstrated the hydrophobic domain of BI-1001 and CX14442 engages one subunit of HIV-1 IN CCD dimer through hydrophobic interactions, and the hydrophilic group forms hydrogen bonds with HIV-1 IN CCD residues from other subunit. CX14442 has a larger tert-butyl group than the methyl of BI-1001, and forms better interactions with the highly hydrophobic binding pocket of HIV-1 IN CCD dimer interface, which can explain the stronger affinity of CX14442 than BI-1001. Analysis of the binding mode of LEDGF/p75 with HIV-1 IN CCD reveals that the LEDGF/p75 integrase binding domain residues Ile365, Asp366, Phe406 and Val408 have significant contributions to the binding of the LEDGF/p75 to HIV1-IN. Remarkably, we found that binding of BI-1001 and CX14442 to HIV-1 IN CCD induced the structural rearrangements of the 140 s loop and oration displacements of the side chains of the three conserved catalytic residues Asp64, Asp116, and Glu152 located at the active site. These results we obtained will be valuable not only for understanding the allosteric inhibition mechanism of LEDGINs but also for the rational design of allosteric inhibitors of HIV-1 IN targeting LEDGF/p75 binding site.

  18. Prediction of interface residue based on the features of residue interaction network.

    Science.gov (United States)

    Jiao, Xiong; Ranganathan, Shoba

    2017-11-07

    Protein-protein interaction plays a crucial role in the cellular biological processes. Interface prediction can improve our understanding of the molecular mechanisms of the related processes and functions. In this work, we propose a classification method to recognize the interface residue based on the features of a weighted residue interaction network. The random forest algorithm is used for the prediction and 16 network parameters and the B-factor are acting as the element of the input feature vector. Compared with other similar work, the method is feasible and effective. The relative importance of these features also be analyzed to identify the key feature for the prediction. Some biological meaning of the important feature is explained. The results of this work can be used for the related work about the structure-function relationship analysis via a residue interaction network model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Finite element modeling to determine thermal residual strain distribution of bonded composite repairs for structural health monitoring design

    Science.gov (United States)

    Baker, Wayne; Jones, Rhys; Davis, Claire; Galea, Stephen C.

    2002-11-01

    The economic implication of fleet upgrades, particularly in Australia with military aircraft such as the F-111 and F/A-18, has led to an increasing reliance on composite repair technology to address fatigue and corrosion-affected aircraft components. The increasing use of such repairs has led to a research effort to develop various in-situ health monitoring systems that may be incorporated with a repair. This paper reports on the development of a theoretical methodology that uses finite element analysis (FEA) to model the strain profiles which optical sensors, on or within the patch, will be exposed to under various operational scenarios, including load and disbond. Numerical techniques are then used to predict the fibre Bragg grating (FBG) reflections which occur with these strain profiles. The quality of these reflection are a key consideration when designing FBG based structural health monitoring (SHM) systems. This information can be used to optimise the location of both surface mounted, and embedded sensors, and determine feasibility of SHM system design. Research was conducted into the thermal residual strain (TRS) within the patch. A finite element study revealed the presence of significant thermal residual strain gradients along the surface of the tapered region of the patch. As Bragg gratings are particularly sensitive to strain gradients, (producing a result similar to a chirped grating) the strain gradient on the composite at potential sensor locations both under load, and in the event of disbond was considered. A sufficiently high gradient leads to an altered Bragg reflection. These spurious reflections need to be considered, and theoretically obtained reflections can provide information to allow for load scenarios where the Bragg shift is not a smooth, well defined peak. It can also be shown that embedded fibres offer a higher average thermal residual strain reading, while being subject to a much lower strain gradient. This particularly favors the

  20. Sensitivity analysis of six soil organic matter models applied to the decomposition of animal manures and crop residues

    Directory of Open Access Journals (Sweden)

    Daniele Cavalli

    2016-09-01

    Full Text Available Two features distinguishing soil organic matter simulation models are the type of kinetics used to calculate pool decomposition rates, and the algorithm used to handle the effects of nitrogen (N shortage on carbon (C decomposition. Compared to widely used first-order kinetics, Monod kinetics more realistically represent organic matter decomposition, because they relate decomposition to both substrate and decomposer size. Most models impose a fixed C to N ratio for microbial biomass. When N required by microbial biomass to decompose a given amount of substrate-C is larger than soil available N, carbon decomposition rates are limited proportionally to N deficit (N inhibition hypothesis. Alternatively, C-overflow was proposed as a way of getting rid of excess C, by allocating it to a storage pool of polysaccharides. We built six models to compare the combinations of three decomposition kinetics (first-order, Monod, and reverse Monod, and two ways to simulate the effect of N shortage on C decomposition (N inhibition and C-overflow. We conducted sensitivity analysis to identify model parameters that mostly affected CO2 emissions and soil mineral N during a simulated 189-day laboratory incubation assuming constant water content and temperature. We evaluated model outputs sensitivity at different stages of organic matter decomposition in a soil amended with three inputs of increasing C to N ratio: liquid manure, solid manure, and low-N crop residue. Only few model parameters and their interactions were responsible for consistent variations of CO2 and soil mineral N. These parameters were mostly related to microbial biomass and to the partitioning of applied C among input pools, as well as their decomposition constants. In addition, in models with Monod kinetics, CO2 was also sensitive to a variation of the half-saturation constants. C-overflow enhanced pool decomposition compared to N inhibition hypothesis when N shortage occurred. Accumulated C in the

  1. Hanford Tanks 241-C-202 and 241-C-203 Residual Waste Contaminant Release Models and Supporting Data

    Energy Technology Data Exchange (ETDEWEB)

    Deutsch, William J.; Krupka, Kenneth M.; Lindberg, Michael J.; Cantrell, Kirk J.; Brown, Christopher F.; Mattigod, Shas V.; Schaef, Herbert T.; Arey, Bruce W.

    2007-09-13

    As directed by Congress, the U. S. Department of Energy (DOE) established the Office of River Protection in 1998 to manage DOE's largest, most complex environmental cleanup project – retrieval of radioactive waste from Hanford tanks for treatment and eventual disposal. Sixty percent by volume of the nation's high-level radioactive waste is stored at Hanford in aging deteriorating tanks. If not cleaned up, this waste is a threat to the Columbia River and the Pacific Northwest. CH2M Hill Hanford Group, Inc., is the Office of River Protection's prime contractor responsible for the storage, retrieval, and disposal of Hanford's tank waste. As part of this effort, CH2M HILL Hanford Group, Inc. contracted with Pacific Northwest National Laboratory (PNNL) to develop release models for key contaminants that are present in residual sludge remaining after closure of Hanford Tanks 241-C-203 (C-203) and 241-C-204 (C-204). The release models were developed from data generated by laboratory characterization and testing of samples from these two tanks. These release models are being developed to support the tank closure risk assessments performed by CH2M HILL Hanford Group, Inc., for DOE.

  2. Hanford Tanks 241-C-203 and 241-C-204: Residual Waste Contaminant Release Model and Supporting Data

    Energy Technology Data Exchange (ETDEWEB)

    Deutsch, William J.; Krupka, Kenneth M.; Lindberg, Michael J.; Cantrell, Kirk J.; Brown, Christopher F.; Schaef, Herbert T.

    2004-10-28

    This report describes the development of release models for key contaminants that are present in residual sludge remaining after closure of Hanford Tanks 241-C-203 (C-203) and 241-C-204 (C-204). The release models were developed from data generated by laboratory characterization and testing of samples from these two tanks. Key results from this work are (1) future releases from the tanks of the primary contaminants of concern (99Tc and 238U) can be represented by relatively simple solubility relationships between infiltrating water and solid phases containing the contaminants; and (2) high percentages of technetium-99 in the sludges (20 wt% in C-203 and 75 wt% in C-204) are not readily water leachable, and, in fact, are very recalcitrant. This is similar to results found in related studies of sludges from Tank AY-102. These release models are being developed to support the tank closure risk assessments performed by CH2M HILL Hanford Group, Inc., for the U.S. Department of Energy.

  3. Hanford Tanks 241-C-203 and 241 C 204: Residual Waste Contaminant Release Model and Supporting Data

    Energy Technology Data Exchange (ETDEWEB)

    Deutsch, William J.; Krupka, Kenneth M.; Lindberg, Michael J.; Cantrell, Kirk J.; Brown, Christopher F.; Schaef, Herbert T.

    2007-05-23

    This report was revised in May 2007 to correct 90Sr values in Chapter 3. The changes were made on page 3.9, paragraph two and Table 3.10; page 3.16, last paragraph on the page; and Tables 3.21 and 3.31. The rest of the text remains unchanged from the original report issued in October 2004. This report describes the development of release models for key contaminants that are present in residual sludge remaining after closure of Hanford Tanks 241-C-203 (C-203) and 241-C-204 (C-204). The release models were developed from data generated by laboratory characterization and testing of samples from these two tanks. Key results from this work are (1) future releases from the tanks of the primary contaminants of concern (99Tc and 238U) can be represented by relatively simple solubility relationships between infiltrating water and solid phases containing the contaminants; and (2) high percentages of technetium-99 in the sludges (20 wt% in C-203 and 75 wt% in C-204) are not readily water leachable, and, in fact, are very recalcitrant. This is similar to results found in related studies of sludges from Tank AY-102. These release models are being developed to support the tank closure risk assessments performed by CH2M HILL Hanford Group, Inc., for the U.S. Department of Energy.

  4. Hanford Tanks 241-C-203 and 241-C-204: Residual Waste Contaminant Release Model and Supporting Data

    International Nuclear Information System (INIS)

    Deutsch, William J.; Krupka, Kenneth M.; Lindberg, Michael J.; Cantrell, Kirk J.; Brown, Christopher F.; Schaef, Herbert T.

    2004-01-01

    This report describes the development of release models for key contaminants that are present in residual sludge remaining after closure of Hanford Tanks 241-C-203 (C-203) and 241-C-204 (C-204). The release models were developed from data generated by laboratory characterization and testing of samples from these two tanks. Key results from this work are (1) future releases from the tanks of the primary contaminants of concern (99Tc and 238U) can be represented by relatively simple solubility relationships between infiltrating water and solid phases containing the contaminants; and (2) high percentages of technetium-99 in the sludges (20 wt% in C-203 and 75 wt% in C-204) are not readily water leachable, and, in fact, are very recalcitrant. This is similar to results found in related studies of sludges from Tank AY-102. These release models are being developed to support the tank closure risk assessments performed by CH2M HILL Hanford Group, Inc., for the U.S. Department of Energy

  5. Efficient dynamic molecular simulation using QSAR model to know inhibition activity in breast cancer medicine

    Science.gov (United States)

    Zharifah, A.; Kusumowardani, E.; Saputro, A.; Sarwinda, D.

    2017-07-01

    According to data from GLOBOCAN (IARC) at 2012, breast cancer was the highest rated of new cancer case by 43.3 % (after controlled by age), with mortality rated as high as 12.9 %. Oncology is a major field which focusing on improving the development of drug and therapeutics cancer in pharmaceutical and biotechnology companies. Nowadays, many researchers lead to computational chemistry and bioinformatic for pharmacophore generation. A pharmacophore describes as a group of atoms in the molecule which is considered to be responsible for a pharmacological action. Prediction of biological function from chemical structure in silico modeling reduces the use of chemical reagents so the risk of environmental pollution decreased. In this research, we proposed QSAR model to analyze the composition of cancer drugs which assumed to be homogenous in character and treatment. Atomic interactions which analyzed are learned through parameters such as log p as descriptors hydrophobic, n_poinas descriptor contour strength and molecular structure, and also various concentrations inhibitor (micromolar and nanomolar) from NCBI drugs bank. The differences inhibitor activity was observed by the presence of IC 50 residues value from inhibitor substances at various concentration. Then, we got a general overview of the state of safety for drug stability seen from its IC 50 value. In our study, we also compared between micromolar and nanomolar inhibitor effect from QSAR model results. The QSAR model analysis shows that the drug concentration with nanomolar is better than micromolar, related with the content of inhibitor substances concentration. This QSAR model got the equation: Log 1/IC50 = (0.284) (±0.195) logP + (0.02) (±0.012) n_poin + (-0.005) (±0.083) Inhibition10.2nanoM + (0.1) (±0.079) Inhibition30.5nanoM + (-0.016) (±0.045) Inhibition91.5nanoM + (-2.572) (±1.570) (n = 13; r = 0.813; r2 = 0.660; s = 0.764; F = 2.720; q2 = 0.660).

  6. The interaction of 2-mercaptobenzimidazole with human serum albumin as determined by spectroscopy, atomic force microscopy and molecular modeling.

    Science.gov (United States)

    Li, Yuqin; Jia, Baoxiu; Wang, Hao; Li, Nana; Chen, Gaopan; Lin, Yuejuan; Gao, Wenhua

    2013-04-01

    The interaction of 2-mercaptobenzimidazole (MBI) with human serum albumin (HSA) was studied in vitro by equilibrium dialysis under normal physiological conditions. This study used fluorescence, ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FT-IR), circular dichroism (CD) and Raman spectroscopy, atomic force microscopy (AFM) and molecular modeling techniques. Association constants, the number of binding sites and basic thermodynamic parameters were used to investigate the quenching mechanism. Based on the fluorescence resonance energy transfer, the distance between the HSA and MBI was 2.495 nm. The ΔG(0), ΔH(0), and ΔS(0) values across temperature indicated that the hydrophobic interaction was the predominant binding Force. The UV, FT-IR, CD and Raman spectra confirmed that the HSA secondary structure was altered in the presence of MBI. In addition, the molecular modeling showed that the MBI-HSA complex was stabilized by hydrophobic forces, which resulted from amino acid residues. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with MBI. Overall, this study suggested a method for characterizing the weak intermolecular interaction. In addition, this method is potentially useful for elucidating the toxigenicity of MBI when it is combined with the biomolecular function effect, transmembrane transport, toxicological testing and other experiments. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The Jukes-Cantor Model of Molecular Evolution

    Science.gov (United States)

    Erickson, Keith

    2010-01-01

    The material in this module introduces students to some of the mathematical tools used to examine molecular evolution. This topic is standard fare in many mathematical biology or bioinformatics classes, but could also be suitable for classes in linear algebra or probability. While coursework in matrix algebra, Markov processes, Monte Carlo…

  8. Autonomous model protocell division driven by molecular replication.

    Science.gov (United States)

    Taylor, J W; Eghtesadi, S A; Points, L J; Liu, T; Cronin, L

    2017-08-10

    The coupling of compartmentalisation with molecular replication is thought to be crucial for the emergence of the first evolvable chemical systems. Minimal artificial replicators have been designed based on molecular recognition, inspired by the template copying of DNA, but none yet have been coupled to compartmentalisation. Here, we present an oil-in-water droplet system comprising an amphiphilic imine dissolved in chloroform that catalyses its own formation by bringing together a hydrophilic and a hydrophobic precursor, which leads to repeated droplet division. We demonstrate that the presence of the amphiphilic replicator, by lowering the interfacial tension between droplets of the reaction mixture and the aqueous phase, causes them to divide. Periodic sampling by a droplet-robot demonstrates that the extent of fission is increased as the reaction progresses, producing more compartments with increased self-replication. This bridges a divide, showing how replication at the molecular level can be used to drive macroscale droplet fission.Coupling compartmentalisation and molecular replication is essential for the development of evolving chemical systems. Here the authors show an oil-in-water droplet containing a self-replicating amphiphilic imine that can undergo repeated droplet division.

  9. Variational cellular model of the molecular and crystal electronic structure

    International Nuclear Information System (INIS)

    Ferreira, L.G.; Leite, J.R.

    1977-12-01

    A variational version of the cellular method is developed to calculate the electronic structure of molecules and crystals. Due to the simplicity of the secular equation, the method is easy to be implemented. Preliminary calculations on the hydrogen molecular ion suggest that it is also accurate and of fast convergence [pt

  10. Contaminant transport at a waste residue deposit: 1. Inverse flow and non-reactive transport modelling

    DEFF Research Database (Denmark)

    Sonnenborg, Torben Obel; Engesgaard, Peter Knudegaard; Rosbjerg, Dan

    1996-01-01

    An application of an inverse flow and transport model to a contaminated aquifer is presented. The objective of the study is to identify physical and nonreactive flow and transport parameters through an optimization approach. The approach can be classified as a statistical procedure, where a flow...... to steady state versus transient flow conditions and to the amount of hydraulic and solute data used is investigated. The flow parameters, transmissivity and leakage factor, are estimated simultaneously with the transport parameters: source strength, porosity, and longitudinal dispersivity. This paper...

  11. X-Ray Diffraction Techniques and Finite Element Modeling to Control Residual Stress in High-Temperature Pressure Vessels

    National Research Council Canada - National Science Library

    Lee, S

    1999-01-01

    Manufacturing operations, such as swage autofrettage, shot peening, and overload processes, have been used to impart advantageous residual stresses to improve fatigue life in components used in high...

  12. NMR and molecular modeling: application to wine ageing

    Science.gov (United States)

    Saucier, C.; Pianet, I.; Laguerre, M.; Glories, Y.

    1998-02-01

    Red wine contains polyphenols called tannins which are very important for its taste and longevity. These polymers consist in repeating units of catechin and its epimer epicatechin. During ageing, slow condensation reactions take place which lead to new chemical structures. Among the possible reactions, we have focused our attention on acetaldehyde cross-linking. Catechin was used as a model for the production of polymers with acetaldehyde. Two reaction product fractions have been isolated by liquid chromatography. Mass measurement indicated that these fractions contain dimers. NMR (1D and 2D) and molecular modelling were then used to study the structure and conformations of these products. The first product consist in a pure dimer with the two catechin moieties connected with an ethyl bridge on the carbon 6 and 8. The second fraction was a mixture of two dimers (50/50). NMR measurements showed that it could be two symmetrical dimers involving the same carbon for each catechin moiety (6 or8). Le vin rouge contient des polyphénols appelés tanins qui sont très importants pour son goût et sa longévité. Il s'agit principalement de polymères de catéchine et d'épicatéchine. Durant le vieillissement du vin, des réactions de condensation interviennent lentement et conduisent à de nouvelles structures. Parmi les réactions possibles, nous avons plus spécialement étudié la polymérisation par pontage avec l'éthanal. La catéchine a été utilisée comme modèle de tannin et mise en présence d'éthanal en milieu acide proche du vin. Deux fractions de produits de réaction ont été isolées par chromatographie liquide. La spectrométrie de masse a révélé la présence de dimères. La RMN (1D et 2D) et la modélisation moléculaire ont ensuite été utilisées pour déterminer la structure et la conformation de ces produits. La première fraction a été identifiée comme étant un dimère de deux unités catéchines reliées par un pont éthyle par leur

  13. Hydrodynamic Modelling of Municipal Solid Waste Residues in a Pilot Scale Fluidized Bed Reactor

    Directory of Open Access Journals (Sweden)

    João Cardoso

    2017-11-01

    Full Text Available The present study investigates the hydrodynamics and heat transfer behavior of municipal solid waste (MSW gasification in a pilot scale bubbling fluidized bed reactor. A multiphase 2-D numerical model following an Eulerian-Eulerian approach within the FLUENT framework was implemented. User defined functions (UDFs were coupled to improve hydrodynamics and heat transfer phenomena, and to minimize deviations between the experimental and numerical results. A grid independence study was accomplished through comparison of the bed volume fraction profiles and by reasoning the grid accuracy and computational cost. The standard deviation concept was used to determine the mixing quality indexes. Simulated results showed that UDFs improvements increased the accuracy of the mathematical model. Smaller size ratio of the MSW-dolomite mixture revealed a more uniform mixing, and larger ratios enhanced segregation. Also, increased superficial gas velocity promoted the solid particles mixing. Heat transfer within the fluidized bed showed strong dependence on the MSW solid particles sizes, with smaller particles revealing a more effective process.

  14. The Effectiveness of Natural Diarylheptanoids against Trypanosoma cruzi: Cytotoxicity, Ultrastructural Alterations and Molecular Modeling Studies.

    Directory of Open Access Journals (Sweden)

    Vitor Sueth-Santiago

    Full Text Available Curcumin (CUR is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 μM on epimastigotes. Demethoxycurcumin (DMC was equipotent to CUR (IC50 11.07 μM, but bisdemethoxycurcumin (BDMC was less active (IC50 45.33 μM and cyclocurcumin (CC was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel`s mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.

  15. The relationship between multilevel models and non-parametric multilevel mixture models: Discrete approximation of intraclass correlation, random coefficient distributions, and residual heteroscedasticity.

    Science.gov (United States)

    Rights, Jason D; Sterba, Sonya K

    2016-11-01

    Multilevel data structures are common in the social sciences. Often, such nested data are analysed with multilevel models (MLMs) in which heterogeneity between clusters is modelled by continuously distributed random intercepts and/or slopes. Alternatively, the non-parametric multilevel regression mixture model (NPMM) can accommodate the same nested data structures through discrete latent class variation. The purpose of this article is to delineate analytic relationships between NPMM and MLM parameters that are useful for understanding the indirect interpretation of the NPMM as a non-parametric approximation of the MLM, with relaxed distributional assumptions. We define how seven standard and non-standard MLM specifications can be indirectly approximated by particular NPMM specifications. We provide formulas showing how the NPMM can serve as an approximation of the MLM in terms of intraclass correlation, random coefficient means and (co)variances, heteroscedasticity of residuals at level 1, and heteroscedasticity of residuals at level 2. Further, we discuss how these relationships can be useful in practice. The specific relationships are illustrated with simulated graphical demonstrations, and direct and indirect interpretations of NPMM classes are contrasted. We provide an R function to aid in implementing and visualizing an indirect interpretation of NPMM classes. An empirical example is presented and future directions are discussed. © 2016 The British Psychological Society.

  16. Structural characterization of asphaltenes from vacuum residue distillation

    International Nuclear Information System (INIS)

    Silva, Ronaldo C.; Seidl, Peter R.; Menezes, Sonia M.C. de; Teixeira, Marco A.G.

    2001-01-01

    The aim of this work was to do structural characterization of asphaltenes from different vacuum residues distillation. Several average molecular parameters using some analytical techniques were obtained and these techniques were: nuclear magnetic resonance ( 1 H and 13 C NMR), elemental analysis (C,H,N,O and S content), Fourier transform infrared (FT-IR), vapor pressure osmometry and gel permeation chromatography. Particularly from NMR, some important molecular parameters were obtained, such as aromatic carbon fraction, aliphatic carbons fraction, alkyl substituted aromatic carbons, unsubstituted aromatic carbons, etc. Molecular modeling will be employed to build the structure of asphaltenes using the experimental data. (author)

  17. Effect of process variables on the Drucker-Prager cap model and residual stress distribution of tablets estimated by the finite element method.

    Science.gov (United States)

    Hayashi, Yoshihiro; Otoguro, Saori; Miura, Takahiro; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

    2014-01-01

    A multivariate statistical technique was applied to clarify the causal correlation between variables in the manufacturing process and the residual stress distribution of tablets. Theophylline tablets were prepared according to a Box-Behnken design using the wet granulation method. Water amounts (X1), kneading time (X2), lubricant-mixing time (X3), and compression force (X4) were selected as design variables. The Drucker-Prager cap (DPC) model was selected as the method for modeling the mechanical behavior of pharmaceutical powders. Simulation parameters, such as Young's modulus, Poisson rate, internal friction angle, plastic deformation parameters, and initial density of the powder, were measured. Multiple regression analysis demonstrated that the simulation parameters were significantly affected by process variables. The constructed DPC models were fed into the analysis using the finite element method (FEM), and the mechanical behavior of pharmaceutical powders during the tableting process was analyzed using the FEM. The results of this analysis revealed that the residual stress distribution of tablets increased with increasing X4. Moreover, an interaction between X2 and X3 also had an effect on shear and the x-axial residual stress of tablets. Bayesian network analysis revealed causal relationships between the process variables, simulation parameters, residual stress distribution, and pharmaceutical responses of tablets. These results demonstrated the potential of the FEM as a tool to help improve our understanding of the residual stress of tablets and to optimize process variables, which not only affect tablet characteristics, but also are risks of causing tableting problems.

  18. In-situ observation of dislocation and analysis of residual stresses by FEM/DDM modeling in water cavitation peening of pure titanium

    International Nuclear Information System (INIS)

    Ju, D Y; Han, B

    2015-01-01

    In this paper, in order to approach this problem, specimens of pure titanium were treated with WCP, and the subsequent changes in microstructure, residual stress, and surface morphologies were investigated as a function of WCP duration. The influence of water cavitation peening (WCP) treatment on the microstructure of pure titanium was investigated. A novel combined finite element and dislocation density method (FEM/DDM), proposed for predicting macro and micro residual stresses induced on the material subsurface treated with water cavitation peening, is also presented. A bilinear elastic-plastic finite element method was conducted to predict macro-residual stresses and a dislocation density method was conducted to predict micro-residual stresses. These approaches made possible the prediction of the magnitude and depth of residual stress fields in pure titanium. The effect of applied impact pressures on the residual stresses was also presented. The results of the FEM/DDM modeling were in good agreement with those of the experimental measurements. (paper)

  19. FROM ATOMISTIC TO SYSTEMATIC COARSE-GRAINED MODELS FOR MOLECULAR SYSTEMS

    KAUST Repository

    Harmandaris, Vagelis

    2017-10-03

    The development of systematic (rigorous) coarse-grained mesoscopic models for complex molecular systems is an intense research area. Here we first give an overview of methods for obtaining optimal parametrized coarse-grained models, starting from detailed atomistic representation for high dimensional molecular systems. Different methods are described based on (a) structural properties (inverse Boltzmann approaches), (b) forces (force matching), and (c) path-space information (relative entropy). Next, we present a detailed investigation concerning the application of these methods in systems under equilibrium and non-equilibrium conditions. Finally, we present results from the application of these methods to model molecular systems.

  20. Molecular Modeling as a Self-Taught Component of a Conventional Undergraduate Chemical Reaction Engineering Course

    Science.gov (United States)

    Rothe, Erhard W.; Zygmunt, William E.

    2016-01-01

    We inserted a self-taught molecular modeling project into an otherwise conventional undergraduate chemical-reaction-engineering course. Our objectives were that students should (a) learn with minimal instructor intervention, (b) gain an appreciation for the relationship between molecular structure and, first, macroscopic state functions in…

  1. Digital learning material for experimental design and model building in molecular biology

    NARCIS (Netherlands)

    Aegerter-Wilmsen, T.

    2005-01-01

    Designing experimental approaches is a major cognitive skill in molecular biology research, and building models, including quantitative ones, is a cognitive skill which is rapidly gaining importance. Since molecular biology education at university level is aimed at educating future researchers, we

  2. The Distribution of Charged Amino Acid Residues and the Ca2+ Permeability of Nicotinic Acetylcholine Receptors: A Predictive Model

    Directory of Open Access Journals (Sweden)

    Sergio Fucile

    2017-05-01

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are cation-selective ligand-gated ion channels exhibiting variable Ca2+ permeability depending on their subunit composition. The Ca2+ permeability is a crucial functional parameter to understand the physiological role of nAChRs, in particular considering their ability to modulate Ca2+-dependent processes such as neurotransmitter release. The rings of extracellular and intracellular charged amino acid residues adjacent to the pore-lining TM2 transmembrane segment have been shown to play a key role in the cation selectivity of these receptor channels, but to date a quantitative relationship between these structural determinants and the Ca2+ permeability of nAChRs is lacking. In the last years the Ca2+ permeability of several nAChR subtypes has been experimentally evaluated, in terms of fractional Ca2+ current (Pf, i.e., the percentage of the total current carried by Ca2+ ions. In the present study, the available Pf-values of nAChRs are used to build a simplified modular model describing the contribution of the charged residues in defined regions flanking TM2 to the selectivity filter controlling Ca2+ influx. This model allows to predict the currently unknown Pf-values of existing nAChRs, as well as the hypothetical Ca2+ permeability of subunit combinations not able to assemble into functional receptors. In particular, basing on the amino acid sequences, a Pf > 50% would be associated with homomeric nAChRs composed by different α subunits, excluding α7, α9, and α10. Furthermore, according to the model, human α7β2 receptors should have Pf-values ranging from 3.6% (4:1 ratio to 0.1% (1:4 ratio, much lower than the 11.4% of homomeric α7 nAChR. These results help to understand the evolution and the function of the large diversity of the nicotinic receptor family.

  3. Model parameter estimations from residual gravity anomalies due to simple-shaped sources using Differential Evolution Algorithm

    Science.gov (United States)

    Ekinci, Yunus Levent; Balkaya, Çağlayan; Göktürkler, Gökhan; Turan, Seçil

    2016-06-01

    An efficient approach to estimate model parameters from residual gravity data based on differential evolution (DE), a stochastic vector-based metaheuristic algorithm, has been presented. We have showed the applicability and effectiveness of this algorithm on both synthetic and field anomalies. According to our knowledge, this is a first attempt of applying DE for the parameter estimations of residual gravity anomalies due to isolated causative sources embedded in the subsurface. The model parameters dealt with here are the amplitude coefficient (A), the depth and exact origin of causative source (zo and xo, respectively) and the shape factors (q and ƞ). The error energy maps generated for some parameter pairs have successfully revealed the nature of the parameter estimation problem under consideration. Noise-free and noisy synthetic single gravity anomalies have been evaluated with success via DE/best/1/bin, which is a widely used strategy in DE. Additionally some complicated gravity anomalies caused by multiple source bodies have been considered, and the results obtained have showed the efficiency of the algorithm. Then using the strategy applied in synthetic examples some field anomalies observed for various mineral explorations such as a chromite deposit (Camaguey district, Cuba), a manganese deposit (Nagpur, India) and a base metal sulphide deposit (Quebec, Canada) have been considered to estimate the model parameters of the ore bodies. Applications have exhibited that the obtained results such as the depths and shapes of the ore bodies are quite consistent with those published in the literature. Uncertainty in the solutions obtained from DE algorithm has been also investigated by Metropolis-Hastings (M-H) sampling algorithm based on simulated annealing without cooling schedule. Based on the resulting histogram reconstructions of both synthetic and field data examples the algorithm has provided reliable parameter estimations being within the sampling limits of

  4. Molecular Modeling of Enzyme Dynamics Towards Understanding Solvent Effects

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar

    This thesis describes the development of a molecular simulation methodology to study properties of enzymes in non-aqueous media at fixed thermodynamic water activities. The methodology is applied in a molecular dynamics study of the industrially important enzyme Candida antarctica lipase B (CALB...... of enzyme kinetics in non-aqueous media, it has been a fruitful approach to fix the enzyme hydration level by controlling the water activity of the medium. In this work, a protocol is therefore developed for determining the water activity in non-aqueous protein simulations. The method relies on determining...... integration, while for small systems, it seems to be even better. The method is applied to compute the excess Gibbs energy of the mixtures of water and organic solvents used in the simulations of CALB. This allows to determine the water activity of the simulated systems and thus to compare protein properties...

  5. Time-varying effect moderation using the structural nested mean model: estimation using inverse-weighted regression with residuals

    Science.gov (United States)

    Almirall, Daniel; Griffin, Beth Ann; McCaffrey, Daniel F.; Ramchand, Rajeev; Yuen, Robert A.; Murphy, Susan A.

    2014-01-01

    This article considers the problem of examining time-varying causal effect moderation using observational, longitudinal data in which treatment, candidate moderators, and possible confounders are time varying. The structural nested mean model (SNMM) is used to specify the moderated time-varying causal effects of interest in a conditional mean model for a continuous response given time-varying treatments and moderators. We present an easy-to-use estimator of the SNMM that combines an existing regression-with-residuals (RR) approach with an inverse-probability-of-treatment weighting (IPTW) strategy. The RR approach has been shown to identify the moderated time-varying causal effects if the time-varying moderators are also the sole time-varying confounders. The proposed IPTW+RR approach provides estimators of the moderated time-varying causal effects in the SNMM in the presence of an additional, auxiliary set of known and measured time-varying confounders. We use a small simulation experiment to compare IPTW+RR versus the traditional regression approach and to compare small and large sample properties of asymptotic versus bootstrap estimators of the standard errors for the IPTW+RR approach. This article clarifies the distinction between time-varying moderators and time-varying confounders. We illustrate the methodology in a case study to assess if time-varying substance use moderates treatment effects on future substance use. PMID:23873437

  6. Improved prediction of residue flexibility by embedding optimized amino acid grouping into RSA-based linear models.

    Science.gov (United States)

    Zhang, Hua; Kurgan, Lukasz

    2014-12-01

    Knowledge of protein flexibility is vital for deciphering the corresponding functional mechanisms. This knowledge would help, for instance, in improving computational drug design and refinement in homology-based modeling. We propose a new predictor of the residue flexibility, which is expressed by B-factors, from protein chains that use local (in the chain) predicted (or native) relative solvent accessibility (RSA) and custom-derived amino acid (AA) alphabets. Our predictor is implemented as a two-stage linear regression model that uses RSA-based space in a local sequence window in the first stage and a reduced AA pair-based space in the second stage as the inputs. This method is easy to comprehend explicit linear form in both stages. Particle swarm optimization was used to find an optimal reduced AA alphabet to simplify the input space and improve the prediction performance. The average correlation coefficients between the native and predicted B-factors measured on a large benchmark dataset are improved from 0.65 to 0.67 when using the native RSA values and from 0.55 to 0.57 when using the predicted RSA values. Blind tests that were performed on two independent datasets show consistent improvements in the average correlation coefficients by a modest value of 0.02 for both native and predicted RSA-based predictions.

  7. Residual sweeping errors in turbulent particle pair diffusion in a Lagrangian diffusion model.

    Science.gov (United States)

    Malik, Nadeem A

    2017-01-01

    Thomson, D. J. & Devenish, B. J. [J. Fluid Mech. 526, 277 (2005)] and others have suggested that sweeping effects make Lagrangian properties in Kinematic Simulations (KS), Fung et al [Fung J. C. H., Hunt J. C. R., Malik N. A. & Perkins R. J. J. Fluid Mech. 236, 281 (1992)], unreliable. However, such a conclusion can only be drawn under the assumption of locality. The major aim here is to quantify the sweeping errors in KS without assuming locality. Through a novel analysis based upon analysing pairs of particle trajectories in a frame of reference moving with the large energy containing scales of motion it is shown that the normalized integrated error [Formula: see text] in the turbulent pair diffusivity (K) due to the sweeping effect decreases with increasing pair separation (σl), such that [Formula: see text] as σl/η → ∞; and [Formula: see text] as σl/η → 0. η is the Kolmogorov turbulence microscale. There is an intermediate range of separations 1 < σl/η < ∞ in which the error [Formula: see text] remains negligible. Simulations using KS shows that in the swept frame of reference, this intermediate range is large covering almost the entire inertial subrange simulated, 1 < σl/η < 105, implying that the deviation from locality observed in KS cannot be atributed to sweeping errors. This is important for pair diffusion theory and modeling. PACS numbers: 47.27.E?, 47.27.Gs, 47.27.jv, 47.27.Ak, 47.27.tb, 47.27.eb, 47.11.-j.

  8. Modelling dust polarization observations of molecular clouds through MHD simulations

    Science.gov (United States)

    King, Patrick K.; Fissel, Laura M.; Chen, Che-Yu; Li, Zhi-Yun

    2018-03-01

    The BLASTPol observations of Vela C have provided the most detailed characterization of the polarization fraction p and dispersion in polarization angles S for a molecular cloud. We compare the observed distributions of p and S with those obtained in synthetic observations of simulations of molecular clouds, assuming homogeneous grain alignment. We find that the orientation of the mean magnetic field relative to the observer has a significant effect on the p and S distributions. These distributions for Vela C are most consistent with synthetic observations where the mean magnetic field is close to the line of sight. Our results point to apparent magnetic disorder in the Vela C molecular cloud, although it can be due to either an inclination effect (i.e. observing close to the mean field direction) or significant field tangling from strong turbulence/low magnetization. The joint correlations of p with column density and of S with column density for the synthetic observations generally agree poorly with the Vela C joint correlations, suggesting that understanding these correlations requires a more sophisticated treatment of grain alignment physics.

  9. Modelos de regressão aleatória com diferentes estruturas de variância residual para descrever o tamanho da leitegada Random regression models with different residual variance structures for describing litter size in swine

    Directory of Open Access Journals (Sweden)

    Aderbal Cavalcante-Neto

    2011-12-01

    Full Text Available Objetivou-se comparar modelos de regressão aleatória com diferentes estruturas de variância residual, a fim de se buscar a melhor modelagem para a característica tamanho da leitegada ao nascer (TLN. Utilizaram-se 1.701 registros de TLN, que foram analisados por meio de modelo animal, unicaracterística, de regressão aleatória. As regressões fixa e aleatórias foram representadas por funções contínuas sobre a ordem de parto, ajustadas por polinômios ortogonais de Legendre de ordem 3. Para averiguar a melhor modelagem para a variância residual, considerou-se a heterogeneidade de variância por meio de 1 a 7 classes de variância residual. O modelo geral de análise incluiu grupo de contemporâneo como efeito fixo; os coeficientes de regressão fixa para modelar a trajetória média da população; os coeficientes de regressão aleatória do efeito genético aditivo-direto, do comum-de-leitegada e do de ambiente permanente de animal; e o efeito aleatório residual. O teste da razão de verossimilhança, o critério de informação de Akaike e o critério de informação bayesiano de Schwarz apontaram o modelo que considerou homogeneidade de variância como o que proporcionou melhor ajuste aos dados utilizados. As herdabilidades obtidas foram próximas a zero (0,002 a 0,006. O efeito de ambiente permanente foi crescente da 1ª (0,06 à 5ª (0,28 ordem, mas decrescente desse ponto até a 7ª ordem (0,18. O comum-de-leitegada apresentou valores baixos (0,01 a 0,02. A utilização de homogeneidade de variância residual foi mais adequada para modelar as variâncias associadas à característica tamanho da leitegada ao nascer nesse conjunto de dado.The objective of this work was to compare random regression models with different residual variance structures, so as to obtain the best modeling for the trait litter size at birth (LSB in swine. One thousand, seven hundred and one records of LSB were analyzed. LSB was analyzed by means of a

  10. Using a consensus approach based on the conservation of inter-residue contacts to rank CAPRI models

    KAUST Repository

    Vangone, Anna

    2013-10-17

    Herein we propose the use of a consensus approach, CONSRANK, for ranking CAPRI models. CONSRANK relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. Models are ranked according to their ability to match the most frequently observed contacts. We applied CONSRANK to 19 CAPRI protein-protein targets, covering a wide range of prediction difficulty and involved in a variety of biological functions. CONSRANK results are consistently good, both in terms of native-like (NL) solutions ranked in the top positions and of values of the Area Under the receiver operating characteristic Curve (AUC). For targets having a percentage of NL solutions above 3%, an excellent performance is found, with AUC values approaching 1. For the difficult target T46, having only 3.4% NL solutions, the number of NL solutions in the top 5 and 10 ranked positions is enriched by a factor 30, and the AUC value is as high as 0.997. AUC values below 0.8 are only found for targets featuring a percentage of NL solutions within 1.1%. Remarkably, a false consensus emerges only in one case, T42, which happens to be an artificial protein, whose assembly details remain uncertain, based on controversial experimental data. We also show that CONSRANK still performs very well on a limited number of models, provided that more than 1 NL solution is included in the ensemble, thus extending its applicability to cases where few dozens of models are available.© 2013 Wiley Periodicals, Inc.

  11. Residual basins

    International Nuclear Information System (INIS)

    D'Elboux, C.V.; Paiva, I.B.

    1980-01-01

    Exploration for uranium carried out over a major portion of the Rio Grande do Sul Shield has revealed a number of small residual basins developed along glacially eroded channels of pre-Permian age. Mineralization of uranium occurs in two distinct sedimentary units. The lower unit consists of rhythmites overlain by a sequence of black shales, siltstones and coal seams, while the upper one is dominated by sandstones of probable fluvial origin. (Author) [pt

  12. The Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge Developments from the Field of Molecular Modeling

    Directory of Open Access Journals (Sweden)

    Edward J. Bertaccini

    2010-07-01

    Full Text Available For over 160 years, general anesthetics have been given for the relief of pain and suffering. While many theories of anesthetic action have been purported, it has become increasingly apparent that a significant molecular focus of anesthetic action lies within the family of ligand-gated ion channels (LGIC’s. These protein channels have a transmembrane region that is composed of a pentamer of four helix bundles, symmetrically arranged around a central pore for ion passage. While initial and some current models suggest a possible cavity for binding within this four helix bundle, newer calculations postulate that the actual cavity for anesthetic binding may exist between four helix bundles. In either scenario, these cavities have a transmembrane mode of access and may be partially bordered by lipid moieties. Their physicochemical nature is amphiphilic. Anesthetic binding may alter the overall motion of a ligand-gated ion channel by a “foot-in-door” motif, resulting in the higher likelihood of and greater time spent in a specific channel state. The overall gating motion of these channels is consistent with that shown in normal mode analyses carried out both in vacuo as well as in explicitly hydrated lipid bilayer models. Molecular docking and large scale molecular dynamics calculations may now begin to show a more exact mode by which anesthetic molecules actually localize themselves and bind to specific protein sites within LGIC’s, making the design of future improvements to anesthetic ligands a more realizable possibility.