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

    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.

  4. 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:

  5. 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.

  6. 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

  7. 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.

  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. Reexamining the molecular/macromolecular model of coal from comparative in situ variable-temperature {sup 1}H NMR studies of Argonne Premium coal 601 and its pyridine extraction residue

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, J.; Maciel, G.E. [Colorado State University, Fort Collins, CO (United States). Dept. of Chemistry

    2002-06-01

    We have carried out the first systematic in situ variable-temperature {sup 1}H NMR study, using the CRAMPS (combined rotation and multiple pulse spectroscopy) technique of the residue from pyridine extraction of Argonne premium coal 601. The change of molecular mobility in the residue under various thermal treatments and pyridine swelling conditions were monitored quantitatively through a proton dipolar-dephasing experiment based on CRAMPS detection. Correlations among molecular structure, molecular mobility and solvent-extraction components were established through comparative variable-temperature {sup 1}H CRAMPS studies on the C{sub 5}D{sub 5}N-saturated original coal and its extraction residue. A critical review of the molecular/macromolecular (M/M) structural model of coal has been made on the basis of the new results, showing that the relationships between the M/M model and molecular dynamics is much more complicated than previously thought. Both the molecular phase and the macromolecular phase can show molecular dynamics behavior ranging from a lack of substantial motion to extremely mobile behaviour with correlation times as short as 30 ns. Without systematic variable temperature studies, correlation between molecular mobility and the M/M model cannot be established correctly by NMR. 28 refs., 7 figs., 6 tabs.

  10. 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.

  11. Automatic prediction of catalytic residues by modeling residue structural neighborhood

    Directory of Open Access Journals (Sweden)

    Passerini Andrea

    2010-03-01

    Full Text Available Abstract Background Prediction of catalytic residues is a major step in characterizing the function of enzymes. In its simpler formulation, the problem can be cast into a binary classification task at the residue level, by predicting whether the residue is directly involved in the catalytic process. The task is quite hard also when structural information is available, due to the rather wide range of roles a functional residue can play and to the large imbalance between the number of catalytic and non-catalytic residues. Results We developed an effective representation of structural information by modeling spherical regions around candidate residues, and extracting statistics on the properties of their content such as physico-chemical properties, atomic density, flexibility, presence of water molecules. We trained an SVM classifier combining our features with sequence-based information and previously developed 3D features, and compared its performance with the most recent state-of-the-art approaches on different benchmark datasets. We further analyzed the discriminant power of the information provided by the presence of heterogens in the residue neighborhood. Conclusions Our structure-based method achieves consistent improvements on all tested datasets over both sequence-based and structure-based state-of-the-art approaches. Structural neighborhood information is shown to be responsible for such results, and predicting the presence of nearby heterogens seems to be a promising direction for further improvements.

  12. Molecular studies of organic residues preserved in ancient vessels

    NARCIS (Netherlands)

    Oudemans, Tatiana Frederica Margreta

    2006-01-01

    This study is aimed at the molecular characterisation of solid organic (food) residues preserved in an assemblage of vessels recovered from an indigenous settlement dating back to the Iron Age and Roman period at Uitgeest – Groot Dorregeest (The Netherlands). Analytical thermal-fragmentation

  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. 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......The geomagnetic field varies on a variety of time- and length scales, which are only rudimentary considered in most present field models. The part of the observed field that can not be explained by a given model, the model residuals, is often considered as an estimate of the data uncertainty (which...... on 5 years of Ørsted and CHAMP data, and includes secular variation and acceleration, as well as low-degree external (magnetospheric) and induced fields. The analysis is done in order to find the statistical behaviour of the space-time structure of the residuals, as a proxy for the data covariances...

  15. The Molecular Model Game

    Science.gov (United States)

    Myers, Stephanie A.

    2003-04-01

    The Molecular Model Game is used to review Lewis structures and VSEPR theory. In this game, teams of students compete to complete problems quickly. Variations with other types of problems involving stoichiometry or equilibria are also possible.

  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. A-site residues move independently from P-site residues in all-atom molecular dynamics simulations of the 70S bacterial ribosome.

    Directory of Open Access Journals (Sweden)

    Relly Brandman

    Full Text Available The ribosome is a large macromolecular machine, and correlated motion between residues is necessary for coordinating function across multiple protein and RNA chains. We ran two all-atom, explicit solvent molecular dynamics simulations of the bacterial ribosome and calculated correlated motion between residue pairs by using mutual information. Because of the short timescales of our simulation (ns, we expect that dynamics are largely local fluctuations around the crystal structure. We hypothesize that residues that show coupled dynamics are functionally related, even on longer timescales. We validate our model by showing that crystallographic B-factors correlate well with the entropy calculated as part of our mutual information calculations. We reveal that A-site residues move relatively independently from P-site residues, effectively insulating A-site functions from P-site functions during translation.

  18. Mechanically induced residual stresses: Modelling and characterisation

    Science.gov (United States)

    Stranart, Jean-Claude E.

    Accurate characterisation of residual stress represents a major challenge to the engineering community. This is because it is difficult to validate the measurement and the accuracy is doubtful. It is with this in mind that the current research program concerning the characterisation of mechanically induced residual stresses was undertaken. Specifically, the cold expansion of fastener holes and the shot peening treatment of aerospace alloys, aluminium 7075 and titanium Ti-6Al-4V, are considered. The objective of this study is to characterise residual stresses resulting from cold working using three powerful techniques. These are: (i) theoretical using three dimensional non-linear finite element modelling, (ii) semi-destructive using a modified incremental hole drilling technique and (iii) nondestructive using a newly developed guided wave method supplemented by traditional C-scan measurements. The three dimensional finite element results of both simultaneous and sequential cold expansion of two fastener holes revealed the importance of the separation distance, the expansion level and the loading history upon the development and growth of the plastic zone and unloading residual stresses. It further showed that the commonly adopted two dimensional finite element models are inaccurate and incapable of predicting these residual stresses. Similarly, the dynamic elasto-plastic finite element studies of shot peening showed that the depth of the compressed layer, surface and sub-surface residual stresses are significantly influenced by the shot characteristics. Furthermore, the results reveal that the separation distance between two simultaneously impacting shots governs the plastic zone development and its growth. In the semi-destructive incremental hole drilling technique, the accuracy of the newly developed calibration coefficients and measurement techniques were verified with a known stress field and the method was used to measure peening residual stresses. Unlike

  19. 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…

  20. Molecular Dynamics with the United-Residue Model of Polypeptide Chains. I. Lagrange Equations of Motion and Tests of Numerical Stability in the Microcanonical Mode

    Science.gov (United States)

    Khalili, Mey; Liwo, Adam; Rakowski, Franciszek; Grochowski, Paweł; Scheraga, Harold A.

    2008-01-01

    The Lagrange formalism was implemented to derive the equations of motion for the physics-based united-residue (UNRES) force field developed in our laboratory. The Cα…Cα and Cα…SC (SC denoting a side-chain center) virtual-bond vectors were chosen as variables. The velocity Verlet algorithm was adopted to integrate the equations of motion. Tests on the unblocked Ala10 polypeptide showed that the algorithm is stable in short periods of time up to the time step of 1.467 fs; however, even with the shorter time step of 0.489 fs, some drift of the total energy occurs because of momentary jumps of the acceleration. These jumps are caused by numerical instability of the forces arising from the Urot component of UNRES that describes the energetics of side-chain-rotameric states. Test runs on the Gly10 sequence (in which Urot is not present) and on the Ala10 sequence with Urot replaced by a simple numerically stable harmonic potential confirmed this observation; oscillations of the total energy were observed only up to the time step of 7.335 fs, and some drift in the total energy or instability of the trajectories started to appear in long-time (2 ns and longer) trajectories only for the time step of 9.78 fs. These results demonstrate that the present Urot components (which are statistical potentials derived from the Protein Data Bank) must be replaced with more numerically stable functions; this work is under way in our laboratory. For the purpose of our present work, a nonsymplectic variable-time-step algorithm was introduced to reduce the energy drift for regular polypeptide sequences. The algorithm scales down the time step at a given point of a trajectory if the maximum change of acceleration exceeds a selected cutoff value. With this algorithm, the total energy is reasonably conserved up to a time step of 2.445 fs, as tested on the unblocked Ala10 polypeptide. We also tried a symplectic multiple-time-step reversible RESPA algorithm and achieved satisfactory

  1. Residual-based model diagnosis methods for mixture cure models.

    Science.gov (United States)

    Peng, Yingwei; Taylor, Jeremy M G

    2017-06-01

    Model diagnosis, an important issue in statistical modeling, has not yet been addressed adequately for cure models. We focus on mixture cure models in this work and propose some residual-based methods to examine the fit of the mixture cure model, particularly the fit of the latency part of the mixture cure model. The new methods extend the classical residual-based methods to the mixture cure model. Numerical work shows that the proposed methods are capable of detecting lack-of-fit of a mixture cure model, particularly in the latency part, such as outliers, improper covariate functional form, or nonproportionality in hazards if the proportional hazards assumption is employed in the latency part. The methods are illustrated with two real data sets that were previously analyzed with mixture cure models. © 2016, The International Biometric Society.

  2. Computer modeling of the neurotoxin binding site of acetylcholine receptor spanning residues 185 through 196

    Science.gov (United States)

    Garduno-Juarez, R.; Shibata, M.; Zielinski, T. J.; Rein, R.

    1987-01-01

    A model of the complex between the acetylcholine receptor and the snake neurotoxin, cobratoxin, was built by molecular model building and energy optimization techniques. The experimentally identified functionally important residues of cobratoxin and the dodecapeptide corresponding to the residues 185-196 of acetylcholine receptor alpha subunit were used to build the model. Both cis and trans conformers of cyclic L-cystine portion of the dodecapeptide were examined. Binding residues independently identified on cobratoxin are shown to interact with the dodecapeptide AChR model.

  3. finite element model for predicting residual stresses in shielded

    African Journals Online (AJOL)

    eobe

    Diffractometer (XRD 6000). From the Finite Element Model Simulation, the transverse residual stress in the x ... Keywords: Residual stress, 3D FEM, Shielded manual metal arc welding, Low Carbon Steel (ASTM A36), X-Ray diffraction, degree of ..... I. ''Residual stress effects on fatigue life of welded structures using LEFM'',.

  4. 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.

  5. FINITE ELEMENT MODEL FOR PREDICTING RESIDUAL ...

    African Journals Online (AJOL)

    direction (σx) had a maximum value of 375MPa (tensile) and minimum value of ... These results shows that the residual stresses obtained by prediction from the finite element method are in fair agreement with the experimental results.

  6. An Additive-Multiplicative Restricted Mean Residual Life Model

    DEFF Research Database (Denmark)

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

    2016-01-01

    The mean residual life measures the expected remaining life of a subject who has survived up to a particular time. When survival time distribution is highly skewed or heavy tailed, the restricted mean residual life must be considered. In this paper, we propose an additive-multiplicative restricted...... 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...

  7. Molecular Models: Construction of Models with Magnets

    Directory of Open Access Journals (Sweden)

    Kalinovčić P.

    2015-07-01

    Full Text Available Molecular models are indispensable tools in teaching chemistry. Beside their high price, commercially available models are generally too small for classroom demonstration. This paper suggests how to make space-filling (callote models from Styrofoam with magnetic balls as connectors and disc magnets for showing molecular polarity

  8. 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.

  9. 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.

  10. 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

    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...... 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....

  11. 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...

  12. 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...... noise residual learning techniques that take residues from previously decoded frames into account to estimate the decoding residue more precisely. Moreover, the techniques calculate a number of candidate noise residual distributions within a frame to adaptively optimize the soft side information during...

  13. Economic Modeling of Residual Generation for the Lingayen Gulf Watershed

    Directory of Open Access Journals (Sweden)

    Douglas McGlone

    2000-12-01

    Full Text Available The Philippines is one of four countries involved in the Southeast Asian core project of LOICZ (Land Ocean Interactions in the Coastal Zone which has among its general goals the determination of how changes in human activities affect the fluxes of materials between land, sea, and atmosphere through the coastal zone. The economic component of the Philippine project addresses the question: “How does a change in economic activity affect coastal waters?” Of particular concern is the introduction of anthropogenically-derived residuals (N, P, C, SS into coastal waters. A regional input-output (IO model for Region 1 of the Philippines has been developed to estimate how projected changes in economic activity may affect residual flows into Lingayen Gulf. A residual coefficient matrix, derived from information obtained with a rapid assessment model (RA of residual generation in the Lingayen Gulf watershed, has been incorporated into the IO model. Such a model allows for analysis of various economic scenarios for the region, with projections of residual generation as the output. The resulting changes in residual flows may then serve as inputs to biogeochemical models of Lingayen Gulf. From this process, the impact of various economic scenarios on the water quality of Lingayen Gulf may be ascertained.This paper discusses and compares the RA and IO models of residual generation for the Lingayen Gulf watershed and provides examples of the scenario analysis process.

  14. Models of molecular geometry.

    Science.gov (United States)

    Gillespie, Ronald J; Robinson, Edward A

    2005-05-01

    Although the structure of almost any molecule can now be obtained by ab initio calculations chemists still look for simple answers to the question "What determines the geometry of a given molecule?" For this purpose they make use of various models such as the VSEPR model and qualitative quantum mechanical models such as those based on the valence bond theory. The present state of such models, and the support for them provided by recently developed methods for analyzing calculated electron densities, are reviewed and discussed in this tutorial review.

  15. 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

  16. 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.

  17. 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.

  18. GEOCHEMICAL TESTING AND MODEL DEVELOPMENT - RESIDUAL TANK WASTE TEST PLAN

    Energy Technology Data Exchange (ETDEWEB)

    CANTRELL KJ; CONNELLY MP

    2010-03-09

    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.

  19. 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 ...

  20. Design of thermolabile bacteriophage repressor mutants by comparative molecular modeling

    NARCIS (Netherlands)

    Nauta, A; vandenBurg, B; Karsens, H; Venema, G; Kok, J; Burg, Bertus van den

    1997-01-01

    Comparative molecular modeling was performed with repressor protein Rro of the temperate Lactococcus lactis bacteriophage r1t using the known 3D-structures of related repressors in order to obtain thermolabile derivatives of Rro. Rro residues presumed to stabilize a nonhomologous but structurally

  1. 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.

  2. The Residual Value Models: A Framework for Business Administration

    OpenAIRE

    Konstantinos J. Liapis

    2010-01-01

    This article investigates the relationship between a firm’s performance and Residual Value Models (RVM) which serve as decision making tools in corporate management. The main measures are the Economic Value Added (EVA®) and Cash Value Added (CVA®), with key components the Residual Income (RI), Free Cash Flow (FCF) and Weighted Average Cost of Capital (WACC). These measures have attracted considerable interest among scientists, practitioners and organizations in recent years. This work focuses...

  3. 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...

  4. 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.

  5. 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...

  6. Exploring the molecular mechanism of cross-resistance to HIV-1 integrase strand transfer inhibitors by molecular dynamics simulation and residue interaction network analysis.

    Science.gov (United States)

    Xue, Weiwei; Jin, Xiaojie; Ning, Lulu; Wang, Meixia; Liu, Huanxiang; Yao, Xiaojun

    2013-01-28

    The rapid emergence of cross-resistance to the integrase strand transfer inhibitors (INSTIs) has become a serious problem in the therapy of human immunodeficiency virus type 1 (HIV-1) infection. Understanding the detailed molecular mechanism of INSTIs cross-resistance is therefore critical for the development of new effective therapy against cross-resistance. On the basis of the homology modeling constructed structure of tetrameric HIV-1 intasome, the detailed molecular mechanism of the cross-resistance mutation E138K/Q148K to three important INSTIs (Raltegravir (RAL, FDA approved in 2007), Elvitegravir (EVG, FDA approved in 2012), and Dolutegravir (DTG, phase III clinical trials)) was investigated by using molecular dynamics (MD) simulation and residue interaction network (RIN) analysis. The results from conformation analysis and binding free energy calculation can provide some useful information about the detailed binding mode and cross-resistance mechanism for the three INSTIs to HIV-1 intasome. Binding free energy decomposition analysis revealed that Pro145 residue in the 140s 1oop (Gly140 to Gly149) of the HIV-1 intasome had strong hydrophobic interactions with INSTIs and played an important role in the binding of INSTIs to HIV-1 intasome active site. A systematic comparison and analysis of the RIN proves that the communications between the residues in the resistance mutant is increased when compared with that of the wild-type HIV-1 intasome. Further analysis indicates that residue Pro145 may play an important role and is relevant to the structure rearrangement in HIV-1 intasome active site. In addition, the chelating ability of the oxygen atoms in INSTIs (e.g., RAL and EVG) to Mg(2+) in the active site of the mutated intasome was reduced due to this conformational change and is also responsible for the cross-resistance mechanism. Notably, the cross-resistance mechanism we proposed could give some important information for the future rational design of novel

  7. 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.

  8. 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

  9. Modeling irregularly spaced residual series as a continuous stochastic process

    NARCIS (Netherlands)

    Von Asmuth, J.R.; Bierkens, M.F.P.

    2005-01-01

    In this paper, the background and functioning of a simple but effective continuous time approach for modeling irregularly spaced residual series is presented. The basic equations were published earlier by von Asmuth et al. (2002), who used them as part of a continuous time transfer function noise

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    , 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....... The extracted values were in good agreement with the expected and it showed that the behavior of devices with a plate could easily be predicted with a low uncertainty....

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

    Indian Academy of Sciences (India)

    Molecular modeling has become a valuable and essential tool to medicinal chemists in the drug design process. Molecular modeling describes the generation, manipula- tion or representation of three-dimensional structures of molecules and associated physico-chemical properties. It involves a range of computerized ...

  12. 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

  13. 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.

  14. 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...

  15. In-Situ Residual Tracking in Reduced Order Modelling

    Directory of Open Access Journals (Sweden)

    Joseph C. Slater

    2002-01-01

    Full Text Available Proper orthogonal decomposition (POD based reduced-order modelling is demonstrated to be a weighted residual technique similar to Galerkin's method. Estimates of weighted residuals of neglected modes are used to determine relative importance of neglected modes to the model. The cumulative effects of neglected modes can be used to estimate error in the reduced order model. Thus, once the snapshots have been obtained under prescribed training conditions, the need to perform full-order simulations for comparison is eliminates. This has the potential to allow the analyst to initiate further training when the reduced modes are no longer sufficient to accurately represent the predominant phenomenon of interest. The response of a fluid moving at Mach 1.2 above a panel to a forced localized oscillation of the panel at and away from the training operating conditions is used to demonstrate the evaluation method.

  16. 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.

  17. Molecular modeling of protein A affinity chromatography.

    Science.gov (United States)

    Salvalaglio, Matteo; Zamolo, Laura; Busini, Valentina; Moscatelli, Davide; Cavallotti, Carlo

    2009-12-11

    The properties of the complex between fragment B of Protein A and the Fc domain of IgG were investigated adopting molecular dynamics with the intent of providing useful insight that might be exploited to design mimetic ligands with properties similar to those of Protein A. Simulations were performed both for the complex in solution and supported on an agarose surface, which was modeled as an entangled structure constituted by two agarose double chains. The energetic analysis was performed by means of the molecular mechanics Poisson Boltzmann surface area (MM/PBSA), molecular mechanics generalized Born surface area (MM/GBSA), and the linear interaction energy (LIE) approaches. An alanine scan was performed to determine the relative contribution of Protein A key amino acids to the complex interaction energy. It was found that three amino acids play a dominant role: Gln 129, Phe 132 and Lys 154, though also four other residues, Tyr 133, Leu 136, Glu 143 and Gln 151 contribute significantly to the overall binding energy. A successive molecular dynamics analysis of Protein A re-organization performed when it is not in complex with IgG has however shown that Phe 132 and Tyr 133 interact among themselves establishing a significant pi-pi interaction, which is disrupted upon formation of the complex with IgG and thus reduces consistently their contribution to the protein-antibody bond. The effect that adsorbing fragment B of Protein A on an agarose support has on the stability of the protein-antibody bond was investigated using a minimal molecular model and compared to a similar study performed for a synthetic ligand. It was found that the interaction with the surface does not hinder significantly the capability of Protein A to interact with IgG, while it is crucial for the synthetic ligand. These results indicate that ligand-surface interactions should be considered in the design of new synthetic affinity ligands in order to achieve results comparable to those of Protein A

  18. 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

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

    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:

  20. Simple model for molecular scattering

    Science.gov (United States)

    Mehta, Nirav; Ticknor, Christopher; Hazzard, Kaden

    2017-04-01

    The collisions of ultracold molecules are qualitatively different from the collisions of ultracold atoms due to the high density of bimolecular resonances near the collision energy. We present results from a simple N-channel scattering model with square-well channel potentials and constant channel couplings (inside the well) designed to reproduce essential features of chaotic molecular scattering. The potential depths and channel splittings are tuned to reproduce the appropriate density of states for the short-range bimolecular collision complex (BCC), which affords a direct comparison of the resulting level-spacing distribution to that expected from random matrix theory (RMT), namely the so-called Wigner surmise. The density of states also sets the scale for the rate of dissociation from the BCC to free molecules, as approximated by transition state theory (TST). Our model affords a semi-analytic solution for the scattering amplitude in the open channel, and a determinantal equation for the eigenenergies of the short-ranged BCC. It is likely the simplest finite-ranged scattering model that can be compared to expectations from the approximations of RMT, and TST. The validity of these approximations has implications for the many-channel Hubbard model recently developed. This research was funded in part by the National Science Foundation under Grant No. NSF PHY-1125915.

  1. 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.

  2. 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

  3. 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.

  4. 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,…

  5. Current challenges in glioblastoma: intratumour heterogeneity, residual disease and models to predict disease recurrence

    Directory of Open Access Journals (Sweden)

    Hayley Patricia Ellis

    2015-11-01

    Full Text Available Glioblastoma (GB is the most common malignant primary brain tumour, and despite the availability of chemotherapy and radiotherapy to combat the disease, overall survival remains low with a high incidence of tumour recurrence. Technological advances are continually improving our understanding of the disease and in particular our knowledge of clonal evolution, intratumour heterogeneity and possible reservoirs of residual disease. These may inform how we approach clinical treatment and recurrence in GB. Mathematical modelling (including neural networks, and strategies such as multiple-sampling during tumour resection and genetic analysis of circulating cancer cells, may be of great future benefit to help predict the nature of residual disease and resistance to standard and molecular therapies in GB.

  6. Molecular Modeling of Nafion Permselective Membranes

    National Research Council Canada - National Science Library

    Vishnyakov, Aleksey M; Neimark, Alexander V

    2005-01-01

    .... We developed molecular models for Nafion and nerve agent simulant DMMP and explored microphase segregation and mechanisms of DMMP sorption and transport in hydrated membranes with K+ counterion...

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

    OpenAIRE

    Simkovic, Felix; Thomas, Jens M. H.; Keegan, Ronan M.; Winn, Martyn D.; Mayans, Olga; Rigden, Daniel J.

    2016-01-01

    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 sea...

  8. Ratchet models of molecular motors

    Science.gov (United States)

    Jaster, Nicole

    2003-09-01

    Transport processes in and of cells are of major importance for the survival of the organism. Muscles have to be able to contract, chromosomes have to be moved to opposing ends of the cell during mitosis, and organelles, which are compartments enclosed by membranes, have to be transported along molecular tracks. Molecular motors are proteins whose main task is moving other molecules.For that purpose they transform the chemical energy released in the hydrolysis of ATP into mechanical work. The motors of the cytoskeleton belong to the three super families myosin, kinesin and dynein. Their tracks are filaments of the cytoskeleton, namely actin and the microtubuli. Here, we examine stochastic models which are used for describing the movements of these linear molecular motors. The scale of the movements comprises the regime of single steps of a motor protein up to the directed walk along a filament. A single step bridges around 10 nm, depending on the protein, and takes about 10 ms, if there is enough ATP available. Our models comprise M states or conformations the motor can attain during its movement along a one-dimensional track. At K locations along the track transitions between the states are possible. The velocity of the protein depending on the transition rates between the single states can be determined analytically. We calculate this velocity for systems of up to four states and locations and are able to derive a number of rules which are helpful in estimating the behaviour of an arbitrary given system. Beyond that we have a look at decoupled subsystems, i.e., one or a couple of states which have no connection to the remaining system. With a certain probability a motor undergoes a cycle of conformational changes, with another probability an independent other cycle. Active elements in real transport processes by molecular motors will not be limited to the transitions between the states. In distorted networks or starting from the discrete Master equation of the

  9. Teaching Molecular Geometry with the VSEPR Model

    Science.gov (United States)

    Gillespie, Ronald J.

    2004-01-01

    The first introduction to molecular geometry should be through the simple and easily understood VSEPR model, as the Valence Bond Theory and MO Theory suffer from limitations as far as understanding molecular geometry is concerned. The VSEPR model gives a perfectly satisfactory description of the bonding that follows directly from the Lewis model…

  10. Estimation of residue depletion of cyadox and its marker residue in edible tissues of pigs using physiologically based pharmacokinetic modelling.

    Science.gov (United States)

    Huang, Lingli; Lin, Zhoumeng; Zhou, Xuan; Zhu, Meiling; Gehring, Ronette; Riviere, Jim E; Yuan, Zonghui

    2015-01-01

    Physiologically based pharmacokinetic (PBPK) models are powerful tools to predict tissue distribution and depletion of veterinary drugs in food animals. However, most models only simulate the pharmacokinetics of the parent drug without considering their metabolites. In this study, a PBPK model was developed to simultaneously describe the depletion in pigs of the food animal antimicrobial agent cyadox (CYA), and its marker residue 1,4-bisdesoxycyadox (BDCYA). The CYA and BDCYA sub-models included blood, liver, kidney, gastrointestinal tract, muscle, fat and other organ compartments. Extent of plasma-protein binding, renal clearance and tissue-plasma partition coefficients of BDCYA were measured experimentally. The model was calibrated with the reported pharmacokinetic and residue depletion data from pigs dosed by oral gavage with CYA for five consecutive days, and then extrapolated to exposure in feed for two months. The model was validated with 14 consecutive day feed administration data. This PBPK model accurately simulated CYA and BDCYA in four edible tissues at 24-120 h after both oral exposure and 2-month feed administration. There was only slight overestimation of CYA in muscle and BDCYA in kidney at earlier time points (6-12 h) when dosed in feed. Monte Carlo analysis revealed excellent agreement between the estimated concentration distributions and observed data. The present model could be used for tissue residue monitoring of CYA and BDCYA in food animals, and provides a foundation for developing PBPK models to predict residue depletion of both parent drugs and their metabolites in food animals.

  11. Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia.

    Science.gov (United States)

    Oran, Betül; Jorgensen, Jeff L; Marin, David; Wang, Sa; Ahmed, Sairah; Alousi, Amin M; Andersson, Borje S; Bashir, Qaiser; Bassett, Roland; Lyons, Genevieve; Chen, Julianne; Rezvani, Katy; Popat, Uday; Kebriaei, Partow; Patel, Keyur; Rondon, Gabriela; Shpall, Elizabeth J; Champlin, Richard E

    2017-01-01

    Our aim was to improve outcome prediction after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia by combining cytogenetic and molecular data at diagnosis with minimal residual disease assessment by multicolor flow-cytometry at transplantation. Patients with acute myeloid leukemia in first complete remission in whom minimal residual disease was assessed at transplantation were included and categorized according to the European LeukemiaNet classification. The primary outcome was 1-year relapse incidence after transplantation. Of 152 patients eligible, 48 had minimal residual disease at the time of their transplant. Minimal residual disease-positive patients were older, required more therapy to achieve first remission, were more likely to have incomplete recovery of blood counts and had more adverse risk features by cytogenetics. Relapse incidence at 1 year was higher in patients with minimal residual disease (32.6% versus 14.4%, P=0.002). Leukemia-free survival (43.6% versus 64%, P=0.007) and overall survival (48.8% versus 66.9%, P=0.008) rates were also inferior in patients with minimal residual disease. In multivariable analysis, minimal residual disease status at transplantation independently predicted 1-year relapse incidence, identifying a subgroup of intermediate-risk patients, according to the European LeukemiaNet classification, with a particularly poor outcome. Assessment of minimal residual disease at transplantation in combination with cytogenetic and molecular findings provides powerful independent prognostic information in acute myeloid leukemia, lending support to the incorporation of minimal residual disease detection to refine risk stratification and develop a more individualized approach during hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

  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.

    then analyse the model results to define characteristics of residual estuarine circulation in the Mandovi. Our motivation to study this aspect of the Mandovi`s dynamics is derived from the following three considerations. First, residual circulation is important...

  13. 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

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

    Indian Academy of Sciences (India)

    data. GENERAL I ARTICLE of programmable calculators (starting around 1956 with the introduction of Fortran), computers as visualization aids (around. 1970) .... ous applications of computer assisted molecular modeling tech- niques are .... thods are less complicated, fast, and are able to handle very large systems ...

  15. Optimal Calculation of Residuals for ARMAX Models with Applications to Model Verification

    DEFF Research Database (Denmark)

    Knudsen, Torben

    1997-01-01

    Residual tests for sufficient model orders are based on the assumption that prediction errors are white when the model is correct. If an ARMAX system has zeros in the MA part which are close to the unit circle, then the standard predictor can have large transients. Even when the correct model...

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

    Science.gov (United States)

    Simkovic, Felix; Thomas, Jens M H; Keegan, Ronan M; Winn, Martyn D; Mayans, Olga; Rigden, Daniel J

    2016-07-01

    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.

  17. Markov state models and molecular alchemy

    Science.gov (United States)

    Schütte, Christof; Nielsen, Adam; Weber, Marcus

    2015-01-01

    In recent years, Markov state models (MSMs) have attracted a considerable amount of attention with regard to modelling conformation changes and associated function of biomolecular systems. They have been used successfully, e.g. for peptides including time-resolved spectroscopic experiments, protein function and protein folding , DNA and RNA, and ligand-receptor interaction in drug design and more complicated multivalent scenarios. In this article, a novel reweighting scheme is introduced that allows to construct an MSM for certain molecular system out of an MSM for a similar system. This permits studying how molecular properties on long timescales differ between similar molecular systems without performing full molecular dynamics simulations for each system under consideration. The performance of the reweighting scheme is illustrated for simple test cases, including one where the main wells of the respective energy landscapes are located differently and an alchemical transformation of butane to pentane where the dimension of the state space is changed.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Model Of Relaxation Of Residual Stresses In Hot-Rolled Strips

    Directory of Open Access Journals (Sweden)

    Milenin A.

    2015-09-01

    Full Text Available Residual stresses in hot-rolled strips are of practical importance when the laser cutting of these strip is applied. The factors influencing the residual stresses include the non uniform distribution of elastic-plastic deformations, phase transformation occurring during cooling and stress relaxation during rolling and cooling. The latter factor, despite its significant effect on the residual stress, is scarcely considered in the scientific literature. The goal of the present study was development of a model of residual stresses in hot-rolled strips based on the elastic-plastic material model, taking into account the stress relaxation.

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

    African Journals Online (AJOL)

    In this study, biomass yield residue was quantified and equations developed for Triplochiton scleroxylon, in secondary forests, Ondo State, Nigeria. Plotless sampling technique was used for the study. A total of 31 Triplochiton scleroxylon were randomly selected. Tree identification and detailed growing stock of outside bark ...

  5. 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...

  6. Exploring RNA structure by integrative molecular modelling

    DEFF Research Database (Denmark)

    Masquida, Benoît; Beckert, Bertrand; Jossinet, Fabrice

    2010-01-01

    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...

  7. Modeling the chemistries of technical molecular plasmas

    Science.gov (United States)

    Munro, James J.; Tennyson, Jonathan; Brown, Daniel B.; Varambhia, Hemal N.; Doss, Natasha

    2008-10-01

    Plasma chemistries, especially for molecular gases, are complicated. With a limited amount of molecular data available, it is hard to model these plasmas accurately; just a couple of feedstock gases can lead to a minimal model containing perhaps dozens of gas-phase species. The possible gas-phase and surface reactions that can occur could be in the tens of thousands; less than a hundred are typically used in chemistry models. Understanding the importance of various species and reactions to a chemical model is vital. Here we present the progress on constructing a package (Quantemol-P)[1] to simplify and automate the process of building and analyzing plasma chemistries e.g. SF6/O2, CF4/O2 and O2/He. [1] J.J. Munro, J. Tennyson, J. Vac. Sci. Tech. A, accepted

  8. 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

  9. 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...

  10. 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 ...

  11. Detecting Local Residue Environment Similarity for Recognizing Near-Native Structure Models

    Science.gov (United States)

    Kim, Hyungrae; Kihara, Daisuke

    2014-01-01

    We developed a new representation of local amino acid environments in protein structures called the Side-chain Depth Environment (SDE). An SDE defines a local structural environment of a residue considering the coordinates and the depth of amino acids that locate in the vicinity of the side-chain centroid of the residue. SDEs are general enough that similar SDEs are found in protein structures with globally different folds. Using SDEs, we developed a procedure called PRESCO (Protein Residue Environment SCOre) for selecting native or near-native models from a pool of computational models. The procedure searches similar residue environments observed in a query model against a set of representative native protein structures to quantify how native-like SDEs in the model are. When benchmarked on commonly used computational model datasets, our PRESCO compared favorably with the other existing scoring functions in selecting native and near-native models. PMID:25132526

  12. Model checks for Cox-type regression models based on optimally weighted martingale residuals.

    Science.gov (United States)

    Gandy, Axel; Jensen, Uwe

    2009-12-01

    We introduce directed goodness-of-fit tests for Cox-type regression models in survival analysis. "Directed" means that one may choose against which alternatives the tests are particularly powerful. The tests are based on sums of weighted martingale residuals and their asymptotic distributions.We derive optimal tests against certain competing models which include Cox-type regression models with different covariates and/or a different link function. We report results from several simulation studies and apply our test to a real dataset.

  13. Understanding the molecular basis of stability in Kunitz (STI) family of inhibitors in terms of a conserved core tryptophan residue: A theoretical investigation.

    Science.gov (United States)

    Datta Sharma, Ravi; Goswami, Nabajyoti; Ghosh, Debasree; Majumder, Sudip

    2017-08-01

    β-trefoil is one of the superfolds among proteins. Important classes of proteins like Interleukins (ILs), FibroblastGrowth Factors (FGFs), Kunitz (STI) family of inhibitors etc. belong to this fold. Kunitz (STI) family of inhibitors of proteins possess a highly conserved and structurally important Trytophan 91 (W91) residue, which stitches the top layer of the barrel with the lid. In this article we have investigated the molecular insights of the involvement of this W91 residue in the stability and folding pathway of Kunitz (STI) family. Winged bean Chymotrypsin inhibitor (WCI), a member of Kunitz (STI) family was chosen as a model system for carrying out the work. Molecular dynamics (MD) simulations were run with a set of total six proteins, including wild type WCI (WT) & five mutants namely W91F, W91M, W91A, W91H and W91I. Among all of them the coordinates of four proteins were taken from their crystal structures deposited in the Protein Data Bank (PDB), where as the coordinates for the rest two was generated using in-silico modelling. Our results suggest that truly this W91 residue plays a determining role in stability and folding pathway of Kunitz (STI) family. The mutants are less stable and more susceptible to quicker unfolding at higher temperatures compared to the wild type WCI. These effects are most pronounced for the smallest mutants namely W91H and W91A, indicating more is the cavity created by mutation at W91 position more the proteins becomes unstable. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Normal linear models with genetically structured residual variance heterogeneity: a case study

    DEFF Research Database (Denmark)

    Sorensen, Daniel; Waagepetersen, Rasmus Plenge

    2003-01-01

    Normal mixed models with different levels of heterogeneity in the residual variance are fitted to pig litter size data. Exploratory analysis and model assessment is based on examination of various posterior predictive distributions. Comparisons based on Bayes factors and related criteria favour...... models with a genetically structured residual variance heterogeneity. There is, moreover, strong evidence of a negative correlation between the additive genetic values affecting litter size and those affecting residual variance. The models are also compared according to the purposes for which they might...... be used, such as prediction of 'future' data, inference about response to selection and ranking candidates for selection. A brief discussion is given of some implications for selection of the genetically structured residual variance model....

  15. 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

  16. 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...

  17. Interaction of residue tetracycline hydrochloride in milk with β-galactosidase protein by multi-spectrum methods and molecular docking

    Science.gov (United States)

    Gao, Xin; Bi, Hongna; Zuo, Huijun; Jia, Jingjing; Tang, Lin

    2017-08-01

    The purpose of this study was to explore the effect of residue tetracycline hydrochloride (TCH) in milk on molecular structure and activity of β-Gal. Inhibition kinetics assay showed the TCH inhibited β-Gal activity reversibly in a competitive manner. In addition, differences in the activity of β-Gal in the absence and presence of TCH as a function of pH and temperature were found although the optimum pH and temperature of β-Gal remained similar. Fluorescence experiment results showed that TCH effectively quenched the intrinsic fluorescence of β-Gal via static quenching. Thermodynamic parameters delineated the major roles of electrostatic forces played between β-Gal and TCH. Additionally, synchronous fluorescence and circular dichroism spectra (CD spectra) results indicated the secondary structure of β-Gal was changed due to the formation of β-Gal-TCH complexes. The molecular docking further revealed that TCH interacted with some amino acid residues of β-Gal, affecting the active site of the enzyme and thus leading to change in enzyme activity. These alterations in conformation and activity of β-Gal should be taken into consideration while using β-Gal for producing oligosaccharide prebiotics on dairy industries.

  18. Detección molecular de enfermedad mínima residual en melanoma y otros tumores sólidos Molecular detection of minimal residual disease in melanoma and solid tumors

    Directory of Open Access Journals (Sweden)

    Valeria Vázquez

    2009-02-01

    Full Text Available La disponibilidad de métodos altamente sensibles y específicos para la detección de enfermedad mínima residual en pacientes con tumores sólidos podría tener importantes consecuencias pronósticas y terapéuticas. Uno de los métodos más usados para la detección molecular de células cancerosas es la técnica de RT-PCR, que permite la amplificación de secuencias de ARNm específicas de distintos tejidos. La misma fue aplicada por primera vez en la detección de células tumorales circulantes en sangre periférica de pacientes con melanoma avanzado, poco tiempo después fue adaptada para la búsqueda de enfermedad mínima residual en otros tumores sólidos. El objetivo de la presente revisión es evaluar la información publicada desde el primer estudio sobre este tema en 1991 y analizar el valor clínico de los hallazgos obtenidos. Se discute también la importancia del manejo de la muestra y de la estandarización de los procedimientos de RT-PCR.The availability of highly sensitive and specific methods for the detection of minimal residual disease in patients with solid tumors may have important prognostic and therapeutic implications. One of the most widely used methods for the molecular detection of cancer cells is the RT-PCR technique, which leads to the amplification of tissue-specific mRNA. It was firstly applied in the detection of circulating tumor cells in peripheral blood of patients with advanced melanoma; and soon it was adapted for the detection of minimal residual disease in other solid tumors. The aim of the present review is to evaluate the published data since the first study in 1991 and to analyze the clinical value of the findings obtained. The importance of sample handling and standardization of RT-PCR procedures is also discussed.

  19. Modeling and experimental verification of thermally induced residual stress in RF-MEMS

    International Nuclear Information System (INIS)

    Somà, Aurelio; Saleem, Muhammad Mubasher

    2015-01-01

    Electrostatically actuated radio frequency microelectromechanical systems (RF-MEMS) generally consist of microcantilevers and clamped–clamped microbeams. The presence of residual stress in these microstructures affects the static and dynamic behavior of the device. In this study, nonlinear finite element method (FEM) modeling and the experimental validation of residual stress induced in the clamped–clamped microbeams and the symmetric toggle RF-MEMS switch (STS) is presented. The formation of residual stress due to plastic deformation during the thermal loading-unloading cycle in the plasma etching step of the microfabrication process is explained and modeled using the Bauschinger effect. The difference between the designed and the measured natural frequency and pull-in voltage values for the clamped–clamped microbeams is explained by the presence of the nonhomogenous tensile residual stress. For the STS switch specimens, three-dimensional (3D) FEM models are developed and the initial deflection at zero bias voltage, observed during the optical profile measurements, is explained by the residual stress developed during the plasma etching step. The simulated residual stress due to the plastic deformation is included in the STS models to obtain the switch pull-in voltage. At the end of the simulation process, a good correspondence is obtained between the FEM model results and the experimental measurements for both the clamped–clamped microbeams and the STS switch specimens. (paper)

  20. Modeling molecular mechanisms in the axon

    Science.gov (United States)

    de Rooij, R.; Miller, K.E.; Kuhl, E.

    2016-01-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena–both in isolation and in interaction–to explore emergent cellular-level features under physiological and pathological conditions. PMID:28603326

  1. A Series of Molecular Dynamics and Homology Modeling Computer Labs for an Undergraduate Molecular Modeling Course

    Science.gov (United States)

    Elmore, Donald E.; Guayasamin, Ryann C.; Kieffer, Madeleine E.

    2010-01-01

    As computational modeling plays an increasingly central role in biochemical research, it is important to provide students with exposure to common modeling methods in their undergraduate curriculum. This article describes a series of computer labs designed to introduce undergraduate students to energy minimization, molecular dynamics simulations,…

  2. Molecular Models of Liquid Crystal Elastomers

    Science.gov (United States)

    Rajshekhar

    Liquid crystal elastomers combine the elastic properties of conventional rubbers with the optical properties of liquid crystals. This dual nature gives rise to unusual physical properties, including the stress induced transition from a polydomain state, consisting of multiple nematic regions with independent orientations, to a monodomain state consisting of a single nematic region with a uniform director. We propose several molecular-scale coarse-grained models of liquid crystal elastomers with varying degrees of resolution. The models employ the Gay-Berne soft potential, and exhibit the chain connectivity of a diamond network. Simulation results show that these models are able to capture the polydomain state exhibited by liquid crystal elastomers in the absence of any external stress. When subjected to uniaxial stress, our models exhibit a polydomain to monodomain transition. We explain that the polydomain state occurs through the aggregation of liquid crystal molecules assisted by crosslinking sites, and conclude that the transition mechanism to the monodomain state is based on the reorientation of nematic domains along the direction of applied stress. Our modeling efforts are primarily focused on three models. The first two models consider the effects of rigid and flexible crosslinkers in liquid crystal elastomers with a diamond topology for chain connectivity. The third model deviates from the diamond network topology and adopts a random network topology.

  3. 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

  4. Molecular Sieve Bench Testing and Computer Modeling

    Science.gov (United States)

    Mohamadinejad, Habib; DaLee, Robert C.; Blackmon, James B.

    1995-01-01

    The design of an efficient four-bed molecular sieve (4BMS) CO2 removal system for the International Space Station depends on many mission parameters, such as duration, crew size, cost of power, volume, fluid interface properties, etc. A need for space vehicle CO2 removal system models capable of accurately performing extrapolated hardware predictions is inevitable due to the change of the parameters which influences the CO2 removal system capacity. The purpose is to investigate the mathematical techniques required for a model capable of accurate extrapolated performance predictions and to obtain test data required to estimate mass transfer coefficients and verify the computer model. Models have been developed to demonstrate that the finite difference technique can be successfully applied to sorbents and conditions used in spacecraft CO2 removal systems. The nonisothermal, axially dispersed, plug flow model with linear driving force for 5X sorbent and pore diffusion for silica gel are then applied to test data. A more complex model, a non-darcian model (two dimensional), has also been developed for simulation of the test data. This model takes into account the channeling effect on column breakthrough. Four FORTRAN computer programs are presented: a two-dimensional model of flow adsorption/desorption in a packed bed; a one-dimensional model of flow adsorption/desorption in a packed bed; a model of thermal vacuum desorption; and a model of a tri-sectional packed bed with two different sorbent materials. The programs are capable of simulating up to four gas constituents for each process, which can be increased with a few minor changes.

  5. 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...

  6. 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.

  7. 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...

  8. 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.

  9. Modeling ion sensing in molecular electronics

    Science.gov (United States)

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

    2014-02-01

    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 (Ca2+), and hydronium ions (H3O+) 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, C9H7NS2), 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.

  10. 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.

  11. 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 fracti...... 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.......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...

  12. Molecular modeling of amorphous and crosslinked cellulose

    Science.gov (United States)

    Chen, Wei

    2001-07-01

    Structure-property relationships in cellulose crosslinked with both conventional and elastomeric crosslinking agents were successfully calculated using molecular modeling. The observed yielding for these amorphous cellulose models, which occurred at approximately 8% strain according to the calculated stress-strain relationship, is due to the disruption of hydrogen bonds, the secondary crosslinks, between cellulose chain segments. Crosslinks hold cellulose chain segments together and block chain slippage to give cellulose fibers a higher initial modulus and better elastic response. However, these crosslinks restrict chain movement so that stress is concentrated in regions of the structure and cavities are formed and developed in these regions of the models, which correlate to final fiber failure. The flexibility and response to applied external force for some potential crosslink structures were examined by molecular modeling. These molecules, which have small energy differences between conformational states, are highly coiled and have small mean end-to-end distances (accounting for 40% to 50% of the length of their fully extended chains). The presence of oxygen atoms in the backbone along with asymmetric non-polar side groups, such as methyl groups, can greatly reduce the energy difference and the energy barrier between conformational states and can thus make chains highly coiled and easy to be extended. Decane crosslinks introduced more freedom to cellulose chain segments but didn't improve the deformation recovery in cellulose models. Conformational transitions were observed in decane crosslinks during deformation. Cellulose models crosslinked with poly(propylene oxide) pentamers or with the N-methyl substituted peptide pentamers show good deformation recovery without affecting the breaking strain. Both crosslinks didn't significantly change the initial modulus and the yielding behavior of cellulose. No conformation transitions were observed in these crosslinks

  13. Modeling of the devolatilization kinetics during pyrolysis of grape residues.

    Science.gov (United States)

    Fiori, Luca; Valbusa, Michele; Lorenzi, Denis; Fambri, Luca

    2012-01-01

    Thermo-gravimetric analysis (TGA) was performed on grape seeds, skins, stalks, marc, vine-branches, grape seed oil and grape seeds depleted of their oil. The TGA data was modeled through Gaussian, logistic and Miura-Maki distributed activation energy models (DAEMs) and a simpler two-parameter model. All DAEMs allowed an accurate prediction of the TGA data; however, the Miura-Maki model could not account for the complete range of conversion for some substrates, while the Gaussian and logistic DAEMs suffered from the interrelation between the pre-exponential factor k0 and the mean activation energy E0--an obstacle that can be overcome by fixing the value of k0 a priori. The results confirmed the capabilities of DAEMs but also highlighted some drawbacks in their application to certain thermodegradation experimental data. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. A modeled experiment of gas behavior in aquifer and residual gas formation

    Science.gov (United States)

    Takahashi, K.; Yamada, Y.; Murata, S.; Nakano, M.; Matsuoka, T.

    2007-12-01

    National and international concern is rising about the possible effects of greenhouse gases (GHGs) on the climate. Several methods are proposed to reduce the gas in the atmosphere and underground sequestration is recently expected as an effective concept. Especially, residual gas can be the most effective method to store the gas in reservoir. Underground sequestration requires the gas injected into a reservoir. When the gas is injected into a water- saturated aquifer, it pushes water out of the pore space. As the gas bubbles go upward, the gas space is filled with water again, but small gas bubbles are trapped in the pore space by surface force and capillary pressure of water. This is the residual gas formation. Once the residual gas is formed, it seldom moves again from the pore space. Residual gas formation needs neither cap-rock nor structural trap, thus has a potential to be applied to broader regions. The purpose of this study is to examine the fundamental mechanism of residual gas formation and gas migration underground by injecting the gas into a modeled and visualized aquifer. We designed and constructed an experimental apparatus to measure the distribution and the saturation of the residual gas. We used glass beads of 1 or 2mm diameters as porous media to construct some reservoir models that have various porosity, permeability, and wettability. The glass beads packed in our apparatus which has 30cm width, 33.5cm height, and 1cm thickness. It has 1§¤volume in amount. The pore space was filled with viscous liquid, then air was injected from the bottom. Some conditions in the injection time and rate were tested. We observed air behavior and measured the volume of the distribution area of residual gas from its digital photographs, and the volume of residual gas from the amount of water that was pushed out from the apparatus. The experimental results showed that differences of reservoir properties made changes in the gas behavior and residual gas volume. It

  1. Major leaching processes of combustion residues - Characterisation, modelling and experimental investigation

    Energy Technology Data Exchange (ETDEWEB)

    Yan Jinying

    1998-12-31

    Characterising leaching behaviour provides ample evidence to identify the major leaching processes of combustion residues. Neutralisation and chemical weathering govern the leaching reactions and control the release of elements from combustion residues, and are thus considered to be the major leaching processes. According to experimental investigations and geochemical simulations, the leaching kinetics of buffering materials are key issues for the understanding of the neutralizing processes. The acid neutralizing capacity at different pH levels depends mainly on the mineralogy of the combustion residues. In combustion residues, the dissolution of glass phases is expected to play an important role in a long-term neutralizing process. The neutralizing process in a flow system is significantly different from that in a batch system. The neutralizing ability of a combustion residue may be strongly affected by solute transport and carbonation reactions in a natural leaching environment. The chemical weathering mainly involves the matrix of combustion residues consisting mostly of glass phases. The dissolution kinetics of waste glass and other possible processes involved in the chemical weathering have been investigated and incorporated into a kinetic reactive transport model. Most important processes in the chemical weathering can be simulated simultaneously using this model. The results show that there is a complicated relationship between the factors controlling the long-term chemical weathering. The environmental impact of the glass dissolution cannot be neglected. Although the glass dissolution provides considerable buffering capacity in long-term weathering, the carbonate is usually a dominant buffering mineral in actual weathering processes. The transformation of carbonate should be considered as an important process in the chemical weathering. The formation of secondary minerals may considerably alter the mineralogy of the waste, and thus change the leaching

  2. Mass residuals in implicit finite volume models for overland and groundwater flow

    Science.gov (United States)

    Lal, A. M. Wasantha; Wang, Naming; Moustafa, M. Z.; Brown, M. C.

    2010-04-01

    SummaryA primary advantage in using the finite volume method for simulating groundwater flow and overland flow is the conservation property or the ability to conserve mass. However, when implicit finite volume methods are used with large time steps, small cell areas, or parameters with extreme value ranges, the conservation of mass equation becomes slightly unbalanced with a residual. Problems with large mass residuals can be predicted using the condition number of the solution matrix, and the convergence criterion used in the sparse matrix solver. The amount of practical guidance available on how to manage the magnitude of the mass residual or the matrix condition number is limited. To address this need, the current paper shows the usefulness of the mesh ratio. The mesh ratio is a dimensionless number that is a function of the mesh resolution and the temporal resolution. It is directly related to the condition number of the matrix, which in turn affects the mass residual and the model run time. During the current study, several numerical experiments are carried out to determine how the mesh ratio and the water level are related to the condition number, how the critical mesh ratio is related to the number of cells, how the run time is related to the mesh ratio, and how the mass residual is related to the mesh ratio. The results are useful in creating guidelines for mesh design during large-scale model applications. These guidelines can be applied to reducing the mass residual and the run time. The usefulness of the mesh ratio is illustrated using a Regional Simulation Model (RSM) (Lal, A.M.W., Van Zee, Randy, Belnap, Mark, 2005. Case study: model to simulate regional flow in South Florida. Journal of Hydraulic Engineering 131 (4), 247-258) application in south Florida.

  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. 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.

  5. Influence of variable selection on partial least squares discriminant analysis models for explosive residue classification

    Energy Technology Data Exchange (ETDEWEB)

    De Lucia, Frank C., E-mail: frank.delucia@us.army.mil; Gottfried, Jennifer L.

    2011-02-15

    Using a series of thirteen organic materials that includes novel high-nitrogen energetic materials, conventional organic military explosives, and benign organic materials, we have demonstrated the importance of variable selection for maximizing residue discrimination with partial least squares discriminant analysis (PLS-DA). We built several PLS-DA models using different variable sets based on laser induced breakdown spectroscopy (LIBS) spectra of the organic residues on an aluminum substrate under an argon atmosphere. The model classification results for each sample are presented and the influence of the variables on these results is discussed. We found that using the whole spectra as the data input for the PLS-DA model gave the best results. However, variables due to the surrounding atmosphere and the substrate contribute to discrimination when the whole spectra are used, indicating this may not be the most robust model. Further iterative testing with additional validation data sets is necessary to determine the most robust model.

  6. Model validation through long-term promising sustainable maize/pigeon pea residue management in Malawi

    NARCIS (Netherlands)

    Mwale, C.D.; Kabambe, V.H.; Sakale, W.D.; Giller, K.E.; Kauwa, A.A.; Ligowe, I.; Kamalongo, D.

    2013-01-01

    In the 2005/2006 season, the Model Validation Through Long-Term Promising Sustainable Maize/Pigeon Pea Residue Management experiment was in the 11th year at Chitedze and Chitala, and in the 8th year at Makoka and Zombwe. The experiment was a split-plot design with cropping system as the main plot

  7. 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

    The sequence of the primary welding process and the following secondary processes of machining, and heat treatment has been modelled to predict the residual conditions in a Stellite 6 overlay weld on a P91 steam turbine valve. The different process steps are coupled in order to transfer the resid...

  8. 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.

  9. Determination and modeling of residual stress in functionally graded WC-Co

    Science.gov (United States)

    Tahvilian, Leila

    Gradual variations in composition and/or structure through the volume of functionally graded materials (FGMs) generally result in corresponding continuous spatial variations in mechanical/physical properties, and often in significant residual stresses that develop during processing. Due to inhomogeneous properties in these materials, residual stress measurement in FGMs can be a very challenging problem. In this study, residual stresses in functionally graded cemented tungsten carbide (FG-WC-Co) were investigated by numerical, analytical and experimental approaches by means of a layer removal technique. The numerical method consisted of finite element analysis (FEA) modeling for the FGM plate, in order to calculate residual stress distribution over the volume and to develop a method for predicting residual stress levels in closely related materials. The analytical procedure embodied a mathematical approach to determine residual stress distributions, and analytically determined values are compared with those obtained from FEA modeling and experimental results. The experimental approach consisted of fabricating and heat treating FG-WC-Co flat samples, then measuring strain changes by strain gauge after each sequential layer removal from the opposite side of the specimen from the graded region. Good agreement was found between analytical, numerical and experimental results. Furthermore, thermal residual stress distribution in FG-WC-Co hollow cylinder was examined with an emphasis on the effects of key variables, the gradient profile and the gradient thickness, on the magnitude and distribution of the stress field. An analytical direct solution based on solving the governing equations of a cylinder composed of a uniform inner core and a functionally graded outer shell was developed. The cylindrical compound was considered as two separate elements: homogeneous cylinder and functionally graded shell. Material properties, such as the elastic modulus and the coefficient of

  10. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Cele FN

    2016-04-01

    Full Text Available Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621 showed a significant potential with regard to free binding energy. Reported results obtained from

  11. Plant uptake of pesticides and human health: dynamic modeling of residues in wheat and ingestion intake.

    Science.gov (United States)

    Fantke, Peter; Charles, Raphaël; de Alencastro, Luiz Felippe; Friedrich, Rainer; Jolliet, Olivier

    2011-11-01

    Human intake of pesticide residues from consumption of processed food plays an important role for evaluating current agricultural practice. We take advantage of latest developments in crop-specific plant uptake modeling and propose an innovative dynamic model to estimate pesticide residues in the wheat-environment system, dynamiCROP. We used this model to analyze uptake and translocation of pesticides in wheat after foliar spray application and subsequent intake fractions by humans. Based on the evolution of residues in edible parts of harvested wheat we predict that between 22 mg and 2.1 g per kg applied pesticide are taken in by humans via consumption of processed wheat products. Model results were compared with experimentally derived concentrations in wheat ears and with estimated intake via inhalation and ingestion caused by indirect emissions, i.e. the amount lost to the environment during pesticide application. Modeled and measured concentrations in wheat fitted very well and deviate from less than a factor 1.5 for chlorothalonil to a maximum factor 3 for tebuconazole. Main aspects influencing pesticide fate behavior are degradation half-life in plant and time between pesticide application and crop harvest, leading to variations in harvest fraction of at least three orders of magnitude. Food processing may further reduce residues by approximately 63%. Intake fractions from residues in sprayed wheat were up to four orders of magnitude higher than intake fractions estimated from indirect emissions, thereby demonstrating the importance of exposure from consumption of food crops after direct pesticide treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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.

  14. Modeling of Prosthetic Limb Rotation Control by Sensing Rotation of Residual Arm Bone

    Science.gov (United States)

    Kuiken, Todd A.

    2011-01-01

    We proposed a new approach to improve the control of prosthetic arm rotation in amputees. Arm rotation is sensed by implanting a small permanent magnet into the distal end of the residual bone, which produces a magnetic field. The position of the bone rotation can be derived from magnetic field distribution detected with magnetic sensors on the arm surface, and then conveyed to the prosthesis controller to manipulate the rotation of the prosthesis. Proprioception remains intact for residual limb skeletal structures; thus, this control system should be natural and easy-to-use. In this study, simulations have been conducted in an upper arm model to assess the feasibility and performance of sensing the voluntary rotation of residual humerus with an implanted magnet. A sensitivity analysis of the magnet size and arm size was presented. The influence of relative position of the magnet to the magnetic sensors, orientation of the magnet relative to the limb axis, and displacement of the magnetic sensors on the magnetic field was evaluated. The performance of shielding external magnetostatic interference was also investigated. The simulation results suggest that the direction and angle of rotation of residual humerus could be obtained by decoding the magnetic field signals with magnetic sensors built into a prosthetic socket. This pilot study provides important guidelines for developing a practical interface between the residual bone rotation and the prosthesis for control of prosthetic rotation. PMID:18713682

  15. 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.

  16. 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

  17. 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 ...

  18. Estimating parameter and predictive uncertainty when model residuals are correlated, heteroscedastic, and non-Gaussian

    Science.gov (United States)

    Schoups, Gerrit; Vrugt, Jasper A.

    2010-05-01

    Estimation of parameter and predictive uncertainty of hydrologic models usually relies on the assumption of additive residual errors that are independent and identically distributed according to a normal distribution with a mean of zero and a constant variance. Here, we investigate to what extent estimates of parameter and predictive uncertainty are affected when these assumptions are relaxed. Parameter and predictive uncertainty are estimated by Monte Carlo Markov Chain sampling from a generalized likelihood function that accounts for correlation, heteroscedasticity, and non-normality of residual errors. Application to rainfall-runoff modeling using daily data from a humid basin reveals that: (i) residual errors are much better described by a heteroscedastic, first-order auto-correlated error model with a Laplacian density characterized by heavier tails than a Gaussian density, and (ii) proper representation of the statistical distribution of residual errors yields tighter predictive uncertainty bands and more physically realistic parameter estimates that are less sensitive to the particular time period used for inference. The latter is especially useful for regionalization and extrapolation of parameter values to ungauged basins. Application to daily rainfall-runoff data from a semi-arid basin shows that allowing skew in the error distribution yields improved estimates of predictive uncertainty when flows are close to zero.

  19. Applications of Molecular and Materials Modeling

    Science.gov (United States)

    2002-01-01

    have included the following: • Hare Research, founded by Dennis Hare in 1982 in Washington • BioDesign Ltd., founded in 1984 by Barry Olafson, Stephen...software In 1991, BioDesign changed its name to Molecular Simulations, Inc., acquired Cambridge Molecular Design and its Cerius package, and then merged with

  20. 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...

  1. 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.

  2. 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

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

    Science.gov (United States)

    Dixit, Anshuman; Verkhivker, Gennady M

    2012-01-01

    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 residue clusters may be

  4. 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

  5. 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

  6. Fitting correlated residual error structures in nonlinear mixed-effects models using SAS PROC NLMIXED.

    Science.gov (United States)

    Harring, Jeffrey R; Blozis, Shelley A

    2014-06-01

    Nonlinear mixed-effects (NLME) models remain popular among practitioners for analyzing continuous repeated measures data taken on each of a number of individuals when interest centers on characterizing individual-specific change. Within this framework, variation and correlation among the repeated measurements may be partitioned into interindividual variation and intraindividual variation components. The covariance structure of the residuals are, in many applications, consigned to be independent with homogeneous variances, [Formula: see text], not because it is believed that intraindividual variation adheres to this structure, but because many software programs that estimate parameters of such models are not well-equipped to handle other, possibly more realistic, patterns. In this article, we describe how the programmatic environment within SAS may be utilized to model residual structures for serial correlation and variance heterogeneity. An empirical example is used to illustrate the capabilities of the module.

  7. A residue level protein-protein interaction model in electrolyte solutions

    Science.gov (United States)

    Song, Xueyu

    2014-03-01

    The osmotic second virial coefficients B2 are directly related to the solubility of protein molecules in electrolyte solutions and can be useful to narrow down the search parameter space of protein crystallization conditions. Using a residue level model of protein-protein interaction in electrolyte solutions B2 of bovine pancreatic trypsin inhibitor and lysozyme in various solution conditions such as salt concentration, pH and temperature are calculated using an extended Fast Multipole Methods in combination with the boundary element formulation. Overall, the calculated B2 are well correlated with the experimental observations for various solution conditions. In combination with our previous work on the binding affinity calculations of protein complexes it is demonstrated that our residue level model can be used as a reliable model to describe protein-protein interaction in solutions.

  8. Generalized Residual Terrain Model and Its Application in Regional Gravity Field Approximation

    Directory of Open Access Journals (Sweden)

    WU Yihao

    2016-05-01

    Full Text Available We studied the so-called non-harmonic problem in residual terrain model (RTM and compared the RTM corrections based on prisms and tesseroids. Moreover, we proposed the generalized RTM based on tesseroids, together with which the regional gravity field was modeled based on Poisson wavelets basis function by using heterogeneous gravity data sets. The results show that the RTM correction based on prism integral has a poor performance in mountainous regions, which may introduce errors with the magnitude of several mGal. Thus, we suggest using RTM based on tesseroids, which lead to a better approximation of the topography. Compared to original residual terrain model,the generalized one leads a better approximation of the regional gravity filed at the high-frequency part caused by local topographical variation.

  9. Digital Learning Material for Model Building in Molecular Biology

    Science.gov (United States)

    Aegerter-Wilmsen, Tinri; Janssen, Fred; Hartog, Rob; Bisseling, Ton

    2005-01-01

    Building models to describe processes forms an essential part of molecular biology research. However, in molecular biology curricula little attention is generally being paid to the development of this skill. In order to provide students the opportunity to improve their model building skills, we decided to develop a number of digital cases about…

  10. 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)

  11. 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

  12. Exactly solvable models for multiatomic molecular Bose-Einstein condensates

    Energy Technology Data Exchange (ETDEWEB)

    Santos, G, E-mail: gfilho@if.ufrgs.br, E-mail: gfilho@cbpf.br [Instituto de Fisica da UFRGS, Av. Bento Goncalves, 9500, Agronomia, Porto Alegre, RS (Brazil)

    2011-08-26

    I introduce two families of exactly solvable models for multiatomic hetero-nuclear and homo-nuclear molecular Bose-Einstein condensates through the algebraic Bethe ansatz method. The conserved quantities of the respective models are also shown. (paper)

  13. Systematic Identification of Machine-Learning Models Aimed to Classify Critical Residues for Protein Function from Protein Structure.

    Science.gov (United States)

    Corral-Corral, Ricardo; Beltrán, Jesús A; Brizuela, Carlos A; Del Rio, Gabriel

    2017-10-09

    Protein structure and protein function should be related, yet the nature of this relationship remains unsolved. Mapping the critical residues for protein function with protein structure features represents an opportunity to explore this relationship, yet two important limitations have precluded a proper analysis of the structure-function relationship of proteins: (i) the lack of a formal definition of what critical residues are and (ii) the lack of a systematic evaluation of methods and protein structure features. To address this problem, here we introduce an index to quantify the protein-function criticality of a residue based on experimental data and a strategy aimed to optimize both, descriptors of protein structure (physicochemical and centrality descriptors) and machine learning algorithms, to minimize the error in the classification of critical residues. We observed that both physicochemical and centrality descriptors of residues effectively relate protein structure and protein function, and that physicochemical descriptors better describe critical residues. We also show that critical residues are better classified when residue criticality is considered as a binary attribute (i.e., residues are considered critical or not critical). Using this binary annotation for critical residues 8 models rendered accurate and non-overlapping classification of critical residues, confirming the multi-factorial character of the structure-function relationship of proteins.

  14. 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.

  15. 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

  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. 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.

  18. Influences of model structure and calibration data size on predicting chlorine residuals in water storage tanks.

    Science.gov (United States)

    Hua, Pei; de Oliveira, Keila Roberta Ferreira; Cheung, Peter; Gonçalves, Fábio Veríssimo; Zhang, Jin

    2018-04-09

    This study evaluated the influences of model structure and calibration data size on the modelling performance for the prediction of chlorine residuals in household drinking water storage tanks. The tank models, which consisted of two modules, i.e., hydraulic mixing and water quality modelling processes, were evaluated under identical calibration conditions. The hydraulic mixing modelling processes investigated included the continuously stirred tank reactor (CSTR) and multi-compartment (MC) methods, and the water quality modelling processes included first order (FO), single-reactant second order (SRSO), and variable reaction rate coefficients (VRRC) second order chlorine decay kinetics. Different combinations of these hydraulic mixing and water quality methods formed six tank models. Results show that by applying the same calibration datasets, the tank models that included the MC method for modelling the hydraulic mixing provided better predictions compared to the CSTR method. In terms of water quality modelling, VRRC kinetics showed better predictive abilities compared to FO and SRSO kinetics. It was also found that the overall tank model performance could be substantially improved when a proper method was chosen for the simulation of hydraulic mixing, i.e., the accuracy of the hydraulic mixing modelling plays a critical role in the accuracy of the tank model. Advances in water quality modelling improve the calibration process, i.e., the size of the datasets used for calibration could be reduced when a suitable kinetics method was applied. Although the accuracies of all six models increased with increasing calibration dataset size, the tank model that consisted of the MC and VRRC methods was the most suitable of the tank models as it could satisfactorily predict chlorine residuals in household tanks by using invariant parameters calibrated against the minimum dataset size. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Investigating Mars South Residual CO2 Cap with a Global Climate Model

    Science.gov (United States)

    Kahre, M. A.; Dequaire, J.; Hollingsworth, J. L.; Haberle, R. M.

    2016-01-01

    The CO2 cycle is one of the three controlling climate cycles on Mars. One aspect of the CO2 cycle that is not yet fully understood is the existence of a residual CO2 ice cap that is offset from the south pole. Previous investigations suggest that the atmosphere may control the placement of the south residual cap (e.g., Colaprete et al., 2005). These investigations show that topographically forced stationary eddies in the south during southern hemisphere winter produce colder atmospheric temperatures and increased CO2 snowfall over the hemisphere where the residual cap resides. Since precipitated CO2 ice produces higher surface albedos than directly deposited CO2 ice, it is plausible that CO2 snowfall resulting from the zonally asymmetric atmospheric circulation produces surface ice albedos high enough to maintain a residual cap only in one hemisphere. The goal of the current work is to further evaluate Colaprete et al.'s hypothesis by investigating model-predicted seasonally varying snowfall patterns in the southern polar region and the atmospheric circulation components that control them.

  20. As-Cast Residual Stresses in an Aluminum Alloy AA6063 Billet: Neutron Diffraction Measurements and Finite Element Modeling

    OpenAIRE

    Drezet, Jean-Marie; Phillion, André

    2010-01-01

    The presence of thermally induced residual stresses, created during the industrial direct chill (DC) casting process of aluminum alloys, can cause both significant safety concerns and the formation of defects during downstream processing. Although numerical models have been previously developed to compute these residual stresses, most of the computations have been validated only against measured surface distortions. Recently, the variation in residual elastic strains in the steady-state regim...

  1. 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.

  2. Hanford Tank 241-C-106: 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.

    2005-06-03

    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.

  3. 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

  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. 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

  7. Trend-Residual Dual Modeling for Detection of Outliers in Low-Cost GPS Trajectories.

    Science.gov (United States)

    Chen, Xiaojian; Cui, Tingting; Fu, Jianhong; Peng, Jianwei; Shan, Jie

    2016-12-01

    Low-cost GPS (receiver) has become a ubiquitous and integral part of our daily life. Despite noticeable advantages such as being cheap, small, light, and easy to use, its limited positioning accuracy devalues and hampers its wide applications for reliable mapping and analysis. Two conventional techniques to remove outliers in a GPS trajectory are thresholding and Kalman-based methods, which are difficult in selecting appropriate thresholds and modeling the trajectories. Moreover, they are insensitive to medium and small outliers, especially for low-sample-rate trajectories. This paper proposes a model-based GPS trajectory cleaner. Rather than examining speed and acceleration or assuming a pre-determined trajectory model, we first use cubic smooth spline to adaptively model the trend of the trajectory. The residuals, i.e., the differences between the trend and GPS measurements, are then further modeled by time series method. Outliers are detected by scoring the residuals at every GPS trajectory point. Comparing to the conventional procedures, the trend-residual dual modeling approach has the following features: (a) it is able to model trajectories and detect outliers adaptively; (b) only one critical value for outlier scores needs to be set; (c) it is able to robustly detect unapparent outliers; and (d) it is effective in cleaning outliers for GPS trajectories with low sample rates. Tests are carried out on three real-world GPS trajectories datasets. The evaluation demonstrates an average of 9.27 times better performance in outlier detection for GPS trajectories than thresholding and Kalman-based techniques.

  8. Trend-Residual Dual Modeling for Detection of Outliers in Low-Cost GPS Trajectories

    Directory of Open Access Journals (Sweden)

    Xiaojian Chen

    2016-12-01

    Full Text Available Low-cost GPS (receiver has become a ubiquitous and integral part of our daily life. Despite noticeable advantages such as being cheap, small, light, and easy to use, its limited positioning accuracy devalues and hampers its wide applications for reliable mapping and analysis. Two conventional techniques to remove outliers in a GPS trajectory are thresholding and Kalman-based methods, which are difficult in selecting appropriate thresholds and modeling the trajectories. Moreover, they are insensitive to medium and small outliers, especially for low-sample-rate trajectories. This paper proposes a model-based GPS trajectory cleaner. Rather than examining speed and acceleration or assuming a pre-determined trajectory model, we first use cubic smooth spline to adaptively model the trend of the trajectory. The residuals, i.e., the differences between the trend and GPS measurements, are then further modeled by time series method. Outliers are detected by scoring the residuals at every GPS trajectory point. Comparing to the conventional procedures, the trend-residual dual modeling approach has the following features: (a it is able to model trajectories and detect outliers adaptively; (b only one critical value for outlier scores needs to be set; (c it is able to robustly detect unapparent outliers; and (d it is effective in cleaning outliers for GPS trajectories with low sample rates. Tests are carried out on three real-world GPS trajectories datasets. The evaluation demonstrates an average of 9.27 times better performance in outlier detection for GPS trajectories than thresholding and Kalman-based techniques.

  9. Modelling the global tropospheric molecular hydrogen cycle

    NARCIS (Netherlands)

    Pieterse, G.

    2013-01-01

    Would urban air quality and climate improve if we replaced the fossil fuels by molecular hydrogen (H2) as an energy carrier? A quantitative answer to this question requires a thorough understanding of the current role of H2 in the Earth’s atmosphere. On its own, H2 does not impact climate, as for

  10. Molecular dynamics modeling of structural battery components

    NARCIS (Netherlands)

    Verners, O.; Van Duin, A.C.T.; Wagemaker, M.; Simone, A.

    2015-01-01

    A crosslinked polymer based solid electrolyte prototype material –poly(propylene glycol) diacrylate– is studied using the reactive molecular dynamics force field ReaxFF. The focus of the study is the evaluation of the effects of equilibration and added plasticizer (ethylene carbonate) or anion

  11. Network-Based Models in Molecular Biology

    Science.gov (United States)

    Beyer, Andreas

    Biological systems are characterized by a large number of diverse interactions. Interaction maps have been used to abstract those interactions at all biological scales ranging from food webs at the ecosystem level down to protein interaction networks at the molecular scale.

  12. SU-D-16A-06: Modeling Biological Effects of Residual Uncertainties For Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Ma, L; Larson, D; McDermott, M; Sneed, P [UCSF Comprehensive Cancer Center, San Francisco, CA (United States); Sahgal, A [University of Toronto, Toronto, ON (Canada)

    2014-06-01

    Purpose: Residual uncertainties on the order of 1-2 mm are frequently observed when delivering stereotactic radiosurgery via on-line imaging guidance with a relocatable frame. In this study, a predictive model was developed to evalute potentiral late radiation effects associated with such uncertainties. Methods: A mathematical model was first developed to correlate the peripherial isodose volume with the internal and/or setup margins for a radiosurgical target. Such a model was then integrated with a previoulsy published logistic regression normal tissue complication model for determining the symptomatic radiation necrosis rate at various target sizes and prescription dose levels. The model was tested on a cohort of 15 brain tumor and tumor resection cavity patient cases and model predicted results were compared with the clinical results reported in the literature. Results: A normalized target diameter (D{sub 0}) in term of D{sub 0} = 6V/S, where V is the volume of a radiosurgical target and S is the surface of the target, was found to correlate excellently with the peripheral isodose volume for a radiosurgical delivery (logarithmic regression R{sup 2} > 0.99). The peripheral isodose volumes were found increase rapidly with increasing uncertainties levels. In general, a 1-mm residual uncertainties as calculated to result in approximately 0.5%, 1%, and 3% increases in the symptomatic radiation necrosis rate for D{sub 0} = 1 cm, 2 cm, and 3 cm based on the prescription guideline of RTOG 9005, i.e., 21 Gy to a lesion of 1 cm in diameter, 18 Gy to a lesion 2 cm in diameter, and 15 Gy to a lesion 3 cm in diameter respectively. Conclusion: The results of study suggest more stringent criteria on residual uncertainties are needed when treating a large target such as D{sub 0}≤ 3 cm with stereotactic radiosurgery. Dr. Ma and Dr. Sahgal are currently serving on the board of international society of stereotactic radiosurgery (ISRS)

  13. 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

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

    Science.gov (United States)

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

    2011-05-01

    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.

  15. Study on Colloidal Model of Petroleum Residues through the Attraction Potential between Colloids

    Directory of Open Access Journals (Sweden)

    Long-li Zhang

    2016-01-01

    Full Text Available The samples of DaGang atmospheric residue (DG-AR, Middle East atmospheric residue (ME-AR, TaHe atmospheric residue (TH-AR, and their thermal reaction samples were chosen for study. All the samples were fractioned into six components separately, including saturates plus light aromatics, heavy aromatics, light resins, middle resins, heavy resins, and asphaltenes. The dielectric permittivity of the solutions of these components was measured, and the dielectric permittivity values of the components can be determined by extrapolation, which increased steadily from saturates plus light aromatics to asphaltenes. Moreover, the Hamaker constants of the components were calculated from their dielectric permittivity values. The Van der Waals attractive potential energy between colloids corresponding to various models could be calculated from the fractional composition and the Hamaker constants of every component. It was assumed that the cores of colloidal particles were formed by asphaltenes and heavy resins mainly; the other fractions acted as dispersion medium. For the three serials of thermal reaction samples, the Van der Waals attraction potential energy between colloids for this kind of model was calculated. For TH-AR thermal reaction samples, the Van der Waals attraction potential energy presented the maximum as thermal reaction is going on, which was near to the end of coke induction period.

  16. Using cumulative sums of martingale residuals for model checking in nested case-control studies.

    Science.gov (United States)

    Borgan, Ørnulf; Zhang, Ying

    2015-09-01

    Standard use of Cox regression requires collection of covariate information for all individuals in a cohort even when only a small fraction of them experiences the event of interest (fail). This may be very expensive for large cohorts. Further in biomarker studies, it will imply a waste of valuable biological material that one may want to save for future studies. A nested case-control study offers a useful alternative. For this design, covariate information is only needed for the failing individuals (cases) and a sample of controls selected from the cases' at-risk sets. Methods based on martingale residuals are useful for checking the fit of Cox's regression model for cohort data. But similar methods have so far not been developed for nested case-control data. In this article, it is described how one may define martingale residuals for nested case-control data, and it is shown how plots and tests based on cumulative sums of martingale residuals may be used to check model fit. The plots and tests may be obtained using available software. © 2015, The International Biometric Society.

  17. Neutron diffraction measurements and modeling of residual strains in metal matrix composites

    Science.gov (United States)

    Saigal, A.; Leisk, G. G.; Hubbard, C. R.; Misture, S. T.; Wang, X. L.

    1996-01-01

    Neutron diffraction measurements at room temperature are used to characterize the residual strains in tungsten fiber-reinforced copper matrix, tungsten fiber-reinforced Kanthal matrix, and diamond particulate-reinforced copper matrix composites. Results of finite element modeling are compared with the neutron diffraction data. In tungsten/Kanthal composites, the fibers are in compression, the matrix is in tension, and the thermal residual strains are a strong function of the volume fraction of fibers. In copper matrix composites, the matrix is in tension and the stresses are independent of the volume fraction of tungsten fibers or diamond particles and the assumed stress free temperature because of the low yield strength of the matrix phase.

  18. 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.

  19. 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

  20. Threshold conditions for integrated pest management models with pesticides that have residual effects.

    Science.gov (United States)

    Tang, Sanyi; Liang, Juhua; Tan, Yuanshun; Cheke, Robert A

    2013-01-01

    Impulsive differential equations (hybrid dynamical systems) can provide a natural description of pulse-like actions such as when a pesticide kills a pest instantly. However, pesticides may have long-term residual effects, with some remaining active against pests for several weeks, months or years. Therefore, a more realistic method for modelling chemical control in such cases is to use continuous or piecewise-continuous periodic functions which affect growth rates. How to evaluate the effects of the duration of the pesticide residual effectiveness on successful pest control is key to the implementation of integrated pest management (IPM) in practice. To address these questions in detail, we have modelled IPM including residual effects of pesticides in terms of fixed pulse-type actions. The stability threshold conditions for pest eradication are given. Moreover, effects of the killing efficiency rate and the decay rate of the pesticide on the pest and on its natural enemies, the duration of residual effectiveness, the number of pesticide applications and the number of natural enemy releases on the threshold conditions are investigated with regard to the extent of depression or resurgence resulting from pulses of pesticide applications and predator releases. Latin Hypercube Sampling/Partial Rank Correlation uncertainty and sensitivity analysis techniques are employed to investigate the key control parameters which are most significantly related to threshold values. The findings combined with Volterra's principle confirm that when the pesticide has a strong effect on the natural enemies, repeated use of the same pesticide can result in target pest resurgence. The results also indicate that there exists an optimal number of pesticide applications which can suppress the pest most effectively, and this may help in the design of an optimal control strategy.

  1. 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.

  2. [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.

  3. 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.

  4. Molecular model of the action potential sodium channel.

    OpenAIRE

    Guy, H R; Seetharamulu, P

    1986-01-01

    Secondary and tertiary structural models of sodium channel transmembrane segments were developed from its recently determined primary sequence in Electrophorus electricus. The model has four homologous domains, and each domain has eight homologous transmembrane segments, S1 through S8. Each domain contains three relatively apolar segments (S1, S2 and S3) and two very apolar segments (S5 and S8), all postulated to be transmembrane alpha-helices. S4 segments have positively charged residues, ma...

  5. A dynamic styrofoam-ball model for simulating molecular motion

    Science.gov (United States)

    Mak, Se-yuen; Cheung, Derek

    2001-01-01

    In this paper we introduce a simple styrofoam-ball model that can be used for simulating molecular motion in all three states. As the foam balls are driven by a vibrator that is in turn driven by a signal generator, the frequency and the amplitude of vibration can be adjusted independently. Thus, the model is appropriate for simulating molecular motion in the liquid state, which is a combination of vibration and meandering motion.

  6. 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.

  7. 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.

  8. A model of the ideal molecular surface

    Science.gov (United States)

    Henson, Bryan; Smilowitz, Laura

    2014-03-01

    We utilize two manifestations of the phenomena of the quasiliquid phase on the surface of molecular crystals to formulate a universal thermodynamic theory describing the thickness of the layer as a function of the liquid phase activity. We use direct measurements of the liquid thickness as a function of temperature and measurements of the acceleration of thermal decomposition as a function of temperature approaching the melting point to illustrate the mechanism. We show that given the existence of a liquid phase below the melting point the ideal liquid activity is necessarily a fixed function of the free energies of sublimation and vaporization. We use this activity to create a reduced formula for the liquid thickness generally applicable to the molecular surface. We provide a prediction of the mechanism and kinetics of quasiliquid formation and show that the phase exists as a metastable kinetic steady state. We show that to first order the principle controlling feature of the system is the configurational entropy of the liquid/solid interface, rather than the specifics of the surface potential energy. This is analogous to other bulk colligative phenomena such as ideal gas and solution theories, and is thus an ideal, universal formulation of inherent, thermodynamically driven, surface disorder.

  9. 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.

  10. 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

  11. 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

  12. Uncertainty "escalation" and use of machine learning to forecast residual and data model uncertainties

    Science.gov (United States)

    Solomatine, Dimitri

    2016-04-01

    When speaking about model uncertainty many authors implicitly assume the data uncertainty (mainly in parameters or inputs) which is probabilistically described by distributions. Often however it is look also into the residual uncertainty as well. It is hence reasonable to classify the main approaches to uncertainty analysis with respect to the two main types of model uncertainty that can be distinguished: A. The residual uncertainty of models. In this case the model parameters and/or model inputs are considered to be fixed (deterministic), i.e. the model is considered to be optimal (calibrated) and deterministic. Model error is considered as the manifestation of uncertainty. If there is enough past data about the model errors (i.e. it uncertainty), it is possible to build a statistical or machine learning model of uncertainty trained on this data. The following methods can be mentioned: (a) quantile regression (QR) method by Koenker and Basset in which linear regression is used to build predictive models for distribution quantiles [1] (b) a more recent approach that takes into account the input variables influencing such uncertainty and uses more advanced machine learning (non-linear) methods (neural networks, model trees etc.) - the UNEEC method [2,3,7] (c) and even more recent DUBRAUE method (Dynamic Uncertainty Model By Regression on Absolute Error), a autoregressive model of model residuals (it corrects the model residual first and then carries out the uncertainty prediction by a autoregressive statistical model) [5] B. The data uncertainty (parametric and/or input) - in this case we study the propagation of uncertainty (presented typically probabilistically) from parameters or inputs to the model outputs. In case of simple functions representing models analytical approaches can be used, or approximation methods (e.g., first-order second moment method). However, for real complex non-linear models implemented in software there is no other choice except using

  13. Quantitative and logic modelling of gene and molecular networks

    Science.gov (United States)

    Le Novère, Nicolas

    2015-01-01

    Behaviours of complex biomolecular systems are often irreducible to the elementary properties of their individual components. Explanatory and predictive mathematical models are therefore useful for fully understanding and precisely engineering cellular functions. The development and analyses of these models require their adaptation to the problems that need to be solved and the type and amount of available genetic or molecular data. Quantitative and logic modelling are among the main methods currently used to model molecular and gene networks. Each approach comes with inherent advantages and weaknesses. Recent developments show that hybrid approaches will become essential for further progress in synthetic biology and in the development of virtual organisms. PMID:25645874

  14. Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar

    Science.gov (United States)

    Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F. Javier

    2010-12-01

    Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar ( Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

  15. 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...

  16. 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.

  17. Hepatocytes contribute to residual glucose production in a mouse model for glycogen storage disease type Ia.

    Science.gov (United States)

    Hijmans, Brenda S; Boss, Andreas; van Dijk, Theo H; Soty, Maud; Wolters, Henk; Mutel, Elodie; Groen, Albert K; Derks, Terry G J; Mithieux, Gilles; Heerschap, Arend; Reijngoud, Dirk-Jan; Rajas, Fabienne; Oosterveer, Maaike H

    2017-12-01

    It is a long-standing enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production despite the loss of glucose-6-phosphatase activity. Insight into the source of residual endogenous glucose production is of clinical importance given the risk of sudden death in these patients, but so far contradictory mechanisms have been proposed. We investigated glucose-6-phosphatase-independent endogenous glucose production in hepatocytes isolated from a liver-specific GSD Ia mouse model (L-G6pc -/- mice) and performed real-time analysis of hepatic glucose fluxes and glycogen metabolism in L-G6pc -/- mice using state-of-the-art stable isotope methodologies. Here we show that G6pc-deficient hepatocytes are capable of producing glucose. In vivo analysis of hepatic glucose metabolism revealed that the hepatic glucokinase flux was decreased by 95% in L-G6pc -/- mice. It also showed increased glycogen phosphorylase flux in L-G6pc -/- mice, which is coupled to the release of free glucose through glycogen debranching. Although the ex vivo activities of debranching enzyme and lysosomal acid maltase, two major hepatic α-glucosidases, were unaltered in L-G6pc -/- mice, pharmacological inhibition of α-glucosidase activity almost completely abolished residual glucose production by G6pc-deficient hepatocytes. Our data indicate that hepatocytes contribute to residual glucose production in GSD Ia. We show that α-glucosidase activity, i.e. glycogen debranching and/or lysosomal glycogen breakdown, contributes to residual glucose production by GSD Ia hepatocytes. A strong reduction in hepatic GCK flux in L-G6pc-/- mice furthermore limits the phosphorylation of free glucose synthesized by G6pc-deficient hepatocytes, allowing the release of glucose into the circulation. The almost complete abrogation of GCK flux in G6pc-deficient liver also explains the contradictory reports on residual glucose production in GSD Ia patients. (Hepatology

  18. Modelling of pharmaceutical residues in Australian sewage by quantities of use and fugacity calculations.

    Science.gov (United States)

    Khan, Stuart J; Ongerth, Jerry E

    2004-01-01

    A conceptual model is presented for determining which currently prescribed pharmaceutical compounds are most likely to be found in sewage, and for estimating their concentrations, both in raw sewage and after successive stages of secondary sewage treatment. A ranking of the "top-50" pharmaceutical compounds (by total mass dispensed) in Australia over the 1998 calendar year was prepared. Information on the excretion ratios and some metabolites of the pharmaceuticals enabled prediction of the overall rates of excretion into Australian sewage. Mass-balance and fugacity modelling, applied to sewage generation and to a sewage treatment plant, allowed calculation of predicted concentrations of the compounds in raw, primary and secondary treated sewage effluents. Twenty nine of the modelled pharmaceutical residuals were predicted to be present in raw sewage influent at concentrations of 1 microgl(-1) or greater. Twenty of the compounds were predicted to remain in secondary effluent at concentrations of 1 microgl(-1) or greater.

  19. 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

    estimators to model potential right censoring. Furthermore, we show how to extend the models and the estimators to deal with delayed entries. We demonstrate that the restricted residual mean life estimator is equivalent to integrals of Kaplan-Meier estimates in the case of simple factor variables. Estimation...... 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...

  20. 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.

  1. Molecular modeling of amorphous, non-woven polymer networks.

    Science.gov (United States)

    Krausse, Constantin A; Milek, Theodor; Zahn, Dirk

    2015-10-01

    We outline a simple and efficient approach to generating molecular models of amorphous polymer networks. Similar to established techniques of preparing woven polymer networks from quenching high-temperature molecular simulation runs, we use a molecular dynamics simulations of a generic melt as starting points. This generic melt is however only used to describe parts of the polymers, namely the cross-linker units which positions are adopted from particle positions of the quenched melt. Specific degrees of network connectivity are tuned by geometric criteria for linker-linker connections and by suitable multi-body interaction potentials applied to the generic melt simulations. Using this technique we demonstrate adjusting fourfold linker coordination in amorphous polymer networks comprising 10-20% under-coordinated linkers. Graphical Abstract Molecular modeling of amorphous, non-woven polymer networks.

  2. 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.

  3. Comparative behaviour of organochlorine insecticides and related chemical residues in model ecosystems

    International Nuclear Information System (INIS)

    Klein, W.; Anagnostopoulos, M.; Begum, S.; Elsner, E.; Freitag, D.; Gaeb, W.; Greb, W.; Haque, A.; Hustert, K.; Kilzer, L.; Kohli, J.; Korte, F.; Kotzias, D.; Lay, J.P.; Moza, P.N.; Mueller, H.; Mueller, Werner; Mueller, Wolfgang; Nohynek, G.; Parlar, A.; Prestel, D.; Sandrock, K.; Sotiriou, N.; Viswanathan, P.; Viswanathan, S.; Vockel, D.; Weisgerber, I.

    1975-01-01

    A comprehensive series of isotopictracer-aided studies of the behaviour of organochlorine residues in model ecosystems is reported. Studies of the fate of 14 C-labelled aldrin or dieldrin in soil supporting carrots and potatoes under simulated conditions of agricultural practice have been extended. The formation of the polar metabolite dihydrochlordene dicarboxylic acid was confirmed. The metabolism of these compounds, and of 14 C-heptachlor and 14 C-lindane by green algae were also studied. Aldrin and heptachlor underwent epoxidation and lindane dehydrochlorination. Comparative studies were made of the metabolism of 14 C-PCBs in rat, monkey, microorganisms, higher plants and of their movement from contaminated soil into crops. Experiments on abiotic transformation of organochlorine residues by ultraviolet radiation are reported. The significance of some of the ratios observed in the context of environmental behaviour is discussed. The fate of dieldrin in soil-plant-food-animal systems is discussed as a model ''trace contaminant'' in view of the relative wealth of data now available, some as a result of experiments initiated 20 years ago. (author)

  4. The role of continuity in residual-based variational multiscale modeling of turbulence

    Science.gov (United States)

    Akkerman, I.; Bazilevs, Y.; Calo, V. M.; Hughes, T. J. R.; Hulshoff, S.

    2008-02-01

    This paper examines the role of continuity of the basis in the computation of turbulent flows. We compare standard finite elements and non-uniform rational B-splines (NURBS) discretizations that are employed in Isogeometric Analysis (Hughes et al. in Comput Methods Appl Mech Eng, 194:4135 4195, 2005). We make use of quadratic discretizations that are C 0-continuous across element boundaries in standard finite elements, and C 1-continuous in the case of NURBS. The variational multiscale residual-based method (Bazilevs in Isogeometric analysis of turbulence and fluid-structure interaction, PhD thesis, ICES, UT Austin, 2006; Bazilevs et al. in Comput Methods Appl Mech Eng, submitted, 2007; Calo in Residual-based multiscale turbulence modeling: finite volume simulation of bypass transition. PhD thesis, Department of Civil and Environmental Engineering, Stanford University, 2004; Hughes et al. in proceedings of the XXI international congress of theoretical and applied mechanics (IUTAM), Kluwer, 2004; Scovazzi in Multiscale methods in science and engineering, PhD thesis, Department of Mechanical Engineering, Stanford Universty, 2004) is employed as a turbulence modeling technique. We find that C 1-continuous discretizations outperform their C 0-continuous counterparts on a per-degree-of-freedom basis. We also find that the effect of continuity is greater for higher Reynolds number flows.

  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. 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...

  7. Active site modeling in copper azurin molecular dynamics simulations

    NARCIS (Netherlands)

    Rizzuti, B; Swart, M; Sportelli, L; Guzzi, R

    Active site modeling in molecular dynamics simulations is investigated for the reduced state of copper azurin. Five simulation runs (5 ns each) were performed at room temperature to study the consequences of a mixed electrostatic/constrained modeling for the coordination between the metal and the

  8. 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.

  9. 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

  10. 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.

  11. Extracting Structure Parameters of Dimers for Molecular Tunneling Ionization Model

    Science.gov (United States)

    Zhao, Song-Feng; Huang, Fang; Wang, Guo-Li; Zhou, Xiao-Xin

    2016-03-01

    We determine structure parameters of the highest occupied molecular orbital (HOMO) of 27 dimers for the molecular tunneling ionization (so called MO-ADK) model of Tong et al. [Phys. Rev. A 66 (2002) 033402]. The molecular wave functions with correct asymptotic behavior are obtained by solving the time-independent Schrödinger equation with B-spline functions and molecular potentials which are numerically created using the density functional theory. We examine the alignment-dependent tunneling ionization probabilities from MO-ADK model for several molecules by comparing with the molecular strong-field approximation (MO-SFA) calculations. We show the molecular Perelomov–Popov–Terent'ev (MO-PPT) can successfully give the laser wavelength dependence of ionization rates (or probabilities). Based on the MO-PPT model, two diatomic molecules having valence orbital with antibonding systems (i.e., Cl2, Ne2) show strong ionization suppression when compared with their corresponding closest companion atoms. Supported by National Natural Science Foundation of China under Grant Nos. 11164025, 11264036, 11465016, 11364038, the Specialized Research Fund for the Doctoral Program of Higher Education of China under Grant No. 20116203120001, and the Basic Scientific Research Foundation for Institution of Higher Learning of Gansu Province

  12. Molecular interaction study of flavonoid derivative 3d with human serum albumin using multispectroscopic and molecular modeling approach.

    Science.gov (United States)

    Wei, Juntong; Jin, Feng; Wu, Qin; Jiang, Yuyang; Gao, Dan; Liu, Hongxia

    2014-08-01

    Human serum albumin (HSA) has been developed as a model protein to study drug-protein interaction. In the present work, the interaction between our synthesized flavonoid derivative 3d (possessing potent antitumor activity against HepG2 cells) and HSA was investigated using fluorescence spectroscopy, circular dichroism spectroscopy, UV-vis spectroscopy and molecular modeling approach. Fluorescence spectroscopy showed that the fluorescence of HSA can be quenched remarkably by 3d under physiological condition with a slight shift of maximum fluorescence emission bands from 360nm to 363nm. Calculated results from Stern-Volmer equation and modified Stern-Volmer equation indicated that the fluorescence was quenched by static quenching processing with association constant 5.26±0.04×10(4)L mol(-1) at 298K. After comprehensive consideration of the free energy change ΔG, enthalpy change ΔH and entropy change ΔS, electrostatic interactions were confirmed as the main factor that participate in stabilizing the 3d-HSA complex. Both dichroism spectroscopy and UV-vis spectroscopy indicated conformational change of HSA after binding to 3d. Moreover, the structure of HSA was loosened and the percentage of α-helix decreased with increasing concentration of 3d. Molecular modeling results demonstrated that 3d could bind to HSA well into subdomain IIA, which is related to its capability of deposition and delivery. Three cation-π interactions and three hydrogen bonds occurred between 3d and amino acid residuals ARG218, ARG222 and LYS199. In conclusion, flavonoid derivative 3d can bind to HSA with noncovalent bond in a relatively stable way, so it can be delivered by HSA in a circulatory system. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Channel Model Optimization with Reflection Residual Component for Indoor MIMO-VLC System

    Science.gov (United States)

    Chen, Yong; Li, Tengfei; Liu, Huanlin; Li, Yichao

    2017-12-01

    A fast channel modeling method is studied to solve the problem of reflection channel gain for multiple input multiple output-visible light communications (MIMO-VLC) in the paper. For reducing the computational complexity when associating with the reflection times, no more than 3 reflections are taken into consideration in VLC. We think that higher order reflection link consists of corresponding many times line of sight link and firstly present reflection residual component to characterize higher reflection (more than 2 reflections). We perform computer simulation results for point-to-point channel impulse response, receiving optical power and receiving signal to noise ratio. Based on theoretical analysis and simulation results, the proposed method can effectively reduce the computational complexity of higher order reflection in channel modeling.

  14. 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 ...... is the first in a two-paper series describing contaminant transport at a waste residue site. III the second paper, reactive transport at the site is investigated.......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...

  15. An additive-multiplicative mean residual life model for right-censored data.

    Science.gov (United States)

    Cai, Jingheng; He, Haijin; Song, Xinyuan; Sun, Liuquan

    2017-05-01

    Many studies have focused on determining the effect of the body mass index (BMI) on the mortality in different cohorts. In this article, we propose an additive-multiplicative mean residual life (MRL) model to assess the effects of BMI and other risk factors on the MRL function of survival time in a cohort of Chinese type 2 diabetic patients. The proposed model can simultaneously manage additive and multiplicative risk factors and provide a comprehensible interpretation of their effects on the MRL function of interest. We develop an estimation procedure through pseudo partial score equations to obtain parameter estimates. We establish the asymptotic properties of the proposed estimators and conduct simulations to demonstrate the performance of the proposed method. The application of the procedure to a study on the life expectancy of type 2 diabetic patients reveals new insights into the extension of the life expectancy of such patients. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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.

  17. 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)

  18. A Coupled Creep Plasticity Model for Residual Stress Relaxation of a Shot Peened Nickel-Base Superalloy (Postprint)

    Science.gov (United States)

    2008-09-01

    recovery into a single viscoplastic model. Chaboche and Jung [10] and Ahmad et al. [5], using viscoplasticity models, predict residual stress relaxation... UMAT ) for implementation into ABAQUS/Standard. Details of the physical deformation mechanism, constitutive equations and solution procedure follow...range of operating conditions. Many of the viscoplastic models in the literature follow similar arguments about microstructural behavior in the

  19. 3-D numerical evaluation of residual stress and deformation due welding process using simplified heat source models

    Energy Technology Data Exchange (ETDEWEB)

    Eslampanah, Amir Hossein [Islamic Azad University, Arak (Iran, Islamic Republic of); Aalami-aleagha, Mohammad Ebrahim; Feli, Saeid [Razi University, Kermanshah (Iran, Islamic Republic of); Ghaderi, Mohammad Reza [Islamic Azad University, Sanandaj (Iran, Islamic Republic of)

    2015-01-15

    Thermal elastic-plastic finite element method has been employed to predict residual stress and deformation in a T-Fillet welded joint. An uncoupled thermal-mechanical three-dimensional (3-D) model has been developed. A nonlinear-transient heat flow analysis was used to obtain the temperature distribution; then by applying thermal results in the three dimensional elastic-plastic model, residual stress and deformation distribution were obtained. Experiments were carried out to find fusion zone dimensions and displacement. Two heat source models with infinite speed are proposed and the mechanical result of the mentioned models and normal moving heat source are compared.

  20. 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.

  1. 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.

  2. Molecular modelling of zinc sulphide nanoparticles stabilized by cetyltrimethylammonium bromide

    Directory of Open Access Journals (Sweden)

    Kovář Petr

    2014-01-01

    Full Text Available ZnS nanoparticles stabilized by cetyltrimethylammonium bromide (CTAB were modelled in the Materials Studio environment. Four types of models with different distances between ZnS nanoparticles and different amounts of CTA cations without water and in water environment were built and characterized by calculated sublimation energies. The results of molecular modelling without water showed that the most favourable model consisted of two ZnS nanoparticles with a distance of 8-9 nm separated without immersing of CTAs. On the contrary, the most favourable model in water environment was composed of ZnS nanoparticles that nearly touched each other. CTA cations exhibited tendency to be located on the ZnS surface forming sparse covers. Size distributions of ZnS-CTA particles obtained by TEM measurements well agreed with molecular modelling results.

  3. Comparative molecular modelling study of the calcium channel blockers nifedipine and black mamba toxin FS2

    Science.gov (United States)

    Schleifer, Klaus-Jürgen

    1997-09-01

    The identification and structural determination of the criticalamino acid residues causing the calcium channel blocking effects of theangusticeps type III toxin FS2 is described. Alignments withmore than 200 different short and long neuro-, cyto-, muscarinic and otherangusticeps-type toxins yielded 12 amino acid residues at the tips of loopsII and III which are unique to the type III toxins. The competitive bindingbehaviour between the 1,4-dihydropyridine derivative nifedipine and toxinFS2 was used for a further delimitation of the relevant toxinbinding domain. Using the ab initio geometry optimized nifedipine X-raystructure as a template, a model based on the sequenceMet45-Trp46-cis-Pro47-Tyr48has been elaborated. This sequence shows the same hydrophobic andhydrogen bond forming properties as nifedipine. In addition, qualitativelysimilar molecular electrostatic potentials are observed for both structures,leading to the assumption that these amino acid residues of the toxin act asthe potential attachment region at the calcium channel receptor site.

  4. 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.

  5. 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.

  6. 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

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

    Science.gov (United States)

    Haritova, Aneliya Milanova; Fink-Gremmels, Johanna

    2010-09-01

    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 likelihood of residue disposition of licensed veterinary products in natural casings used as envelope for a variety of meat products, such as sausages. The model proved suitable for the calculation of drug concentrations in the muscles of pigs, cattle and sheep, the major species of which intestines are used. On the basis of drug concentrations in muscle tissue, the model allowed a prediction of intestinal concentrations and residues in the intestines that remained equal to or below the concentrations in muscle tissue, the major consumable product of slaughter animals. Subsequently, residues in intestines were found to be below the maximum residue limit value for muscle tissue when drugs were used according to prescribed procedures, including the application of appropriate withdrawal times. Considering the low consumption of natural casings (which represents only about 1-2% of the weight of a normal sausage), it was concluded that the exposure to drug residues from casings is negligible. Copyright 2009 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Sequence-alignment modelling and molecular docking studies of the epoxygenase component of alkene monooxygenase from Nocardia corallina B-276.

    Science.gov (United States)

    Gallagher, S C; George, A; Dalton, H

    1998-06-15

    Whole cells of Nocardia corallina B-276 catalyse the stereoselective epoxygenation of alkenes to chiral epoxides. The bacterium expresses an enzyme, alkene monooxygenase, which catalyses the epoxygenation reaction stereoselectively. The enzyme consists of a terminal oxygenase (epoxygenase), an NADH-dependent reductase (reductase) and a regulatory component (coupling protein). The epoxygenase component contains a bridged diiron centre similar to that found in the hydroxylase component of soluble methane monooxygenase. Sequence-alignment modelling, supported by chemical modification and fluorescence probing, identified a hydrophobic oxygen/substrate binding site within the epoxygenase. The diiron centre was coordinated by the two His and two Glu residues from two conserved Glu-Xaa-Xaa-His sequences and by two further Glu residues. Molecular docking of substrates and products into the proposed active-site model of the epoxygenase suggested that Ala91 and Ala185 were responsible for the stereoselectivity exerted by AMO. It is proposed that these residues clamped the intermediate and/or product of the reaction, thereby controlling the configuration of the epoxide produced. In soluble methane monooxygenase these residues are replaced by two Gly residues which do not provide sufficient steric hindrance to prevent rotation of the intermediate in the active site and, therefore, the product of the reaction catalysed by this enzyme is achiral.

  10. 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.

  11. Modelling of thermal processes during extrusion based densification of agricultural biomass residues

    International Nuclear Information System (INIS)

    Mikulandrić, Robert; Vermeulen, Brecht; Nicolai, Bart; Saeys, Wouter

    2016-01-01

    Highlights: • Thermal models have been coupled in finite element modelling program for process analysis. • Process has been simulated based on available model parameters from literature. • Model has been validated based on measurement data from field tests. • Heat losses during biomass densification have been estimated to be 10–25%. • Suggestions for process improvement have been proposed. - Abstract: Biomass residues are increasing their share as a feedstock for renewable heat and power systems. Agricultural biomass is available in large quantities but to be utilised in energy systems the bulk density of the material should be increased. A large number of process parameters influence biomass compression and thus affect machinery efficiency and particular energy consumption. Increased concerns related to energy efficiency and environmental impacts of agricultural machinery have led to an increased interest in simulation models which can be used for process optimisation. In this study the influence of temperature on the biomass compression process performance has been analysed. For this purpose, mathematical models describing the thermal processes in the biomass material and the surrounding compression chamber have been elaborated. The heat transfer in the biological material has been described with time dependent Navier–Stokes equations for non-isothermal flow, while time dependent Navier–Stokes equations for heat transfer in solids have been utilised to describe heat transfer in metal structures of the chamber. The prediction performance of the model has been verified by comparing the simulated temperature evolution in the biomass and chamber walls to the corresponding values measured from a biomass compression machine through dedicated tests. The model was found to be able to predict the measured values with an average R 2 of 0.82. The influence of friction heat in the compression chamber has been simulated and heat losses during the process have

  12. Quantum interference in thermoelectric molecular junctions: A toy model perspective

    Science.gov (United States)

    Nozaki, Daijiro; Avdoshenko, Stas M.; Sevinçli, Hâldun; Cuniberti, Gianaurelio

    2014-08-01

    Quantum interference (QI) phenomena between electronic states in molecular circuits offer a new opportunity to design new types of molecular devices such as molecular sensors, interferometers, and thermoelectric devices. Controlling the QI effect is a key challenge for such applications. For the development of single molecular devices employing QI effects, a systematic study of the relationship between electronic structure and the quantum interference is needed. In order to uncover the essential topological requirements for the appearance of QI effects and the relationship between the QI-affected line shape of the transmission spectra and the electronic structures, we consider a homogeneous toy model where all on-site energies are identical and model four types of molecular junctions due to their topological connectivities. We systematically analyze their transmission spectra, density of states, and thermoelectric properties. Even without the degree of freedom for on-site energies an asymmetric Fano peak could be realized in the homogeneous systems with the cyclic configuration. We also calculate the thermoelectric properties of the model systems with and without fluctuation of on-site energies. Even under the fluctuation of the on-site energies, the finite thermoelectrics are preserved for the Fano resonance, thus cyclic configuration is promising for thermoelectric applications. This result also suggests the possibility to detect the cyclic configuration in the homogeneous systems and the presence of the QI features from thermoelectric measurements.

  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. Molecular modeling of protein materials: case study of elastin

    Science.gov (United States)

    Tarakanova, Anna; Buehler, Markus J.

    2013-09-01

    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.

  15. Hanford Tank 241-C-106: 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 values in Section 3.4.1.7, second paragraph, last sentence; 90Sr values in Tables 3.22 and 3.32; and 99Tc values Table 4.3 and in Chapter 5. In addition, the tables in Appendix F were updated to reflect corrections to the 90Sr values. The rest of the text remains unchanged from the original report issued in May 2005. 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 contam¬inants 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.

  16. Does high pressure have any effect on the structure of alpha amylase and its ability to binding to the oligosaccharides having 3-7 residues? Molecular dynamics study.

    Science.gov (United States)

    Vahidi, S Hooman; Bozorgmehr, Mohammad Reza; Morsali, Ali; Beyramabadi, S Ali

    2018-03-01

    Studies have shown that deletion of amino acids from the C-terminus of amylase do not alter its amylolytic activity. Although high pressure is used to modify the structure and function of this enzyme, the effects of high pressures on the structures of the wild-type and truncated amylases have not yet been understood at the molecular level. Using molecular dynamic simulations and docking, we studied the structures of wild-type and truncated Taka-amylases at high pressures (1000-4000 bar). To construct the truncated Taka-amylase, 50 and 100 C-terminal residues were removed in two separate steps. Results of simulation showed that, although the overall shape partly agglomerates with rise in pressure, high pressure fails to modify the structure of the barrel-like region of the β-sheet in the wild-type and truncated enzymes. A comparison of contact graphs revealed that the changes at the N-terminus were less extensive than those at the C-terminus. Further analysis showed that 10 regions of the secondary structures changed due to pressure change in wild-type amylase, of which 6 regions were associated with the loops and 4 with helix, while the structure of β-sheets remained unchanged. The docking of maltotriose, maltotetraose, maltopentaose, maltohexaose, and maltoheptaose with the averaged structures obtained from different simulations was conducted to characterize the influence of pressure on the activities of the wild-type and truncated enzymes. The results showed that maltoheptaose made hydrophobic contacts with residues Tyr238-Asp117-Tyr82-Leu166-Leu232-Tyr155 and hydrogen contacts with residues Asp233-Gly234-Asp206-Arg204-His296-Glu230. Similar results were obtained for other malto-oligosaccharides. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Residual deposits (residual soil)

    International Nuclear Information System (INIS)

    Khasanov, A.Kh.

    1988-01-01

    Residual soil deposits is accumulation of new formate ore minerals on the earth surface, arise as a result of chemical decomposition of rocks. As is well known, at the hyper genes zone under the influence of different factors (water, carbonic acid, organic acids, oxygen, microorganism activity) passes chemical weathering of rocks. Residual soil deposits forming depends from complex of geologic and climatic factors and also from composition and physical and chemical properties of initial rocks

  18. 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.

  19. Transient Changes in Molecular Geometries and How to Model Them

    DEFF Research Database (Denmark)

    Dohn, Asmus Ougaard

    by the solvent. The simulations has also served as benchmarks on this newly developed implementation First, we establish that the chosen model provides a trustworthy description of the systems; since transition metals are heavier than purely organic systems, we test a range of approximations to relativistic...... changes in molecular structure, vibrations and solvation. In this thesis, we employ our recently developed Quantum-/Molecular -Mechanical Direct Dynamics method to do simulations of transition metal complexes in solution, to uncover their energy dissipation channels, and how they are affected...... quantum mechanic descriptions, to ascertain the accuracy of the quantum model in the Direct Dynamics simulations. We then test - and improve - the framework for calculating the experimental X-ray Diffuse Scattering Difference signal from (any kind of) Molecular Dynamics (MD) simulations. Comparisons...

  20. Residual waste from Hanford tanks 241-C-203 and 241-C-204. 2. Contaminant release model.

    Science.gov (United States)

    Cantrell, Kirk J; Krupka, Kenneth M; Deutsch, William J; Lindberg, Michael J

    2006-06-15

    Release of U and 99Tc from residual sludge in Hanford waste tanks 241-C-203 and 241-C-204 atthe U.S. Department of Energy's (DOE) Hanford Site in southeastern Washington state was quantified by water-leaching, selective extractions, empirical solubility measurements, and thermodynamic modeling. A contaminant release model was developed based on these experimental results and solid-phase characterization results presented elsewhere. Uranium release was determined to be controlled by two phases and occurred in three stages. In the first stage, U release is controlled by the solubility of tejkaite, which is suppressed by high concentrations of sodium released from the dissolution of NaNO3 in the residual sludges. Equilibrium solubility calculations indicate the U released during this stage will have a maximum concentration of 0.021 M. When all the NaNO3 has dissolved from the sludge, the solubility of the remaining cejkaite will increase to 0.28 M. After cejkaite has completely dissolved, the majority of the remaining U is in the form of poorly crystalline Na2U2O7 [or clarkeite Na[(UO2)O(OH)](H20)0-1]. In contact with Hanford groundwater this phase is not stable, and becquerelite becomes the U solubility controlling phase, with a calculated equilibrium concentration of 1.2 x 10(-4) M. For Tc, a significant fraction of its concentration in the residual sludge was determined to be relatively insoluble (20 wt % for C-203 and 80 wt % for C-204). Because of the low concentrations of Tc in these sludge materials, the characterization studies did not identify any discrete Tc solids phases. Release of the soluble fraction of Tc was found to occur concomitantly with NO3-. It was postulated that a NaNO3-NaTcO4 solid solution could be responsible for this behavior. The Tc release concentrations for the soluble fraction were estimated to be 2.4 x 10-6 M for C-203 and 2.7 x 10(-5) M for C-204. Selective extraction results indicated that the recalcitrant fraction of Tc was

  1. 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

  2. United polarizable multipole water model for molecular mechanics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Rui; Wang, Qiantao; Ren, Pengyu, E-mail: pren@mail.utexas.edu [Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712 (United States); Wang, Lee-Ping; Pande, Vijay S. [Department of Chemistry, Stanford University, Stanford, California 94305 (United States)

    2015-07-07

    We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3–5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interaction site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self-diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water.

  3. 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.

  4. 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...

  5. 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)

  6. 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...

  7. Theoretical model analysis of molecular orientations in liquid protein ...

    African Journals Online (AJOL)

    In this study, some theoretical model functions have been used to explain the molecular behaviour of four different types of proteins; human haemoglobin, Insulin, egg-white lysozyme and β - globulin molecules in solution. The results of the computational fitting procedures showed that the dielectric dispersion of the protein ...

  8. Promoting Representational Competence with Molecular Models in Organic Chemistry

    Science.gov (United States)

    Stull, Andrew T.; Gainer, Morgan; Padalkar, Shamin; Hegarty, Mary

    2016-01-01

    Mastering the many different diagrammatic representations of molecules used in organic chemistry is challenging for students. This article summarizes recent research showing that manipulating 3-D molecular models can facilitate the understanding and use of these representations. Results indicate that students are more successful in translating…

  9. Molecular modelling studies on 2-amino 6-aryl ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 119; Issue 6. Molecular modelling studies on 2-amino 6-aryl-sulphonylbenzonitriles as non-nucleoside reverse transcriptase inhibitors of HIV-1: A QSPR approach. Nitin S Sapre Nilanjana Pancholi Swagata Gupta Arun Sikrwar Neelima Sapre. Volume 119 Issue 6 ...

  10. Synthesis, evaluation and molecular modelling studies of some ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 122; Issue 2. Synthesis, evaluation and molecular modelling studies of some novel 3-(3 ... The compounds have been characterized on the basis of elemental analysis and spectral data. All the compounds were evaluated for their HIV-1 RT inhibitory activity. Among ...

  11. Lilium longiflorum and molecular floral development: the ABCDE model

    NARCIS (Netherlands)

    Benedito, V.A.; Angenent, G.C.; Tuyl, van J.M.; Krens, F.A.

    2004-01-01

    Because lily (Lilium longiflorum Thunb.) is an important cut-flower crop, molecular characterisation of genes that are involved in flower morphology could help breeders to develop novel floral architectures in this species. The early ABC model for flower development emerged more than 10 years ago

  12. Numerical modeling of residual stresses generation due to 316L turning. A new experimental and numerical approach

    International Nuclear Information System (INIS)

    Valiorgue, F.

    2008-12-01

    The main goal of this thesis proposed by AREVA NP is to predict the residual stresses induced by finishing turning of AISI 316L. The numerical model is simulating the residual stresses generation with a new approach by applying directly equivalent thermo-mechanical loadings onto the finished work piece surface without modeling the chip removal process. Thus, this study is divided in two complementary main subsections. On one hand, an experimental campaign is carried out to record data and to compute thermomechanical loadings. This task is made using the AREVA NP parameters. On the other hand numerical models are set up using previous measured values. They are made to reproduce the residual stresses generation by applying and moving the thermo mechanical loadings. The study leads to interesting results because the shapes of the residual stresses curves agree with previous works concerning this topic and with XRD measured residual stresses. The new approach seems to be pertinent because it is possible to simulate several tool passages like no other numerical model. (author)

  13. Molecular model and ReaxFF molecular dynamics simulation of coal vitrinite pyrolysis.

    Science.gov (United States)

    Li, Wu; Zhu, Yan-ming; Wang, Geoff; Wang, Yang; Liu, Yu

    2015-08-01

    Vitrinite in coal, the mainly generating methane maceral, plays an important role in hydrocarbon generation of coal. This study aims at obtaining products formation mechanism of vitrinite pyrolysis, and hence determining the chemical bond, molecular liquefaction activity, and reactions mechanism of methane and C2-4 during pyrolysis. The ReaxFF molecular dynamics (MD) simulation was carried out at temperature of 1500 K in order to investigate the mechanism of vitrinite pyrolysis. Initially, a minimum energy conformational structure model was constrained by a combination of elemental and carbon-13 nuclear magnetic resonance ((13)C NMR) literature data. The model analysis shows the chemical and physical parameters of vitrinite pyrolysis are broadly consistent with the experimental data. Based on the molecular model, ReaxFF MD simulations further provide information of unimolecule such as bond length, and chemical shift, and hence the total population and energy of main products. Molecules bond and pyrolysis fragments, based on active bond analyzed, revealed pyrolysis products of single vitrinite molecule with aliphatic C-C bond, especially ring and chain aliphatic as liquefaction activity. The molecular cell whose density is 0.9 g/cm(3) with lowest energy accords with the experimental density 1.33 g/cm(3). The content of main products after pyrolysis, classifying as CH4, H2O, and H2, was changed along with the increasing temperature. The gas molecule, fragments and generation pathways of CO2, H2, CH4, and C2H6 were also elucidated. These results show agreement with experimental observations, implying that MD simulation can provide reasonable explanation for the reaction processes involved in coal vitrinite pyrolysis. Thus the mechanism of coal hydrocarbon generation was revealed at the molecular level.

  14. MFI-molecular sieve membranes:synthesis, characterization and modelling

    OpenAIRE

    Jareman, Fredrik

    2002-01-01

    This work concerns evaluation by permeation measurements and modeling of thin (<2µm) MFI molecular sieve membranes and, to a smaller extent, synthesis of such materials. The membranes have been synthesized on graded a-alumina microfiltration filters using The seed film method. Scanning electron microscopy and x-ray diffraction were used for characterization in addition to permeation measurements. Mathematical models describing membrane flux for real membranes and defect distributions were ...

  15. 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.

    Directory of Open Access Journals (Sweden)

    Sandra Witz

    Full Text Available 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.

  16. 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.

    Science.gov (United States)

    Witz, Sandra; Panwar, Pankaj; Schober, Markus; Deppe, Johannes; Pasha, Farhan Ahmad; Lemieux, M Joanne; Möhlmann, Torsten

    2014-01-01

    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.

  17. 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

    Science.gov (United States)

    Witz, Sandra; Panwar, Pankaj; Schober, Markus; Deppe, Johannes; Pasha, Farhan Ahmad; Lemieux, M. Joanne; Möhlmann, Torsten

    2014-01-01

    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. PMID:24621654

  18. 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.

  19. 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

  20. 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)

  1. Bonding and Molecular Geometry without Orbitals- The Electron Domain Model

    Science.gov (United States)

    Gillespie, Ronald J.; Spencer, James N.; Moog, Richard S.

    1996-07-01

    An alternative to the conventional valence bond approach to bonding and geometry-the electron domain model-is presented. This approach avoids some of the problems with the standard approach and presents fewer difficulties for the student, while still providing a physical basis for the VSEPR model and a link to the valence bond model. The electron domain model also emphasizes the importance of the Pauli principle in understanding the chemical bond and molecular geometry. A letter from Derek W. Smith in our April 2000 issue addresses the above.

  2. 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

  3. Cytotoxic and molecular impacts of allelopathic effects of leaf residues of Eucalyptus globulus on soybean (Glycine max

    Directory of Open Access Journals (Sweden)

    Hala M. Abdelmigid

    2017-12-01

    Full Text Available Eucalyptus trees litter plays a crucial role in structuring plant populations and regulating crop quality. To help characterize the allelopathic impact of Eucalyptus plantations and understand the interactions between tree litter and understorey plant populations, we performed two different genomic approaches to determine soybean (Glycine max crop plant response to biotic stress induced by leaf residues of Eucalyptus globulus trees. For assessing cell death, a qualitative method of DNA fragmentation test (comet assay was employed to detect cleavage of the genomic DNA into oligonucleosomal fragments and help to characterize the apoptotic event among the experimental samples. In addition, quantitative method of genome analysis at the transcriptional level also was conducted to investigate the expression responses of soybean genome to allelochemicals. Expression of specific genes, which are responsible for the breakdown of proteins during programmed cell death PCD (cysteine proteases and their inhibitors, was examined using semi-quantitative RT-PCR (sqPCR. Results of both conducted analyses proved significant genetic effects of Eucalyptus leaf residues on soybean crop genome, revealed by steady increase in DNA damage as well as variation in the transcript levels of cysteine proteases and inhibitors. Further detailed studies using more sensitive methods are necessary for a comprehensive understanding of the allelopathic effects of Eucalyptus plantations on crops.

  4. 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.

  5. Pharmacophore modeling for anti-Chagas drug design using the fragment molecular orbital method.

    Science.gov (United States)

    Yoshino, Ryunosuke; Yasuo, Nobuaki; Inaoka, Daniel Ken; Hagiwara, Yohsuke; Ohno, Kazuki; Orita, Masaya; Inoue, Masayuki; Shiba, Tomoo; Harada, Shigeharu; Honma, Teruki; Balogun, Emmanuel Oluwadare; da Rocha, Josmar Rodrigues; Montanari, Carlos Alberto; Kita, Kiyoshi; Sekijima, Masakazu

    2015-01-01

    Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that causes severe human health problems. To develop a new chemotherapeutic agent for the treatment of Chagas disease, we predicted a pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH) by fragment molecular orbital (FMO) calculation for orotate, oxonate, and 43 orotate derivatives. Intermolecular interactions in the complexes of TcDHODH with orotate, oxonate, and 43 orotate derivatives were analyzed by FMO calculation at the MP2/6-31G level. The results indicated that the orotate moiety, which is the base fragment of these compounds, interacts with the Lys43, Asn67, and Asn194 residues of TcDHODH and the cofactor flavin mononucleotide (FMN), whereas functional groups introduced at the orotate 5-position strongly interact with the Lys214 residue. FMO-based interaction energy analyses revealed a pharmacophore model for TcDHODH inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214, hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194, and the aromatic ring pharmacophore corresponds to FMN, which shows important characteristics of compounds that inhibit TcDHODH. In addition, the Lys214 residue is not conserved between TcDHODH and human DHODH. Our analysis suggests that these orotate derivatives should preferentially bind to TcDHODH, increasing their selectivity. Our results obtained by pharmacophore modeling provides insight into the structural requirements for the design of TcDHODH inhibitors and their development as new anti-Chagas drugs.

  6. 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.

  7. ORTH: R and SAS software for regression models of correlated binary data based on orthogonalized residuals and alternating logistic regressions.

    Science.gov (United States)

    By, Kunthel; Qaqish, Bahjat F; Preisser, John S; Perin, Jamie; Zink, Richard C

    2014-02-01

    This article describes a new software for modeling correlated binary data based on orthogonalized residuals, a recently developed estimating equations approach that includes, as a special case, alternating logistic regressions. The software is flexible with respect to fitting in that the user can choose estimating equations for association models based on alternating logistic regressions or orthogonalized residuals, the latter choice providing a non-diagonal working covariance matrix for second moment parameters providing potentially greater efficiency. Regression diagnostics based on this method are also implemented in the software. The mathematical background is briefly reviewed and the software is applied to medical data sets. Published by Elsevier Ireland Ltd.

  8. Estimation of pharmaceutical residues in primary and secondary sewage sludge based on quantities of use and fugacity modelling.

    Science.gov (United States)

    Khan, S J; Ongerth, J E

    2002-01-01

    A general procedure was developed for estimating the concentrations of pharmaceutical residues in fresh primary and secondary sewage sludge. Prescribed quantities coupled with information on the various excretion ratios of 20 pharmaceuticals and 2 of their metabolites enabled prediction of the overall rates of excretion into Australian sewage. Fugacity modelling was applied to predict concentrations of these residues in fresh primary and secondary sludge. Predicted concentrations ranged from 10(-3)-884 microg/L in primary sludge and 10(-4)-36 microg/L in secondary sludge. Overall rates of removal to sludges ranged from 1-39%. The accuracy of the model was verified by comparison to analytical data.

  9. A physically-motivated model describing the dynamic interactions between residual limb and socket in lower limb prostheses

    Directory of Open Access Journals (Sweden)

    Noll Veronika

    2017-03-01

    Full Text Available The amputee’s well-being and mobility are distinclty related to socket fit and resulting biomechanical interaction between residual limb and prosthetic socket. Understanding the dynamic interactions at the interface may lead to new socket standards. This paper introduces a physically-motivated reduced model of the interface, describing the dynamic interactions between residual limb and prosthetic socket. The model allows to investigate the sensitivity to changes of specific parameters in an isolated matter. A simulation study shows how stress distribution changes if friction coefficients are varied which might advance liner design.

  10. As-Cast Residual Stresses in an Aluminum Alloy AA6063 Billet: Neutron Diffraction Measurements and Finite Element Modeling

    Science.gov (United States)

    Drezet, J.-M.; Phillion, A. B.

    2010-12-01

    The presence of thermally induced residual stresses, created during the industrial direct chill (DC) casting process of aluminum alloys, can cause both significant safety concerns and the formation of defects during downstream processing. Although numerical models have been previously developed to compute these residual stresses, most of the computations have been validated only against measured surface distortions. Recently, the variation in residual elastic strains in the steady-state regime of casting has been measured as a function of radial position using neutron diffraction (ND) in an AA6063 grain-refined cylindrical billet. In the present study, these measurements are used to show that a well-designed thermomechanical finite element (FE) process model can reproduce relatively well the experimental results. A sensitivity analysis is then carried out to determine the relative effect of the various mechanical parameters when computing the as-cast residual stresses in a cylindrical billet. Two model parameters have been investigated: the temperature when the alloy starts to thermally contract and the plasticity behavior. It is shown that the mechanical properties at low temperatures have a much larger influence on the residual stresses than those at high temperatures.

  11. Molecular Dynamics Simulations of Intrinsically Disordered Proteins: On the Accuracy of the TIP4P-D Water Model and the Representativeness of Protein Disorder Models.

    Science.gov (United States)

    Henriques, João; Skepö, Marie

    2016-07-12

    Here, we first present a follow-up to a previous work by our group on the problematic of molecular dynamics simulations of intrinsically disordered proteins (IDPs) [ Henriques et al. J. Chem. Theory Comput. 2015 , 11 , 3420 - 3431 ], using the recently developed TIP4P-D water model. When used in conjunction with the standard AMBER ff99SB-ILDN force field and applied to the simulation of Histatin 5, our IDP model, we obtain results which are in excellent agreement with the best performing IDP-suitable force field from the earlier study and with experiment. We then assess the representativeness of the IDP models used in these and similar studies, finding that most are too short in comparison to the average IDP and contain a bias toward hydrophilic amino acid residues. Moreover, several key order- and disorder-promoting residues are also found to be misrepresented. It seems appropriate for future studies to address these issues.

  12. 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...

  13. Classical and molecular genetics of the model legume Lotus japonicus.

    Science.gov (United States)

    Jiang, Q; Gresshoff, P M

    1997-01-01

    The model legume Lotus japonicus was demonstrated to be amenable to classical and molecular genetic analysis, providing the basis for the genetic dissection of the plant processes underlying nodulation and nitrogen fixation. We have developed an efficient method for the sexual hybridization of L. japonicus and obtained F1 progeny derived from a cross of L. japonicus B-129-S9 Gifu x B-581 Funakura. Over half of the cross-pollinations resulted in fertile hybrid seed, which were confirmed morphologically and by single arbitrary primer DNA amplification polymorphisms using the DAF technique. Molecular and morphological markers segregated in true Mendelian fashion in a F2 population of 100 plants. Several DAF loci were linked using the MAPMAKER software to create the first molecular linkage groups of this model legume. The mapping population was advanced to generate a set of immortal recombinant inbred lines (F6; RILs), useful for sharing plant material fixed genetically at most genomic regions. Morphological loci for waved stem shape (Ssh), dark leaf color (Lco), and short flowering period (Fpe) were inherited as single dominant Mendelian loci. DAF markers were dominant and were detected between Gifu and Funakura at about one per primer, suggesting that the parents are closely related. One polymorphism (270G generated by single octomer primer 8.6m) was linked to a morphological locus controlling leaf coloration. The results demonstrate that (i) Lotus japonicus is amenable to diploid genetic analysis, (ii) morphological and molecular markers segregate in true diploid fashion, (iii) molecular polymorphisms can be obtained at a reasonable frequency between the related Gifu and Funakura lines, and iv) the possibility exists for map-based cloning, marker assisted selection and mapping of symbiotic mutations through a genetic and molecular map.

  14. Probing the outer mouth structure of the HERG channel with peptide toxin footprinting and molecular modeling.

    Science.gov (United States)

    Tseng, Gea-Ny; Sonawane, Kailas D; Korolkova, Yuliya V; Zhang, Mei; Liu, Jie; Grishin, Eugene V; Guy, H Robert

    2007-05-15

    Previous studies have shown that the unusually long S5-P linker lining human ether a-go-go related gene's (hERG's) outer vestibule is critical for its channel function: point mutations at high-impact positions here can interfere with the inactivation process and, in many cases, also reduce the pore's K+ selectivity. Because no data are available on the equivalent region in the available K channel crystal structures to allow for homology modeling, we used alternative approaches to model its three-dimensional structure. The first part of this article describes mutant cycle analysis used to identify residues on hERG's outer vestibule that interact with specific residues on the interaction surface of BeKm-1, a peptide toxin with known NMR structure and a high binding affinity to hERG. The second part describes molecular modeling of hERG's pore domain. The transmembrane region was modeled after the crystal structure of KvAP pore domain. The S5-P linker was docked to the transmembrane region based on data from previous NMR and mutagenesis experiments, as well as a set of modeling criteria. The models were further restrained by contact points between hERG's outer vestibule and the bound BeKm-1 toxin molecule deduced from the mutant cycle analysis. Based on these analyses, we propose a working model for the open conformation of the outer vestibule of the hERG channel, in which the S5-P linkers interact with the pore loops to influence ion flux through the pore.

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

    Science.gov (United States)

    Martinez-Archundia, Marlet; Cordomi, Arnau; Garriga, Pere; Perez, Juan J.

    2012-01-01

    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. PMID:22500107

  16. 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.

  17. Molecular dynamics modeling and characterization of graphene/polymer nanocomposites

    Science.gov (United States)

    Rahman, Rezwanur

    The current work focuses on the characterization of graphene based nanocomposites using molecular dynamic simulation and multiscale modeling approaches. Both graphene-epoxy and graphene-cellulose nanocomposites were considered in this study. A hierarchical multiscale modeling approach has been proposed using peridynamics and molecular dynamics simulation. Firstly, the mechanical properties of crosslinked graphene/epoxy (G-Ep) nanocomposites were investigated by molecular mechanics (MM) and molecular dynamics (MD) simulations. The influence of graphene's weight concentration, aspect ratio and dispersion on stress-strain response and elastic properties were studied. The results show significant improvement in Young's modulus and shear modulus for the G-Ep system in comparison to the neat epoxy resin. It appears that the RDF, molecular energy and aspect ratios are influenced by both graphene concentrations and aspect ratios. The graphene concentrations in the range of 1-3% are seen to improve Young's modulus and shorter graphenes are observed to be more effective than larger ones. In addition, the dispersed graphene system is more promising in enhancing in-plane elastic modulus than the agglomerated graphene system. The cohesive and pullout forces versus displacements data were plotted under normal and shear modes in order to characterize interfacial properties. The cohesive force is significantly improved by attaching the graphene with a chemical bond at the graphene-epoxy interface. In the second part of the work, cellulose was considered to study the mechanical properties of graphene-cellulose bionanocomposite. Similar to graphene-epoxy systems, the effect of graphene dispersion and agglomeration were studied in the stress-strain plots of graphene-cellulose system. A pcff forcefield was used to define intermolecular and intramolecular interactions. The effect of graphene's aspect ratio and weight concentration on the structural property of each unitcell was

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Prediction of residual stress in the welding zone of dissimilar metals using data-based models and uncertainty analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Dong Hyuk; Bae, In Ho [Department of Nuclear Engineering, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of); Na, Man Gyun, E-mail: magyna@chosun.ac.k [Department of Nuclear Engineering, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of); Kim, Jin Weon [Department of Nuclear Engineering, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759 (Korea, Republic of)

    2010-10-15

    Since welding residual stress is one of the major factors in the generation of primary water stress-corrosion cracking (PWSCC), it is essential to examine the welding residual stress to prevent PWSCC. Therefore, several artificial intelligence methods have been developed and studied to predict these residual stresses. In this study, three data-based models, support vector regression (SVR), fuzzy neural network (FNN), and their combined (FNN + SVR) models were used to predict the residual stress for dissimilar metal welding under a variety of welding conditions. By using a subtractive clustering (SC) method, informative data that demonstrate the characteristic behavior of the system were selected to train the models from the numerical data obtained from finite element analysis under a range of welding conditions. The FNN model was optimized using a genetic algorithm. The statistical and analytical uncertainty analysis methods of the models were applied, and their uncertainties were evaluated using 60 sampled training and optimization data sets, as well as a fixed test data set.

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

    Science.gov (United States)

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

    2017-05-20

    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 estimators to model potential right censoring. Furthermore, we show how to extend the models and the estimators to deal with delayed entries. We demonstrate that the restricted residual mean life estimator is equivalent to integrals of Kaplan-Meier estimates in the case of simple factor variables. Estimation performance is investigated by simulation studies. Using real data from Danish Monitoring Cardiovascular Risk Factor Surveys, we illustrate an application to additive regression models and discuss the general assumption of right censoring and left truncation being dependent on covariates. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Lp-norm-residual constrained regularization model for estimation of particle size distribution in dynamic light scattering.

    Science.gov (United States)

    Zhu, Xinjun; Li, Jing; Thomas, John C; Song, Limei; Guo, Qinghua; Shen, Jin

    2017-07-01

    In particle size measurement using dynamic light scattering (DLS), noise makes the estimation of the particle size distribution (PSD) from the autocorrelation function data unreliable, and a regularization technique is usually required to estimate a reasonable PSD. In this paper, we propose an Lp-norm-residual constrained regularization model for the estimation of the PSD from DLS data based on the Lp norm of the fitting residual. Our model is a generalization of the existing, commonly used L2-norm-residual-based regularization methods such as CONTIN and constrained Tikhonov regularization. The estimation of PSDs by the proposed model, using different Lp norms of the fitting residual for p=1, 2, 10, and ∞, is studied and their performance is determined using simulated and experimental data. Results show that our proposed model with p=1 is less sensitive to noise and improves stability and accuracy in the estimation of PSDs for unimodal and bimodal systems. The model with p=1 is particularly applicable to the noisy or bimodal PSD cases.

  5. 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.

  6. 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.

  7. Molecular modelling studies of substrate binding to the lipase from Rhizomucor miehei

    Science.gov (United States)

    Yagnik, Asutosh T.; Littlechild, Jennifer A.; Turner, Nicholas J.

    1997-05-01

    Lipase enzymes have found increasingly widespread use, especially in biotransformation reactions in organic synthesis. Due to their efficiency and high enantioselectivity, they can be employed in a variety of reactions to carry out asymmetric hydrolyses, esterifications and transesterifications. However, the reasons for their stereospecificity have not been fully correlated with the enzyme structure. Employing molecular modelling techniques and existing experimental data, a transesterification reaction using Rhizomucor miehei lipase was studied. The results indicate that the major controlling factor for this reaction is hydrophobic in nature, providing support for previous literature hypotheses. In addition, computational experiments suggest that the origin of enantioselectivity is the formation of essential hydrogen bonds in and around the catalytic triad of active site residues. Only one enantiomer of the substrate is able to form these hydrogen bonds during the formation of the first tetrahedral transition state.

  8. 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)

  9. 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.

  10. 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......The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high...... 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...

  11. Structural modeling and molecular dynamics simulation of the actin filament.

    Science.gov (United States)

    Splettstoesser, Thomas; Holmes, Kenneth C; Noé, Frank; Smith, Jeremy C

    2011-07-01

    Actin is a major structural protein of the eukaryotic cytoskeleton and enables cell motility. Here, we present a model of the actin filament (F-actin) that not only incorporates the global structure of the recently published model by Oda et al. but also conserves internal stereochemistry. A comparison is made using molecular dynamics simulation of the model with other recent F-actin models. A number of structural determents such as the protomer propeller angle, the number of hydrogen bonds, and the structural variation among the protomers are analyzed. The MD comparison is found to reflect the evolution in quality of actin models over the last 6 years. In addition, simulations of the model are carried out in states with both ADP or ATP bound and local hydrogen-bonding differences characterized. Copyright © 2011 Wiley-Liss, Inc.

  12. 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

  13. 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

  14. Derivation of Distributed Models of Atomic Polarizability for Molecular Simulations.

    Science.gov (United States)

    Soteras, Ignacio; Curutchet, Carles; Bidon-Chanal, Axel; Dehez, François; Ángyán, János G; Orozco, Modesto; Chipot, Christophe; Luque, F Javier

    2007-11-01

    The main thrust of this investigation is the development of models of distributed atomic polarizabilities for the treatment of induction effects in molecular mechanics simulations. The models are obtained within the framework of the induced dipole theory by fitting the induction energies computed via a fast but accurate MP2/Sadlej-adjusted perturbational approach in a grid of points surrounding the molecule. Particular care is paid in the examination of the atomic quantities obtained from models of implicitly and explicitly interacting polarizabilities. Appropriateness and accuracy of the distributed models are assessed by comparing the molecular polarizabilities recovered from the models and those obtained experimentally and from MP2/Sadlej calculations. The behavior of the models is further explored by computing the polarization energy for aromatic compounds in the context of cation-π interactions and for selected neutral compounds in a TIP3P aqueous environment. The present results suggest that the computational strategy described here constitutes a very effective tool for the development of distributed models of atomic polarizabilities and can be used in the generation of new polarizable force fields.

  15. The Role of Molecular Modeling in TiO₂ Photocatalysis.

    Science.gov (United States)

    Cinar, Zekiye

    2017-03-30

    Molecular Modeling methods play a very important role in TiO₂ photocatalysis. Recent advances in TiO₂ photocatalysis have produced a number of interesting surface phenomena, reaction products, and various novel visible light active photocatalysts with improved properties. Quantum mechanical calculations appear promising as a means of describing the mechanisms and the product distributions of the photocatalytic degradation reactions of organic pollutants in both gas and aqueous phases. Since quantum mechanical methods utilize the principles of particle physics, their use may be extended to the design of new photocatalysts. This review introduces molecular modeling methods briefly and emphasizes the use of these methods in TiO₂ photocatalysis. The methods used for obtaining information about the degradabilities of the pollutant molecules, predicting reaction mechanisms, and evaluating the roles of the dopants and surface modifiers are explained.

  16. Genomic prediction and genomic variance partitioning of daily and residual feed intake in pigs using Bayesian Power Lasso models

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Janss, L. L. G.; Strathe, Anders Bjerring

    Improvement of feed efficiency is essential in pig breeding and selection for reduced residual feed intake (RFI) is an option. The study applied Bayesian Power LASSO (BPL) models with different power parameter to investigate genetic architecture, to predict genomic breeding values, and to partition...

  17. 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

  18. 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.

  19. Modelling the Molecular Transportation of Subcutaneously Injected Salubrinal

    OpenAIRE

    Andy Chen; Ping Zhang; Zhiyao Duan; Guofeng Wang; Hiroki Yokota

    2011-01-01

    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 ...

  20. 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

  1. Assessment of HRSC Digital Terrain Models Produced for the South Polar Residual Cap

    Science.gov (United States)

    Putri, Alfiah Rizky Diana; Sidiropoulos, Panagiotis; Muller, Jan-Peter

    2017-04-01

    The current Digital Terrain Models available for Mars consist of NASA MOLA (Mars Orbital Laser Altimeter) Digital Terrain Models with an average resolution of 112 m/ pixel (512 pixels/degree) for the polar region. The ESA/DLR High Resolution Stereo Camera is currently orbiting Mars and mapping its surface, 98% with resolution of ≤100 m/pixel and better and 100% at lower resolution [1]. It is possible to produce Digital Terrain Models from HRSC images using various methods. In this study, the method developed on Kim and Muller [2] which uses the VICAR open source program together with photogrammetry sofrware from DLR (Deutschen Zentrums für Luft- und Raumfahrt) with image matching based on the GOTCHA (Gruen-Otto-Chau) algorithm [3]. Digital Terrain Models have been processed over the South Pole with emphasis on areas around South Polar Residual Cap from High Resolution Stereo Camera images [4]. Digital Terrain Models have been produced for 31 orbits out of 149 polar orbits available. This study analyses the quality of the DTMs including an assessment of accuracy of elevations using the MOLA MEGDR (Mission Experiment Gridded Data Records) which has roughly 42 million MOLA PEDR (Precision Experiment Data Records) points between latitudes of 78 o -90 o S. The issues encountered in the production of Digital Terrain Models will be described and the statistical results and assessment method will be presented. The resultant DTMs will be accessible via http://i-Mars.eu/web-GIS References: [1] Neukum, G. et. al, 2004. Mars Express: The Scientific Payload pp. 17-35. [2] Kim, J.-R. and J.-P. Muller. 2009. PSS vol. 57, pp. 2095-2112. [3] Shin, D. and J.-P. Muller. 2012. Pattern Recognition, 45(10), 3795 -3809. [4] Putri, A.R. D., et al., Int. Arch. Photogramm. Remote Sens. Spatial Inf. Sci., XLI-B4, 463-469 Acknowledgements: The research leading to these results has received partial funding from the STFC "MSSL Consolidated Grant" ST/K000977/1 and partial support from the

  2. Classification and modelling of non-extractable residue (NER) formation from xenobiotics in soil - a synthesis

    Science.gov (United States)

    Kaestner, Matthias; Nowak, Karolina; Miltner, Anja; Trapp, Stefan; Schaeffer, Andreas

    2014-05-01

    This presentation provides a comprehensive overview about the formation of non-extractable residues (NER) from organic pesticides and contaminants in soil and tries classifying the different types. Anthropogenic organic chemicals are deliberately (e.g. pesticides) or unintentionally (e.g. polyaromatic hydrocarbons [PAH], chlorinated solvents, pharmaceuticals) released in major amounts to nearly all compartments of the environment. Soils and sediments as complex matrices provide a wide variety of binding sites and are the major sinks for these compounds. Many of the xenobiotics entering soil undergo turnover processes and can be volatilised, leached to the groundwater, degraded by microorganisms or taken up and enriched by living organisms. Xenobiotic NER may be derived from parent compounds and primary metabolites that are sequestered (sorbed or entrapped) within the soil organic matter (type I NER) or can be covalently bound (type II NER). Especially type I NER may pose a considerably environmental risk of potential release. However, NER resulting from productive biodegradation, which means the conversion of carbon (or nitrogen) from the compounds into microbial biomass molecules during microbial degradation (type III, bioNER), do not pose any risk. Experimental and analytical approaches to clearly distinguish between the types are provided and a model to prospectively estimate their fate in soil is proposed.

  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. 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

  5. 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

  6. 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.

  7. Energetics and efficiency of a molecular motor model

    OpenAIRE

    Fogedby, Hans C.; 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 with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor is addressed using a many body scheme with focus on the efficiency at maximum power (EMP). It is...

  8. 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.

  9. Study on residues of 14C-fenitrothion in model rice-fish ecosystem and field rice-fish ecosystem

    International Nuclear Information System (INIS)

    Zhang Zhongliang; Wang Huaxin; Guo Dazhi; Chen Zhiyu; wu Suqiong

    1994-01-01

    When equal amounts of the pesticide are applied, the extractable residues in brown rice (equivalent to 34.3 +- 1.9 μg/kg fenitrothion) and rice stems and leaves (20.9 +- 1.5 μg/kg) of the model rice-fish ecosystem are 10-15 times higher than those of the field rice-fish ecosystem (4.48 +- 0.13 μg/kg and 1.27 +- 0.34 μg/kg respectively). Residues in upper part of the soil (6.50 +- 0.1-8.10 +- 0.2 μg/kg) and lower part of the soil (1.30 +- 0.1-1.50 +- 0.1 μg/kg)of the model rice-fish ecosystem are 10-40 times higher than those of the field rice-fish ecosystem (0.17 +- 0.01 μg/kg). The extractable residues in paddy water of the model ecosystem (0.30 +- 0.01 μg/kg) are similar to that the the field ecosystem (0.20 +- 0.02 μg/kg). When the fenitrothion is sprayed on the rice plants, residues in brown rice, fish body, soil and paddy water are lower than those when the pesticide is sprayed on the surface of the soil

  10. Multi-scale Model of Residual Strength of 2D Plain Weave C/SiC Composites in Oxidation Atmosphere

    Science.gov (United States)

    Chen, Xihui; Sun, Zhigang; Sun, Jianfen; Song, Yingdong

    2017-02-01

    Multi-scale models play an important role in capturing the nonlinear response of woven carbon fiber reinforced ceramic matrix composites. In plain weave carbon fiber/silicon carbon (C/SiC) composites, the carbon fibers and interphases will be oxidized at elevated temperature and the strength of the composite will be degraded when oxygen enters micro-cracks formed in the as-produced parts due to the mismatch in thermal properties between constituents. As a result of the oxidation on fiber surface, fiber shows a notch-like morphology. In this paper, the change rule of fiber notch depth is fitted by circular function. And a multi-scale model based upon the change rule of fiber notch depth is developed to simulate the residual strength and post-oxidation stress-strain curves of the composite. The multi-scale model is able to accurately predict the residual strength and post-oxidation stress-strain curves of the composite. Besides, the simulated residual strength and post-oxidation stress-strain curves of 2D plain weave C/SiC composites in oxidation atmosphere show good agreements with experimental results. Furthermore, the oxidation time and temperature of the composite are investigated to show their influences upon the residual strength and post-oxidation stress-strain curves of plain weave C/SiC composites.

  11. Biological activities and molecular interactions of the C-terminal residue of thrombospondin-4, an epitome of acidic amphipathic peptides.

    Science.gov (United States)

    Congote, Luis F; Sadvakassova, Gulzhakhan; Dobocan, Monica C; Difalco, Marcos R; Kriazhev, Leonid

    2010-04-01

    C21, the C-terminal residue of thrombospondin-4 (TSP-4), was identified as a peptide growth factor during an investigation concerning erythropoietin-dependent, erythroid stimulating factors of endothelial origin. It is active in cultures of several human hematopoietic stem cells, skin fibroblasts and kidney epithelial cells and stimulates red cell formation in anemic mice. A method of affinity chromatography in the presence of high concentrations of Triton X-100, previously developed for identifying proteins associated with the TSP-1 receptor CD47, was utilized for the detection of C21 binding molecules and their detergent-resistant, associated partners. These experiments helped to delineate two different mechanisms of C21 action, which are compatible with its cell proliferating activity. As a cell matrix peptide, C21 binds to the osteopontin receptor CD44 and could act as an osteopontin antagonist, preventing the inhibition of primitive hematopoietic stem cell proliferation. TSP-1, another matrix protein, binds to C21 and could indirectly act as an antagonist, by shunting C21-CD44 interactions. The second mechanism is a direct effect of C21 on cell proliferation. The extremely rapid internalization and nuclear localization of the peptide could be explained by CD44-mediated internalization, followed by a microtubule-mediated transport towards the nucleus, or, eventually, direct membrane insertion. These alternative hypotheses are supported by previously observed membrane insertion of similar synthetic and viral acidic amphipathic peptides, the presence of microtubule-associated protein 1B (MAP1B) and dynactin in the triton-soluble complexes associated with C21 and the presence in such complexes of dual compartment proteins for nuclei and plasma membranes, such as MAP1B, AHNAK and CD44. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  12. Modeling of Prosthetic Limb Rotation Control by Sensing Rotation of Residual Arm Bone

    OpenAIRE

    Li, Guanglin; Kuiken, Todd A.

    2008-01-01

    We proposed a new approach to improve the control of prosthetic arm rotation in amputees. Arm rotation is sensed by implanting a small permanent magnet into the distal end of the residual bone, which produces a magnetic field. The position of the bone rotation can be derived from magnetic field distribution detected with magnetic sensors on the arm surface, and then conveyed to the prosthesis controller to manipulate the rotation of the prosthesis. Proprioception remains intact for residual l...

  13. G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations.

    Science.gov (United States)

    Isberg, Vignir; Balle, Thomas; Sander, Tommy; Jørgensen, Flemming Steen; Gloriam, David E

    2011-02-28

    A 5-HT(2A) receptor model was constructed by homology modeling based on the β(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(αq) peptide in four subsequent steered molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability of the activated receptor model as well as revealed new information about stabilizing residues and bonds. The active 5-HT(2A) receptor model was further validated by retrospective ligand screening of more than 9400 compounds, whereof 182 were known ligands. The results show that the model can be used in drug discovery for virtual screening and structure-based ligand design as well as in GPCR activation studies.

  14. 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.

  15. Coarse-Grained Modeling of Molecular Machines in AAA+ Family

    Science.gov (United States)

    Yoshimoto, Kenji; Brooks, Charles L., III

    2007-03-01

    We present a new coarse-grained model of the large protein complexes which belong to AAA+ (ATPase associated with diverse cellular activities) family. The AAA+ proteins are highly efficient molecular machines driven by the ATP (adenosine triphosphate) binding and hydrolysis and are involved in various cellular events. While a number of groups are developing various coarse-grained models for different AAA+ proteins, the molecular details of ATP binding and hydrolysis are often neglected. In this study, we provide a robust approach to coarse-graining both the AAA+ protein and the ATP (or ADP) molecules. By imposing the distance restraints between the phosphates of the ATP and the neighboring Cα of the proteins, which are used to conserve a typical motif of ATP binding pocket, we are able to predict large conformational changes of the AAA+ proteins, such as replicative hexameric helicases. In the case of the hexameric LTag (large tumor antigen), the backbone RMSD between the predicted ATP-bound structure and the X-ray structure is 1.2 å, and the RMSD between the predicted ADP-bound structure and the X-ray structure is 1.5 å. Using the same approach, we also investigate conformational changes in the hexameric E1 protein, whose X-ray structure was recently solved with ssDNA, and give some insights into the molecular mechanisms of DNA translocation.

  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. 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.

  19. Molecular Modeling Study for the Design of Novel Peroxisome Proliferator-Activated Receptor Gamma Agonists using 3D-QSAR and Molecular Docking.

    Science.gov (United States)

    Jian, Yaning; He, Yuyu; Yang, Jingjing; Han, Wei; Zhai, Xifeng; Zhao, Ye; Li, Yang

    2018-02-23

    Type 2 diabetes is becoming a global pandemic disease. As an important target for the generation and development of diabetes mellitus, peroxisome proliferator-activated receptor γ (PPARγ) has been widely studied. PPARγ agonists have been designed as potential anti-diabetic agents. The advanced development of PPARγ agonists represents a valuable research tool for diabetes therapy. To explore the structural requirements of PPARγ agonists, three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking studies were performed on a series of N -benzylbenzamide derivatives employing comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and surflex-dock techniques. The generated models of CoMFA and CoMSIA exhibited a high cross-validation coefficient ( q ²) of 0.75 and 0.551, and a non-cross-validation coefficient ( r ²) of 0.958 and 0.912, respectively. The predictive ability of the models was validated using external validation with predictive factor ( r ² pred ) of 0.722 and 0.682, respectively. These results indicate that the model has high statistical reliability and good predictive power. The probable binding modes of the best active compounds with PPARγ active site were analyzed, and the residues His323, Tyr473, Ser289 and Ser342 were found to have hydrogen bond interactions. Based on the analysis of molecular docking results, and the 3D contour maps generated from CoMFA and CoMSIA models, the key structural features of PPARγ agonists responsible for biological activity could be determined, and several new molecules, with potentially higher predicted activity, were designed thereafter. This work may provide valuable information in further optimization of N -benzylbenzamide derivatives as PPARγ agonists.

  20. 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.

  1. 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)

  2. Molecular model for solubility of gases in flexible polymers

    DEFF Research Database (Denmark)

    Neergaard, Jesper; Hassager, Ole; Szabo, Peter

    1999-01-01

    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......(dimethylsiloxane) reveals agreement between the data and the model predictions within a factor of 7 and that better model results are achieved for temperatures below the critical temperature of the gas. The model predicts a decreasing solubility with increasing temperature (because of the increasing vapor pressure......) and that smaller gas molecules exhibit a lower solubility than larger ones (e.g., CH4 has a smaller solubility than CO2), which agrees with the experimental data....

  3. 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.

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

    Science.gov (United States)

    Salleh, M S; Mazzoni, G; Höglund, J K; Olijhoek, D W; Lund, P; Løvendahl, P; Kadarmideen, H N

    2017-03-24

    The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-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 cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.

  5. Tridimensional model structure and patterns of molecular evolution of Pepino mosaic virus TGBp3 protein.

    Science.gov (United States)

    Hasiów-Jaroszewska, Beata; Czerwoniec, Anna; Pospieszny, Henryk; Elena, Santiago F

    2011-06-24

    Pepino mosaic virus (PepMV) is considered one of the most dangerous pathogens infecting tomatoes worldwide. The virus is highly diverse and four distinct genotypes, as well as inter-strain recombinants, have already been described. The isolates display a wide range on symptoms on infected plant species, ranging from mild mosaic to severe necrosis. However, little is known about the mechanisms and pattern of PepMV molecular evolution and about the role of individual proteins in host-pathogen interactions. The nucleotide sequences of the triple gene block 3 (TGB3) from PepMV isolates varying in symptomatology and geographic origin have been analyzed. The modes and patterns of molecular evolution of the TGBp3 protein were investigated by evaluating the selective constraints to which particular amino acid residues have been subjected during the course of diversification. The tridimensional structure of TGBp3 protein has been modeled de novo using the Rosetta algorithm. The correlation between symptoms development and location of specific amino acids residues was analyzed. The results have shown that TGBp3 has been evolving mainly under the action of purifying selection operating on several amino acid sites, thus highlighting its functional role during PepMV infection. Interestingly, amino acid 67, which has been previously shown to be a necrosis determinant, was found to be under positive selection. Identification of diverse selection events in TGB3p3 will help unraveling its biological functions and is essential to an understanding of the evolutionary constraints exerted on the Potexvirus genome. The estimated tridimensional structure of TGBp3 will serve as a platform for further sequence, structural and function analysis and will stimulate new experimental advances.

  6. Generalized Potential Energy Finite Elements for Modeling Molecular Nanostructures.

    Science.gov (United States)

    Chatzieleftheriou, Stavros; Adendorff, Matthew R; Lagaros, Nikos D

    2016-10-24

    The potential energy of molecules and nanostructures is commonly calculated in the molecular mechanics formalism by superimposing bonded and nonbonded atomic energy terms, i.e. bonds between two atoms, bond angles involving three atoms, dihedral angles involving four atoms, nonbonded terms expressing the Coulomb and Lennard-Jones interactions, etc. In this work a new, generalized numerical simulation is presented for studying the mechanical behavior of three-dimensional nanostructures at the atomic scale. The energy gradient and Hessian matrix of such assemblies are usually computed numerically; a potential energy finite element model is proposed herein where these two components are expressed analytically. In particular, generalized finite elements are developed that express the interactions among atoms in a manner equivalent to that invoked in simulations performed based on the molecular dynamics method. Thus, the global tangent stiffness matrix for any nanostructure is formed as an assembly of the generalized finite elements and is directly equivalent to the Hessian matrix of the potential energy. The advantages of the proposed model are identified in terms of both accuracy and computational efficiency. In the case of popular force fields (e.g., CHARMM), the computation of the Hessian matrix by implementing the proposed method is of the same order as that of the gradient. This analysis can be used to minimize the potential energy of molecular systems under nodal loads in order to derive constitutive laws for molecular systems where the entropy and solvent effects are neglected and can be approximated as solids, such as double stranded DNA nanostructures. In this context, the sequence dependent stretch modulus for some typical base pairs step is calculated.

  7. 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.

  8. Biomembrane modeling: molecular dynamics simulation of phospholipid monolayers

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, T.R.

    1979-01-01

    As a first step toward a computer model of a biomembrane-like bilayer, a dynamic, deterministric model of a phospholipid monolayer has been constructed. The model moves phospholipid-like centers of force according to an integrated law of motion in finite difference form. Forces on each phospholipid analogue are derived from the gradient of the local potential, itself the sum of Coulombic and short-range terms. The Coulombic term is approximated by use of a finite-difference form of Poisson's equation, while the short-range term results from finite-radius, pairwise summation of a Lennard-Jones potential. Boundary potentials are treated in such a way that the model is effectively infinite in extent in the plane of the monolayer. The two-dimensional virial theorem is used to find the surface pressure of the monolayer as a function of molecular area. Pressure-versus-area curves for simulated monolayers are compared to those of real monolayers. Dependence of the simulator's behavior on Lennard-Jones parameters and the specific geometry of the molecular analogue is discussed. Implications for the physical theory of phospholipid monolayers and bilayers are developed.

  9. Discrete model in the analysis of residual stresses in unidirectional winding cylinders made of fiber-reinforced plastic

    Directory of Open Access Journals (Sweden)

    Turusov Robert Alekseevich

    2015-01-01

    Full Text Available Today works in cosmos and at great sea depths are becoming very current. In order to execute these works tanks with great mass perfection are needed, which represents the relation of the product of pressure and inner volume to its mass. Usually such tanks are usually produced as a cocoon by winding methods, which can be automated. The simplest model of a cocoon is a cylinder with hemispheric blinds at the edges. The radial stresses arise in thick walled composite cylinders due to anisotropic thermal shrinkage during cooling process after curing. It also can lead to formation of radial cracks. The results of the analyses when a material is simplified to a homogenous orthotropic material show a very small residual radial stress value. In this paper we have used discrete model to evaluate residual radial stresses in thick-walled unidirectional filament wound cylinder and the results were compared to the results of homogenous orthotropic model.

  10. 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

    In the present paper, a numerical model consisting of a heat transfer analysis based on the Thermal Pseudo Mechanical (TPM) model for heat generation, and a sequentially coupled quasi-static stress analysis with a built-in metallurgical softening model was implemented in ABAQUS. Both isotropic...... 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...

  11. 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.}

  12. ATOMIC AND MOLECULAR PHYSICS: Modelling of a DNA packaging motor

    Science.gov (United States)

    Qian, Jun; Xie, Ping; Xue, Xiao-Guang; Wang, Peng-Ye

    2009-11-01

    During the assembly of many viruses, a powerful molecular motor packages the genome into a preassembled capsid. The Bacillus subtilis phage phi29 is an excellent model system to investigate the DNA packaging mechanism because of its highly efficient in vitro DNA packaging activity and the development of a single-molecule packaging assay. Here we make use of structural and biochemical experimental data to build a physical model of DNA packaging by the phi29 DNA packaging motor. Based on the model, various dynamic behaviours such as the packaging rate, pause frequency and slip frequency under different ATP concentrations, ADP concentrations, external loads as well as capsid fillings are studied by using Monte Carlo simulation. Good agreement is obtained between the simulated and available experimental results. Moreover, we make testable predictions that should guide future experiments related to motor function.

  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. Quantum Monte Carlo method for models of molecular nanodevices

    Science.gov (United States)

    Arrachea, Liliana; Rozenberg, Marcelo J.

    2005-07-01

    We introduce a quantum Monte Carlo technique to calculate exactly at finite temperatures the Green function of a fermionic quantum impurity coupled to a bosonic field. While the algorithm is general, we focus on the single impurity Anderson model coupled to a Holstein phonon as a schematic model for a molecular transistor. We compute the density of states at the impurity in a large range of parameters, to demonstrate the accuracy and efficiency of the method. We also obtain the conductance of the impurity model and analyze different regimes. The results show that even in the case when the effective attractive phonon interaction is larger than the Coulomb repulsion, a Kondo-like conductance behavior might be observed.

  15. Exploring the multiscale signaling behavior of phototropin1 from Chlamydomonas reinhardtii using a full-residue space kinetic Monte Carlo molecular dynamics technique.

    Science.gov (United States)

    Peter, Emanuel; Dick, Bernhard; Stambolic, Ivan; Baeurle, Stephan A

    2014-09-01

    Devising analysis tools for elucidating the regulatory mechanism of complex enzymes has been a challenging task for many decades. It generally requires the determination of the structural-dynamical information of protein solvent systems far from equilibrium over multiple length and time scales, which is still difficult both theoretically and experimentally. To cope with the problem, we introduce a full-residue space multiscale simulation method based on a combination of the kinetic Monte Carlo and molecular dynamics techniques, in which the rates of the rate-determining processes are evaluated from a biomolecular forcefield on the fly during the simulation run by taking into account the full space of residues. To demonstrate its reliability and efficiency, we explore the light-induced functional behavior of the full-length phototropin1 from Chlamydomonas reinhardtii (Cr-phot1) and its various subdomains. Our results demonstrate that in the dark state the light oxygen voltage-2-Jα (LOV2-Jα) photoswitch inhibits the enzymatic activity of the kinase, whereas the LOV1-Jα photoswitch controls the dimerization with the LOV2 domain. This leads to the repulsion of the LOV1-LOV2 linker out of the interface region between both LOV domains, which results in a positively charged surface suitable for cell-membrane interaction. By contrast, in the light state, we observe that the distance between both LOV domains is increased and the LOV1-LOV2 linker forms a helix-turn-helix (HTH) motif, which enables gene control through nucleotide binding. Finally, we find that the kinase is activated through the disruption of the Jα-helix from the LOV2 domain, which is followed by a stretching of the activation loop (A-loop) and broadening of the catalytic cleft of the kinase. © 2014 Wiley Periodicals, Inc.

  16. 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.

  17. Molecular mechanisms of isocitrate dehydrogenase 1 (IDH1) mutations identified in tumors: The role of size and hydrophobicity at residue 132 on catalytic efficiency.

    Science.gov (United States)

    Avellaneda Matteo, Diego; Grunseth, Adam J; Gonzalez, Eric R; Anselmo, Stacy L; Kennedy, Madison A; Moman, Precious; Scott, David A; Hoang, An; Sohl, Christal D

    2017-05-12

    Isocitrate dehydrogenase 1 (IDH1) catalyzes the reversible NADP + -dependent conversion of isocitrate (ICT) to α-ketoglutarate (αKG) in the cytosol and peroxisomes. Mutations in IDH1 have been implicated in >80% of lower grade gliomas and secondary glioblastomas and primarily affect residue 132, which helps coordinate substrate binding. However, other mutations found in the active site have also been identified in tumors. IDH1 mutations typically result in a loss of catalytic activity, but many also can catalyze a new reaction, the NADPH-dependent reduction of αKG to d-2-hydroxyglutarate (D2HG). D2HG is a proposed oncometabolite that can competitively inhibit αKG-dependent enzymes. Some kinetic parameters have been reported for several IDH1 mutations, and there is evidence that mutant IDH1 enzymes vary widely in their ability to produce D2HG. We report that most IDH1 mutations identified in tumors are severely deficient in catalyzing the normal oxidation reaction, but that D2HG production efficiency varies among mutant enzymes up to ∼640-fold. Common IDH1 mutations have moderate catalytic efficiencies for D2HG production, whereas rarer mutations exhibit either very low or very high efficiencies. We then designed a series of experimental IDH1 mutants to understand the features that support D2HG production. We show that this new catalytic activity observed in tumors is supported by mutations at residue 132 that have a smaller van der Waals volume and are more hydrophobic. We report that one mutation can support both the normal and neomorphic reactions. These studies illuminate catalytic features of mutations found in the majority of patients with lower grade gliomas. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. 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.

  19. 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.

  20. 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.)

  1. Prediction of hydrodynamic and other solution properties of rigid proteins from atomic- and residue-level models.

    Science.gov (United States)

    Ortega, A; Amorós, D; García de la Torre, J

    2011-08-17

    Here we extend the ability to predict hydrodynamic coefficients and other solution properties of rigid macromolecular structures from atomic-level structures, implemented in the computer program HYDROPRO, to models with lower, residue-level resolution. Whereas in the former case there is one bead per nonhydrogen atom, the latter contains one bead per amino acid (or nucleotide) residue, thus allowing calculations when atomic resolution is not available or coarse-grained models are preferred. We parameterized the effective hydrodynamic radius of the elements in the atomic- and residue-level models using a very large set of experimental data for translational and rotational coefficients (intrinsic viscosity and radius of gyration) for >50 proteins. We also extended the calculations to very large proteins and macromolecular complexes, such as the whole 70S ribosome. We show that with proper parameterization, the two levels of resolution yield similar and rather good agreement with experimental data. The new version of HYDROPRO, in addition to considering various computational and modeling schemes, is far more efficient computationally and can be handled with the use of a graphical interface. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Preparation, characterization and molecular modeling of PEGylated human growth hormone with agonist activity.

    Science.gov (United States)

    Khameneh, Bahman; Jaafari, Mahmoud Reza; Hassanzadeh-Khayyat, Mohammad; Varasteh, AbdolReza; Chamani, JamshidKhan; Iranshahi, Mehrdad; Mohammadpanah, Hamid; Abnous, Khalil; Saberi, Mohammad Reza

    2015-09-01

    In this study, site-specific PEGylated human growth hormone (hGH) was prepared by microbial transglutaminase, modeled and characterized. To this end, the effects of different reaction parameters including reaction media, PEG:protein ratios, reaction time and pH value were investigated. PEG-hGH was purified by size exclusion chromatography method and analyzed by SDS-PAGE, BCA, peptide mapping, ESI and MALDI-TOF-TOF mass spectroscopy methods. Biophysical and biological properties of PEG-hGH were evaluated. Molecular simulation was utilized to provide molecular insight into the protein-receptor interaction. The optimum conditions that were obtained for PEGylation were phosphate buffer with pH of 7.4, 48 h of stirring and PEG:protein ratio of 40:1. By this method, mono-PEG-hGH with high reaction yield was obtained and PEGylation site was at Gln-40 residue. The circular dichroism and fluorescence spectrum indicated that PEGylation did not change the secondary structure while tertiary structure was altered. Upon enzymatic PEGylation, agonistic activity of hGH was preserved; however, Somavert(®), which is prepared by chemical PEGylation, is an antagonist form of protein. These data were confirmed by the total energy of affinity obtained by computational protein-receptor interaction. In conclusion, PEGylation of hGH was led to prepare a novel form of hormone with an agonist activity which merits further investigations. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 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.

  4. RESIDUAL RISK ASSESSMENTS - RESIDUAL RISK ...

    Science.gov (United States)

    This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Coke Ovens. These assesments utilize existing models and data bases to examine the multi-media and multi-pollutant impacts of air toxics emissions on human health and the environment. Details on the assessment process and methodologies can be found in EPA's Residual Risk Report to Congress issued in March of 1999 (see web site). To assess the health risks imposed by air toxics emissions from Coke Ovens to determine if control technology standards previously established are adequately protecting public health.

  5. 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

  6. 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...

  7. 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

  8. Hepatocytes Contribute to Residual Glucose Production in a Mouse Model for Glycogen Storage Disease Type Ia

    NARCIS (Netherlands)

    Hijmans, Brenda S.; Boss, Andreas; van Dijk, Theo H.; Soty, Maud; Wolters, Henk; Mutel, Elodie; Groen, Albert K.; Derks, Terry G. J.; Mithieux, Gilles; Heerschap, Arend; Reijngoud, Dirk-Jan; Rajas, Fabienne; Oosterveer, Maaike H.

    2017-01-01

    It is a long-standing enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production despite the loss of glucose-6-phosphatase activity. Insight into the source of residual endogenous glucose production is of clinical importance given the risk

  9. 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

  10. A molecular model for epsilon-caprolactam-based intercalated polymer clay nanocomposite: Integrating modeling and experiments.

    Science.gov (United States)

    Sikdar, Debashis; Katti, Dinesh R; Katti, Kalpana S

    2006-08-29

    In studying the morphology, molecular interactions, and physical properties of organically modified montmorillonite (OMMT) and polymer clay nanocomposites (PCNs) through molecular dynamics (MD), the construction of the molecular model of OMMT and PCN is important. Better understanding of interaction between various constituents of PCN will improve the design of polymer clay nanocomposite systems. MD is an excellent tool to study interactions, which require accurate modeling of PCN under consideration. Previously, the PCN models were constructed by different researchers on the basis of specific criteria such as minimum energy configuration, density of the polymer clay nanocomposite, and so forth. However, in this article we describe the development of models combining experimental and conventional molecular modeling to develop models, which are more representative of true intercalated PCN systems. The models were used for studying the morphological interactions and physical properties. These studies gave useful information regarding orientation of organic modifiers, area of coverage of organic modifiers over the interlayer clay surface, interaction of organic modifiers with clay in OMMT, interaction among different constituents of PCN, conformational and density change, and actual proportion of mixing of polymer with clay in PCN. We have X-ray diffraction and photoacoustic Fourier transform infrared spectroscopy to verify the model.

  11. Understanding molecular interactions between scavenger receptor A and its natural product inhibitors through molecular modeling studies.

    Science.gov (United States)

    Pagare, Piyusha P; Zaidi, Saheem A; Zhang, Xiaomei; Li, Xia; Yu, Xiaofei; Wang, Xiang-Yang; Zhang, Yan

    2017-10-01

    Scavenger receptor A (SRA), as an immune regulator, has been shown to play important roles in lipid metabolism, cardiovascular diseases, and pathogen recognition. Several natural product inhibitors of SRA have been studied for their potential application in modulating SRA functions. To understand the binding mode of these inhibitors on SRA, we conducted systematic molecular modeling studies in order to identify putative binding domain(s) that may be responsible for their recognition to the receptor as well as their inhibitory activity. Treatment of SRA with one of the natural product inhibitors, rhein, led to significant dissociation of SRA oligomers to its trimer and dimer forms, which further supported our hypothesis on their putative mechanism of action. Such information is believed to shed light on design of more potent inhibitors for the receptor in order to develop potential therapeutics through immune system modulation. Published by Elsevier Inc.

  12. Modelling interacting molecular motors with an internal degree of freedom

    Science.gov (United States)

    Pinkoviezky, Itai; Gov, Nir S.

    2013-02-01

    The mechanisms underlying the collective motion of molecular motors in living cells are not yet fully understood. One such open puzzle is the observed pulses of backward-moving myosin-X in the filopodia structure. Motivated by this phenomenon we introduce two generalizations of the ‘total asymmetric exclusion process’ (TASEP) that might be relevant to the formation of such pulses. The first is adding a nearest-neighbours attractive interaction between motors, while the second is adding an internal degree of freedom corresponding to a processive and immobile form of the motors. Switching between the two states occurs stochastically, without a conservation law. Both models show strong deviations from the mean field behaviour and lack particle-hole symmetry. We use approximations borrowed from the research on vehicular traffic models to calculate the current and jam size distribution in a system with periodic boundary conditions and introduce a novel modification to one of these approximation schemes.

  13. Modelling interacting molecular motors with an internal degree of freedom

    International Nuclear Information System (INIS)

    Pinkoviezky, Itai; Gov, Nir S

    2013-01-01

    The mechanisms underlying the collective motion of molecular motors in living cells are not yet fully understood. One such open puzzle is the observed pulses of backward-moving myosin-X in the filopodia structure. Motivated by this phenomenon we introduce two generalizations of the ‘total asymmetric exclusion process’ (TASEP) that might be relevant to the formation of such pulses. The first is adding a nearest-neighbours attractive interaction between motors, while the second is adding an internal degree of freedom corresponding to a processive and immobile form of the motors. Switching between the two states occurs stochastically, without a conservation law. Both models show strong deviations from the mean field behaviour and lack particle–hole symmetry. We use approximations borrowed from the research on vehicular traffic models to calculate the current and jam size distribution in a system with periodic boundary conditions and introduce a novel modification to one of these approximation schemes. (paper)

  14. Energetics and efficiency of a molecular motor model

    DEFF Research Database (Denmark)

    Fogedby, Hans C.; 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...... with coupled master equations for the ATP hydrolysis. Here the energetics and efficiency of the motor is 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 pct 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....

  15. 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.

  16. 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.

  17. Molecular Dynamics Simulations and Structural Analysis to Decipher Functional Impact of a Twenty Residue Insert in the Ternary Complex of Mus musculus TdT Isoform.

    Science.gov (United States)

    Mutt, Eshita; Sowdhamini, Ramanathan

    2016-01-01

    Insertions/deletions are common evolutionary tools employed to alter the structural and functional repertoire of protein domains. An insert situated proximal to the active site or ligand binding site frequently impacts protein function; however, the effect of distal indels on protein activity and/or stability are often not studied. In this paper, we have investigated a distal insert, which influences the function and stability of a unique DNA polymerase, called terminal deoxynucleotidyl transferase (TdT). TdT (EC:2.7.7.31) is a monomeric 58 kDa protein belonging to family X of eukaryotic DNA polymerases and known for its role in V(D)J recombination as well as in non-homologous end-joining (NHEJ) pathways. Two murine isoforms of TdT, with a length difference of twenty residues and having different biochemical properties, have been studied. All-atom molecular dynamics simulations at different temperatures and interaction network analyses were performed on the short and long-length isoforms. We observed conformational changes in the regions distal to the insert position (thumb subdomain) in the longer isoform, which indirectly affects the activity and stability of the enzyme through a mediating loop (Loop1). A structural rationale could be provided to explain the reduced polymerization rate as well as increased thermosensitivity of the longer isoform caused by peripherally located length variations within a DNA polymerase. These observations increase our understanding of the roles of length variants in introducing functional diversity in protein families in general.

  18. Simulation of balloon angioplasty in residually stressed blood vessels-Application of a gradient-enhanced fibre damage model.

    Science.gov (United States)

    Polindara, César; Waffenschmidt, Tobias; Menzel, Andreas

    2016-08-16

    In this contribution we study the balloon angioplasty in a residually stressed artery by means of a non-local gradient-enhanced fibre damage model. The balloon angioplasty is a common surgical intervention used to extend or reopen narrowed blood vessels in order to restore the continuous blood flow in, for instance, atherosclerotic arteries. Inelastic, i.e. predominantly damage-related and elastoplastic processes are induced in the artery during its inflation resulting in an irreversible deformation. As a beneficial consequence, provided that the inelastic deformations do not exceed a specific limit, higher deformations can be obtained within the same pressure level and a continuous blood flow can be guaranteed. In order to study the mechanical response of the artery in this scenario, we make use of the non-local gradient-enhanced model proposed in Waffenschmidt et al. (2014). In this contribution, we extend this model to make use of an incompressible format in connection with a Q1Q1P0 finite element implementation. The residual stresses in the artery are also taken into account following the framework presented in Waffenschmidt (2015). From the results it becomes apparent that, when the artery is subjected to radial stresses beyond the physiological range, damage evolution is triggered in the collagen fibres. The impact of the residual stresses on the structural response and on the circumferential stress distribution along the thickness of the arterial wall is also studied. It is observed that the residual stresses have a beneficial effect on the mechanical response of the arterial wall. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Insights into cytochrome bc 1 complex binding mode of antimalarial 2-hydroxy-1,4-naphthoquinones through molecular modelling

    Science.gov (United States)

    Sodero, Ana Carolina Rennó; Abrahim-Vieira, Bárbara; Torres, Pedro Henrique Monteiro; Pascutti, Pedro Geraldo; Garcia, Célia RS; Ferreira, Vitor Francisco; da Rocha, David Rodrigues; Ferreira, Sabrina Baptista; Silva, Floriano Paes

    2017-01-01

    BACKGROUND Malaria persists as a major public health problem. Atovaquone is a drug that inhibits the respiratory chain of Plasmodium falciparum, but with serious limitations like known resistance, low bioavailability and high plasma protein binding. OBJECTIVES The aim of this work was to perform molecular modelling studies of 2-hydroxy-1,4-naphthoquinones analogues of atovaquone on the Qo site of P. falciparum cytochrome bc 1 complex (Pfbc1) to suggest structural modifications that could improve their antimalarial activity. METHODS We have built the homology model of the cytochrome b (CYB) and Rieske iron-sulfur protein (ISP) subunits from Pfbc1 and performed the molecular docking of 41 2-hydroxy-1,4-naphthoquinones with known in vitro antimalarial activity and predicted to act on this target. FINDINGS Results suggest that large hydrophobic R2 substituents may be important for filling the deep hydrophobic Qo site pocket. Moreover, our analysis indicates that the H-donor 2-hydroxyl group may not be crucial for efficient binding and inhibition of Pfbc1 by these atovaquone analogues. The C1 carbonyl group (H-acceptor) is more frequently involved in the important hydrogen bonding interaction with His152 of the Rieske ISP subunit. MAIN CONCLUSIONS Additional interactions involving residues such as Ile258 and residues required for efficient catalysis (e.g., Glu261) could be explored in drug design to avoid development of drug resistance by the parasite. PMID:28327793

  20. In-situ observation of dislocation and analysis of residual stresses by FEM/DDM modeling in water cavitation peening of pure titanium

    Science.gov (United States)

    Y Ju, D.; Han, B.

    2015-04-01

    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.

  1. 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

  2. Degradation of cefquinome in spiked milk as a model for bioremediation of dairy farm waste milk containing cephalosporin residues.

    Science.gov (United States)

    Horton, R A; Randall, L P; Bailey-Horne, V; Heinrich, K; Sharman, M; Brunton, L A; La Ragione, R M; Jones, J R

    2015-04-01

    The aims of this work were to develop a model of dairy farm waste milk and to investigate methods for the bioremediation of milk containing cefquinome residues. Unpasteurized milk and UHT milk that had both been spiked with cefquinome at a concentration of 2 μg ml(-1) were used as a model for waste milk containing cephalosporin residues. Adjustment of the spiked UHT milk to pH 10 or treatment with conditioned medium from bacterial growth producing cefotaximase, were the most effective methods for decreasing the cefquinome concentrations within 24 h. A large-scale experiment (10 l of cefquinome-spiked unpasteurized milk) suggested that fermentation for 22 h at 37°C followed by heating at 60°C for 2 h was sufficient to decrease cefquinome concentrations to below the limit of quantification (milk. Treatment of waste milk to decrease cephalosporin residue concentrations and also to kill bacteria prior to feeding to dairy calves could decrease the risk of selection for ESBL bacteria on dairy farms. © 2015 Crown copyright. Journal of Applied Microbiology © 2015 The Society for Applied Microbiology. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

  3. 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

    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...... is the first in a two-paper series describing contaminant transport at a waste residue site. III the second paper, reactive transport at the site is investigated....

  4. Genomic dissection and prediction of feed intake and residual feed intake traits using a longitudinal model in F2 chickens

    DEFF Research Database (Denmark)

    Begli, Hakimeh Emamgholi; Torshizi, Rasoul vaez; Masoudi, Ali Akbar

    2017-01-01

    -density single nucleotide polymorphism (S N P ) genotypes , a nd to conduct a GWA study on longitudinal FI and residual feed intake (RFI) in a tot al of 312 chick ens with phenotype and genotype in the F 2 population. The GWA and GS studies reported in this pap er were conducted using β-spline random regression......Feed efficiency trait s (FETs) ar e import ant economic indicators in poultry production. Because feed intake (FI) is a time -dependent variable, longitudinal models can provide insights into the genetic basis of FET variation over time. It is expected that the application of longitudinal models...

  5. 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.

  6. 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.

  7. 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

  8. Multiscale modeling for materials design: Molecular square catalysts

    Science.gov (United States)

    Majumder, Debarshi

    In a wide variety of materials, including a number of heterogeneous catalysts, the properties manifested at the process scale are a consequence of phenomena that occur at different time and length scales. Recent experimental developments allow materials to be designed precisely at the nanometer scale. However, the optimum design of such materials requires capabilities to predict the properties at the process scale based on the phenomena occurring at the relevant scales. The thesis research reported here addresses this need to develop multiscale modeling strategies for the design of new materials. As a model system, a new system of materials called molecular squares was studied in this research. Both serial and parallel multiscale strategies and their components were developed as parts of this work. As a serial component, a parameter estimation tool was developed that uses a hierarchical protocol and consists of two different search elements: a global search method implemented using a genetic algorithm that is capable of exploring large parametric space, and a local search method using gradient search techniques that accurately finds the optimum in a localized space. As an essential component of parallel multiscale modeling, different standard as well as specialized computational fluid dynamics (CFD) techniques were explored and developed in order to identify a technique that is best suited to solve a membrane reactor model employing layered films of molecular squares as the heterogeneous catalyst. The coupled set of non-linear partial differential equations (PDEs) representing the continuum model was solved numerically using three different classes of methods: a split-step method using finite difference (FD); domain decomposition in two different forms, one involving three overlapping subdomains and the other involving a gap-tooth scheme; and the multiple-timestep method that was developed in this research. The parallel multiscale approach coupled continuum

  9. 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.

  10. 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

  11. 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)

  12. 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...

  13. 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

  14. Structural model of a putrescine-cadaverine permease from Trypanosoma cruzi predicts residues vital for transport and ligand binding.

    Science.gov (United States)

    Soysa, Radika; Venselaar, Hanka; Poston, Jacqueline; Ullman, Buddy; Hasne, Marie-Pierre

    2013-06-15

    The TcPOT1.1 gene from Trypanosoma cruzi encodes a high affinity putrescine-cadaverine transporter belonging to the APC (amino acid/polyamine/organocation) transporter superfamily. No experimental three-dimensional structure exists for any eukaryotic member of the APC family, and thus the structural determinants critical for function of these permeases are unknown. To elucidate the key residues involved in putrescine translocation and recognition by this APC family member, a homology model of TcPOT1.1 was constructed on the basis of the atomic co-ordinates of the Escherichia coli AdiC arginine/agmatine antiporter crystal structure. The TcPOT1.1 homology model consisted of 12 transmembrane helices with the first ten helices organized in two V-shaped antiparallel domains with discontinuities in the helical structures of transmembrane spans 1 and 6. The model suggests that Trp241 and a Glu247-Arg403 salt bridge participate in a gating system and that Asn245, Tyr148 and Tyr400 contribute to the putrescine-binding pocket. To test the validity of the model, 26 site-directed mutants were created and tested for their ability to transport putrescine and to localize to the parasite cell surface. These results support the robustness of the TcPOT1.1 homology model and reveal the importance of specific aromatic residues in the TcPOT1.1 putrescine-binding pocket.

  15. 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.

  16. 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

  17. Yeast models of Parkinson's disease-associated molecular pathologies.

    Science.gov (United States)

    Tenreiro, Sandra; Franssens, Vanessa; Winderickx, Joris; Outeiro, Tiago Fleming

    2017-06-01

    The aging of the human population is resulting in an increase in the number of people afflicted by neurodegenerative disorders such as Parkinson's disease (PD), creating tremendous socio-economic challenges. This requires the urgent for the development of effective therapies, and of tools for early diagnosis of the disease. However, our understanding of the molecular mechanisms underlying PD pathogenesis is still incomplete, hampering progress in those areas. In recent years, the progression made in genetics has considerably contributed to our knowledge, by identifying several novel PD genes. Furthermore, many cellular and animal models have proven their value to decipher pathways involved in PD development. In this review we highlight the value of the yeast Saccharomyces cerevisiae as a model for PD. This unicellular eukaryote has contributed to our understanding of the cellular mechanisms targeted by most important PD genes and offers an excellent tool for discovering novel players via powerful and informative high throughput screens that accelerate further validation in more complex models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Modeling Carbon and Hydrocarbon Molecular Structures in EZTB

    Science.gov (United States)

    Lee, Seungwon; vonAllmen, Paul

    2007-01-01

    A software module that models the electronic and mechanical aspects of hydrocarbon molecules and carbon molecular structures on the basis of first principles has been written for incorporation into, and execution within, the Easy (Modular) Tight-Binding (EZTB) software infrastructure, which is summarized briefly in the immediately preceding article. Of particular interest, this module can model carbon crystals and nanotubes characterized by various coordinates and containing defects, without need to adjust parameters of the physical model. The module has been used to study the changes in electronic properties of carbon nanotubes, caused by bending of the nanotubes, for potential utility as the basis of a nonvolatile, electriccharge- free memory devices. For example, in one application of the module, it was found that an initially 50-nmlong carbon, (10,10)-chirality nanotube, which is a metallic conductor when straight, becomes a semiconductor with an energy gap of .3 meV when bent to a lateral displacement of 4 nm at the middle.

  19. Quantitative prediction of residual wetting film generated in mobilizing a two-phase liquid in a capillary model

    Directory of Open Access Journals (Sweden)

    Harsh Joshi

    2015-12-01

    Full Text Available This research studies the motion of immiscible two-phase liquid flow in a capillary tube through a numerical approach employing the volume of fluid method, for simulating the core-annular flow and water flooding in oil reservoirs of porous media. More specifically, the simulations are a representation of water flooding at a pore scale. A capillary tube model is established with ANSYS Fluent and verified. The numerical results matches well with the existing data available in the literature. Penetration of a less viscous liquid in a liquid of higher viscosity and the development of a residual wetting film of the higher viscosity liquid are thoroughly investigated. The effects of Capillary number, Reynolds Number and Viscosity ratio on the residual wetting film are studied in detail, as the thickness is directly related to the residual oil left in the porous media after water flooding. It should be noticed that the liquids considered in this research can be any liquids of different viscosity not necessarily oil and water. The results of this study can be used as guidance in the field of water flooding.

  20. Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.

    Science.gov (United States)

    Bhaskara, Ramachandra M; Padhi, Amrita; Srinivasan, Narayanaswamy

    2014-07-01

    With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. © 2013 Wiley Periodicals, Inc.

  1. 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.

  2. 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

  3. 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.

  4. Probing the conformation of FhaC with small-angle neutron scattering and molecular modeling.

    Science.gov (United States)

    Gabel, Frank; Lensink, Marc F; Clantin, Bernard; Jacob-Dubuisson, Françoise; Villeret, Vincent; Ebel, Christine

    2014-07-01

    Probing the solution structure of membrane proteins represents a formidable challenge, particularly when using small-angle scattering. Detergent molecules often present residual scattering contributions even at their match point in small-angle neutron scattering (SANS) measurements. Here, we studied the conformation of FhaC, the outer-membrane, β-barrel transporter of the Bordetella pertussis filamentous hemagglutinin adhesin. SANS measurements were performed on homogeneous solutions of FhaC solubilized in n-octyl-d17-βD-glucoside and on a variant devoid of the α helix H1, which critically obstructs the FhaC pore, in two solvent conditions corresponding to the match points of the protein and the detergent, respectively. Protein-bound detergent amounted to 142 ± 10 mol/mol as determined by analytical ultracentrifugation. By using molecular modeling and starting from three distinct conformations of FhaC and its variant embedded in lipid bilayers, we generated ensembles of protein-detergent arrangement models with 120-160 detergent molecules. The scattered curves were back-calculated for each model and compared with experimental data. Good fits were obtained for relatively compact, connected detergent belts, which occasionally displayed small detergent-free patches on the outer surface of the β barrel. The combination of SANS and modeling clearly enabled us to infer the solution structure of FhaC, with H1 inside the pore as in the crystal structure. We believe that our strategy of combining explicit atomic detergent modeling with SANS measurements has significant potential for structural studies of other detergent-solubilized membrane proteins. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Molecular modeling and structural characterization of a high glycine-tyrosine hair keratin associated protein.

    Science.gov (United States)

    Singh, Rakesh S; Palmer, Jeremy C; Pudney, Paul D A; Paul, Prem K C; Johannessen, Christian; Debenedetti, Pablo G; Raut, Janhavi; Lee, Ken; Noro, Massimo; Tiemessen, David

    2017-03-22

    High glycine-tyrosine (HGT) proteins are an important constituent of the keratin associated proteins (KAPs) present in human hair. The glassy state physics of hair fibres are thought to be largely regulated by KAPs, which exist in an amorphous state and are readily affected by environmental conditions. However, there are no studies characterizing the individual KAPs. In this paper, we present the first step to fill this gap by computational modeling and experimental studies on a HGT protein, KAP8.1. In particular, we have modeled the three-dimensional structure of this 63-residue protein using homology information from an anti-freeze protein in snow flea. The model for KAP8.1 is characterized by four strands of poly-proline II (or PPII) type helical secondary structures, held together by two cysteine disulphide bridges. Computer simulations confirm the stability of the modelled structure and show that the protein largely samples the PPII and β-sheet conformations during the molecular dynamics simulations. Spectroscopic studies including Raman, IR and vibrational circular dichroism have also been performed on synthesized KAP8.1. The experimental studies suggest that KAP8.1 is characterised by β-sheet and PPII structures, largely consistent with the simulation studies. The model built in this work is a good starting point for further simulations to study in greater depth the glassy state physics of hair, including its water sorption isotherms, glass transition, and the effect of HGT proteins on KAP matrix plasticization. These results are a significant step towards our goal of understanding how the properties of hair can be affected and manipulated under different environmental conditions of temperature, humidity, ageing and small molecule additives.

  6. 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.

  7. pKa determination of histidine residues in α-conotoxin MII peptides by 1H NMR and constant pH molecular dynamics simulation.

    Science.gov (United States)

    McDougal, Owen M; Granum, David M; Swartz, Mark; Rohleder, Conrad; Maupin, C Mark

    2013-03-07

    α-Conotoxin MII (α-CTxMII) is a potent and selective peptide antagonist of neuronal nicotinic acetylcholine receptors (nAChR's). Studies have shown that His9 and His12 are significant determinants of toxin binding affinity for nAChR, while Glu11 may dictate differential toxin affinity between nAChR isoforms. The protonation state of these histidine residues and therefore the charge on the α-CTx may contribute to the observed differences in binding affinity and selectivity. In this study, we assess the pH dependence of the protonation state of His9 and His12 by (1)H NMR spectroscopy and constant pH molecular dynamics (CpHMD) in α-CTxMII, α-CTxMII[E11A], and the triple mutant, α-CTxMII[N5R:E11A:H12K]. The E11A mutation does not significantly perturb the pKa of His9 or His12, while N5R:E11A:H12K results in a significant decrease in the pKa value of His9. The pKa values predicted by CpHMD simulations are in good agreement with (1)H NMR spectroscopy, with a mean absolute deviation from experiment of 0.3 pKa units. These results support the use of CpHMD as an efficient and inexpensive predictive tool to determine pKa values and structural features of small peptides critical to their function.

  8. Molecular Dynamics Simulations and Structural Analysis to Decipher Functional Impact of a Twenty Residue Insert in the Ternary Complex of Mus musculus TdT Isoform.

    Directory of Open Access Journals (Sweden)

    Eshita Mutt

    Full Text Available Insertions/deletions are common evolutionary tools employed to alter the structural and functional repertoire of protein domains. An insert situated proximal to the active site or ligand binding site frequently impacts protein function; however, the effect of distal indels on protein activity and/or stability are often not studied. In this paper, we have investigated a distal insert, which influences the function and stability of a unique DNA polymerase, called terminal deoxynucleotidyl transferase (TdT. TdT (EC:2.7.7.31 is a monomeric 58 kDa protein belonging to family X of eukaryotic DNA polymerases and known for its role in V(DJ recombination as well as in non-homologous end-joining (NHEJ pathways. Two murine isoforms of TdT, with a length difference of twenty residues and having different biochemical properties, have been studied. All-atom molecular dynamics simulations at different temperatures and interaction network analyses were performed on the short and long-length isoforms. We observed conformational changes in the regions distal to the insert position (thumb subdomain in the longer isoform, which indirectly affects the activity and stability of the enzyme through a mediating loop (Loop1. A structural rationale could be provided to explain the reduced polymerization rate as well as increased thermosensitivity of the longer isoform caused by peripherally located length variations within a DNA polymerase. These observations increase our understanding of the roles of length variants in introducing functional diversity in protein families in general.

  9. 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...

  10. Modelling tide-driven currents and residual eddies in the Gulf of Kachchh and their seasonal variability: A marine environmental planning perspective

    Digital Repository Service at National Institute of Oceanography (India)

    Babu, M.T.; Vethamony, P.; Desa, E.

    -monsoon transition. Irregular topography of the western gulf slows down the tidal wave propagation and induces a phase shift. Tidal residual currents computed from the model results exhibit the presence of three eddies in the western gulf. The tide...

  11. Residual tumour detection in post-treatment granulation tissue by using advanced diffusion models in head and neck squamous cell carcinoma patients.

    Science.gov (United States)

    Fujima, Noriyuki; Yoshida, Daisuke; Sakashita, Tomohiro; Homma, Akihiro; Kudo, Kohsuke; Shirato, Hiroki

    2017-05-01

    To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0-1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (D s ) obtained by the SDM. The multivariate analysis revealed that the D s and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour. DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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

  13. 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.

  14. Residuation theory

    CERN Document Server

    Blyth, T S; Sneddon, I N; Stark, M

    1972-01-01

    Residuation Theory aims to contribute to literature in the field of ordered algebraic structures, especially on the subject of residual mappings. The book is divided into three chapters. Chapter 1 focuses on ordered sets; directed sets; semilattices; lattices; and complete lattices. Chapter 2 tackles Baer rings; Baer semigroups; Foulis semigroups; residual mappings; the notion of involution; and Boolean algebras. Chapter 3 covers residuated groupoids and semigroups; group homomorphic and isotone homomorphic Boolean images of ordered semigroups; Dubreil-Jacotin and Brouwer semigroups; and loli

  15. 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…

  16. 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.

  17. 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.

  18. Molecular modeling study for inhibition mechanism of human chymase and its application in inhibitor design.

    Directory of Open Access Journals (Sweden)

    Mahreen Arooj

    Full Text Available Human chymase catalyzes the hydrolysis of peptide bonds. Three chymase inhibitors with very similar chemical structures but highly different inhibitory profiles towards the hydrolase function of chymase were selected with the aim of elucidating the origin of disparities in their biological activities. As a substrate (angiotensin-I bound crystal structure is not available, molecular docking was performed to dock the substrate into the active site. Molecular dynamics simulations of chymase complexes with inhibitors and substrate were performed to calculate the binding orientation of inhibitors and substrate as well as to characterize conformational changes in the active site. The results elucidate details of the 3D chymase structure as well as the importance of K40 in hydrolase function. Binding mode analysis showed that substitution of a heavier Cl atom at the phenyl ring of most active inhibitor produced a great deal of variation in its orientation causing the phosphinate group to interact strongly with residue K40. Dynamics simulations revealed the conformational variation in region of V36-F41 upon substrate and inhibitor binding induced a shift in the location of K40 thus changing its interactions with them. Chymase complexes with the most active compound and substrate were used for development of a hybrid pharmacophore model which was applied in databases screening. Finally, hits which bound well at the active site, exhibited key interactions and favorable electronic properties were identified as possible inhibitors for chymase. This study not only elucidates inhibitory mechanism of chymase inhibitors but also provides key structural insights which will aid in the rational design of novel potent inhibitors of the enzyme. In general, the strategy applied in the current study could be a promising computational approach and may be generally applicable to drug design for other enzymes.

  19. Video compressed sensing using iterative self-similarity modeling and residual reconstruction

    Science.gov (United States)

    Kim, Yookyung; Oh, Han; Bilgin, Ali

    2013-04-01

    Compressed sensing (CS) has great potential for use in video data acquisition and storage because it makes it unnecessary to collect an enormous amount of data and to perform the computationally demanding compression process. We propose an effective CS algorithm for video that consists of two iterative stages. In the first stage, frames containing the dominant structure are estimated. These frames are obtained by thresholding the coefficients of similar blocks. In the second stage, refined residual frames are reconstructed from the original measurements and the measurements corresponding to the frames estimated in the first stage. These two stages are iterated until convergence. The proposed algorithm exhibits superior subjective image quality and significantly improves the peak-signal-to-noise ratio and the structural similarity index measure compared to other state-of-the-art CS algorithms.

  20. 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)

  1. Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau.

    Science.gov (United States)

    Fichou, Yann; Heyden, Matthias; Zaccai, Giuseppe; Weik, Martin; Tobias, Douglas J

    2015-10-01

    The tau protein, whose aggregates are involved in Alzheimer's disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition is shown to be attenuated, but not suppressed, in the parts of the protein that are not exposed to the solvent. In addition, we find similarities in the mean-squared displacements of the core of a globular protein and "dry" clusters formed by the IDP in hydrated powders. Thus, the ps to ns dynamics of proteins in hydrated powders originate mainly from those residues in contact with solvent. We propose that by measuring the dynamics of protein assemblies, such as aggregates, one might assess qualitatively their state of hydration.

  2. Molecular dynamics of model compounds of polymers with chlorocyclohexyl groups in their structure

    Science.gov (United States)

    Saiz, Enrique; Riande, Evaristo

    1995-09-01

    The conformational mobility of 2-chlorocyclohexyl isobutyrate (CCHI), a model compound for the repeating unit of vinyl polymers containing chlorocyclohexane residues as side groups, is analyzed employing molecular dynamics (MD) procedures. Close to room temperature (ca. 300 K), the interconversion between axial (i.e., both chlorine atom and ester group in axial positions) and equatorial (both substituents in equatorial orientations) is not observed within the total time of 5 ns allowed to the MD trajectories. The analysis was then performed at temperatures in the range 1000 to 1500 K and the results extrapolated to lower temperatures. These extrapolations give energetic barriers of 5.72 and 8.15 kcal/mol, respectively for axial→equatorial and equatorial→axial transformations, with life times of τax≊9.6 and τeq≊46.3 ns for these two conformations at 300 K. The same procedure applied to unsubstituted cyclohexane gives an energetic barrier of 10.6 kcal/mol for the chair to chair interconversion, in excellent agreement with literature values. Further extrapolation to the temperatures at which the β subglass relaxation processes take place indicate that this interconversion is practically forbidden and therefore could not be invoked to explain the absorptions exhibited by this kind of polymers. The dipole moment of CCHI is also measured and calculated. Concordance between experimental (2.9±0.1 D) and calculated (2.7 D) values is very good.

  3. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies.

    Science.gov (United States)

    Doğan, İnci Selin; Saraç, Selma; Sari, Suat; Kart, Didem; Eşsiz Gökhan, Şebnem; Vural, İmran; Dalkara, Sevim

    2017-04-21

    Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0.25 μg/mL), were potent against resistant C. glabrata, a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action, we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  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. Membrane re-modelling by BAR domain superfamily proteins via molecular and non-molecular factors.

    Science.gov (United States)

    Nishimura, Tamako; Morone, Nobuhiro; Suetsugu, Shiro

    2018-03-14

    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.

  6. 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.

  7. Modeling of aging in plutonium by molecular dynamics

    CERN Document Server

    Pochet, P

    2003-01-01

    The origin of aging in plutonium lies in the extra formation of defects due to self-decay of sup 2 sup 3 sup 9 Pu. The modeling of the formation of these defects is achieved by molecular dynamics (MD). In this work a simple EAM potential has been used to study defects formation in fcc plutonium and a 2 keV cascade is analyzed. A large pressure wave is generated around the cascade core. In the used MD code the pressure wave is not absorbed at the box boundaries and due to the periodic boundary conditions, the use of a very large box is crucial in order to avoid interaction of the cascade with itself. More than 800 000 atoms are needed to deal with this small 2 keV cascade without any artifacts. This effect comes from the very low bulk modulus of fcc Pu. The relative long time to achieve the annealing is also connected to the bulk modulus. These results are discussed in terms of large pressure wave: alloying effects are predicted using that viewpoint.

  8. Biomimetic polymers of plant cutin: an approach from molecular modeling.

    Science.gov (United States)

    San-Miguel, Miguel A; Oviedo, Jaime; Heredia-Guerrero, Jose Alejandro; Heredia, Antonio; Benitez, Jose Jesus

    2014-07-01

    Biomimetics of materials is based on adopting and reproducing a model in nature with a well-defined functionality optimized through evolution. An example is barrier polymers that protect living tissues from the environment. The protecting layer of fruits, leaves, and non-lignified stems is the plant cuticle. The cuticle is a complex system in which the cutin is the main component. Cutin is a biopolyester made of polyhydroxylated carboxylic acids of 16 and 18 carbon atoms. The biosynthesis of cutin in plants is not well understood yet, but a direct chemical route involving the self-assembly of either molecules or molecular aggregates has been proposed. In this work, we present a combined study using experimental and simulation techniques on self-assembled layers of monomers selectively functionalized with hydroxyl groups. Our results demonstrate that the number and position of the hydroxyl groups are critical for the interaction between single molecules and the further rearrangement. Also, the presence of lateral hydroxyl groups reinforces lateral interactions and favors the bi-dimensional growth (2D), while terminal hydroxyl groups facilitate the formation of a second layer caused by head-tail interactions. The balance of 2D/3D growth is fundamental for the plant to create a protecting layer both large enough in 2D and thick enough in 3D.

  9. Antibacterial kaolinite/urea/chlorhexidine nanocomposites: Experiment and molecular modelling

    Science.gov (United States)

    Holešová, Sylva; Valášková, Marta; Hlaváč, Dominik; Madejová, Jana; Samlíková, Magda; Tokarský, Jonáš; Pazdziora, Erich

    2014-06-01

    Clay minerals are commonly used materials in pharmaceutical production both as inorganic carriers or active agents. The purpose of this study is the preparation and characterization of clay/antibacterial drug hybrids which can be further included in drug delivery systems for treatment oral infections. Novel nanocomposites with antibacterial properties were successfully prepared by ion exchange reaction from two types of kaolinite/urea intercalates and chlorhexidine diacetate. Intercalation compounds of kaolinite were prepared by reaction with solid urea in the absence of solvents (dry method) as well as with urea aqueous solution (wet method). The antibacterial activity of two prepared samples against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa was evaluated by finding the minimum inhibitory concentration (MIC). Antibacterial studies of both samples showed the lowest MIC values (0.01%, w/v) after 1 day against E. faecalis, E. coli and S. aureus. A slightly worse antibacterial activity was observed against P. aeruginosa (MIC 0.12%, w/v) after 1 day. Since samples showed very good antibacterial activity, especially after 1 day of action, this means that these samples can be used as long-acting antibacterial materials. Prepared samples were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental data are supported by results of molecular modelling.

  10. 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.

  11. 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.

  12. 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

  13. Quantitative estimation of nonmonotonic residual stress depth-profiles using an extended Kypris-Jiles model of the magnetic Barkhausen noise spectrum

    Science.gov (United States)

    Lasaosa, Aitor; Gurruchaga, Kizkitza; Arizti, Fernando; Martínez-de-Guerenu, Ane

    2018-01-01

    Using nondestructive techniques to quantitatively estimate residual stresses along the depth is necessary to improve the ability to predict the real fatigue life of pieces for many applications. Magnetic Barkhausen noise has been proven to successfully estimate the residual stress at the surface produced by machining, plastic deformation, phase transformation or surface treatments such as shot peening, also allowing one to obtain information of the residual stress depth-profile in shot peened pieces which presented similar depth-profile shapes. However, residual stress depth-profiles with nonmonotonic or different shapes have not been successfully estimated. In the present study, an extended approach is developed in order to estimate these stresses independent of the shape of the residual stress depth-profile. The approach proposed here improves an existing model of the Barkhausen noise spectrum (Kypris-Jiles model) by adding the effect of the attenuation of the applied magnetic field on the Barkhausen noise. This extended approach is used to estimate the residual stress depth-profiles of samples with different depth-profiles using a calibration process. The approach is validated by estimating the residual stress depth-profiles, with errors smaller than 70 MPa in a depth of 130 μm, in all the samples studied.

  14. Mechanism of diffusive transport in molecular spider models

    Science.gov (United States)

    Semenov, Oleg; Olah, Mark J.; Stefanovic, Darko

    2011-02-01

    Recent advances in single-molecule chemistry have led to designs for artificial multipedal walkers that follow tracks of chemicals. We investigate the motion of a class of walkers, called molecular spiders, which consist of a rigid chemically inert body and several flexible enzymatic legs. The legs can reversibly bind to chemical substrates on a surface and through their enzymatic action convert them to products. The legs can also reversibly bind to products, but at a different rate. Antal and Krapivsky have proposed a model for molecular spider motion over regular one-dimensional lattices [T. Antal and P. L. Krapivsky, Phys. Rev. ENATUAS1539-375510.1103/PhysRevE.76.021121 76, 021121 (2007).]. In the model the legs hop from site to site under constraints imposed by connection to a common body. The first time a leg visits a site, the site is an uncleaved substrate, and the leg hops from this site only once it has cleaved it into a product. This cleavage happens at a rate rr=1. The effect of cleavage is to slow down the hopping rate for legs that visit a site for the first time. Along with the constraints imposed on the legs, this leads to an effective bias in the direction of unvisited sites that decreases the average time needed to visit n sites. The overall motion, however, remains diffusive in the long time limit. We have reformulated the Antal-Krapivsky model as a continuous-time Markov process and simulated many traces of this process using kinetic Monte Carlo techniques. Our simulations show a previously unpredicted transient behavior wherein spiders with small r values move superdiffusively over significant distances and times. We explain this transient period of superdiffusive behavior by describing the spider process as switching between two metastates: a diffusive state D wherein the spider moves in an unbiased manner over previously visited sites, and a boundary state B wherein the spider is on the boundary between regions of visited and unvisited sites

  15. 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...... 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...

  16. 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.

  17. Measurement and modelling of the residual stresses in autogenous and narrow gap laser welded AISI grade 316L stainless steel plates

    International Nuclear Information System (INIS)

    Elmesalamy, A.S.; Abdolvand, H.; Walsh, J.N.; Francis, J.A.; Suder, W.; Williams, S.; Li, L.

    2016-01-01

    Thick-section austenitic stainless steels have widespread industrial applications, where stress-corrosion cracking is often of major concern. Problems tend to arise in the vicinity of welds, where substantial residual stresses often reside. This paper describes an investigation into the residual stresses in autogenous high power laser welds and narrow gap laser welds (NGLW) in 10 mm thick AISI grade 316L steel plates, using both neutron diffraction and the contour method. The influences of laser power, welding speed and the time interval between weld passes on residual stress were analysed. For the NGLW process, finite element modelling was employed to understand the influence of thermal history on residual stress. The results for the NGLW technique show that the laser power has a significant effect on the peak value of residual stress, while the welding speed has a more significant influence on the width of the region sustaining tensile stresses. - Highlights: • We compare the residual stress behaviour in high power autogenous laser welding and Narrow gap laser welding [NGLW] of 10 mm thickplates of 316L stainless steel. • We use contour method for residual stress evaluation. The results have been validated by using neutron diffraction. • The experimental results show that, lower residual stress distribution can be achieved by using the NGLW technique. • We investigate the influence of the power and speed on both peak value and width of the tensile region for both autogenous laser welding and NGLW technique. • The welding speed in NGLW technique has a more significant influence on the width of the tensile region. The laser power shows a more significant influence on the peak value of the residual stress with respect to width of the residual stress tensile region.

  18. 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

  19. 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…

  20. 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…

  1. 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

  2. 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

  3. Fast and accurate multivariate Gaussian modeling of protein families: predicting residue contacts and protein-interaction partners.

    Directory of Open Access Journals (Sweden)

    Carlo Baldassi

    Full Text Available In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids, exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i the prediction of residue-residue contacts in proteins, and (ii the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/code.

  4. Fast and accurate multivariate Gaussian modeling of protein families: predicting residue contacts and protein-interaction partners.

    Science.gov (United States)

    Baldassi, Carlo; Zamparo, Marco; Feinauer, Christoph; Procaccini, Andrea; Zecchina, Riccardo; Weigt, Martin; Pagnani, Andrea

    2014-01-01

    In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our method aims at extracting such constraints from rapidly accumulating sequence data, and thereby at inferring protein structure and function from sequence information alone. Recently, global statistical inference methods (e.g. direct-coupling analysis, sparse inverse covariance estimation) have achieved a breakthrough towards this aim, and their predictions have been successfully implemented into tertiary and quaternary protein structure prediction methods. However, due to the discrete nature of the underlying variable (amino-acids), exact inference requires exponential time in the protein length, and efficient approximations are needed for practical applicability. Here we propose a very efficient multivariate Gaussian modeling approach as a variant of direct-coupling analysis: the discrete amino-acid variables are replaced by continuous Gaussian random variables. The resulting statistical inference problem is efficiently and exactly solvable. We show that the quality of inference is comparable or superior to the one achieved by mean-field approximations to inference with discrete variables, as done by direct-coupling analysis. This is true for (i) the prediction of residue-residue contacts in proteins, and (ii) the identification of protein-protein interaction partner in bacterial signal transduction. An implementation of our multivariate Gaussian approach is available at the website http://areeweb.polito.it/ricerca/cmp/code.

  5. 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.

  6. 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

  7. 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...

  8. Molecular Recognition of Azelaic Acid and Related Molecules with DNA Polymerase I Investigated by Molecular Modeling Calculations.

    Science.gov (United States)

    Shawon, Jakaria; Khan, Akib Mahmud; Rahman, Adhip; Hoque, Mohammad Mazharol; Khan, Mohammad Abdul Kader; Sarwar, Mohammed G; Halim, Mohammad A

    2016-10-01

    Molecular recognition has central role on the development of rational drug design. Binding affinity and interactions are two key components which aid to understand the molecular recognition in drug-receptor complex and crucial for structure-based drug design in medicinal chemistry. Herein, we report the binding affinity and the nonbonding interactions of azelaic acid and related compounds with the receptor DNA polymerase I (2KFN). Quantum mechanical calculation was employed to optimize the modified drugs using B3LYP/6-31G(d,p) level of theory. Charge distribution, dipole moment and thermodynamic properties such as electronic energy, enthalpy and free energy of these optimized drugs are also explored to evaluate how modifications impact the drug properties. Molecular docking calculation was performed to evaluate the binding affinity and nonbonding interactions between designed molecules and the receptor protein. We notice that all modified drugs are thermodynamically more stable and some of them are more chemically reactive than the unmodified drug. Promise in enhancing hydrogen bonds is found in case of fluorine-directed modifications as well as in the addition of trifluoroacetyl group. Fluorine participates in forming fluorine bonds and also stimulates alkyl, pi-alkyl interactions in some drugs. Designed drugs revealed increased binding affinity toward 2KFN. A1, A2 and A3 showed binding affinities of -8.7, -8.6 and -7.9 kcal/mol, respectively against 2KFN compared to the binding affinity -6.7 kcal/mol of the parent drug. Significant interactions observed between the drugs and Thr358 and Asp355 residues of 2KFN. Moreover, designed drugs demonstrated improved pharmacokinetic properties. This study disclosed that 9-octadecenoic acid and drugs containing trifluoroacetyl and trifluoromethyl groups are the best 2KFN inhibitors. Overall, these results can be useful for the design of new potential candidates against DNA polymerase I.

  9. A critical study on the interactions of hesperitin with human hemoglobin: Fluorescence spectroscopic and molecular modeling approach

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sandipan [Saroj Mohan Institute of Technology, Hooghly (India); Chaudhuri, Sudip; Pahari, Biswapathik [Biophysics Division, Saha Institute of Nuclear Physics, Kolkata 700064 (India); Taylor, Jasmine [Chemistry Department, Tougaloo College, Tougaloo, MS 39174 (United States); Sengupta, Pradeep K. [Biophysics Division, Saha Institute of Nuclear Physics, Kolkata 700064 (India); Sengupta, Bidisha, E-mail: bsengupta@tougaloo.edu [Chemistry Department, Tougaloo College, Tougaloo, MS 39174 (United States)

    2012-06-15

    Hesperitin, a ubiquitous bioactive flavonoid abundant in citrus fruits is known to possess antioxidant, anti-carcinogenic, hypolipidemic, vasoprotective and other important therapeutic properties. Here we have explored the interactions of hesperitin with normal human hemoglobin (HbA), using steady state and time resolved fluorescence spectroscopy, far UV circular dicroism (CD) spectroscopy, combined with molecular modeling computations. Specific interaction of the flavonoid with HbA is confirmed from flavonoid-induced static quenching which is evident from steady state fluorescence as well as lifetime data. Both temperature dependent fluorescence measurements and molecular docking studies reveal that apart from hydrogen bonding and van der Waals interactions, electrostatic interactions also play crucial role in hesperitin-HbA interactions. Furthermore, electrostatic surface potential calculations indicate that the hesperitin binding site in HbA is intensely positive due to the presence of several lysine and histidine residues. - Highlights: Black-Right-Pointing-Pointer Absorption spectra of hesperitin bound HbA indicates ground state complex formation. Black-Right-Pointing-Pointer Binding induces static quenching of intrinsic fluorescence of the tryptophan of HbA. Black-Right-Pointing-Pointer Molecular docking and electrostatic surface potential calculations were performed. Black-Right-Pointing-Pointer Contrasting binding modes of hesperitin compared to other flavonoids were observed.

  10. 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.

  11. A critical study on the interactions of hesperitin with human hemoglobin: Fluorescence spectroscopic and molecular modeling approach

    International Nuclear Information System (INIS)

    Chakraborty, Sandipan; Chaudhuri, Sudip; Pahari, Biswapathik; Taylor, Jasmine; Sengupta, Pradeep K.; Sengupta, Bidisha

    2012-01-01

    Hesperitin, a ubiquitous bioactive flavonoid abundant in citrus fruits is known to possess antioxidant, anti-carcinogenic, hypolipidemic, vasoprotective and other important therapeutic properties. Here we have explored the interactions of hesperitin with normal human hemoglobin (HbA), using steady state and time resolved fluorescence spectroscopy, far UV circular dicroism (CD) spectroscopy, combined with molecular modeling computations. Specific interaction of the flavonoid with HbA is confirmed from flavonoid-induced static quenching which is evident from steady state fluorescence as well as lifetime data. Both temperature dependent fluorescence measurements and molecular docking studies reveal that apart from hydrogen bonding and van der Waals interactions, electrostatic interactions also play crucial role in hesperitin-HbA interactions. Furthermore, electrostatic surface potential calculations indicate that the hesperitin binding site in HbA is intensely positive due to the presence of several lysine and histidine residues. - Highlights: ► Absorption spectra of hesperitin bound HbA indicates ground state complex formation. ► Binding induces static quenching of intrinsic fluorescence of the tryptophan of HbA. ► Molecular docking and electrostatic surface potential calculations were performed. ► Contrasting binding modes of hesperitin compared to other flavonoids were observed.

  12. 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.

  13. 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)

  14. 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.

  15. Residue processing

    Energy Technology Data Exchange (ETDEWEB)

    Gieg, W.; Rank, V.

    1942-10-15

    In the first stage of coal hydrogenation, the liquid phase, light and heavy oils were produced; the latter containing the nonliquefied parts of the coal, the coal ash, and the catalyst substances. It was the problem of residue processing to extract from these so-called let-down oils that which could be used as pasting oils for the coal. The object was to obtain a maximum oil extraction and a complete removal of the solids, because of the latter were returned to the process they would needlessly burden the reaction space. Separation of solids in residue processing could be accomplished by filtration, centrifugation, extraction, distillation, or low-temperature carbonization (L.T.C.). Filtration or centrifugation was most suitable since a maximum oil yield could be expected from it, since only a small portion of the let-down oil contained in the filtration or centrifugation residue had to be thermally treated. The most satisfactory centrifuge at this time was the Laval, which delivered liquid centrifuge residue and centrifuge oil continuously. By comparison, the semi-continuous centrifuges delivered plastic residues which were difficult to handle. Various apparatus such as the spiral screw kiln and the ball kiln were used for low-temperature carbonization of centrifuge residues. Both were based on the idea of carbonization in thin layers. Efforts were also being made to produce electrode carbon and briquette binder as by-products of the liquid coal phase.

  16. 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,

  17. 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 

  18. DOE Final Report: A Unified Understanding of Residual Stress in Thin Films: Kinetic Models, Experiments and Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Chason, Eric

    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.

  19. 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.

  20. Spectra modelling combining molecular dynamics and quantum mechanics

    Czech Academy of Sciences Publication Activity Database

    Novák, Vít; Bouř, Petr

    2015-01-01

    Roč. 22, č. 1 (2015), s. 48 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] R&D Projects: GA ČR GAP208/11/0105; GA ČR GA15-09072S Grant - others:GA MŠk(CZ) LM2010005; GA MŠk(CZ) ED3.2.00/08.0144 Institutional support: RVO:61388963 Keywords : Raman scattering * molecular dynamics * autocorrelation function Subject RIV: CF - Physical ; Theoretical Chemistry

  1. Incorporation of 13C labelled root-shoot residues in soil in the presence of Lumbricus terrestris: An isotopic and molecular approach

    Science.gov (United States)

    Vidal, Alix; Alexis, Marie; Nguyen Tu, Thanh Tu; Anquetil, Christelle; Vaury, Véronique; Derenne, Sylvie; Quenea, Katell

    2016-04-01

    Litter from plant biomass deposited on soil surface can either be mineralized; releasing CO2 to the atmosphere, or transferred into the soil as organic compounds. Both pathways depend on biotic factors such as litter characteristics and the of soil organism activity. During the last decades, many studies have focused on the origin of organic matter, with a particular attention to the fate of root and shoot litter. It is generally admitted that roots decompose at a slower rate than shoots, resulting in a higher carbon sequestration in soil for compounds originating from roots. Earthworms play a central role in litter decomposition and carbon cycling, ingesting both organic and mineral compounds which are mixed, complexed and dejected in the form of casts at the soil surface or along earthworm burrows. The simultaneous impact of earthworms and root-shoot on soil carbon cycling is still poorly understood. This study aimed at (1) defining the rate of incorporation of root and shoot litter with or without earthworms and (2) characterizing the molecular composition of soil organic matter upon litter decomposition, after one year of experimentation. A mesocosm experiment was set up to follow the incorporation of 13C labelled Ryegrass root and shoot litter in the soil, in the presence of anecic earthworms (Lumbricus terrestris). Soil samples were collected at 0-20 and 40-60 cm, as well as surface casts, at the beginning and after 1, 2, 4, 8, 24 and 54 weeks of experiment. Organic carbon content and δ13C values were determined for all the samples with Elemental Analysis - Isotope Ratio Mass Spectrometry. Lipid-free soil and cast samples after 54 weeks of incubation were analyzed with Pyrolysis-Gas Chromatography-Mass Spectrometry. Pyrolysis products were grouped into six classes: polysaccharides, lignin derived compounds, phenols, N-compounds, aliphatic compounds and sterols. Each pyrolysis product was quantified thanks to its peak area, relative to the total area of the

  2. 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...

  3. 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.

  4. 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).

  5. Panel 4: Recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models.

    Science.gov (United States)

    Li, Jian-Dong; Hermansson, Ann; Ryan, Allen F; Bakaletz, Lauren O; Brown, Steve D; Cheeseman, Michael T; Juhn, Steven K; Jung, Timothy T K; Lim, David J; Lim, Jae Hyang; Lin, Jizhen; Moon, Sung-Kyun; Post, J Christopher

    2013-04-01

    Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications.

  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. 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

  8. 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…

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

    Science.gov (United States)

    2010-03-01

    conditions of cutting speed, feed , radial and 29 axial depths of cut, cutter geometry (including edge preparation, axial and radial rake angles ...sharp. • Chip formation is of continuous type (no serrations). • The width of cut must be more than 10 times the feed rate to satisfy the plane...captured in the 2-D axisymmetric model. • Inaccuracy in extrapolated low strain rate stress-strain data. • Sag in the furnace: effect of heat treat

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Molecular recognition of carboxylates in the protein leucine zipper by a multivalent supramolecular ligand: residue-specific, sensitive and label-free probing by UV resonance Raman spectroscopy.

    Science.gov (United States)

    Zakeri, B; Niebling, S; Martinéz, A G; Sokkar, P; Sanchez-Garcia, E; Schmuck, C; Schlücker, S

    2018-01-17

    Ultraviolet resonance Raman (UVRR) spectroscopy is a selective, sensitive and label-free vibrational spectroscopic technique. Here, we demonstrate as proof of concept that UVRR can be used for probing the recognition between a multivalent supramolecular ligand and acidic residues in leucine zipper, an α-helical structural motif of many proteins.

  17. 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.

  18. 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.

  19. 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.

  20. Comparative modeling and molecular dynamics suggest high carboxylase activity of the Cyanobium sp. CACIAM14 RbcL protein.

    Science.gov (United States)

    Siqueira, Andrei Santos; Lima, Alex Ranieri Jerônimo; Dall'Agnol, Leonardo Teixeira; de Azevedo, Juliana Simão Nina; da Silva Gonçalves Vianez, João Lídio; Gonçalves, Evonnildo Costa

    2016-03-01

    Rubisco catalyzes the first step reaction in the carbon fixation pathway, bonding atmospheric CO2/O2 to ribulose 1,5-bisphosphate; it is therefore considered one of the most important enzymes in the biosphere. Genetic modifications to increase the carboxylase activity of rubisco are a subject of great interest to agronomy and biotechnology, since this could increase the productivity of biomass in plants, algae and cyanobacteria and give better yields in crops and biofuel production. Thus, the aim of this study was to characterize in silico the catalytic domain of the rubisco large subunit (rbcL gene) of Cyanobium sp. CACIAM14, and identify target sites to improve enzyme affinity for ribulose 1,5-bisphosphate. A three-dimensional model was built using MODELLER 9.14, molecular dynamics was used to generate a 100 ns trajectory by AMBER12, and the binding free energy was calculated using MM-PBSA, MM-GBSA and SIE methods with alanine scanning. The model obtained showed characteristics of form-I rubisco, with 15 beta sheets and 19 alpha helices, and maintained the highly conserved catalytic site encompassing residues Lys175, Lys177, Lys201, Asp203, and Glu204. The binding free energy of the enzyme-substrate complexation of Cyanobium sp. CACIAM14 showed values around -10 kcal mol(-1) using the SIE method. The most important residues for the interaction with ribulose 1,5-bisphosphate were Arg295 followed by Lys334. The generated model was successfully validated, remaining stable during the whole simulation, and demonstrated characteristics of enzymes with high carboxylase activity. The binding analysis revealed candidates for directed mutagenesis sites to improve rubisco's affinity.

  1. Solubility of gases and solvents in silicon polymers: molecular simulation and equation of state modeling

    DEFF Research Database (Denmark)

    Economou, Ioannis; Makrodimitri, Zoi A.; Kontogeorgis, Georgios

    2007-01-01

    The solubility of n-alkanes, perfluoroalkanes, noble gases and light gases in four elastomer polymers containing silicon is examined based on molecular simulation and macroscopic equation of state modelling. Polymer melt samples generated from molecular dynamics ( MD) are used for the calculation...

  2. 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

  3. 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…

  4. 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)

  5. Mechanism of Adefovir, Tenofovir and Entecavir Resistance: Molecular Modeling Studies of How A Novel Anti-HBV Agent (FMCA) Can Overcome the Drug Resistance.

    Science.gov (United States)

    Rawal, R K; Konreddy, A K; Chu, C K

    2015-01-01

    Regardless of significant improvement in the area of anti-HBV therapy, resistance and cross-resistance against available therapeutic agents are the major consideration in drug discovery of new agents. The present study is to obtain the insight of the molecular basis of drug resistance conferred by the B and C domain mutations of HBV-polymerase on the binding affinity of four anti-HBV agents [Adefovir (ADV), Tenofovir (TNF), Entecavir (ETV) & 2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA)]. In this regard, homology modeled structure of HBV polymerase was used for minimization, conformational search and Glide XP docking followed by binding energy calculation on wild-type as well as on mutant HBV-polymerases (N236T, L180M+M204V+S202G & A194T). Our studies suggest a significant correlation between the fold resistances and the binding affinity of anti-HBV nucleosides. The domain B residue, L180 is indirectly associated with other active-site hydrophobic residues such as A87, F88 and M204, whereas the domain C residue, M204 is closely associated with sugar/pseudosugar ring positioning in the active site. These hydrophobic residues can directly influence the interaction of the incoming nucleoside triphosphates and change the binding efficacy. The carbohydrate ring part of natural substrate dATP, dGTP, FMCA and ETV, are occupied in similar passion in the grooves of HBV polymerase active site. The exocyclic double bond of Entecavir and FMCA occupies in the backside hydrophobic pocket (made by residues A87, F88, L180and M204), which enhances the overall binding affinity. Additional hydrogen bonding interaction of 2'-fluorine of FMCA with R41 residue of polymerase promotes a positive binding in wild-type as well as in ADVr, ETVr and TNFr with respect to that of entecavir.

  6. UOE Pipe Numerical Model: Manufacturing Process And Von Mises Residual Stresses Resulted After Each Technological Step

    Science.gov (United States)

    Delistoian, Dmitri; Chirchor, Mihael

    2017-12-01

    Fluid transportation from production areas to final customer is effectuated by pipelines. For oil and gas industry, pipeline safety and reliability represents a priority. From this reason, pipe quality guarantee directly influence pipeline designed life, but first of all protects environment. A significant number of longitudinally welded pipes, for onshore/offshore pipelines, are manufactured by UOE method. This method is based on cold forming. In present study, using finite element method is modeled UOE pipe manufacturing process and is obtained von Mises stresses for each step. Numerical simulation is performed for L415 MB (X60) steel plate with 7,9 mm thickness, length 30 mm and width 1250mm, as result it is obtained a DN 400 pipe.

  7. Molecular Modeling of Enzyme Dynamics Towards Understanding Solvent Effects

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar

    ) in water and organic solvents. The effects of solvent on structural and dynamical enzyme properties are studied, and special attention is given to how enzyme properties in organic solvents are affected by the hydration level, which is shown to be related to the water activity. In experimental studies...... 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......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...

  8. 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

  9. Molecular distributions in interphases: statistical mechanical theory combined with molecular dynamics simulation of a model lipid bilayer.

    Science.gov (United States)

    Xiang, T X; Anderson, B D

    1994-03-01

    A mean-field statistical mechanical theory has been developed to describe molecular distributions in interphases. The excluded volume interaction has been modeled in terms of a reversible work that is required to create a cavity of the solute size against a pressure tensor exerted by the surrounding interphase molecules. The free energy change associated with this compression process includes the configuration entropy as well as the change in conformational energy of the surrounding chain molecules. The lateral pressure profile in a model lipid bilayer (30.5 A2/chain molecule) has been calculated as a function of depth in the bilayer interior by molecular dynamics simulation. The lateral pressure has a plateau value of 309 +/- 48 bar in the highly ordered region and decreases abruptly in the center of the bilayer. Model calculations have shown that for solute molecules with ellipsoidal symmetry, the orientational order increases with the ratio of the long to short molecular axes at a given solute volume and increases with solute volume at a given axial ratio, in accordance with recent experimental data. Increased lateral pressure (p perpendicular) results in higher local order and exclusion of solute from the interphase, in parallel with the effect of surface density on the partitioning and local order. The logarithm of the interphase/water partition coefficient for spherical solutes decreases linearly with solute volume. This is also an excellent approximation for elongated solutes because of the relatively weak dependence of solute partitioning on molecular shape. The slope is equal to (2p perpendicular - p parallel)/3KBT, where p parallel is the normal pressure component, and different from that predicted by the mean-field lattice theory. Finally, the lattice theory has been extended herein to incorporate an additional constraint on chain packing in the interphase and to account for the effect of solute size on partitioning.

  10. 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.

  11. Residual risk

    African Journals Online (AJOL)

    ing the residual risk of transmission of HIV by blood transfusion. An epidemiological approach assumed that all HIV infections detected serologically in first-time donors were pre-existing or prevalent infections, and that all infections detected in repeat blood donors were new or incident infections. During 1986 - 1987,0,012%.

  12. Indoor Residual Spraying Delivery Models to Prevent Malaria: Comparison of Community- and District-Based Approaches in Ethiopia

    Science.gov (United States)

    Johns, Benjamin; Yihdego, Yemane Yeebiyo; Kolyada, Lena; Dengela, Dereje; Chibsa, Sheleme; Dissanayake, Gunawardena; George, Kristen; Taffese, Hiwot Solomon; Lucas, Bradford

    2016-01-01

    ABSTRACT Background: Indoor residual spraying (IRS) for malaria prevention has traditionally been implemented in Ethiopia by the district health office with technical and operational inputs from regional, zonal, and central health offices. The United States President's Malaria Initiative (PMI) in collaboration with the Government of Ethiopia tested the effectiveness and efficiency of integrating IRS into the government-funded community-based rural health services program. Methods: Between 2012 and 2014, PMI conducted a mixed-methods study in 11 districts of Oromia region to compare district-based IRS (DB IRS) and community-based IRS (CB IRS) models. In the DB IRS model, each district included 2 centrally located operational sites where spray teams camped during the IRS campaign and from which they traveled to the villages to conduct spraying. In the CB IRS model, spray team members were hired from the communities in which they operated, thus eliminating the need for transport and camping facilities. The study team evaluated spray coverage, the quality of spraying, compliance with environmental and safety standards, and cost and performance efficiency. Results: The average number of eligible structures found and sprayed in the CB IRS districts increased by 19.6% and 20.3%, respectively, between 2012 (before CB IRS) and 2013 (during CB IRS). Between 2013 and 2014, the numbers increased by about 14%. In contrast, in the DB IRS districts the number of eligible structures found increased by only 8.1% between 2012 and 2013 and by 0.4% between 2013 and 2014. The quality of CB IRS operations was good and comparable to that in the DB IRS model, according to wall bioassay tests. Some compliance issues in the first year of CB IRS implementation were corrected in the second year, bringing compliance up to the level of the DB IRS model. The CB IRS model had, on average, higher amortized costs per district than the DB IRS model but lower unit costs per structure sprayed and per

  13. Residual circulation and thermohaline distribution of the Ría de Vigo: A 3-D hydrodynamical model

    Directory of Open Access Journals (Sweden)

    S. Torres López

    2001-07-01

    Full Text Available A three-dimensional, non-linear, baroclinic model is described and tested for the first time to study the residual circulation and the thermohaline distribution of the Ría de Vigo (NW Spain at short time scales and under different wind stress regimes. Two markedly different realistic scenarios were chosen: northerly upwelling-favourable winds and southerly downwelling-favourable winds. The numerical experiments carried out indicate that the hydrodynamic regime of the Ría de Vigo is mostly a consequence of wind events. As could be expected, moderately strong North winds reinforce the normal (positive Ría circulation, while winds blowing from the South, when sufficiently strong, reverse the typical circulation pattern and reduce the characteristic outgoing velocities and the flushing time inside the Ría. The temperature and salinity fields generated by the model in both situations were compared with observations and found to be in qualitatively good agreement, supporting the 3D velocity field distribution.

  14. Identification of porcine polycystic kidney disease 1 (PKD1) gene: molecular cloning, expression profile, and implication in disease model.

    Science.gov (United States)

    He, Jin; Wang, Qingsong; Ye, Jianhua; Hu, Xiaoxiang; Li, Ning

    2011-12-15

    The polycystic kidney disease 1 (PKD1) gene, which accounts for ~85% of human autosomal dominant polycystic kidney disease (ADPKD) cases, has been extensively studied in human and mouse. Much information about the pathogenesis of and treatments for ADPKD has been gained from the use of mouse models. However, because mouse models pose some limitations, further studies in other model systems are needed to investigate the biological basis of ADPKD. The pig is regarded as an important biomedical model. Thus, we isolated a pig PKD1 homolog and characterized its cDNA sequence, genomic structure, expression profile, alternative splicing, methylation status, protein characteristics, and immunohistochemical features in both neonatal and adult pigs. The pig PKD1 cDNA is 14,209bp long and encodes a 4305-residue polypeptide. The genomic sequence of PKD1 is ~50kb with 46 exons. An alternative splice acceptor site was identified in intron 9. PKD1 is expressed in all tissues tested in both neonatal and adult pigs and exhibits a developmentally regulated expression pattern. Western blotting revealed that the molecular mass of polycystin-1 is ~460kDa, but its expression level is relatively low. Immunohistochemical study of the kidneys shows that polycystin-1 is mainly expressed in the tubular epithelia. Bisulfite methylation analysis of CpG islands in the promoter region does not show a direct correlation between methylation status and expression level among different tissues/cells. The cloning and characterization of pig PKD1 indicates that the pig and human genes are highly similar in length of genomic and cDNA sequences, genomic structure and context, expression patterns, conserved transcription factor binding sites, and the molecular mass of the encoded polycystin-1. These data support our current understanding of PKD1, and suggest that the pig is an ideal candidate for development of an ADPKD disease model. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Residual sweeping errors in turbulent particle pair diffusion in a Lagrangian diffusion model.

    Directory of Open Access Journals (Sweden)

    Nadeem A Malik

    Full Text Available 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.

  16. 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.

  17. Molecular weight kinetics and chain scission models for dextran polymers during ultrasonic degradation.

    Science.gov (United States)

    Pu, Yuanyuan; Zou, Qingsong; Hou, Dianzhi; Zhang, Yiping; Chen, Shan

    2017-01-20

    Ultrasonic degradation of six dextran samples with different initial molecular weights (IMW) has been performed to investigate the degradation behavior and chain scission mechanism of dextrans. The weight-average molecular weight (Mw) and polydispersity index (D value) were monitored by High Performance Gel Permeation Chromatography (HPGPC). Results showed that Mw and D value decreased with increasing ultrasonic time, resulting in a more homologous dextran solution with lower molecular weight. A significant degradation occurred in dextrans with higher IMW, particularly at the initial stage of the ultrasonic treatment. The Malhotra model was found to well describe the molecular weight kinetics for all dextran samples. Experimental data was fitted into two chain scission models to study dextran chain scission mechanism and the model performance was compared. Results indicated that the midpoint scission model agreed well with experimental results, with a linear regression factor of R 2 >0.99. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 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

  19. Local elastic expansion model for viscous-flow activation energies of glass-forming molecular liquids

    DEFF Research Database (Denmark)

    Dyre, Jeppe; Olsen, Niels Boye; Christensen, Tage Emil

    1996-01-01

    A model for the viscosity of glass-forming molecular liquids is proposed in which a "flow event" requires a local volume increase. The activation energy for a flow event is identified with the work done in shoving aside the surrounding liquid; this work is proportional to the high-frequency shear...... modulus, which increases as the temperature decreases. The model is confirmed by experiments on a number of molecular liquids....

  20. Digital Learning Material for Student-Directed Model Building in Molecular Biology

    Science.gov (United States)

    Aegerter-Wilmsen, Tinri; Coppens, Marjolijn; Janssen, Fred; Hartog, Rob; Bisseling, Ton

    2005-01-01

    The building of models to explain data and make predictions constitutes an important goal in molecular biology research. To give students the opportunity to practice such model building, two digital cases had previously been developed in which students are guided to build a model step by step. In this article, the development and initial…

  1. High throughput ab initio modeling of charge transport for bio-molecular-electronics

    Science.gov (United States)

    Bruque, Nicolas Alexander

    2009-12-01

    Self-assembled nanostructures, composed of inorganic and organic materials, have multiple applications in the fields of engineering and nanotechnology. Experimental research using nanoscaled materials, such as semiconductor/metallic nanocrystals, nanowires (NW), and carbon nanotube (CNT)-molecular systems have potential applications in next generation nano electronic devices. Many of these molecular systems exhibit electronic device functionality. However, experimental analytical techniques to determine how the chemistry and geometry affects electron transport through these devices does not yet exist. Using theory and modeling, one can approximate the chemistry and geometry at the atomic level and also determine how the chemistry and geometry governs electron current. Nanoelectronic devices however, contain several thousand atoms which makes quantum modeling difficult. Popular atomistic modeling approaches are capable of handling small molecular systems, which are of scientific interest, but have little engineering value. The lack of large scale modeling tools has left the scientific and engineering community with a limited ability to understand, explore, and design complex systems of engineering interest. To address these issues, I have developed a high performance general quantum charge transport model based on the non-equilibrium Green function (NEGF) formalism using density functional theory (DFT) as implemented in the FIREBALL software. FIREBALL is a quantum molecular dynamics code which has demonstrated the ability to model large molecular systems. This dissertation project of integrating NEGF into FIREBALL provides researchers with a modeling tool capable of simulating charge current in large inorganic/organic systems. To provide theoretical support for experimental efforts, this project focused on CNT-molecular systems, which includes the discovery of a CNT-molecular resonant tunneling diode (RTD) for electronic circuit applications. This research also

  2. 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

  3. Adaptive radiotherapy with an average anatomy model: Evaluation and quantification of residual deformations in head and neck cancer patients

    International Nuclear Information System (INIS)

    Kranen, Simon van; Mencarelli, Angelo; Beek, Suzanne van; Rasch, Coen; Herk, Marcel van; Sonke, Jan-Jakob

    2013-01-01

    Background and purpose: To develop and validate an adaptive intervention strategy for radiotherapy of head-and-neck cancer that accounts for systematic deformations by modifying the planning-CT (pCT) to the average misalignments in daily cone beam CT (CBCT) measured with deformable registration (DR). Methods and materials: Daily CBCT scans (808 scans) for 25 patients were retrospectively registered to the pCT with B-spline DR. The average deformation vector field ( ) was used to deform the pCT for adaptive intervention. Two strategies were simulated: single intervention after 10 fractions and weekly intervention with an from the previous week. The model was geometrically validated with the residual misalignment of anatomical landmarks both on bony-anatomy (BA; automatically generated) and soft-tissue (ST; manually identified). Results: Systematic deformations were 2.5/3.4 mm vector length (BA/ST). Single intervention reduced deformations to 1.5/2.7 mm (BA/ST). Weekly intervention resulted in 1.0/2.2 mm (BA/ST) and accounted better for progressive changes. 15 patients had average systematic deformations >2 mm (BA): reductions were 1.1/1.9 mm (single/weekly BA). ST improvements were underestimated due to observer and registration variability. Conclusions: Adaptive intervention with a pCT modified to the average anatomy during treatment successfully reduces systematic deformations. The improved accuracy could possibly be exploited in margin reduction and/or dose escalation

  4. A partial least squares model for non-volatile residue quantification using diffuse reflectance infrared reflectance spectroscopy

    Science.gov (United States)

    Chen, Amylynn; Moision, Robert M.

    2016-09-01

    Traditionally, quantification of non-volatile residue (NVR) on surfaces relevant to space systems has been performed using solvent wipes for NVR removal followed by gravimetric analysis. In this approach the detectable levels of NVR are ultimately determined by the mass sensitivity of the analytical balance employed. Unfortunately, for routine samples, gravimetric measurement requires large sampling areas, on the order of a square foot, in order to clearly distinguish sample and background levels. Diffuse Reflectance Infrared Reflectance Spectroscopy (DRIFTS) is one possible alternative to gravimetric analysis for NVR measurement. DRIFTS is an analytical technique used for the identification and quantification of organic compounds that has two primary advantages relative to gravimetric based methods: increased sensitivity and the ability to identify classes of organic species present. However, the use of DRIFTS is not without drawbacks, most notably repeatability of sample preparation and the additive quantification uncertainty arising from overlapping infrared signatures. This can result in traditional calibration methods greatly overestimating the concentration of species in mixtures. In this work, a partial least squares (PLS) regression model is shown to be an effective method for removing the over prediction error of a three component mixture of common contaminant species.

  5. A Molecular Modeling Study of the Hydroxyflutamide Resistance Mechanism Induced by Androgen Receptor Mutations

    Directory of Open Access Journals (Sweden)

    Hong-Li Liu

    2017-08-01

    Full Text Available Hydroxyflutamide (HF, an active metabolite of the first generation antiandrogen flutamide, was used in clinic to treat prostate cancer targeting androgen receptor (AR. However, a drug resistance problem appears after about one year’s treatment. AR T877A is the first mutation that was found to cause a resistance problem. Then W741C_T877A and F876L_T877A mutations were also reported to cause resistance to HF, while W741C and F876L single mutations cannot. In this study, molecular dynamics (MD simulations combined with the molecular mechanics generalized Born surface area (MM-GBSA method have been carried out to analyze the interaction mechanism between HF and wild-type (WT/mutant ARs. The obtained results indicate that AR helix 12 (H12 plays a pivotal role in the resistance of HF. It can affect the coactivator binding site at the activation function 2 domain (AF2, surrounded by H3, H4, and H12. When H12 closes to the AR ligand-binding domain (LBD like a lid, the coactivator binding site can be formed to promote transcription. However, once H12 is opened to expose LBD, the coactivator binding site will be distorted, leading to invalid transcription. Moreover, per-residue free energy decomposition analyses indicate that N705, T877, and M895 are vital residues in the agonist/antagonist mechanism of HF.

  6. Numerical Analysis of Particle Interactions with Nuclei in the Framework of Quantum Molecular Dynamic Model

    CERN Document Server

    Amirkhanov, I V; Zemlyanaya, E V; Polanski, A; Puzynina, T P; Uzhinsky, V V

    2004-01-01

    Combinations of the QMD model with various models of nuclear residual de-excitation are considered. The QMD model parameters are fitted; neutron spectra in hadron-nucleus interactions are calculated. The numerical results were compared with analogous calculations by the cascade-evaporation model and with experimental data. The comparison shows that the numerical results are in agreement between each other and with the experimental data for the energies of projectile particles lower than 200-300 MeV for fast neutrons. Cross-sections of isotope yields in the neutron interactions with radioactive iodine, americium, plutonium and others isotopes have been calculated.

  7. Ligands of low electronegativity in the vsepr model: molecular pseudohalides

    Science.gov (United States)

    Glidewell, Christopher; Holden, H. Diane

    Equilibrium structures and force constants at linearity, for the skeletal bending mode δ(RNX) have been calculated in the MNDO approximation for 67 isocyanates, isothio-cyanates and azides, RNXY (XY = CO, CS or N 2) and the corresponding structures and force constants, δ(RCN), for 12 fulminates RCNO. Fulminates all have linear skeletons, but for RNXY the molecular skeleton is linear at atom X only if it is linear at N also ; otherwise the skeleton RNXY has a trans planar structure. Bending force constants are large and negative for all azides studied, negative for methyl and substituted methyl isocyanates and isothiocyanates and very small and positive for silyl and substituted silyl isothiocyanates: for silyl and substituted silyl isocyanales, the force constant is small and positive when the R group has effective C2v symmetry, but small and negative when the R group has only effective Cs symmetry.

  8. Molecular model for annihilation rates in positron complexes

    International Nuclear Information System (INIS)

    Assafrao, Denise; Walters, H.R. James; Mohallem, Jose R.

    2008-01-01

    The molecular approach for positron interaction with atoms is developed further. Potential energy curves for positron motion are obtained. Two procedures accounting for the nonadiabatic effective positron mass are introduced for calculating annihilation rate constants. The first one takes the bound-state energy eigenvalue as an input parameter. The second is a self-contained and self-consistent procedure. The methods are tested with quite different states of the small complexes HPs, e + He (electronic triplet) and e + Be (electronic singlet and triplet). For states yielding the positronium cluster, the annihilation rates are quite stable, irrespective of the accuracy in binding energies. For the e + Be states, annihilation rates are larger and more consistent with qualitative predictions than previously reported ones

  9. Molecular model for annihilation rates in positron complexes

    Energy Technology Data Exchange (ETDEWEB)

    Assafrao, Denise [Laboratorio de Atomos e Moleculas Especiais, Departamento de Fisica, ICEx, Universidade Federal de Minas Gerais, P.O. Box 702, 30123-970 Belo Horizonte, MG (Brazil); Department of Applied Mathematics and Theoretical Physics, Queen' s University of Belfast, Belfast BT7 1NN, Northern Ireland (United Kingdom); Walters, H.R. James [Department of Applied Mathematics and Theoretical Physics, Queen' s University of Belfast, Belfast BT7 1NN, Northern Ireland (United Kingdom); Mohallem, Jose R. [Laboratorio de Atomos e Moleculas Especiais, Departamento de Fisica, ICEx, Universidade Federal de Minas Gerais, P.O. Box 702, 30123-970 Belo Horizonte, MG (Brazil); Department of Applied Mathematics and Theoretical Physics, Queen' s University of Belfast, Belfast BT7 1NN, Northern Ireland (United Kingdom)], E-mail: rachid@fisica.ufmg.br

    2008-02-15

    The molecular approach for positron interaction with atoms is developed further. Potential energy curves for positron motion are obtained. Two procedures accounting for the nonadiabatic effective positron mass are introduced for calculating annihilation rate constants. The first one takes the bound-state energy eigenvalue as an input parameter. The second is a self-contained and self-consistent procedure. The methods are tested with quite different states of the small complexes HPs, e{sup +}He (electronic triplet) and e{sup +}Be (electronic singlet and triplet). For states yielding the positronium cluster, the annihilation rates are quite stable, irrespective of the accuracy in binding energies. For the e{sup +}Be states, annihilation rates are larger and more consistent with qualitative predictions than previously reported ones.

  10. Modeling the Residual Stresses in Reactive Resins-Based Materials: a Case Study of Photo-Sensitive Composites for Dental Applications

    Science.gov (United States)

    Grassia, Luigi; D'Amore, Alberto

    2010-06-01

    Residual stresses in reactive resins-based composites are associated to the net volumetric contraction (shrinkage) arising during the cross-linking reactions. Depending on the restoration geometry (the ratio of the free surface area to the volume of the cavity) the frozen-in stresses can be as high as the strength of the dental composites. This is the main reason why the effectiveness and then the durability of restorations with composites remains quite lower than those realized with metal alloys based materials. In this paper we first explore the possibility to circumvent the mathematical complexity arising from the determination of residual stresses in reactive systems three-dimensionally constrained. Then, the results of our modeling approach are applied to a series of commercially available composites showing that almost all samples develop residual stresses such that the restoration undergoes failure as soon as it is realized.

  11. Modeling the Residual Stresses in Reactive Resins-Based Materials: a Case Study of Photo-Sensitive Composites for Dental Applications

    International Nuclear Information System (INIS)

    Grassia, Luigi; D'Amore, Alberto

    2010-01-01

    Residual stresses in reactive resins-based composites are associated to the net volumetric contraction (shrinkage) arising during the cross-linking reactions. Depending on the restoration geometry (the ratio of the free surface area to the volume of the cavity) the frozen-in stresses can be as high as the strength of the dental composites. This is the main reason why the effectiveness and then the durability of restorations with composites remains quite lower than those realized with metal alloys based materials. In this paper we first explore the possibility to circumvent the mathematical complexity arising from the determination of residual stresses in reactive systems three-dimensionally constrained. Then, the results of our modeling approach are applied to a series of commercially available composites showing that almost all samples develop residual stresses such that the restoration undergoes failure as soon as it is realized.

  12. Molecular modeling of metal complexation by a fluoroquinolone antibiotic.

    Science.gov (United States)

    Aristilde, Ludmilla; Sposito, Garrison

    2008-11-01

    An understanding of the factors controlling the chemodynamics of fluoroquinolone antibiotics in different environmental matrices is a necessary prerequisite to the assessment of their potential impact on nontarget organisms in soils and receiving waters. Of particular interest are the complexes formed between fluoroquinolones and metal cations, which are believed to be important in the mechanism of sequestration of the antibiotic by minerals and natural organic matter. The structures of these complexes have not been fully resolved by conventional spectroscopy; therefore, molecular simulations may provide useful complementary insights. We present results from apparently the first molecular dynamics simulations of a widely used fluoroquinolone antibiotic, ciprofloxacin (Cipro), in aqueous complexes with five metal cations typically found in soils and surface waters: Ca2+, Mg2+, Fe2+, Na+, and K+. The interatomic potential functions employed in the simulations were validated by comparison with available structural data for solid-phase Cipro-hexahydrate and for the metal cations in aqueous solution. Although no comprehensive structural data on the aqueous complexes appear to be available, properties of the metal complexes predicted by our simulations agree with available data for solid-phase metal-Cipro complexes. Our results indicate that the ionic potential of the metal cation controls the stability of the complex formed and that the hydration number of the metal cation in aqueous solution determines its coordination number with O atoms in the metal-Cipro complex. In respect to environmental chemodynamics, our results imply that Cipro will form two configurations of bidendate chelates with metal centers on exposed surfaces of mineral oxides, water-bridged surface complexes with exchangeable cations in clay mineral interlayers, and cation-bridged complexes with functional groups in natural organic matter.

  13. Quantum Mechanics/Molecular Mechanics Modeling of Drug Metabolism

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... are useful for understanding drug metabolism....

  14. Structure-activity relationships of β-hydroxyphosphonate nucleoside analogues as cytosolic 5'-nucleotidase II potential inhibitors: synthesis, in vitro evaluation and molecular modeling studies.

    Science.gov (United States)

    Meurillon, Maïa; Marton, Zsuzsanna; Hospital, Audrey; Jordheim, Lars Petter; Béjaud, Jérôme; Lionne, Corinne; Dumontet, Charles; Périgaud, Christian; Chaloin, Laurent; Peyrottes, Suzanne

    2014-04-22

    The cytosolic 5'-nucleotidase II (cN-II) has been proposed as an attractive molecular target for the development of novel drugs circumventing resistance to cytotoxic nucleoside analogues currently used for treating leukemia and other malignant hemopathies. In the present work, synthesis of β-hydroxyphosphonate nucleoside analogues incorporating modifications either on the sugar residue or the nucleobase, and their in vitro evaluation towards the purified enzyme were carried out in order to determine their potency towards the inhibition of cN-II. In addition to the biochemical investigations, molecular modeling studies revealed important structural features for binding affinities towards the target enzyme. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Mapping allostery through computational glycine scanning and correlation analysis of residue-residue contacts.

    Science.gov (United States)

    Johnson, Quentin R; Lindsay, Richard J; Nellas, Ricky B; Fernandez, Elias J; Shen, Tongye

    2015-02-24

    Understanding allosteric mechanisms is essential for the physical control of molecular switches and downstream cellular responses. However, it is difficult to decode essential allosteric motions in a high-throughput scheme. A general two-pronged approach to performing automatic data reduction of simulation trajectories is presented here. The first step involves coarse-graining and identifying the most dynamic residue-residue contacts. The second step is performing principal component analysis of these contacts and extracting the large-scale collective motions expressed via these residue-residue contacts. We demonstrated the method using a protein complex of nuclear receptors. Using atomistic modeling and simulation, we examined the protein complex and a set of 18 glycine point mutations of residues that constitute the binding pocket of the ligand effector. The important motions that are responsible for the allostery are reported. In contrast to conventional induced-fit and lock-and-key binding mechanisms, a novel "frustrated-fit" binding mechanism of RXR for allosteric control was revealed.

  16. Integrated Computational Tools for Identification of CCR5 Antagonists as Potential HIV-1 Entry Inhibitors: Homology Modeling, Virtual Screening, Molecular Dynamics Simulations and 3D QSAR Analysis

    Directory of Open Access Journals (Sweden)

    Suri Moonsamy

    2014-04-01

    Full Text Available Using integrated in-silico computational techniques, including homology modeling, structure-based and pharmacophore-based virtual screening, molecular dynamic simulations, per-residue energy decomposition analysis and atom-based 3D-QSAR analysis, we proposed ten novel compounds as potential CCR5-dependent HIV-1 entry inhibitors. Via validated docking calculations, binding free energies revealed that novel leads demonstrated better binding affinities with CCR5 compared to maraviroc, an FDA-approved HIV-1 entry inhibitor and in clinical use. Per-residue interaction energy decomposition analysis on the averaged MD structure showed that hydrophobic active residues Trp86, Tyr89 and Tyr108 contributed the most to inhibitor binding. The validated 3D-QSAR model showed a high cross-validated rcv2 value of 0.84 using three principal components and non-cross-validated r2 value of 0.941. It was also revealed that almost all compounds in the test set and training set yielded a good predicted value. Information gained from this study could shed light on the activity of a new series of lead compounds as potential HIV entry inhibitors and serve as a powerful tool in the drug design and development machinery.

  17. The Surface Layer Mechanical Condition and Residual Stress Forming Model in Surface Plastic Deformation Process with the Hardened Body Effect Consideration

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    Mahalov, M. S.; Blumenstein, V. Yu

    2017-10-01

    The mechanical condition and residual stresses (RS) research and computational algorithms creation in complex types of loading on the product lifecycle stages relevance is shown. The mechanical state and RS forming finite element model at surface plastic deformation strengthening machining, including technological inheritance effect, is presented. A model feature is the production previous stages obtained transformation properties consideration, as well as these properties evolution during metal particles displacement through the deformation space in the present loading step.

  18. Characterization of the binding of shikonin to human immunoglobulin using scanning electron microscope, molecular modeling and multi-spectroscopic methods.

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    He, Wenying; Ye, Xinyu; Yao, Xiaojun; Wu, Xiuli; Lin, Qiang; Huang, Guolei; Hua, Yingjie; Hui, Yang

    2015-11-05

    Shikonin, one of the active components isolated from the root of Arnebia euchroma (Royle) Johnst, have anti-tumor, anti-bacterial and anti-inflammatory activities and has been used clinically in phlebitis and vascular purpura. In the present work, the interaction of human immunoglobulin (HIg) with shikonin has been investigated by using scanning electron microscope (SEM), Fourier transform infrared (FT-IR) spectroscopy, fluorescence polarization, synchronous and 3D fluorescence spectroscopy in combination with molecular modeling techniques under physiological conditions with drug concentrations of 3.33-36.67 μM. The results of SEM exhibited visually the special effect on aggregation behavior of the complex formed between HIg and shikonin. The fluorescence polarization values indicated that shikonin molecules were found in a motionally unrestricted environment introduced by HIg. Molecular docking showed the shikonin moiety bound to the hydrophobic cavity of HIg, and there are four hydrogen-bonding interactions between shikonin and the residues of protein. The synchronous and 3D fluorescence spectra confirmed that shikonin could quench the intrinsic fluorescence of HIg and has an effect on the microenvironment around HIg in aqueous solution. The changes in the secondary structure of HIg were estimated by qualitative and quantitative FT-IR spectroscopic analysis. The binding constants and thermodynamic parameters for shikonin-HIg systems were obtained under different temperatures (300 K, 310 K and 320 K). The above results revealed the binding mechanism of shikonin and HIg at the ultrastructure and molecular level. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Prediction of Sliding Friction Coefficient Based on a Novel Hybrid Molecular-Mechanical Model.

    Science.gov (United States)

    Zhang, Xiaogang; Zhang, Yali; Wang, Jianmei; Sheng, Chenxing; Li, Zhixiong

    2018-08-01

    Sliding friction is a complex phenomenon which arises from the mechanical and molecular interactions of asperities when examined in a microscale. To reveal and further understand the effects of micro scaled mechanical and molecular components of friction coefficient on overall frictional behavior, a hybrid molecular-mechanical model is developed to investigate the effects of main factors, including different loads and surface roughness values, on the sliding friction coefficient in a boundary lubrication condition. Numerical modelling was conducted using a deterministic contact model and based on the molecular-mechanical theory of friction. In the contact model, with given external loads and surface topographies, the pressure distribution, real contact area, and elastic/plastic deformation of each single asperity contact were calculated. Then asperity friction coefficient was predicted by the sum of mechanical and molecular components of friction coefficient. The mechanical component was mainly determined by the contact width and elastic/plastic deformation, and the molecular component was estimated as a function of the contact area and interfacial shear stress. Numerical results were compared with experimental results and a good agreement was obtained. The model was then used to predict friction coefficients in different operating and surface conditions. Numerical results explain why applied load has a minimum effect on the friction coefficients. They also provide insight into the effect of surface roughness on the mechanical and molecular components of friction coefficients. It is revealed that the mechanical component dominates the friction coefficient when the surface roughness is large (Rq > 0.2 μm), while the friction coefficient is mainly determined by the molecular component when the surface is relatively smooth (Rq friction coefficient are recommended.

  20. Panel 4: Recent Advances in Otitis Media in Molecular Biology, Biochemistry, Genetics, and Animal Models

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    Li, Jian-Dong; Hermansson, Ann; Ryan, Allen F.; Bakaletz, Lauren O.; Brown, Steve D.; Cheeseman, Michael T.; Juhn, Steven K.; Jung, Timothy T. K.; Lim, David J.; Lim, Jae Hyang; Lin, Jizhen; Moon, Sung-Kyun; Post, J. Christopher

    2014-01-01

    Background Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Objective To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. Data Sources and Review Methods A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Results Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Conclusions and Implications for Practice Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications. PMID:23536532