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Sample records for model molecular system

  1. 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:

  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. Diffusion-controlled interface kinetics-inclusive system-theoretic propagation models for molecular communication systems

    Science.gov (United States)

    Chude-Okonkwo, Uche A. K.; Malekian, Reza; Maharaj, B. T.

    2015-12-01

    Inspired by biological systems, molecular communication has been proposed as a new communication paradigm that uses biochemical signals to transfer information from one nano device to another over a short distance. The biochemical nature of the information transfer process implies that for molecular communication purposes, the development of molecular channel models should take into consideration diffusion phenomenon as well as the physical/biochemical kinetic possibilities of the process. The physical and biochemical kinetics arise at the interfaces between the diffusion channel and the transmitter/receiver units. These interfaces are herein termed molecular antennas. In this paper, we present the deterministic propagation model of the molecular communication between an immobilized nanotransmitter and nanoreceiver, where the emission and reception kinetics are taken into consideration. Specifically, we derived closed-form system-theoretic models and expressions for configurations that represent different communication systems based on the type of molecular antennas used. The antennas considered are the nanopores at the transmitter and the surface receptor proteins/enzymes at the receiver. The developed models are simulated to show the influence of parameters such as the receiver radius, surface receptor protein/enzyme concentration, and various reaction rate constants. Results show that the effective receiver surface area and the rate constants are important to the system's output performance. Assuming high rate of catalysis, the analysis of the frequency behavior of the developed propagation channels in the form of transfer functions shows significant difference introduce by the inclusion of the molecular antennas into the diffusion-only model. It is also shown that for t > > 0 and with the information molecules' concentration greater than the Michaelis-Menten kinetic constant of the systems, the inclusion of surface receptors proteins and enzymes in the models

  4. 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.

  5. 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.

  6. 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.

  7. Parametrizing coarse grained models for molecular systems at equilibrium

    KAUST Repository

    Kalligiannaki, Evangelia

    2016-10-18

    Hierarchical coarse graining of atomistic molecular systems at equilibrium has been an intensive research topic over the last few decades. In this work we (a) review theoretical and numerical aspects of different parametrization methods (structural-based, force matching and relative entropy) to derive the effective interaction potential between coarse-grained particles. All methods approximate the many body potential of mean force; resulting, however, in different optimization problems. (b) We also use a reformulation of the force matching method by introducing a generalized force matching condition for the local mean force in the sense that allows the approximation of the potential of mean force under both linear and non-linear coarse graining mappings (E. Kalligiannaki, et al., J. Chem. Phys. 2015). We apply and compare these methods to: (a) a benchmark system of two isolated methane molecules; (b) methane liquid; (c) water; and (d) an alkane fluid. Differences between the effective interactions, derived from the various methods, are found that depend on the actual system under study. The results further reveal the relation of the various methods and the sensitivities that may arise in the implementation of numerical methods used in each case.

  8. 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…

  9. Origami: A Versatile Modeling System for Visualising Chemical Structure and Exploring Molecular Function

    Science.gov (United States)

    Davis, James; Leslie, Ray; Billington, Susan; Slater, Peter R.

    2010-01-01

    The use of "Origami" is presented as an accessible and transferable modeling system through which to convey the intricacies of molecular shape and highlight structure-function relationships. The implementation of origami has been found to be a versatile alternative to conventional ball-and-stick models, possessing the key advantages of being both…

  10. Molecular modeling in confined polymer and biomembrane systems

    Directory of Open Access Journals (Sweden)

    Jayeeta Ghosh

    2009-07-01

    Full Text Available The computational study of soft materials under confinement for bio- and nanotechnology still poses significantchallenges but has come a long way in the last decade. It is possible to realistically model and understand the fundamentalmechanisms which are at play if soft materials are confined to nanometer dimensions. Here, we present several recentexamples of such studies. Thin polymer films are abundantly used as friction modifiers or steric stabilizers. We show howsystematic modeling can shed light on the interplay between entropic and energetic interactions. Thin glassy films arecritical for the success of nanolithography. For that we have to understand the effect of confinement on the glass transitionbehavior in order to guarantee the stability and integrity of the lithographic masks. Simulations aim to understand the fundamental differences in the densities of states of glass formers in bulk and under confinement. With the advent of bionanotechnology the structure and phase behavior of lipid membranes as models for cellular membranes at the nano scale length is of importance due to implications in understanding the role of the lipids in biochemical membrane processes.

  11. Theory of quantum and classical connections in modeling atomic, molecular and electrodynamical systems

    CERN Document Server

    Popa, Alexandru

    2013-01-01

    Quantum and Classical Connections in Modeling Atomic, Molecular and Electrodynamic Systems is intended for scientists and graduate students interested in the foundations of quantum mechanics and applied scientists interested in accurate atomic and molecular models. This is a reference to those working in the new field of relativistic optics, in topics related to relativistic interactions between very intense laser beams and particles, and is based on 30 years of research. The novelty of this work consists of accurate connections between the properties of quantum equations and correspon

  12. Applications of quantum and classical connections in modeling atomic, molecular and electrodynamic systems

    CERN Document Server

    Popa, Alexandru

    2013-01-01

    Applications of Quantum and Classical Connections in Modeling Atomic, Molecular and Electrodynamical Systems is a reference on the new field of relativistic optics, examining topics related to relativistic interactions between very intense laser beams and particles. Based on 30 years of research, this unique book connects the properties of quantum equations to corresponding classical equations used to calculate the energetic values and the symmetry properties of atomic, molecular and electrodynamical systems. In addition, it examines applications for these methods, and for the calculation of

  13. Quantitative computational models of molecular self-assembly in systems biology

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-06-01

    Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

  14. Quantitative computational models of molecular self-assembly in systems biology.

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-05-23

    Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

  15. Synergetics of molecular systems

    CERN Document Server

    Lupichev, Lev N; Kadantsev, Vasiliy N

    2014-01-01

    Synergetics is the quantitative study of multicomponent systems that exhibit nonlinear dynamics and cooperativity. This book specifically considers basic models of the nonlinear dynamics of molecular systems and discusses relevant applications in biological physics and the polymer sciences.Emphasis is placed on specific solutions to the dynamical equations that correspond to the coherent formation of spatial-temporal structures, such as solitons, kinks and breathers, in particular. The emergence of these patterns in molecular structures provides a variety of information on their structural pro

  16. Molecular modeling information transfer with VRML: from small molecules to large systems in bioscience.

    Science.gov (United States)

    Moeckel, G; Keil, M; Exner, T; Brickmann, J

    1998-01-01

    The suitability of the Virtual Reality Modeling Language (VRML) for the communication of scientists via the internet is demonstrated with recent results from computer assisted cancer research: I. Substrate channels in cytochrome P450 enzymes. II. Binding properties of the wild type and mutated p53 tumor suppressor protein. Complex 3D molecular models were used to visualize new insights in the active site access of cytochrome P450 enzymes and in the p53 protein-DNA binding achieved by the use of computational methods. These 3D models of biomolecular systems were transferred into VRML scenarios. Additional implemented features allow users to receive related information interactively. With these examples it is shown that VRML provides an efficient method for scientific information exchange by the use of complex 3D molecular models.

  17. Comparison of molecular mechanisms mediating cell contact phenomena in model developmental systems: an exploration of universality.

    Science.gov (United States)

    Bowers-Morrow, Vivienne M; Ali, Sinan O; Williams, Keith L

    2004-08-01

    Are there universal molecular mechanisms associated with cell contact phenomena during metazoan ontogenesis? Comparison of adhesion systems in disparate model systems indicates the existence of unifying principles. Requirements for multicellularity are (a) the construction of three-dimensional structures involving a crucial balance between adhesiveness and motility; and (b) the establishment of integration at molecular, cellular, tissue, and organismal levels of organization. Mechanisms for (i) cell-cell and cell-substrate adhesion, (ii) cell movement, (iii) cell-cell communication, (iv) cellular responses, (v) regulation of these processes, and (vi) their integration with patterning, growth, and other developmental processes are all crucial to metazoan development, and must have been present for the emergence and radiation of Metazoa. The principal unifying themes of this review are the dynamics and regulation of cell contact phenomena. Our knowledge of the dynamic molecular mechanisms underlying cell contact phenomena remains fragmentary. Here we examine the molecular bases of cell contact phenomena using extant model developmental systems (representing a wide range of phyla) including the simplest i.e. sponges, and the eukaryotic protist Dictyostelium discoideum, the more complex Drosophila melanogaster, and vertebrate systems. We discuss cell contact phenomena in a broad developmental context. The molecular language of cell contact phenomena is complex; it involves a plethora of structurally and functionally diverse molecules, and diverse modes of intermolecular interactions mediated by protein and/or carbohydrate moieties. Reasons for this are presumably the necessity for a high degree of specificity of intermolecular interactions, the requirement for a multitude of different signals, and the apparent requirement for an increasingly large repertoire of cell contact molecules in more complex developmental systems, such as the developing vertebrate nervous

  18. Mathematical models of non-linear phenomena, processes and systems: from molecular scale to planetary atmosphere

    CERN Document Server

    2013-01-01

    This book consists of twenty seven chapters, which can be divided into three large categories: articles with the focus on the mathematical treatment of non-linear problems, including the methodologies, algorithms and properties of analytical and numerical solutions to particular non-linear problems; theoretical and computational studies dedicated to the physics and chemistry of non-linear micro-and nano-scale systems, including molecular clusters, nano-particles and nano-composites; and, papers focused on non-linear processes in medico-biological systems, including mathematical models of ferments, amino acids, blood fluids and polynucleic chains.

  19. Thermodynamic Modeling of Ag-Ni System Combining Experiments and Molecular Dynamic Simulation

    Science.gov (United States)

    Rajkumar, V. B.; Chen, Sinn-wen

    2017-04-01

    Ag-Ni is a simple and important system with immiscible liquids and (Ag,Ni) phases. Previously, this system has been thermodynamically modeled utilizing certain thermochemical and phase equilibria information based on conjecture. An attempt is made in this study to determine the missing information which are difficult to measure experimentally. The boundaries of the liquid miscibility gap at high temperatures are determined using a pyrometer. The temperature of the liquid ⇌ (Ag) + (Ni) eutectic reaction is measured using differential thermal analysis. Tie-lines of the Ag-Ni system at 1023 K and 1473 K are measured using a conventional metallurgical method. The enthalpy of mixing of the liquid at 1773 K and the (Ag,Ni) at 973 K is calculated by molecular dynamics simulation using a large-scale atomic/molecular massively parallel simulator. These results along with literature information are used to model the Gibbs energy of the liquid and (Ag,Ni) by a calculation of phase diagrams approach, and the Ag-Ni phase diagram is then calculated.

  20. Model systems to unravel the molecular mechanisms of heavy metal tolerance in the ericoid mycorrhizal symbiosis.

    Science.gov (United States)

    Daghino, Stefania; Martino, Elena; Perotto, Silvia

    2016-05-01

    Ericoid mycorrhizal plants dominate in harsh environments where nutrient-poor, acidic soil conditions result in a higher availability of potentially toxic metals. Although metal-tolerant plant species and ecotypes are known in the Ericaceae, metal tolerance in these plants has been mainly attributed to their association with ericoid mycorrhizal fungi. The mechanisms underlying plant protection by the fungal symbiont are poorly understood, whereas some insights have been achieved regarding the molecular mechanisms of heavy metal tolerance in the fungal symbiont. This review will briefly introduce the general features of heavy metal tolerance in mycorrhizal fungi and will then focus on the use of "omics" approaches and heterologous expression in model organisms to reveal the molecular bases of fungal response to heavy metals. Functional complementation in Saccharomyces cerevisiae has allowed the identification of several ericoid mycorrhizal fungi genes (i.e., antioxidant enzymes, metal transporters, and DNA damage repair proteins) that may contribute to metal tolerance in a metal-tolerant ericoid Oidiodendron maius isolate. Although a powerful system, the use of the yeast complementation assay to study metal tolerance in mycorrhizal symbioses has limitations. Thus, O. maius has been developed as a model system to study heavy metal tolerance mechanisms in mycorrhizal fungi, thanks to its high metal tolerance, easy handling and in vitro mycorrhization, stable genetic transformation, genomics, transcriptomic and proteomic resources.

  1. Optimizing a 3D model system for molecular manipulation of tenogenesis.

    Science.gov (United States)

    Chien, Chun; Pryce, Brian; Tufa, Sara F; Keene, Douglas R; Huang, Alice H

    2017-09-22

    Tendon injuries are clinically challenging due to poor healing. A better understanding of the molecular events that regulate tendon differentiation would improve current strategies for repair. The mouse model system has been instrumental to tendon studies and several key molecules were initially established in mouse. However, the study of gene function has been limited by the absence of a standard in vitro tendon system for efficiently testing multiple mutations, physical manipulations, and mis-expression. The purpose of this study is therefore to establish such a system. We adapted an existing design for generating three-dimensional (3D) tendon constructs for use with mouse progenitor cells harboring the ScxGFP tendon reporter and the Rosa26-TdTomato Cre reporter. Using these cells, we optimized the parameters for construct formation, inducing tenogenesis via transforming growth factor-β2 (TGFβ2), and genetic recombination via an adenovirus encoding Cre recombinase. Finally, for proof of concept, we used Smad4 floxed cells and tested the robustness of the system for gene knockdown. We found that TGFβ2 treatment induced a tenogenic phenotype depending on the timing of initiation. Addition of TGFβ2 after 3D "tensioning" enhanced tendon differentiation. Interestingly, while TGFβ2-induced proliferation depended on Smad4, tenogenic parameters such as ScxGFP expression and fibril diameter were independent of Smad4. Our results demonstrate the feasibility of this optimized system for harnessing the power of mouse genetics for in vitro applications.

  2. 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.

  3. Molecular finite-size effects in stochastic models of equilibrium chemical systems.

    Science.gov (United States)

    Cianci, Claudia; Smith, Stephen; Grima, Ramon

    2016-02-28

    The reaction-diffusion master equation (RDME) is a standard modelling approach for understanding stochastic and spatial chemical kinetics. An inherent assumption is that molecules are point-like. Here, we introduce the excluded volume reaction-diffusion master equation (vRDME) which takes into account volume exclusion effects on stochastic kinetics due to a finite molecular radius. We obtain an exact closed form solution of the RDME and of the vRDME for a general chemical system in equilibrium conditions. The difference between the two solutions increases with the ratio of molecular diameter to the compartment length scale. We show that an increase in the fraction of excluded space can (i) lead to deviations from the classical inverse square root law for the noise-strength, (ii) flip the skewness of the probability distribution from right to left-skewed, (iii) shift the equilibrium of bimolecular reactions so that more product molecules are formed, and (iv) strongly modulate the Fano factors and coefficients of variation. These volume exclusion effects are found to be particularly pronounced for chemical species not involved in chemical conservation laws. Finally, we show that statistics obtained using the vRDME are in good agreement with those obtained from Brownian dynamics with excluded volume interactions.

  4. Respectful Modeling: Addressing Uncertainty in Dynamic System Models for Molecular Biology.

    Science.gov (United States)

    Tsigkinopoulou, Areti; Baker, Syed Murtuza; Breitling, Rainer

    2017-06-01

    Although there is still some skepticism in the biological community regarding the value and significance of quantitative computational modeling, important steps are continually being taken to enhance its accessibility and predictive power. We view these developments as essential components of an emerging 'respectful modeling' framework which has two key aims: (i) respecting the models themselves and facilitating the reproduction and update of modeling results by other scientists, and (ii) respecting the predictions of the models and rigorously quantifying the confidence associated with the modeling results. This respectful attitude will guide the design of higher-quality models and facilitate the use of models in modern applications such as engineering and manipulating microbial metabolism by synthetic biology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Multiphotochromic molecular systems

    NARCIS (Netherlands)

    Fihey, Arnaud; Perrier, Aurélie; Browne, Wesley R; Jacquemin, Denis

    2015-01-01

    Molecular systems encompassing more than one photochromic entity can be used to build highly functional materials, thanks to their potential multi-addressability and/or multi-response properties. Over the last decade, the synthesis and spectroscopic and kinetic characterisation as well as the

  7. Toward a molecular understanding of psychostimulant actions using genetically engineered dopamine receptor knockout mice as model systems.

    Science.gov (United States)

    Zhang, J; Xu, M

    2001-01-01

    A major focus in studying the progression and prevention of addictive diseases has been to understand the molecular and cellular mechanisms underlying drug addiction. The brain dopaminergic system plays a central role in reward and motivation and is thought to be the main neural substrate for the actions of abusive drugs. We have used the gene targeting technology to generate dopamine D1 and D3 receptor knockout mice and used these mice as model systems to gain a molecular understanding of acute effects of psychostimulants cocaine and amphetamine. The use of a combined approach involving behavioral, electrophysiological as well as molecular studies has allowed us to define initially the roles of dopamine D1 and D3 receptors in the acute effects of psychostimulants and will enable us to understand mechanisms underlying their chronic actions in the future.

  8. Ames interactive molecular model building system - A 3-D computer modelling system applied to the study of the origin of life

    Science.gov (United States)

    Coeckelenbergh, Y.; Macelroy, R. D.; Rein, R.

    1978-01-01

    The investigation of specific interactions among biological molecules must take into consideration the stereochemistry of the structures. Thus, models of the molecules are essential for describing the spatial organization of potentially interacting groups, and estimations of conformation are required for a description of spatial organization. Both the function of visualizing molecules, and that of estimating conformation through calculations of energy, are part of the molecular modeling system described in the present paper. The potential uses of the system in investigating some aspects of the origin of life rest on the assumption that translation of conformation from genetic elements to catalytic elements would have been required for the development of the first replicating systems subject to the process of biological evolution.

  9. Validation of periodontitis screening model using sociodemographic, systemic, and molecular information in a Korean population.

    Science.gov (United States)

    Kim, Hyun-Duck; Sukhbaatar, Munkhzaya; Shin, Myungseop; Ahn, Yoo-Been; Yoo, Wook-Sung

    2014-12-01

    This study aims to evaluate and validate a periodontitis screening model that includes sociodemographic, metabolic syndrome (MetS), and molecular information, including gingival crevicular fluid (GCF), matrix metalloproteinase (MMP), and blood cytokines. The authors selected 506 participants from the Shiwha-Banwol cohort: 322 participants from the 2005 cohort for deriving the screening model and 184 participants from the 2007 cohort for its validation. Periodontitis was assessed by dentists using the community periodontal index. Interleukin (IL)-6, IL-8, and tumor necrosis factor-α in blood and MMP-8, -9, and -13 in GCF were assayed using enzyme-linked immunosorbent assay. MetS was assessed by physicians using physical examination and blood laboratory data. Information about age, sex, income, smoking, and drinking was obtained by interview. Logistic regression analysis was applied to finalize the best-fitting model and validate the model using sensitivity, specificity, and c-statistics. The derived model for periodontitis screening had a sensitivity of 0.73, specificity of 0.85, and c-statistic of 0.86 (P validated model were 0.64, 0.91, and 0.83 (P periodontitis. A future prospective study is indicated for evaluating this model's ability to predict the occurrence of periodontitis.

  10. Studies on the stability and intermolecular interactions of cellulose and polylactide systems using molecular modeling

    Science.gov (United States)

    Karst, David T.

    The stability and intermolecular interactions of cellulose and polylactide (PLA) systems were studied using molecular modeling. This work explains how grafting various groups onto cellulose increases hydrolysis of the glycosidic linkages of cellulose. A substituent increases hydrolysis of cellulose by serving as an anchor to the end of the cleaved cellulose to which it is bonded, making it less mobile, and allowing it to have stronger interactions than those in pure hydrolyzed cellulose. Hydrolysis increases with the size of the substituent. Molecules sorbed but not grafted to cellulose do not increase hydrolysis. Hydrolysis mainly occurs at glucoses bonded to the substituent. A substituent on the sixth carbon position of cellulose increases hydrolysis to a greater extent than does one on the second or third carbon position. The effect of blending poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) and the effect of various arrangements of L-lactide and D-lactide in poly(L-lactide-co-D-lactide) on the resistance of polylactide (PLA) to hydrolysis has been explained. Among the homopolymer blends, the 50/50 PLLA/PDLA blend has the greatest resistance to hydrolysis due to its having stronger hydrogen-bonding and van der Waals forces than pure PLLA or PDLA. The change in potential energy for hydrolysis decreases linearly with increasing % PLLA or % PDLA from 0 to 50%. Among the copolymers containing a given percentage of L-lactide and D-lactide, those containing longer blocks of L-lactide and D-lactide have greater resistance to hydrolysis compared to those with shorter blocks or random copolymers because copolymers with longer blocks are more stable before hydrolysis compared to the other copolymers. Among the copolymers with long blocks of L- and D-lactide, those containing 50% L-lactide have a greater resistance to hydrolysis compared to the copolymers with 26% or 74% L-lactide. Blends or copolymers that are mirror images of each other have the same resistance to

  11. Associations between the molecular and optical properties of dissolved organic matter in the Florida Everglades, a model coastal wetland system

    Directory of Open Access Journals (Sweden)

    Sasha eWagner

    2015-11-01

    Full Text Available Optical properties are easy-to-measure proxies for dissolved organic matter (DOM composition, source and reactivity. However, the molecular signature of DOM associated with such optical parameters remains poorly defined. The Florida coastal Everglades is a subtropical wetland with diverse vegetation (e.g., sawgrass prairies, mangrove forests, seagrass meadows and DOM sources (e.g., terrestrial, microbial and marine. As such, the Everglades is an excellent model system from which to draw samples of diverse origin and composition to allow classically-defined optical properties to be linked to molecular properties of the DOM pool. We characterized a suite of seasonally- and spatially-collected DOM samples using optical measurements (EEM-PARAFAC, SUVA254, S275-295, S350-400, SR, FI, freshness index and HIX and ultrahigh resolution mass spectrometry (FTICR-MS. Spearman’s rank correlations between FTICR-MS signal intensities of individual molecular formulae and optical properties determined which molecular formulae were associated with each PARAFAC component and optical index. The molecular families that tracked with the optical indices were generally in agreement with conventional biogeochemical interpretations. Therefore, although they represent only a small portion of the bulk DOM pool, absorbance and fluorescence measurements appear to be appropriate proxies for the aquatic cycling of both optically-active and associated optically-inactive DOM in coastal wetlands.

  12. Molecular descriptors of benzenoid systems

    Directory of Open Access Journals (Sweden)

    Nazeran Idrees

    Full Text Available Molecular descriptors are being widely used in QSAR/QSPR studies in chemistry and drug designing as well as modeling of compounds. Different topological descriptors have been formulated to investigate the physio chemical properties and chemical reactivity of compounds. In this article we gave exact relations for first and second Zagreb index, hyper Zagreb index, multiplicative Zagreb indices as well as first and second Zagreb polynomials for some benzenoid systems.

  13. Building New Bridges between In Vitro and In Vivo in Early Drug Discovery: Where Molecular Modeling Meets Systems Biology.

    Science.gov (United States)

    Pearlstein, Robert A; McKay, Daniel J J; Hornak, Viktor; Dickson, Callum; Golosov, Andrei; Harrison, Tyler; Velez-Vega, Camilo; Duca, José

    2017-01-01

    Cellular drug targets exist within networked function-generating systems whose constituent molecular species undergo dynamic interdependent non-equilibrium state transitions in response to specific perturbations (i.e.. inputs). Cellular phenotypic behaviors are manifested through the integrated behaviors of such networks. However, in vitro data are frequently measured and/or interpreted with empirical equilibrium or steady state models (e.g. Hill, Michaelis-Menten, Briggs-Haldane) relevant to isolated target populations. We propose that cells act as analog computers, "solving" sets of coupled "molecular differential equations" (i.e. represented by populations of interacting species)via "integration" of the dynamic state probability distributions among those populations. Disconnects between biochemical and functional/phenotypic assays (cellular/in vivo) may arise with targetcontaining systems that operate far from equilibrium, and/or when coupled contributions (including target-cognate partner binding and drug pharmacokinetics) are neglected in the analysis of biochemical results. The transformation of drug discovery from a trial-and-error endeavor to one based on reliable design criteria depends on improved understanding of the dynamic mechanisms powering cellular function/dysfunction at the systems level. Here, we address the general mechanisms of molecular and cellular function and pharmacological modulation thereof. We outline a first principles theory on the mechanisms by which free energy is stored and transduced into biological function, and by which biological function is modulated by drug-target binding. We propose that cellular function depends on dynamic counter-balanced molecular systems necessitated by the exponential behavior of molecular state transitions under non-equilibrium conditions, including positive versus negative mass action kinetics and solute-induced perturbations to the hydrogen bonds of solvating water versus kT. Copyright© Bentham

  14. Theoretical modeling of large molecular systems. Advances in the local self consistent field method for mixed quantum mechanics/molecular mechanics calculations.

    Science.gov (United States)

    Monari, Antonio; Rivail, Jean-Louis; Assfeld, Xavier

    2013-02-19

    Molecular mechanics methods can efficiently compute the macroscopic properties of a large molecular system but cannot represent the electronic changes that occur during a chemical reaction or an electronic transition. Quantum mechanical methods can accurately simulate these processes, but they require considerably greater computational resources. Because electronic changes typically occur in a limited part of the system, such as the solute in a molecular solution or the substrate within the active site of enzymatic reactions, researchers can limit the quantum computation to this part of the system. Researchers take into account the influence of the surroundings by embedding this quantum computation into a calculation of the whole system described at the molecular mechanical level, a strategy known as the mixed quantum mechanics/molecular mechanics (QM/MM) approach. The accuracy of this embedding varies according to the types of interactions included, whether they are purely mechanical or classically electrostatic. This embedding can also introduce the induced polarization of the surroundings. The difficulty in QM/MM calculations comes from the splitting of the system into two parts, which requires severing the chemical bonds that link the quantum mechanical subsystem to the classical subsystem. Typically, researchers replace the quantoclassical atoms, those at the boundary between the subsystems, with a monovalent link atom. For example, researchers might add a hydrogen atom when a C-C bond is cut. This Account describes another approach, the Local Self Consistent Field (LSCF), which was developed in our laboratory. LSCF links the quantum mechanical portion of the molecule to the classical portion using a strictly localized bond orbital extracted from a small model molecule for each bond. In this scenario, the quantoclassical atom has an apparent nuclear charge of +1. To achieve correct bond lengths and force constants, we must take into account the inner shell of

  15. Molecular model of a type III secretion system needle: Implications for host-cell sensing.

    Science.gov (United States)

    Deane, Janet E; Roversi, Pietro; Cordes, Frank S; Johnson, Steven; Kenjale, Roma; Daniell, Sarah; Booy, Frank; Picking, William D; Picking, Wendy L; Blocker, Ariel J; Lea, Susan M

    2006-08-15

    Type III secretion systems are essential virulence determinants for many Gram-negative bacterial pathogens. The type III secretion system consists of cytoplasmic, transmembrane, and extracellular domains. The extracellular domain is a hollow needle protruding above the bacterial surface and is held within a basal body that traverses both bacterial membranes. Effector proteins are translocated, via this external needle, directly into host cells, where they subvert normal cell functions to aid infection. Physical contact with host cells initiates secretion and leads to formation of a pore, thought to be contiguous with the needle channel, in the host-cell membrane. Here, we report the crystal structure of the Shigella flexneri needle subunit MxiH and a complete model for the needle assembly built into our three-dimensional EM reconstruction. The model, combined with mutagenesis data, reveals that signaling of host-cell contact is relayed through the needle via intersubunit contacts and suggests a mode of binding for a tip complex.

  16. A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

    Science.gov (United States)

    Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

    2015-04-29

    Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

  17. 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.

  18. Effects of Organics on the Adsorption and Mobility of Metal Cations in Clay Systems: Computational Molecular Modeling Approach

    International Nuclear Information System (INIS)

    Kalinichev, Andrey G.; Ngouana Wakou, Brice F.; Loganathan, Narasimhan

    2013-01-01

    Understanding and prediction of many natural and anthropogenic environmental processes ultimately depend on a fundamental understanding of the chemistry occurring at the mineral-fluid inter-faces. Clay-related minerals and natural organic matter (NOM) are ubiquitous in the environment, and metal-NOM complexation induces strong correlations between the NOM concentration in water and the capacity of clay particles to bind metals, thus affecting their speciation, solubility and toxicity in the environment. Despite significant geochemical, environmental and technological interest, the molecular-level mechanisms and dynamics of the physical and chemical processes involving NOM are not yet well understood. In this presentation we compare three different molecular dynamics (MD) computer simulations of metal-NOM complexation in aqueous solutions. The simulation results indicate that despite some obvious quantitative variations in the computed values depending on the size of the simulated system and on the parameters of the force field models used, all three simulations are quite robust and consistent. In particular, approximately 35-50% of Ca 2+ ions in all simulations are associated with the carboxylic groups of NOM at near-neutral pH. The stability of bidentate-coordinated contact ion pair complexes is also always strongly preferred. Easy association of metal cations with negatively charged NOM functional groups and negatively charged clay surfaces allows us to predict that cationic bridging could be the most probable mechanism of NOM association with clays in natural environments. New MD simulations are currently in progress to quantitatively assess these predictions on a molecular scale for nuclear waste disposal applications. New larger-scale clay models incorporate a more realistic representation of the structural and compositional disorder of natural illites and smectites and employ CLAYFF - a fully flexible general force field suitable for the molecular simulations

  19. Top-down models in biology: explanation and control of complex living systems above the molecular level.

    Science.gov (United States)

    Pezzulo, Giovanni; Levin, Michael

    2016-11-01

    It is widely assumed in developmental biology and bioengineering that optimal understanding and control of complex living systems follows from models of molecular events. The success of reductionism has overshadowed attempts at top-down models and control policies in biological systems. However, other fields, including physics, engineering and neuroscience, have successfully used the explanations and models at higher levels of organization, including least-action principles in physics and control-theoretic models in computational neuroscience. Exploiting the dynamic regulation of pattern formation in embryogenesis and regeneration requires new approaches to understand how cells cooperate towards large-scale anatomical goal states. Here, we argue that top-down models of pattern homeostasis serve as proof of principle for extending the current paradigm beyond emergence and molecule-level rules. We define top-down control in a biological context, discuss the examples of how cognitive neuroscience and physics exploit these strategies, and illustrate areas in which they may offer significant advantages as complements to the mainstream paradigm. By targeting system controls at multiple levels of organization and demystifying goal-directed (cybernetic) processes, top-down strategies represent a roadmap for using the deep insights of other fields for transformative advances in regenerative medicine and systems bioengineering. © 2016 The Author(s).

  20. The quantum-chemical modeling of structure and spectral characteristics for molecular complexes in system «penton-terlon»

    Directory of Open Access Journals (Sweden)

    Andrey V. Tokar

    2014-03-01

    Full Text Available The structure and spectral properties for molecular complexes, which formed by added monomer form of pentaplast as well as N-phenylbenzamide with some species of intermolecular interaction in system «penton-terlon» have been investigated at ab initio level of theory. It is shown, that the main contribution in total energy of molecules have included by dispersion forces, which realized between Chlorine atom of CH2Cl-group and Hydrogen atoms of benzene rings with amide fragment. The proposed theoretical models are validated in reflection of spectral and energetic characteristics of investigating system. Finally, the results of calculations are in good agreement with that data, which have been obtained for such type modeling previously.

  1. Vanadium(V) complexes in enzyme systems: aqueous chemistry, inhibition and molecular modeling in inhibitor design.

    Science.gov (United States)

    Bhattacharyya, S; Tracey, A S

    2001-05-01

    Vanadate in aqueous solution is known to influence a number of enzyme-catalyzed reactions. Such effects are well known to carry over to living systems where numerous responses to the influence of vanadium have been well-documented; perhaps the most studied being the insulin-mimetic effect. Studies of the aqueous chemistry of vanadate provide an insight into the mechanisms by which vanadate affects enzyme systems and suggests methods for the elucidation of specific types of responses. Studies of the corresponding enzymes provide complementary information that suggests model vanadate systems be studied and provides clues as to functional groups that might be utilized in the development of selective enzyme inhibition. The insulin-mimetic effect is thought by many workers to originate in the effectiveness of vanadium as an inhibitor of protein tyrosine phosphatase (PTPase) activity. One, or more PTPases regulate the phosphotyrosine levels of the insulin receptor kinase domain. Appropriate ligands allow modification of the reactivity and function of vanadate. For instance, although the complex, ((CH(3))(2)NO)(2)V(O)OH, is not quite as good an inhibitor of PTPase activity as is vanadate, it is much more effective in cell cultures for increasing glucose transport and glycogen synthesis. Studies of the chemistry of this complex provide an explanation of the efficacy of this compound as a PTPase inhibitor that is supported by computer modeling studies. Computer calculations using X-ray data of known PTPases as a basis for homology modeling then suggests functionality that needs to be addressed in developing selective PTPase inhibitors.

  2. 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...

  3. 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

  4. 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.

  5. 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 ...

  6. 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.

  7. 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.

  8. Boolean Networks in Inference and Dynamic Modeling of Biological Systems at the Molecular and Physiological Level

    Science.gov (United States)

    Thakar, Juilee; Albert, Réka

    The following sections are included: * Introduction * Boolean Network Concepts and History * Extensions of the Classical Boolean Framework * Boolean Inference Methods and Examples in Biology * Dynamic Boolean Models: Examples in Plant Biology, Developmental Biology and Immunology * Conclusions * References

  9. 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.

  10. Molecular Thermodynamic Modeling and Design of Microencapsulation Systems for Drug Delivery

    DEFF Research Database (Denmark)

    Abildskov, Jens; O’Connell, John P.

    2011-01-01

    A systematic design strategy is given for computer-aided design of microparticle drug-delivery systems produced by solvent evaporation. In particular, design of solvents, polymer material, and external phase composition are considered for the case when the active ingredient is known. The procedur...

  11. Br and O···Cl halogen bonds in some small model molecular systems

    Indian Academy of Sciences (India)

    Abstract. Halogen bonding interactions of type X···O=C are important in various fields including bio- logical systems. In this work, theoretical calculations were carried out using B3LYP/6-31++G**, MP2/6-. 31++G** and MP2/aug-cc-pVDZ methods on a series of O··· X halogen bonds between CH2O and CH3CHO as halogen ...

  12. A Molecular Survey of the Diversity of Microbial Communities in Different Amazonian Agricultural Model Systems

    Directory of Open Access Journals (Sweden)

    Acácio A. Navarrete

    2010-05-01

    Full Text Available The processes of land conversion and agricultural intensification are a significant cause of biodiversity loss, with consequent negative effects both on the environment and the sustainability of food production.The anthrosols associated with pre-Colombian settlements in the Amazonian region are examples of how anthropogenic activities may sustain the native populations against harsh tropical environments for human establishment, even without a previous intentionality of anthropic soil formation. In a case study (Model I—“Slash-and-Burn” the community structures detected by automated ribosomal intergenic spacer analysis (ARISA revealed that soil archaeal, bacterial and fungal communities are heterogeneous and each capable of responding differently to environmental characteristics. ARISA data evidenced considerable difference in structure existing between microbial communities in forest and agricultural soils. In a second study (Model II—“Anthropogenic Soil”, the bacterial community structures revealed by terminal restriction fragment length polymorphism (T-RFLP differed among an Amazonian Dark Earth (ADE, black carbon (BC and its adjacent non-anthropogenic oxisoil. The bacterial 16S rRNA gene (OTU richness estimated by pyrosequencing was higher in ADE than BC. The most abundant bacterial phyla in ADE soils and BC were Proteobacteria—24% ADE, 15% BC; Acidobacteria—10% ADE, 21% BC; Actinobacteria—7% ADE, 12% BC; Verrucomicrobia, 8% ADE; 9% BC; Firmicutes—3% ADE, 8% BC. Overall, unclassified bacteria corresponded to 36% ADE, and 26% BC. Regardless of current land uses, our data suggest that soil microbial community structures may be strongly influenced by the historical soil management and that anthrosols in Amazonia, of anthropogenic origins, in addition to their capacity of enhancing crop yields, may also improve microbial diversity, with the support of the black carbon, which may sustain a particular and unique habitat for the

  13. Theoretical modelling of photoactive molecular systems: insights using the Density Functional Theory

    Energy Technology Data Exchange (ETDEWEB)

    Ciofini, I.; Adamo, C. [Ecole Nationale Superieure de Chimie de Paris, Lab. d' Electrochimie et Chimie Analytique, CNRS UMR 7575, 75 - Paris (France); Laine, Ph.P. [Universite Rene-Descartes, Lab. de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, 75 - Paris (France); Bedioui, F. [Ecole Nationale Superieure de Chimie de Paris, Lab. de Pharmacologie Chimique et Genetique, CNRS FRE 2463 and INSERM U 640, 75 - Paris (France); Daul, C.A. [Fribourg Univ., Dept. de Chimie (Switzerland)

    2006-02-15

    An account of the performance of a modern and efficient approach to Density Functional Theory (DFT) for the prediction of the photophysical behavior of a series of Ru(II) and Os(II) complexes is given. The time-dependent-DFT method was used to interpret their electronic spectra. Two different types of compounds have been analyzed: (1) a complex undergoing a light induced isomerization of one of its coordination bonds; (2) an inorganic dyads expected to undergo intramolecular photoinduced electron transfer to form a charge separated (CS) sate. Besides the noticeable quantitative agreement between computed and experimental absorption spectra, our results allow to clarify, by first principles, both the nature of the excited states and the photochemical behavior of these complex systems, thus underlying the predictive character of the theoretical approach. (authors)

  14. Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

    Science.gov (United States)

    Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

    2015-04-14

    We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

  15. Reaction dynamics in polyatomic molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Miller, W.H. [Lawrence Berkeley Laboratory, CA (United States)

    1993-12-01

    The goal of this program is the development of theoretical methods and models for describing the dynamics of chemical reactions, with specific interest for application to polyatomic molecular systems of special interest and relevance. There is interest in developing the most rigorous possible theoretical approaches and also in more approximate treatments that are more readily applicable to complex systems.

  16. Modeling Molecular Machinery

    Science.gov (United States)

    Hunter, Christine

    2015-01-01

    Imagine a microscopic world filled with tiny motors, ratchets, switches, and pumps controlled by complex signaling and feedback systems. Now imagine that these parts can assemble themselves. This is the world presented to students in the protein structure unit of a genetic engineering course. Students learn how protein folding gives rise to the…

  17. Molecular structure, dynamics and hydration studies of soybean storage proteins and model systems by nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Kakalis, L.T.

    1989-01-01

    The potential of high-resolution 13 C NMR for the characterization of soybean storage proteins was explored. The spectra of a commercial soy protein isolate as well as those of alkali-denatured 7S and 11S soybean globulins were well resolved and tentatively assigned. Relaxation measurements indicated fast motion for several side chains and the protein backbone. Protein fractions (11S and 7S) were also investigated at various states of molecular association. The large size of the multisubunit soybean storage proteins affected adversely both the resolution and the sensitivity of their 13 C NMR spectra. A comparison of 17 O and 2 H NMR relaxation rates of water in solutions of lysozyme (a model system) as a function of concentration, pH and magnetic field suggested that only 17 O monitors directly the hydration of lysozyme. Analysis of 17 O NMR lysozyme hydration data in terms of a two-state, fast-exchange, anisotropic model resulted in hydration parameters which are consistent with the protein's physico-chemical properties. The same model was applied to the calculation of the amount and mobility of bound water in soy protein dispersions by means of 17 O NMR relaxation measurements as a function of protein concentration. The protein concentration dependences of 1 H transverse NMR relaxation measurements at various pH and ionic strength values were fitted by a viral expansion. The interpretation of the data was based on the effects of protein aggregation, salt binding and protein group ionization on the NMR measurements. In all cases, relaxation rates showed a linear dependence on protein activity

  18. 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

  19. 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...

  20. Modeling convection-diffusion-reaction systems for microfluidic molecular communications with surface-based receivers in Internet of Bio-Nano Things.

    Science.gov (United States)

    Kuscu, Murat; Akan, Ozgur B

    2018-01-01

    We consider a microfluidic molecular communication (MC) system, where the concentration-encoded molecular messages are transported via fluid flow-induced convection and diffusion, and detected by a surface-based MC receiver with ligand receptors placed at the bottom of the microfluidic channel. The overall system is a convection-diffusion-reaction system that can only be solved by numerical methods, e.g., finite element analysis (FEA). However, analytical models are key for the information and communication technology (ICT), as they enable an optimisation framework to develop advanced communication techniques, such as optimum detection methods and reliable transmission schemes. In this direction, we develop an analytical model to approximate the expected time course of bound receptor concentration, i.e., the received signal used to decode the transmitted messages. The model obviates the need for computationally expensive numerical methods by capturing the nonlinearities caused by laminar flow resulting in parabolic velocity profile, and finite number of ligand receptors leading to receiver saturation. The model also captures the effects of reactive surface depletion layer resulting from the mass transport limitations and moving reaction boundary originated from the passage of finite-duration molecular concentration pulse over the receiver surface. Based on the proposed model, we derive closed form analytical expressions that approximate the received pulse width, pulse delay and pulse amplitude, which can be used to optimize the system from an ICT perspective. We evaluate the accuracy of the proposed model by comparing model-based analytical results to the numerical results obtained by solving the exact system model with COMSOL Multiphysics.

  1. 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 ...

  2. Relaxation time in disordered molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Rodrigo P. [Departamento de Física, Universidade Federal de Santa Catarina, 88040-900 Florianópolis-SC (Brazil); Freire, José A., E-mail: jfreire@fisica.ufpr.br [Departamento de Física, Universidade Federal do Paraná, 81531-990 Curitiba-PR (Brazil)

    2015-05-28

    Relaxation time is the typical time it takes for a closed physical system to attain thermal equilibrium. The equilibrium is brought about by the action of a thermal reservoir inducing changes in the system micro-states. The relaxation time is intuitively expected to increase with system disorder. We derive a simple analytical expression for this dependence in the context of electronic equilibration in an amorphous molecular system model. We find that the disorder dramatically enhances the relaxation time but does not affect its independence of the nature of the initial state.

  3. 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.

  4. Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis.

    Science.gov (United States)

    Forrey, Christopher; Saylor, David M; Silverstein, Joshua S; Douglas, Jack F; Davis, Eric M; Elabd, Yossef A

    2014-10-14

    Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems.

  5. Information theory of molecular systems

    CERN Document Server

    Nalewajski, Roman F

    2006-01-01

    As well as providing a unified outlook on physics, Information Theory (IT) has numerous applications in chemistry and biology owing to its ability to provide a measure of the entropy/information contained within probability distributions and criteria of their information ""distance"" (similarity) and independence. Information Theory of Molecular Systems applies standard IT to classical problems in the theory of electronic structure and chemical reactivity. The book starts by introducing the basic concepts of modern electronic structure/reactivity theory based upon the Density Functional Theory

  6. 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:

  7. 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.

  8. Accounting for intra-molecular vibrational modes in open quantum system description of molecular systems.

    Science.gov (United States)

    Roden, Jan; Strunz, Walter T; Whaley, K Birgitta; Eisfeld, Alexander

    2012-11-28

    Electronic-vibrational dynamics in molecular systems that interact with an environment involve a large number of degrees of freedom and are therefore often described by means of open quantum system approaches. A popular approach is to include only the electronic degrees of freedom into the system part and to couple these to a non-Markovian bath of harmonic vibrational modes that is characterized by a spectral density. Since this bath represents both intra-molecular and external vibrations, it is important to understand how to construct a spectral density that accounts for intra-molecular vibrational modes that couple further to other modes. Here, we address this problem by explicitly incorporating an intra-molecular vibrational mode together with the electronic degrees of freedom into the system part and using the Fano theory for a resonance coupled to a continuum to derive an "effective" bath spectral density, which describes the contribution of intra-molecular modes. We compare this effective model for the intra-molecular mode with the method of pseudomodes, a widely used approach in simulation of non-Markovian dynamics. We clarify the difference between these two approaches and demonstrate that the respective resulting dynamics and optical spectra can be very different.

  9. Interaction between ropinirole hydrochloride and aspirin with human serum albumin as binary and ternary systems by multi-spectroscopic, molecular modeling and zeta potential

    International Nuclear Information System (INIS)

    Mahaki, Hanie; Memarpoor-Yazdi, Mina; Chamani, Jamshidkhan; Reza Saberi, Mohammad

    2013-01-01

    The aim of the present study was to describe the competition of ropinirole hydrochloride (RP) and aspirin (ASA) in binding to human serum albumin (HSA) in physiological buffer (pH=7.4) using multi-spectroscopic, molecular modeling and zeta-potential measurements. Fluorescence analysis was used to define the binding and quenching properties of drug-HSA complexes in binary and ternary systems. Fluorescence spectroscopy showed that in the presence of RP, the binding constant of HSA–ASA was increased. Static quenching was confirmed to result in the fluorescence quenching and FRET. The effect of drugs on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy, three-dimensional fluorescence spectra and circular dichroism (CD). The RLS method determined the critical aggregation concentration of drugs on HSA in binary and ternary systems that confirmed the zeta potential results. Structural modeling showed that the affinity of each of the drugs to HSA in binary and ternary systems confirms the spectroscopic results. - Highlights: ► We studied the interaction of ropinirole hydrochloride and aspirin with HSA. ► Molecular modeling and zeta-potential used to describe competitive interaction. ► We determined the critical induced aggregation concentration of both drugs on HSA. ► The binding mechanism of drugs as separate and simultaneous to HSA has been compared. ► The binding site of both drugs as simultaneous effects on HSA has been determined.

  10. Interaction between ropinirole hydrochloride and aspirin with human serum albumin as binary and ternary systems by multi-spectroscopic, molecular modeling and zeta potential

    Energy Technology Data Exchange (ETDEWEB)

    Mahaki, Hanie, E-mail: hanieh.mahaki@gmail.com [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Memarpoor-Yazdi, Mina; Chamani, Jamshidkhan [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Reza Saberi, Mohammad [Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-02-15

    The aim of the present study was to describe the competition of ropinirole hydrochloride (RP) and aspirin (ASA) in binding to human serum albumin (HSA) in physiological buffer (pH=7.4) using multi-spectroscopic, molecular modeling and zeta-potential measurements. Fluorescence analysis was used to define the binding and quenching properties of drug-HSA complexes in binary and ternary systems. Fluorescence spectroscopy showed that in the presence of RP, the binding constant of HSA-ASA was increased. Static quenching was confirmed to result in the fluorescence quenching and FRET. The effect of drugs on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy, three-dimensional fluorescence spectra and circular dichroism (CD). The RLS method determined the critical aggregation concentration of drugs on HSA in binary and ternary systems that confirmed the zeta potential results. Structural modeling showed that the affinity of each of the drugs to HSA in binary and ternary systems confirms the spectroscopic results. - Highlights: Black-Right-Pointing-Pointer We studied the interaction of ropinirole hydrochloride and aspirin with HSA. Black-Right-Pointing-Pointer Molecular modeling and zeta-potential used to describe competitive interaction. Black-Right-Pointing-Pointer We determined the critical induced aggregation concentration of both drugs on HSA. Black-Right-Pointing-Pointer The binding mechanism of drugs as separate and simultaneous to HSA has been compared. Black-Right-Pointing-Pointer The binding site of both drugs as simultaneous effects on HSA has been determined.

  11. 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.

  12. 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,…

  13. 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...

  14. Reactions of small molecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Wittig, C. [Univ. of Southern California, Los Angeles, CA (United States)

    1993-12-01

    This DOE program remains focused on small molecular systems relevant to combustion. Though a number of experimental approaches and machines are available for this research, the authors` activities are centered around the high-n Rydberg time-of-flight (HRTOF) apparatus in this laboratory. One student and one postdoc carry out experiments with this machine and also engage in small intra-group collaborations involving shared equipment. This past year was more productive than the previous two, due to the uninterrupted operation of the HRTOF apparatus. Results were obtained with CH{sub 3}OH, CH{sub 3}SH, Rg-HX complexes, HCOOH, and their deuterated analogs where appropriate. One paper is in print, three have been accepted for publication, and one is under review. Many preliminary results that augur well for the future were obtained with other systems such as HNO{sub 3}, HBr-HI complexes, toluene, etc. Highlights from the past year are presented below that display some of the features of this program.

  15. 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…

  16. 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

  17. A computational systems biology software platform for multiscale modeling and simulation: Integrating whole-body physiology, disease biology, and molecular reaction networks

    Directory of Open Access Journals (Sweden)

    Thomas eEissing

    2011-02-01

    Full Text Available Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multi-scale by nature, project work and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug-drug or drug-metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach.

  18. Development of the Fragment Molecular Orbital Method for Calculating Nonlocal Excitations in Large Molecular Systems.

    Science.gov (United States)

    Fujita, Takatoshi; Mochizuki, Yuji

    2018-04-19

    We developed the fragment-based method for calculating nonlocal excitations in large molecular systems. This method is based on the multilayer fragment molecular orbital method and the configuration interaction single (CIS) wave function using localized molecular orbitals. The excited-state wave function for the whole system is described as a superposition of configuration state functions (CSFs) for intrafragment excitations and for interfragment charge-transfer excitations. The formulation and calculations of singlet excited-state Hamiltonian matrix elements in the fragment CSFs are presented in detail. The efficient approximation schemes for calculating the matrix elements are also presented. The computational efficiency and the accuracy were evaluated using the molecular dimers and molecular aggregates. We confirmed that absolute errors of 50 meV (relative to the conventional calculations) are achievable for the molecular systems in their equilibrium geometries. The perturbative electron correlation correction to the CIS excitation energies is also demonstrated. The present theory can compute a large number of excited states in large molecular systems; in addition, it allows for the systematic derivation of a model exciton Hamiltonian. These features are useful for studying excited-state dynamics in condensed molecular systems based on the ab initio electronic structure theory.

  19. Validation of systems biology models

    NARCIS (Netherlands)

    Hasdemir, D.

    2015-01-01

    The paradigm shift from qualitative to quantitative analysis of biological systems brought a substantial number of modeling approaches to the stage of molecular biology research. These include but certainly are not limited to nonlinear kinetic models, static network models and models obtained by the

  20. General theory for multiple input-output perturbations in complex molecular systems. 1. Linear QSPR electronegativity models in physical, organic, and medicinal chemistry.

    Science.gov (United States)

    González-Díaz, Humberto; Arrasate, Sonia; Gómez-SanJuan, Asier; Sotomayor, Nuria; Lete, Esther; Besada-Porto, Lina; Ruso, Juan M

    2013-01-01

    In general perturbation methods starts with a known exact solution of a problem and add "small" variation terms in order to approach to a solution for a related problem without known exact solution. Perturbation theory has been widely used in almost all areas of science. Bhor's quantum model, Heisenberg's matrix mechanincs, Feyman diagrams, and Poincare's chaos model or "butterfly effect" in complex systems are examples of perturbation theories. On the other hand, the study of Quantitative Structure-Property Relationships (QSPR) in molecular complex systems is an ideal area for the application of perturbation theory. There are several problems with exact experimental solutions (new chemical reactions, physicochemical properties, drug activity and distribution, metabolic networks, etc.) in public databases like CHEMBL. However, in all these cases, we have an even larger list of related problems without known solutions. We need to know the change in all these properties after a perturbation of initial boundary conditions. It means, when we test large sets of similar, but different, compounds and/or chemical reactions under the slightly different conditions (temperature, time, solvents, enzymes, assays, protein targets, tissues, partition systems, organisms, etc.). However, to the best of our knowledge, there is no QSPR general-purpose perturbation theory to solve this problem. In this work, firstly we review general aspects and applications of both perturbation theory and QSPR models. Secondly, we formulate a general-purpose perturbation theory for multiple-boundary QSPR problems. Last, we develop three new QSPR-Perturbation theory models. The first model classify correctly >100,000 pairs of intra-molecular carbolithiations with 75-95% of Accuracy (Ac), Sensitivity (Sn), and Specificity (Sp). The model predicts probabilities of variations in the yield and enantiomeric excess of reactions due to at least one perturbation in boundary conditions (solvent, temperature

  1. Theoretical Modeling and Computer Simulations for the Origins and Evolution of Reproducing Molecular Systems and Complex Systems with Many Interactive Parts

    Science.gov (United States)

    Liang, Shoudan

    2000-01-01

    Our research effort has produced nine publications in peer-reviewed journals listed at the end of this report. The work reported here are in the following areas: (1) genetic network modeling; (2) autocatalytic model of pre-biotic evolution; (3) theoretical and computational studies of strongly correlated electron systems; (4) reducing thermal oscillations in atomic force microscope; (5) transcription termination mechanism in prokaryotic cells; and (6) the low glutamine usage in thennophiles obtained by studying completely sequenced genomes. We discuss the main accomplishments of these publications.

  2. 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

  3. 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.

  4. 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.

  5. A Molecular atlas of Xenopus respiratory system development.

    Science.gov (United States)

    Rankin, Scott A; Thi Tran, Hong; Wlizla, Marcin; Mancini, Pamela; Shifley, Emily T; Bloor, Sean D; Han, Lu; Vleminckx, Kris; Wert, Susan E; Zorn, Aaron M

    2015-01-01

    Respiratory system development is regulated by a complex series of endoderm-mesoderm interactions that are not fully understood. Recently Xenopus has emerged as an alternative model to investigate early respiratory system development, but the extent to which the morphogenesis and molecular pathways involved are conserved between Xenopus and mammals has not been systematically documented. In this study, we provide a histological and molecular atlas of Xenopus respiratory system development, focusing on Nkx2.1+ respiratory cell fate specification in the developing foregut. We document the expression patterns of Wnt/β-catenin, fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) signaling components in the foregut and show that the molecular mechanisms of respiratory lineage induction are remarkably conserved between Xenopus and mice. Finally, using several functional experiments we refine the epistatic relationships among FGF, Wnt, and BMP signaling in early Xenopus respiratory system development. We demonstrate that Xenopus trachea and lung development, before metamorphosis, is comparable at the cellular and molecular levels to embryonic stages of mouse respiratory system development between embryonic days 8.5 and 10.5. This molecular atlas provides a fundamental starting point for further studies using Xenopus as a model to define the conserved genetic programs controlling early respiratory system development. © 2014 Wiley Periodicals, Inc.

  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. 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...

  8. 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...

  9. 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

  10. pysimm: A Python Package for Simulation of Molecular Systems

    Science.gov (United States)

    Fortunato, Michael; Colina, Coray

    pysimm, short for python simulation interface for molecular modeling, is a python package designed to facilitate the structure generation and simulation of molecular systems through convenient and programmatic access to object-oriented representations of molecular system data. This poster presents core features of pysimm and design philosophies that highlight a generalized methodology for incorporation of third-party software packages through API interfaces. The integration with the LAMMPS simulation package is explained to demonstrate this methodology. pysimm began as a back-end python library that powered a cloud-based application on nanohub.org for amorphous polymer simulation. The extension from a specific application library to general purpose simulation interface is explained. Additionally, this poster highlights the rapid development of new applications to construct polymer chains capable of controlling chain morphology such as molecular weight distribution and monomer composition.

  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. Probing Interactions in Complex Molecular Systems through Ordered Assembly

    International Nuclear Information System (INIS)

    De Yoreo, J.J.; Bartelt, M.C.; Orme, C.A.; Villacampa, A.; Weeks, B.L.; Miller, A.E.

    2002-01-01

    Emerging from the machinery of epitaxial science and chemical synthesis, is a growing emphasis on development of self-organized systems of complex molecular species. The nature of self-organization in these systems spans the continuum from simple crystallization of large molecules such as dendrimers and proteins, to assembly into large organized networks of nanometer-scale structures such as quantum dots or nanoparticles. In truth, self-organization in complex molecular systems has always been a central feature of many scientific disciplines including fields as diverse as structural biology, polymer science and geochemistry. But over the past decade, changes in those fields have often been marked by the degree to which researchers are using molecular-scale approaches to understand the hierarchy of structures and processes driven by this ordered assembly. At the same time, physical scientists have begun to use their knowledge of simple atomic and molecular systems to fabricate synthetic self-organized systems. This increasing activity in the field of self-organization is testament to the success of the physical and chemical sciences in building a detailed understanding of crystallization and epitaxy in simple atomic and molecular systems, one that is soundly rooted in thermodynamics and chemical kinetics. One of the fundamental challenges of chemistry and materials science in the coming decades is to develop a similarly well-founded physical understanding of assembly processes in complex molecular systems. Over the past five years, we have successfully used in situ atomic force microscopy (AFM) to investigate the physical controls on single crystal epitaxy from solutions for a wide range of molecular species. More recently, we have combined this method with grazing incidence X-ray diffraction and kinetic Monte Carlo modeling in order to relate morphology to surface atomic structure and processes. The purpose of this proposal was to extend this approach to assemblies

  13. 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.

  14. Molecular alloy with diluted magnetic moments-molecular Kondo system.

    Science.gov (United States)

    Idobata, Yuki; Zhou, Biao; Kobayashi, Akiko; Kobayashi, Hayao

    2012-01-18

    [Ni(1-x)Cu(x)(tmdt)(2)] (tmdt = trimethylenetetrathiafulvalenedithiolate) was prepared for realizing molecular Kondo systems. Magnetic moments (S = (1)/(2)) are considered to exist at the central {CuS(4)} parts of Cu(tmdt)(2) molecules. The χT-versus-T curve of the system with x ≈ 0.15 showed a broad peak at ~10 K. The decrease in the χT value below 10 K is consistent with a singlet ground state, as expected for a Kondo system. However, in the system with x ≈ 0.27, the χT value decreased when the temperature was lowered to 2 K, indicating antiferromagnetic interactions between magnetic moments through π-d interactions. Although the susceptibility anomaly suggested that the π-d interactions become important at T K. However, the differential resistivity Δρ(T) = ρ(obs) - ρ(L)(T) showed a logarithmic resistivity increase at 8-20 K with decreasing temperature, where ρ(L)(T) is a fitted function of ρ(obs) obtained at T > 50 K that is considered to represent approximately the temperature dependence of the resistivity without spin scattering of the conduction electrons. © 2011 American Chemical Society

  15. 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...

  16. Modeling Molecular Systems at Extreme Pressure by an Extension of the Polarizable Continuum Model (PCM) Based on the Symmetry-Adapted Cluster-Configuration Interaction (SAC-CI) Method: Confined Electronic Excited States of Furan as a Test Case.

    Science.gov (United States)

    Fukuda, Ryoichi; Ehara, Masahiro; Cammi, Roberto

    2015-05-12

    Novel molecular photochemistry can be developed by combining high pressure and laser irradiation. For studying such high-pressure effects on the confined electronic ground and excited states, we extend the PCM (polarizable continuum model) SAC (symmetry-adapted cluster) and SAC-CI (SAC-configuration interaction) methods to the PCM-XP (extreme pressure) framework. By using the PCM-XP SAC/SAC-CI method, molecular systems in various electronic states can be confined by polarizable media in a smooth and flexible way. The PCM-XP SAC/SAC-CI method is applied to a furan (C4H4O) molecule in cyclohexane at high pressure (1-60 GPa). The relationship between the calculated free-energy and cavity volume can be approximately represented with the Murnaghan equation of state. The excitation energies of furan in cyclohexane show blueshifts with increasing pressure, and the extents of the blueshifts significantly depend on the character of the excitations. Particularly large confinement effects are found in the Rydberg states. The energy ordering of the lowest Rydberg and valence states alters under high-pressure. The pressure effects on the electronic structure may be classified into two contributions: a confinement of the molecular orbital and a suppression of the mixing between the valence and Rydberg configurations. The valence or Rydberg character in an excited state is, therefore, enhanced under high pressure.

  17. 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...

  18. Scalable Molecular Dynamics for Large Biomolecular Systems

    Directory of Open Access Journals (Sweden)

    Robert K. Brunner

    2000-01-01

    Full Text Available We present an optimized parallelization scheme for molecular dynamics simulations of large biomolecular systems, implemented in the production-quality molecular dynamics program NAMD. With an object-based hybrid force and spatial decomposition scheme, and an aggressive measurement-based predictive load balancing framework, we have attained speeds and speedups that are much higher than any reported in literature so far. The paper first summarizes the broad methodology we are pursuing, and the basic parallelization scheme we used. It then describes the optimizations that were instrumental in increasing performance, and presents performance results on benchmark simulations.

  19. 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.

  20. 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

  1. 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

  2. Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

    Science.gov (United States)

    Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

    2016-03-01

    Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

  3. Intelligent systems for the molecular biologist

    Energy Technology Data Exchange (ETDEWEB)

    Brutlag, D.L.

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. In this paper, one objective is to identify properties of DNA sequences that determine their function, by computer-aided statistical analysis and to accurately predict its function, given a new sequence. A related problem is to predict protein structure and function from the sequence.

  4. Molecular ecology of anaerobic reactor systems

    DEFF Research Database (Denmark)

    Hofman-Bang, H. Jacob Peider; Zheng, D.; Westermann, Peter

    2003-01-01

    for these processes. Only a few percent of Bacteria and Archaea have so far been isolated, and almost nothing is known about the dynamics and interactions between these and other microorganisms. This lack of knowledge is most clearly exemplified by the sometimes unpredictable and unexplainable failures...... to the abundance of each microbe in anaerobic reactor systems by rRNA probing. This chapter focuses on various molecular techniques employed and problems encountered when elucidating the microbial ecology of anaerobic reactor systems. Methods such as quantitative dot blot/fluorescence in-situ probing using various...

  5. 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,…

  6. 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.

  7. 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

  8. Molecular ecology of anaerobic reactor systems

    DEFF Research Database (Denmark)

    Hofman-Bang, H. Jacob Peider; Zheng, D.; Westermann, Peter

    2003-01-01

    Anaerobic reactor systems are essential for the treatment of solid and liquid wastes and constitute a core facility in many waste treatment plants. Although much is known about the basic metabolism in different types of anaerobic reactors, little is known about the microbes responsible for these ......Anaerobic reactor systems are essential for the treatment of solid and liquid wastes and constitute a core facility in many waste treatment plants. Although much is known about the basic metabolism in different types of anaerobic reactors, little is known about the microbes responsible...... and malfunctions of anaerobic digesters occasionally experienced, leading to sub-optimal methane production and wastewater treatment. Using a variety of molecular techniques, we are able to determine which microorganisms are active, where they are active, and when they are active, but we still need to determine...... to the abundance of each microbe in anaerobic reactor systems by rRNA probing. This chapter focuses on various molecular techniques employed and problems encountered when elucidating the microbial ecology of anaerobic reactor systems. Methods such as quantitative dot blot/fluorescence in-situ probing using various...

  9. 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

  10. 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

  11. Compositional Modeling of Biological Systems

    OpenAIRE

    Zámborszky, Judit

    2010-01-01

    Molecular interactions are wired in a fascinating way resulting in complex behavior of bio-logical systems. Theoretical modeling provides us a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological systems calls for conceptual tools that manage the combinatorial explosion of the set of possible interac-tions. A suitable conceptual tool to attack complexity is compositionality, already success-fully used in the process algebra field ...

  12. 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.

  13. 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...

  14. 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

  15. Systems Pharmacology in Small Molecular Drug Discovery.

    Science.gov (United States)

    Zhou, Wei; Wang, Yonghua; Lu, Aiping; Zhang, Ge

    2016-02-18

    Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  16. Systems Pharmacology in Small Molecular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    2016-02-01

    Full Text Available Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity, target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.

  17. Interfacial nanorheology: Probing molecular mobility in mesoscopic polymeric systems

    Science.gov (United States)

    Sills, Scott E.

    Investigating the finite size limited structural relaxations in mesoscopic polymer systems is central to nanotechnological applications involving thin films, complex structures, and nanoscale phase-separated systems; for example, polymer electrolyte membranes, optoelectronic devices, and ultrahigh-density thermomechanical data storage (terabit recording). In such systems, bulk statistical averaging and continuum models are jeopardized. Interfacial constraints lead to bulk-deviating molecular dynamics and dictate material and transport properties. The objective of this dissertation is to provide insight to the exotic mesoscopic behaviors in thin films by developing novel rheological and tribological analytical methods based on scanning probe microscopy (SPM). Activation energies are deduced for the molecular motions associated with internal friction dissipation, and the temperature resolved length scale for cooperative motion during the glass transition is directly obtained for polystyrene. These results confirm the dynamical heterogeneity of the glass transition and reveal a crossover from intra- to inter-molecular relaxation in the transition regime. The impact of dimensional constraints on molecular mobility in ultrathin polymer films is explored through interfacial glass-transition profiles. With these profiles, a structural model of the rheological changes near interfacial boundaries is constructed as function of molecular weight and crosslinking density. The manifestation of interfacial constraints in nanotechnological applications is illustrated for thermomechanical recording, where rheological gradients near the substrate dictate the contact pressure and strain shielding at the substrate compromises film stability. A foundation for the critical aspects of interfacial stability is developed, and mechanically graded interfaces and modulus-matching techniques are explored as a means of improving the stability, durability, and stress transmission characteristics

  18. 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.

  19. 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...

  20. 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.

  1. Hybrid Metaheuristic Approach for Nonlocal Optimization of Molecular Systems.

    Science.gov (United States)

    Dresselhaus, Thomas; Yang, Jack; Kumbhar, Sadhana; Waller, Mark P

    2013-04-09

    Accurate modeling of molecular systems requires a good knowledge of the structure; therefore, conformation searching/optimization is a routine necessity in computational chemistry. Here we present a hybrid metaheuristic optimization (HMO) algorithm, which combines ant colony optimization (ACO) and particle swarm optimization (PSO) for the optimization of molecular systems. The HMO implementation meta-optimizes the parameters of the ACO algorithm on-the-fly by the coupled PSO algorithm. The ACO parameters were optimized on a set of small difluorinated polyenes where the parameters exhibited small variance as the size of the molecule increased. The HMO algorithm was validated by searching for the closed form of around 100 molecular balances. Compared to the gradient-based optimized molecular balance structures, the HMO algorithm was able to find low-energy conformations with a 87% success rate. Finally, the computational effort for generating low-energy conformation(s) for the phenylalanyl-glycyl-glycine tripeptide was approximately 60 CPU hours with the ACO algorithm, in comparison to 4 CPU years required for an exhaustive brute-force calculation.

  2. Low Molecular Weight Glucosamine/L-lactide Copolymers as Potential Carriers for the Development of a Sustained Rifampicin Release System: Mycobacterium Smegmatis as a Tuberculosis Model

    Science.gov (United States)

    Ragusa, Jorge Alejandro

    Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged release (>14 days) of RIF from these particles is demonstrated. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism, and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) (reference material) particles did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated an increment in cell death as particle dose increased, but was not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. GluN-LLA particles led to higher uptakes than the PLA particles. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and the particles showed a favorable long term drug release effect in killing intracellular bacteria compared to free RIF. The studies presented and discussed in this dissertation

  3. Fused eco29kIR- and M genes coding for a fully functional hybrid polypeptide as a model of molecular evolution of restriction-modification systems

    Directory of Open Access Journals (Sweden)

    Solonin Alexander S

    2011-02-01

    Full Text Available Abstract Background The discovery of restriction endonucleases and modification DNA methyltransferases, key instruments of genetic engineering, opened a new era of molecular biology through development of the recombinant DNA technology. Today, the number of potential proteins assigned to type II restriction enzymes alone is beyond 6000, which probably reflects the high diversity of evolutionary pathways. Here we present experimental evidence that a new type IIC restriction and modification enzymes carrying both activities in a single polypeptide could result from fusion of the appropriate genes from preexisting bipartite restriction-modification systems. Results Fusion of eco29kIR and M ORFs gave a novel gene encoding for a fully functional hybrid polypeptide that carried both restriction endonuclease and DNA methyltransferase activities. It has been placed into a subclass of type II restriction and modification enzymes - type IIC. Its MTase activity, 80% that of the M.Eco29kI enzyme, remained almost unchanged, while its REase activity decreased by three times, concurrently with changed reaction optima, which presumably can be caused by increased steric hindrance in interaction with the substrate. In vitro the enzyme preferentially cuts DNA, with only a low level of DNA modification detected. In vivo new RMS can provide a 102-fold less protection of host cells against phage invasion. Conclusions We propose a molecular mechanism of appearing of type IIC restriction-modification and M.SsoII-related enzymes, as well as other multifunctional proteins. As shown, gene fusion could play an important role in evolution of restriction-modification systems and be responsible for the enzyme subclass interconversion. Based on the proposed approach, hundreds of new type IIC enzymes can be generated using head-to-tail oriented type I, II, and III restriction and modification genes. These bifunctional polypeptides can serve a basis for enzymes with altered

  4. The efficacy of dynamic irrigation using a commercially available system (RinsEndo) determined by removal of a collagen 'bio-molecular film' from an ex vivo model.

    Science.gov (United States)

    McGill, S; Gulabivala, K; Mordan, N; Ng, Y-L

    2008-07-01

    To compare the efficacy of three irrigation protocols using an established ex vivo bio-molecular film model. Thirty human teeth with single straight canals were randomly allocated to three groups [static, manual-dynamic, automated-dynamic (RinsEndo]; each with a sub-group (n = 5) for needle position at 4 or 10 mm short of the working length (WL). The root canals were prepared to apical size 40, taper 0.08. The teeth were split longitudinally into two halves and a standard coat of stained-collagen was applied to the canal surfaces. The re-assembled teeth were irrigated using one of the protocols with the irrigation needle at one of two positions. Digital images of the canal surfaces, before and after irrigation with 18 mL of 2.5% NaOCl, were used to score surface coverage with stained-collagen using image-analyses (ipWin4). The data were analysed using linear regression models. The canal area covered with stained-collagen was significantly (P irrigation (manual/automated) compared with static irrigation; but automated-dynamic irrigation was significantly (P = 0.037) less effective than manual-dynamic irrigation. The 'orientation of needle port', 'corono-apical level of canal' and 'apical extent of needle placement' were significant (P irrigation. Residual collagen was most evident in the coronal third. Deeper penetration of the needle tip resulted in significantly (P irrigation was significantly more effective (16%) than static irrigation but significantly less effective (5%) than manual-dynamic irrigation. Irrigation was more effective (7%) when the needle was placed closer to WL.

  5. Reversible uptake of molecular oxygen by heteroligand Co(II)-L-α-amino acid-imidazole systems: equilibrium models at full mass balance.

    Science.gov (United States)

    Pająk, Marek; Woźniczka, Magdalena; Vogt, Andrzej; Kufelnicki, Aleksander

    2017-09-19

    systems with alanine and asparagine-in those cases the of oxygenation reaction is right shifted to a relatively lower extent. The experimental results indicate that the "active" complex, able to take up dioxygen, is a heteroligand CoL 2 L'complex, where L = amac (an amino acid with a non-protonated amine group) while L' = Himid, with the N1 nitrogen protonated within the entire pH range under study. Moreover, the corresponding log  [Formula: see text] value at various initial total Co(II), amino acid and imidazole concentrations was found to be constant within the limits of error, which confirms those results. The highest log [Formula: see text] value, 14.9, occurs for the histidine system; in comparison, asparagine is 7.8 and alanine is 9.7. This high value is most likely due to the participation of the additional effective N3 donor of the imidazole side group of histidine. The Co(II)-amac-Himid systems formed by using a [Co(imid) 2 ] n polymer as starting material demonstrate that the reversible uptake of molecular oxygen occurs by forming dimeric μ-peroxy adducts. The essential impact on the electron structure of the dioxygen bridge, and therefore, on the reversibility of O 2 uptake, is due to the imidazole group at axial position (trans towards O 2 ). However, the results of reversibility measurements of O 2 uptake, unequivocally indicate a much higher effectiveness of dioxygenation than in systems in which the oxygen adducts are formed in equilibrium mixtures during titration of solutions containing Co(II) ions, the amino acid and imidazole, separately.

  6. 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 ...

  7. 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)

  8. 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

  9. 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...

  10. 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.

  11. Energy transfer in (bio)molecular systems

    NARCIS (Netherlands)

    Milder, Maaike Theresia Wilhelmina

    This thesis reports, using a variety of optical techniques, the energy transfer pathways in different potential building blocks for molecular electronic devices, namely an antenna, a molecular wire and fluorescent switches. Using pump-probe spectroscopy the time constants of these transfer processes

  12. 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…

  13. 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.

  14. A Hadoop-based Molecular Docking System

    Science.gov (United States)

    Dong, Yueli; Guo, Quan; Sun, Bin

    2017-10-01

    Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

  15. 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)

  16. 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

  17. Modeling of System Families

    National Research Council Canada - National Science Library

    Feiler, Peter

    2007-01-01

    .... The Society of Automotive Engineers (SAE) Architecture Analysis & Design Language (AADL) is an industry-standard, architecture-modeling notation specifically designed to support a component- based approach to modeling embedded systems...

  18. Molecular communications and nanonetworks from nature to practical systems

    CERN Document Server

    Atakan, Barış

    2014-01-01

    In this book, the concepts of molecular communications and nanonetworks are introduced. Throughout the book, the existing molecular communication paradigms are categorized into two main groups. The first group includes the Passive Molecular Communication (PMC) paradigms in which molecules freely diffuse to transfer information from a transmitter to a receiver. The second group includes the Active Molecular Communication (AMC) paradigms in which molecules are carried or guided by some mediators such as molecular motors, gap junction channels and bacteria. In the book, after briefly discussing why molecular communication is needed for the sophisticated nano and biotechnology applications, the existing molecular communication systems are first presented. Then, the principles of diffusion phenomena and molecular reception with absorbers and the ligand-receptor binding mechanism are introduced. Based on these principles, the communication theories and techniques are given for the PMC. Then, the physical dynamics o...

  19. Modelling Railway Interlocking Systems

    DEFF Research Database (Denmark)

    Lindegaard, Morten Peter; Viuf, P.; Haxthausen, Anne Elisabeth

    2000-01-01

    In this report we present a model of interlocking systems, and describe how the model may be validated by simulation. Station topologies are modelled by graphs in which the nodes denote track segments, and the edges denote connectivity for train traÆc. Points and signals are modelled by annotatio...

  20. 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

  1. Remote Laser Evaporative Molecular Absorption Spectroscopy Sensor System

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a sensor system capable of remotely probing the molecular composition of cold solar system targets (asteroids, comets, planets, moons), such as from a...

  2. 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

  3. A new parallel molecular dynamics algorithm for organic systems

    International Nuclear Information System (INIS)

    Plimpton, S.; Hendrickson, B.; Heffelfinger, G.

    1993-01-01

    A new parallel algorithm for simulating bonded molecular systems such as polymers and proteins by molecular dynamics (MD) is presented. In contrast to methods that extract parallelism by breaking the spatial domain into sub-pieces, the new method does not require regular geometries or uniform particle densities to achieve high parallel efficiency. For very large, regular systems spatial methods are often the best choice, but in practice the new method is faster for systems with tens-of-thousands of atoms simulated on large numbers of processors. It is also several times faster than the techniques commonly used for parallelizing bonded MD that assign a subset of atoms to each processor and require all-to-all communication. Implementation of the algorithm in a CHARMm-like MD model with many body forces and constraint dynamics is discussed and timings on the Intel Delta and Paragon machines are given. Example calculations using the algorithm in simulations of polymers and liquid-crystal molecules will also be briefly discussed

  4. 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.

  5. 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)

  6. 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

  7. 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

  8. Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

    Science.gov (United States)

    De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

    2010-03-01

    The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

  9. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

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

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  10. RSMASS system model development

    International Nuclear Information System (INIS)

    Marshall, A.C.; Gallup, D.R.

    1998-01-01

    RSMASS system mass models have been used for more than a decade to make rapid estimates of space reactor power system masses. This paper reviews the evolution of the RSMASS models and summarizes present capabilities. RSMASS has evolved from a simple model used to make rough estimates of space reactor and shield masses to a versatile space reactor power system model. RSMASS uses unique reactor and shield models that permit rapid mass optimization calculations for a variety of space reactor power and propulsion systems. The RSMASS-D upgrade of the original model includes algorithms for the balance of the power system, a number of reactor and shield modeling improvements, and an automatic mass optimization scheme. The RSMASS-D suite of codes cover a very broad range of reactor and power conversion system options as well as propulsion and bimodal reactor systems. Reactor choices include in-core and ex-core thermionic reactors, liquid metal cooled reactors, particle bed reactors, and prismatic configuration reactors. Power conversion options include thermoelectric, thermionic, Stirling, Brayton, and Rankine approaches. Program output includes all major component masses and dimensions, efficiencies, and a description of the design parameters for a mass optimized system. In the past, RSMASS has been used as an aid to identify and select promising concepts for space power applications. The RSMASS modeling approach has been demonstrated to be a valuable tool for guiding optimization of the power system design; consequently, the model is useful during system design and development as well as during the selection process. An improved in-core thermionic reactor system model RSMASS-T is now under development. The current development of the RSMASS-T code represents the next evolutionary stage of the RSMASS models. RSMASS-T includes many modeling improvements and is planned to be more user-friendly. RSMASS-T will be released as a fully documented, certified code at the end of

  11. Intermolecular thermoelectric-like effects in molecular nano electronic systems

    International Nuclear Information System (INIS)

    Sabzyan, H.; Safari, R.

    2012-01-01

    Intramolecular thermoelectric-like coefficients are introduced and computed of a single molecule nano electronic system. Values of the electronic Intramolecular thermoelectric-like coefficients are calculated based on the density and energy transfers between different parts of the molecule using quantum theory of atoms in molecule. Since, Joule and Peltier heating are even (symmetrical) and odd (antisymmetric) functions of the external bias, it is possible to divide Intramolecular thermoelectric-like coefficients into two components, symmetrical and antisymmetrical Intramolecular thermoelectric-like coefficients, which describe the intramolecular Joule-like and Peltier-like effects, respectively. In addition, a semiclassical temperature model is presented to describe intramolecular temperature mapping (intramolecular energy distributions) in molecular nano electronic systems.

  12. Interactive analysis of systems biology molecular expression data

    OpenAIRE

    Prabhakar Sunil; Salt David E; Kane Michael D; Stephenson Alan; Ouyang Qi; Zhang Mingwu; Burgner John; Buck Charles; Zhang Xiang

    2008-01-01

    Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferr...

  13. 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.

  14. Systemic resilience model

    International Nuclear Information System (INIS)

    Lundberg, Jonas; Johansson, Björn JE

    2015-01-01

    It has been realized that resilience as a concept involves several contradictory definitions, both for instance resilience as agile adjustment and as robust resistance to situations. Our analysis of resilience concepts and models suggest that beyond simplistic definitions, it is possible to draw up a systemic resilience model (SyRes) that maintains these opposing characteristics without contradiction. We outline six functions in a systemic model, drawing primarily on resilience engineering, and disaster response: anticipation, monitoring, response, recovery, learning, and self-monitoring. The model consists of four areas: Event-based constraints, Functional Dependencies, Adaptive Capacity and Strategy. The paper describes dependencies between constraints, functions and strategies. We argue that models such as SyRes should be useful both for envisioning new resilience methods and metrics, as well as for engineering and evaluating resilient systems. - Highlights: • The SyRes model resolves contradictions between previous resilience definitions. • SyRes is a core model for envisioning and evaluating resilience metrics and models. • SyRes describes six functions in a systemic model. • They are anticipation, monitoring, response, recovery, learning, self-monitoring. • The model describes dependencies between constraints, functions and strategies

  15. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  16. Advances in study of molecular imaging reporte gene systems

    International Nuclear Information System (INIS)

    Wu Tao; An Rui

    2010-01-01

    The use of molecular imaging reporter gene systems has allowed gene therapy to move from the laboratory to the clinical application, which provides methodology to monitor the expression of therapeutic gene noninvasively and achieve quantitative outcome in vivo. Recently, the radionuclide reporter gene still is the focus many studies, but MRI and optical reporter gene have gradually played a important part in reporter gene systems. On the basis of combination of multi-subject, for example applied chemistry and molecular biology, more and more new modified reporter genes and molecular probes have spread out. This paper mainly introduces the advantages and disadvantages of reporter gene system and development trends. (authors)

  17. A New Molecular Surveillance System for Leishmaniasis

    Science.gov (United States)

    Pandey, Kishor; Pandey, Basu Dev; Mallik, Arun Kumar; Acharya, Jyoti; Kato, Kentaro; Kaneko, Osamu; Ferreira, Pedro Eduardo

    2014-01-01

    Abstract. Presently, global efforts are being made to control and eradicate the deadliest tropical diseases through the improvement of adequate interventions. A critical point for programs to succeed is the prompt and accurate diagnosis in endemic regions. Rapid diagnostic tests (RDTs) are being massively deployed and used to improve diagnosis in tropical countries. In the present report, we evaluated the hypothesis of, after use for diagnosis, the reuse of the Leishmania RDT kit as a DNA source, which can be used downstream as a molecular surveillance and/or quality control tool. As a proof of principle, a polymerase chain reaction-based method was used to detect Leishmania spp. minicircle kinetoplast DNA from leishmaniasis RDT kits. Our results show that Leishmania spp. DNA can be extracted from used RDTs and may constitute an important, reliable, and affordable tool to assist in future leishmaniasis molecular surveillance methods. PMID:24752687

  18. 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

  19. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  20. 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.

  1. Systems theoretic analysis of the central dogma of molecular biology: some recent results.

    Science.gov (United States)

    Gao, Rui; Yu, Juanyi; Zhang, Mingjun; Tarn, Tzyh-Jong; Li, Jr-Shin

    2010-03-01

    This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.

  2. Modelling of wastewater systems

    DEFF Research Database (Denmark)

    Bechmann, Henrik

    Oxygen Demand) flux and SS flux in the inlet to the WWTP. COD is measured by means of a UV absorption sensor while SS is measured by a turbidity sensor. These models include a description of the deposit of COD and SS amounts, respectively, in the sewer system, and the models can thus be used to quantify......In this thesis, models of pollution fluxes in the inlet to 2 Danish wastewater treatment plants (WWTPs) as well as of suspended solids (SS) concentrations in the aeration tanks of an alternating WWTP and in the effluent from the aeration tanks are developed. The latter model is furthermore used...... to analyze and quantify the effect of the Aeration Tank Settling (ATS) operating mode, which is used during rain events. Furthermore, the model is used to propose a control algorithm for the phase lengths during ATS operation. The models are mainly formulated as state space model in continuous time...

  3. Molecular dynamic simulations of the sputtering of multilayer organic systems

    CERN Document Server

    Postawa, Z; Piaskowy, J; Krantzman, K; Winograd, N; Garrison, B J

    2003-01-01

    Sputtering of organic overlayers has been modeled using molecular dynamics computer simulations. The investigated systems are composed of benzene molecules condensed into one, two and three layers on an Ag left brace 1 1 1 right brace surface. The formed organic overlayers were bombarded with 4 keV Ar projectiles at normal incidence. The development of the collision cascade in the organic overlayer was investigated. The sputtering yield, mass, internal and kinetic energy distributions of ejected particles have been analyzed as a function of the thickness of the organic layer. The results show that all emission characteristics are sensitive to the variation of layer thickness. Although most of the ejected intact benzene molecules originate from the topmost layer, the emission of particles located initially in second and third layers is significant. The analysis indicates that the metallic substrate plays a dominant role in the ejection of intact organic molecules.

  4. Polyethyleneglycol molecular mass and polydispersivity effect on protein partitioning in aqueous two-phase systems.

    Science.gov (United States)

    Picó, Guillermo; Romanini, Diana; Nerli, Bibiana; Farruggia, Beatriz

    2006-01-18

    The partitioning of model proteins (bovine serum albumin, ovalbumin, trypsin and lysozyme) was assayed in aqueous two-phase systems formed by a salt (potassium phosphate, sodium sulfate and ammonium sulfate) and a mixture of two polyethyleneglycols of different molecular mass. The ratio between the PEG masses in the mixtures was changed in order to obtain different polymer average molecular mass. The effect of polymer molecular mass and polydispersivity on the protein partition coefficient was studied. The relationship between the logarithm of the protein partition coefficient and the average molecular mass of the phase-forming polymer was found to depend on the polyethyleneglycol molecular mass, the salt type in the bottom phase and the molecular weight of the partitioned protein. The polymer polydispersivity proved to be a very useful tool to increase the separation between two proteins having similar isoelectrical point.

  5. 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.

  6. The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR

    Directory of Open Access Journals (Sweden)

    Mónica Roxo-Rosa

    2015-11-01

    Full Text Available In autosomal dominant polycystic kidney disease (ADPKD, cyst inflation and continuous enlargement are associated with marked transepithelial ion and fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR. Indeed, the inhibition or degradation of CFTR prevents the fluid accumulation within cysts. The in vivo mechanisms by which the lack of Polycystin-2 leads to CFTR stimulation are an outstanding challenge in ADPKD research and may bring important biomarkers for the disease. However, hampering their study, the available ADPKD in vitro cellular models lack the three-dimensional architecture of renal cysts and the ADPKD mouse models offer limited access for live-imaging experiments in embryonic kidneys. Here, we tested the zebrafish Kupffer's vesicle (KV as an alternative model-organ. KV is a fluid-filled vesicular organ, lined by epithelial cells that express both CFTR and Polycystin-2 endogenously, being each of them easily knocked-down. Our data on the intracellular distribution of Polycystin-2 support its involvement in the KV fluid-flow induced Ca2+-signalling. Mirroring kidney cysts, the KV lumen inflation is dependent on CFTR activity and, as we clearly show, the knockdown of Polycystin-2 results in larger KV lumens through overstimulation of CFTR. In conclusion, we propose the zebrafish KV as a model organ to study the renal cyst inflation. Favouring its use, KV volume can be easily determined by in vivo imaging offering a live readout for screening compounds and genes that may prevent cyst enlargement through CFTR inhibition.

  7. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

    Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

  8. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  9. 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.

  10. Modeling Complex Systems

    International Nuclear Information System (INIS)

    Schreckenberg, M

    2004-01-01

    This book by Nino Boccara presents a compilation of model systems commonly termed as 'complex'. It starts with a definition of the systems under consideration and how to build up a model to describe the complex dynamics. The subsequent chapters are devoted to various categories of mean-field type models (differential and recurrence equations, chaos) and of agent-based models (cellular automata, networks and power-law distributions). Each chapter is supplemented by a number of exercises and their solutions. The table of contents looks a little arbitrary but the author took the most prominent model systems investigated over the years (and up until now there has been no unified theory covering the various aspects of complex dynamics). The model systems are explained by looking at a number of applications in various fields. The book is written as a textbook for interested students as well as serving as a comprehensive reference for experts. It is an ideal source for topics to be presented in a lecture on dynamics of complex systems. This is the first book on this 'wide' topic and I have long awaited such a book (in fact I planned to write it myself but this is much better than I could ever have written it!). Only section 6 on cellular automata is a little too limited to the author's point of view and one would have expected more about the famous Domany-Kinzel model (and more accurate citation!). In my opinion this is one of the best textbooks published during the last decade and even experts can learn a lot from it. Hopefully there will be an actualization after, say, five years since this field is growing so quickly. The price is too high for students but this, unfortunately, is the normal case today. Nevertheless I think it will be a great success! (book review)

  11. 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.

  12. Modeling the earth system

    Energy Technology Data Exchange (ETDEWEB)

    Ojima, D. [ed.

    1992-12-31

    The 1990 Global Change Institute (GCI) on Earth System Modeling is the third of a series organized by the Office for Interdisciplinary Earth Studies to look in depth at particular issues critical to developing a better understanding of the earth system. The 1990 GCI on Earth System Modeling was organized around three themes: defining critical gaps in the knowledge of the earth system, developing simplified working models, and validating comprehensive system models. This book is divided into three sections that reflect these themes. Each section begins with a set of background papers offering a brief tutorial on the subject, followed by working group reports developed during the institute. These reports summarize the joint ideas and recommendations of the participants and bring to bear the interdisciplinary perspective that imbued the institute. Since the conclusion of the 1990 Global Change Institute, research programs, nationally and internationally, have moved forward to implement a number of the recommendations made at the institute, and many of the participants have maintained collegial interactions to develop research projects addressing the needs identified during the two weeks in Snowmass.

  13. 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

  14. 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...

  15. 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

  16. 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

  17. 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.

  18. Molecular Thermodynamic Modeling of Mixed Solvent Solubility

    DEFF Research Database (Denmark)

    Ellegaard, Martin Dela; Abildskov, Jens; O’Connell, John P.

    2010-01-01

    A method based on statistical mechanical fluctuation solution theory for composition derivatives of activity coefficients is employed for estimating dilute solubilities of 11 solid pharmaceutical solutes in nearly 70 mixed aqueous and nonaqueous solvent systems. The solvent mixtures range from ne...

  19. 2:1 Multiplexing Function in a Simple Molecular System

    Directory of Open Access Journals (Sweden)

    Ming Zhao

    2012-03-01

    Full Text Available 1-[(Anthracen-9-ylmethylene] thiosemicarbazide shows weak fluorescence due to a photo-induced electron transfer (PET process from the thiosemicarbazide moiety to the excited anthracene. The anthracene emission can be recovered via protonation of the amine as the protonated aminomethylene as an electron-withdrawing group that suppresses the PET process. Similarly, chelation between the ligand and the metal ions can also suppress the PET process and results in a fluorescence enhancement (CHEF. When solvents are introduced as the third control, a molecular 2:1 multiplexer is constructed to report selectively the inputs. Therefore, a molecular 2:1 multiplexer is realized in a simple molecular system.

  20. Energy conservation in molecular dynamics simulations of classical systems

    DEFF Research Database (Denmark)

    Toxværd, Søren; Heilmann, Ole; Dyre, J. C.

    2012-01-01

    Classical Newtonian dynamics is analytic and the energy of an isolated system is conserved. The energy of such a system, obtained by the discrete “Verlet” algorithm commonly used in molecular dynamics simulations, fluctuates but is conserved in the mean. This is explained by the existence...

  1. 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.

  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. [OsF6]x−: Molecular Models for Spin-Orbit Entangled Phenomena

    DEFF Research Database (Denmark)

    Pedersen, Kasper Steen; Woodruff, Daniel N.; Singh, Saurabh Kumar

    2017-01-01

    . Herein, two molecular osmate analogues, [OsF6]2− and [OsF6]−, are reported as model systems for Os4+ and Os5+ centers found in oxides. Using X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD) techniques, combined with state-of-the-art ab initio calculations, their ground...... state was elucidated; mirroring the osmium electronic structure in osmates. The realization of such molecular model systems provides a unique chemical playground to engineer materials exhibiting spin-orbit entangled phenomena....

  4. 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.

  5. 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.

  6. Molecular response functions for the polarizable continuum model physical basis and quantum mechanical formalism

    CERN Document Server

    Cammi, Roberto

    2013-01-01

    This Brief presents the main aspects of the response functions theory (RFT) for molecular solutes described within the framework of the Polarizable Continuum Model (PCM). PCM is a solvation model for a Quantum Mechanical molecular system in which the solvent is represented as a continuum distribution of matter. Particular attention is devoted to the description of the basic features of the PCM model, and to the problems characterizing the study of the response function theory for molecules in solution with respect to the analogous theory on isolated molecules.

  7. Molecular dynamics

    NARCIS (Netherlands)

    Bergstra, J.A.; Bethke, I.

    2002-01-01

    Molecular dynamics is a model for the structure and meaning of object based programming systems. In molecular dynamics the memory state of a system is modeled as a fluid consisting of a collection of molecules. Each molecule is a collection of atoms with bindings between them. A computation is

  8. 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.

  9. Information Systems Efficiency Model

    Directory of Open Access Journals (Sweden)

    Milos Koch

    2017-07-01

    Full Text Available This contribution discusses the basic concept of creating a new model for the efficiency and effectiveness assessment of company information systems. The present trends in this field are taken into account, and the attributes are retained of measuring the optimal solutions for a company’s ICT (the implementation, functionality, service, innovations, safety, relationships, costs, etc.. The proposal of a new model of assessment comes from our experience with formerly implemented and employed methods, methods which we have modified in time and adapted to companies’ needs but also to the necessaries of our research that has been done through the ZEFIS portal. The most noteworthy of them is the HOS method that we have discussed in a number of forums. Its main feature is the fact that it respects the complexity of an information system in correlation with the balanced state of its individual parts.

  10. Spectroscopic Studies of Molecular Systems relevant in Astrobiology

    Science.gov (United States)

    Fornaro, Teresa

    2016-01-01

    In the Astrobiology context, the study of the physico-chemical interactions involving "building blocks of life" in plausible prebiotic and space-like conditions is fundamental to shed light on the processes that led to emergence of life on Earth as well as to molecular chemical evolution in space. In this PhD Thesis, such issues have been addressed both experimentally and computationally by employing vibrational spectroscopy, which has shown to be an effective tool to investigate the variety of intermolecular interactions that play a key role in self-assembling mechanisms of nucleic acid components and their binding to mineral surfaces. In particular, in order to dissect the contributions of the different interactions to the overall spectroscopic signals and shed light on the intricate experimental data, feasible computational protocols have been developed for the characterization of the spectroscopic properties of such complex systems. This study has been carried out through a multi-step strategy, starting the investigation from the spectroscopic properties of the isolated nucleobases, then studying the perturbation induced by the interaction with another molecule (molecular dimers), towards condensed phases like the molecular solid, up to the case of nucleic acid components adsorbed on minerals. A proper modeling of these weakly bound molecular systems has required, firstly, a validation of dispersion-corrected Density Functional Theory methods for simulating anharmonic vibrational properties. The isolated nucleobases and some of their dimers have been used as benchmark set for identifying a general, reliable and effective computational procedure based on fully anharmonic quantum mechanical computations of the vibrational wavenumbers and infrared intensities within the generalized second order vibrational perturbation theory (GVPT2) approach, combined with the cost-effective dispersion-corrected density functional B3LYP-D3, in conjunction with basis sets of

  11. Systems biology for molecular life sciences and its impact in biomedicine.

    Science.gov (United States)

    Medina, Miguel Ángel

    2013-03-01

    Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

  12. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  13. 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.

  14. 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)

  15. 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

  16. 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 ...

  17. 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…

  18. 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 ...

  19. 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 ...

  20. 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

  1. 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.

  2. 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 ...

  3. Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling.

    Science.gov (United States)

    Wang, M; Lindberg, J; Klevebring, D; Nilsson, C; Mer, A S; Rantalainen, M; Lehmann, S; Grönberg, H

    2017-10-01

    Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

  4. 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.

  5. 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

  6. Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

    Science.gov (United States)

    Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

    2015-11-18

    Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

    Science.gov (United States)

    Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

    2018-01-01

    Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

  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. MacSyFinder: a program to mine genomes for molecular systems with an application to CRISPR-Cas systems.

    Directory of Open Access Journals (Sweden)

    Sophie S Abby

    Full Text Available Biologists often wish to use their knowledge on a few experimental models of a given molecular system to identify homologs in genomic data. We developed a generic tool for this purpose.Macromolecular System Finder (MacSyFinder provides a flexible framework to model the properties of molecular systems (cellular machinery or pathway including their components, evolutionary associations with other systems and genetic architecture. Modelled features also include functional analogs, and the multiple uses of a same component by different systems. Models are used to search for molecular systems in complete genomes or in unstructured data like metagenomes. The components of the systems are searched by sequence similarity using Hidden Markov model (HMM protein profiles. The assignment of hits to a given system is decided based on compliance with the content and organization of the system model. A graphical interface, MacSyView, facilitates the analysis of the results by showing overviews of component content and genomic context. To exemplify the use of MacSyFinder we built models to detect and class CRISPR-Cas systems following a previously established classification. We show that MacSyFinder allows to easily define an accurate "Cas-finder" using publicly available protein profiles.MacSyFinder is a standalone application implemented in Python. It requires Python 2.7, Hmmer and makeblastdb (version 2.2.28 or higher. It is freely available with its source code under a GPLv3 license at https://github.com/gem-pasteur/macsyfinder. It is compatible with all platforms supporting Python and Hmmer/makeblastdb. The "Cas-finder" (models and HMM profiles is distributed as a compressed tarball archive as Supporting Information.

  11. 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.

  12. Modelling dishes and exploring culinary 'precisions': the two issues of molecular gastronomy.

    Science.gov (United States)

    This, Hervé

    2005-04-01

    The scientific strategy of molecular gastronomy includes modelling 'culinary definitions' and experimental explorations of 'culinary precisions'. A formalism that describes complex dispersed systems leads to a physical classification of classical sauces, as well as to the invention of an infinite number of new dishes.

  13. Large-scale molecular dynamics simulations of self-assembling systems.

    Science.gov (United States)

    Klein, Michael L; Shinoda, Wataru

    2008-08-08

    Relentless increases in the size and performance of multiprocessor computers, coupled with new algorithms and methods, have led to novel applications of simulations across chemistry. This Perspective focuses on the use of classical molecular dynamics and so-called coarse-grain models to explore phenomena involving self-assembly in complex fluids and biological systems.

  14. 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.

  15. Molecular biophysics: detection and characterization of damage in molecular, cellular, and physiological systems

    International Nuclear Information System (INIS)

    Danyluk, S.S.

    1979-01-01

    This section contains summaries of research on the detection and characterization of damage in molecular, cellular, and physiological systems. Projects under investigation in this section include: chemical synthesis of nucleic acid derivatives; structural and conformational properties of biological molecules in solution; crystallographic and chemical studies of immunoglobulin structure; instrument design and development for x-ray and neutron scattering studies of biological molecules; and chromobiology and circadian regulation

  16. Multiscale Modeling of Complex Molecular Structure and Dynamics with MBN Explorer

    DEFF Research Database (Denmark)

    Solov'yov, Ilia A.; Korol, Andrei V.; Solov'yov, Andrey V.

    , and guides readers through its applications in numerous areas of research in bio- and chemical physics and material science - ranging from the nano- to the mesoscale. MBN Explorer is particularly suited to computing the system's energy, to optimizing molecular structure, and to exploring the various facets...... practicalities. MBN Studio enables users to easily construct initial geometries for the molecular, liquid, crystalline, gaseous and hybrid systems that serve as input for the subsequent simulations of their physical and chemical properties using MBN Explorer. Despite its universality, the computational...... efficiency of MBN Explorer is comparable to that of other, more specialized software packages, making it a viable multi-purpose alternative for the computational modeling of complex molecular systems. A number of detailed case studies presented in the second part of this book demonstrate MBN Explorer...

  17. 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.

  18. Molecular simulations of self-assembly processes in metal-organic frameworks: Model dependence

    Science.gov (United States)

    Biswal, Debasmita; Kusalik, Peter G.

    2017-07-01

    Molecular simulation is a powerful tool for investigating microscopic behavior in various chemical systems, where the use of suitable models is critical to successfully reproduce the structural and dynamic properties of the real systems of interest. In this context, molecular dynamics simulation studies of self-assembly processes in metal-organic frameworks (MOFs), a well-known class of porous materials with interesting chemical and physical properties, are relatively challenging, where a reasonably accurate representation of metal-ligand interactions is anticipated to play an important role. In the current study, we both investigate the performance of some existing models and introduce and test new models to help explore the self-assembly in an archetypal Zn-carboxylate MOF system. To this end, the behavior of six different Zn-ion models, three solvent models, and two ligand models was examined and validated against key experimental structural parameters. To explore longer time scale ordering events during MOF self-assembly via explicit solvent simulations, it is necessary to identify a suitable combination of simplified model components representing metal ions, organic ligands, and solvent molecules. It was observed that an extended cationic dummy atom (ECDA) Zn-ion model combined with an all-atom carboxylate ligand model and a simple dipolar solvent model can reproduce characteristic experimental structures for the archetypal MOF system. The successful use of these models in extensive sets of molecular simulations, which provide key insights into the self-assembly mechanism of this archetypal MOF system occurring during the early stages of this process, has been very recently reported.

  19. 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.

  20. System Concept for Remote Measurement of Asteroid Molecular Composition

    Science.gov (United States)

    Hughes, G. B.; Lubin, P. M.; Zhang, Q.; Brashears, T.; Cohen, A. N.; Madajian, J.

    2016-12-01

    We propose a method for probing the molecular composition of cold solar system targets (asteroids, comets, planets, moons) from a distant vantage, such as from a spacecraft orbiting the object. A directed energy beam is focused on the target. With sufficient flux, the spot temperature rises rapidly, and evaporation of surface materials occurs. The melted spot creates a high-temperature blackbody source, and ejected material creates a plume of surface materials in front of the spot. Molecular and atomic absorption of the blackbody radiation occurs within the ejected plume. Bulk composition of the surface material is investigated by using a spectrometer to view the heated spot through the ejected material. Our proposed method differs from technologies such as Laser-Induced Breakdown Spectroscopy (LIBS), which atomizes and ionizes materials in the target; scattered ions emit characteristic radiation, and the LIBS detector performs atomic composition analysis by observing emission spectra. Standoff distance for LIBS is limited by the strength of characteristic emission, and distances greater than 10 m are problematic. Our proposed method detects atomic and molecular absorption spectra in the plume; standoff distance is limited by the size of heated spot, and the plume opacity; distances on the order of tens of kilometers are immediately feasible. Simulations have been developed for laser heating of a rocky target, with concomitant evaporation. Evaporation rates lead to determination of plume density and opacity. Absorption profiles for selected materials are estimated from plume properties. Initial simulations of absorption profiles with laser heating show great promise for molecular composition analysis from tens of kilometers distance. This paper explores the feasibility a hypothetical mission that seeks to perform surface molecular composition analysis of a near-earth asteroid while the craft orbits the asteroid. Such a system has compelling potential benefit for

  1. 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.

  2. Reconstruction and validation of RefRec: a global model for the yeast molecular interaction network.

    Directory of Open Access Journals (Sweden)

    Tommi Aho

    2010-05-01

    Full Text Available Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is approximately 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in approximately 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our

  3. 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 ...

  4. 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

  5. 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.

  6. Assembly, destruction and manipulation of atomic, molecular and complex systems

    International Nuclear Information System (INIS)

    Le Padellec, Arnaud Pierre Frederic

    2003-04-01

    In this report for Accreditation to Supervise Researches (HDR), the author first indicates his professional curriculum (diplomas, teaching activities, responsibilities in the field of education and research, publications), and then proposes a presentation of his scientific works and researches. He notably proposes an overview of the different experimental techniques he implemented: CRYRING storage ring, confluent beams, flow post-discharge with mass spectrometry and Langmuir probe, crossed beams, and so on. He reports works dealing with the manipulation and destruction of atomic, molecular and complex systems: detachment of atomic anions by electronic impact, detachment and dissociation of small carbon aggregates by electronic impact, dissociative recombination, dissociative ionisation and excitation, creation of pairs of ions, manipulation of sodium fluoride aggregates. He finally presents research projects regarding the assembly of molecular and complex systems

  7. Extending Molecular Theory to Steady-State Diffusing Systems

    Energy Technology Data Exchange (ETDEWEB)

    FRINK,LAURA J. D.; SALINGER,ANDREW G.; THOMPSON,AIDAN P.

    1999-10-22

    Predicting the properties of nonequilibrium systems from molecular simulations is a growing area of interest. One important class of problems involves steady state diffusion. To study these cases, a grand canonical molecular dynamics approach has been developed by Heffelfinger and van Swol [J. Chem. Phys., 101, 5274 (1994)]. With this method, the flux of particles, the chemical potential gradients, and density gradients can all be measured in the simulation. In this paper, we present a complementary approach that couples a nonlocal density functional theory (DFT) with a transport equation describing steady-state flux of the particles. We compare transport-DFT predictions to GCMD results for a variety of ideal (color diffusion), and nonideal (uphill diffusion and convective transport) systems. In all cases excellent agreement between transport-DFT and GCMD calculations is obtained with diffusion coefficients that are invariant with respect to density and external fields.

  8. 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

  9. 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...

  10. 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.

  11. Towards an identification of the pyrethroid pharmacophore. A molecular modelling study of some pyrethroid esters

    DEFF Research Database (Denmark)

    Byberg, J R; Jørgensen, Flemming Steen; Klemmensen, P D

    1987-01-01

    A molecular modelling and computer graphics study of a series of pyrethroid insecticides has been carried out. The three-dimensional arrangement of the groups essential for the biological activity (pharmacophore) has been identified for the acid and the alcohol moieties, respectively. These pharm......A molecular modelling and computer graphics study of a series of pyrethroid insecticides has been carried out. The three-dimensional arrangement of the groups essential for the biological activity (pharmacophore) has been identified for the acid and the alcohol moieties, respectively....... These pharmacophores are based on the relationship between molecular structure and biological activity for a number of pyrethroid esters. The pharmacophores, which describe the relative location in space of the unsaturated systems, the dimethyl groups and the ester moiety, may be useful in the design of novel...... compounds with pyrethroid activity....

  12. Multiscale Modeling of Complex Molecular Structure and Dynamics with MBN Explorer

    DEFF Research Database (Denmark)

    Solov'yov, Ilia A.; Korol, Andrei V.; Solov'yov, Andrey V.

    This book introduces readers to MesoBioNano (MBN) Explorer - a multi-purpose software package designed to model molecular systems at various levels of size and complexity. In addition, it presents a specially designed multi-task toolkit and interface - the MBN Studio - which enables the set......-up of input files, controls the simulations, and supports the subsequent visualization and analysis of the results obtained. The book subsequently provides a systematic description of the capabilities of this universal and powerful software package within the framework of computational molecular science...... practicalities. MBN Studio enables users to easily construct initial geometries for the molecular, liquid, crystalline, gaseous and hybrid systems that serve as input for the subsequent simulations of their physical and chemical properties using MBN Explorer. Despite its universality, the computational...

  13. Multiscale Modeling of Complex Molecular Structure and Dynamics with MBN Explorer

    DEFF Research Database (Denmark)

    Solov'yov, Ilia A.; Korol, Andrei V.; Solov'yov, Andrey V.

    , and guides readers through its applications in numerous areas of research in bio- and chemical physics and material science - ranging from the nano- to the mesoscale. MBN Explorer is particularly suited to computing the system's energy, to optimizing molecular structure, and to exploring the various facets......This book introduces readers to MesoBioNano (MBN) Explorer - a multi-purpose software package designed to model molecular systems at various levels of size and complexity. In addition, it presents a specially designed multi-task toolkit and interface - the MBN Studio - which enables the set......-up of input files, controls the simulations, and supports the subsequent visualization and analysis of the results obtained. The book subsequently provides a systematic description of the capabilities of this universal and powerful software package within the framework of computational molecular science...

  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. Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

    Science.gov (United States)

    Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

    2017-01-01

    Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

  18. Structure and atomic correlations in molecular systems probed by XAS reverse Monte Carlo refinement

    Science.gov (United States)

    Di Cicco, Andrea; Iesari, Fabio; Trapananti, Angela; D'Angelo, Paola; Filipponi, Adriano

    2018-03-01

    The Reverse Monte Carlo (RMC) algorithm for structure refinement has been applied to x-ray absorption spectroscopy (XAS) multiple-edge data sets for six gas phase molecular systems (SnI2, CdI2, BBr3, GaI3, GeBr4, GeI4). Sets of thousands of molecular replicas were involved in the refinement process, driven by the XAS data and constrained by available electron diffraction results. The equilibrated configurations were analysed to determine the average tridimensional structure and obtain reliable bond and bond-angle distributions. Detectable deviations from Gaussian models were found in some cases. This work shows that a RMC refinement of XAS data is able to provide geometrical models for molecular structures compatible with present experimental evidence. The validation of this approach on simple molecular systems is particularly important in view of its possible simple extension to more complex and extended systems including metal-organic complexes, biomolecules, or nanocrystalline systems.

  19. Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology.

    Science.gov (United States)

    Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-Ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

    2015-01-01

    Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions.

  20. 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....

  1. Learning reduced kinetic Monte Carlo models of complex chemistry from molecular dynamics.

    Science.gov (United States)

    Yang, Qian; Sing-Long, Carlos A; Reed, Evan J

    2017-08-01

    We propose a novel statistical learning framework for automatically and efficiently building reduced kinetic Monte Carlo (KMC) models of large-scale elementary reaction networks from data generated by a single or few molecular dynamics simulations (MD). Existing approaches for identifying species and reactions from molecular dynamics typically use bond length and duration criteria, where bond duration is a fixed parameter motivated by an understanding of bond vibrational frequencies. In contrast, we show that for highly reactive systems, bond duration should be a model parameter that is chosen to maximize the predictive power of the resulting statistical model. We demonstrate our method on a high temperature, high pressure system of reacting liquid methane, and show that the learned KMC model is able to extrapolate more than an order of magnitude in time for key molecules. Additionally, our KMC model of elementary reactions enables us to isolate the most important set of reactions governing the behavior of key molecules found in the MD simulation. We develop a new data-driven algorithm to reduce the chemical reaction network which can be solved either as an integer program or efficiently using L1 regularization, and compare our results with simple count-based reduction. For our liquid methane system, we discover that rare reactions do not play a significant role in the system, and find that less than 7% of the approximately 2000 reactions observed from molecular dynamics are necessary to reproduce the molecular concentration over time of methane. The framework described in this work paves the way towards a genomic approach to studying complex chemical systems, where expensive MD simulation data can be reused to contribute to an increasingly large and accurate genome of elementary reactions and rates.

  2. 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.

  3. Review and application of group theory to molecular systems biology

    Directory of Open Access Journals (Sweden)

    Rietman Edward A

    2011-06-01

    Full Text Available Abstract In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  4. Review and application of group theory to molecular systems biology.

    Science.gov (United States)

    Rietman, Edward A; Karp, Robert L; Tuszynski, Jack A

    2011-06-22

    In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  5. Coarse-grained modelling of triglyceride crystallisation: a molecular insight into tripalmitin tristearin binary mixtures by molecular dynamics simulations

    International Nuclear Information System (INIS)

    Pizzirusso, Antonio; De Nicola, Antonio; Milano, Giuseppe; Brasiello, Antonio; Marangoni, Alejandro G

    2015-01-01

    The first simulation study of the crystallisation of a binary mixture of triglycerides using molecular dynamics simulations is reported. Coarse-grained models of tristearin (SSS) and tripalmitin (PPP) molecules have been considered. The models have been preliminarily tested in the crystallisation of pure SSS and PPP systems. Two different quenching procedures have been tested and their performances have been analysed. The structures obtained from the crystallisation procedures show a high orientation order and a high content of molecules in the tuning fork conformation, comparable with the crystalline α phase. The behaviour of melting temperatures for the α phase of the mixture SSS/PPP obtained from the simulations is in qualitative agreement with the behaviour that was experimentally determined. (paper)

  6. Subtle Monte Carlo Updates in Dense Molecular Systems

    DEFF Research Database (Denmark)

    Bottaro, Sandro; Boomsma, Wouter; Johansson, Kristoffer E.

    2012-01-01

    as correlations in a multivariate Gaussian distribution. We demonstrate that our method reproduces structural variation in proteins with greater efficiency than current state-of-the-art Monte Carlo methods and has real-time simulation performance on par with molecular dynamics simulations. The presented results......Although Markov chain Monte Carlo (MC) simulation is a potentially powerful approach for exploring conformational space, it has been unable to compete with molecular dynamics (MD) in the analysis of high density structural states, such as the native state of globular proteins. Here, we introduce...... a kinetic algorithm, CRISP, that greatly enhances the sampling efficiency in all-atom MC simulations of dense systems. The algorithm is based on an exact analytical solution to the classic chain-closure problem, making it possible to express the interdependencies among degrees of freedom in the molecule...

  7. Multiscale Systems Modeling of Male Reproductive Tract ...

    Science.gov (United States)

    The reproductive tract is a complex, integrated organ system with diverse embryology and unique sensitivity to prenatal environmental exposures that disrupt morphoregulatory processes and endocrine signaling. U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) was used to profile the bioactivity of 54 chemicals with male developmental consequences across ~800 molecular and cellular features [Leung et al., accepted manuscript]. The in vitro bioactivity on molecular targets could be condensed into 156 gene annotations in a bipartite network. These results highlighted the role of estrogen and androgen signaling pathways in male reproductive tract development, and importantly, broadened the list of molecular targets to include GPCRs, cytochrome-P450s, vascular remodeling proteins, and retinoic acid signaling. A multicellular agent-based model was used to simulate the complex interactions between morphoregulatory, endocrine, and environmental influences during genital tubercle (GT) development. Spatially dynamic signals (e.g., SHH, FGF10, and androgen) were implemented in the model to address differential adhesion, cell motility, proliferation, and apoptosis. Urethral tube closure was an emergent feature of the model that was linked to gender-specific rates of ventral mesenchymal proliferation and urethral plate endodermal apoptosis, both under control of androgen signaling [Leung et al., manuscript in preparation]. A systemic parameter sweep w

  8. Application to processing system using intra-molecular BRET

    Science.gov (United States)

    Otsuji, Tomomi; Okuda-Ashitaka, Emiko; Kojima, Satoshi; Akiyama, Hidehumi; Ito, Seiji; Ohmiya, Yoshihiro

    2003-07-01

    Luciferases are used as the reporter gene for promoter activity, whereas a green fluorescent protein (GFP) is used as marker for cellular function and localization. Recently, bioluminescence resonance energy transfer (BRET) between luciferase and YFP is used for analysis of inter-molecular reaction such as ligand-receptor in the living cells. The neuropeptides nocistatin (NST) and nociceptin/orphanin FQ (Noc/OFQ) are derived from the same precursor protein, while NST exhibits antagonism against Noc/OFQ-actions. In this study, we attempt an intra-molecular BRET system for monitoring dynamic biological process of the production of NST and Noc/OFQ in the living cells. At first, we constructed a fusion protein (Rluc-GFP) covalently linking luciferase (Renilla luciferase; Rluc) to Aequorea GFP as an intra-molecular BRET partner. Furthermore, we inserted constructs of mouse NST and Noc/OFQ (Rluc-m-GFP) or bovine NST and Noc/OFQ (Rluc-b-GFP) containing a proteolytic cleavage motif (Lys-Arg) within Rluc-GFP. When these constructions were transfected into Cos7 cells, all fusion proteins had luciferase activity and specific fluorescence. Luminescence spectra of Rluc-GFP, Rluc-m-GFP and Rluc-b-GFP fusion proteins with DeepBlueC as a substrate showed two peaks centered at 400 nm and 510 nm, whereas Rluc showed one peak centered at 400 nm. These results indicate that the proteolytic cleavage motif inserted fusion proteins between luciferase and GFP are available for intra-molecular BRET systems at first step.

  9. Modeling and estimating system availability

    International Nuclear Information System (INIS)

    Gaver, D.P.; Chu, B.B.

    1976-11-01

    Mathematical models to infer the availability of various types of more or less complicated systems are described. The analyses presented are probabilistic in nature and consist of three parts: a presentation of various analytic models for availability; a means of deriving approximate probability limits on system availability; and a means of statistical inference of system availability from sparse data, using a jackknife procedure. Various low-order redundant systems are used as examples, but extension to more complex systems is not difficult

  10. 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.}

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Modelling Molecular Mechanisms: A Framework of Scientific Reasoning to Construct Molecular-Level Explanations for Cellular Behaviour

    Science.gov (United States)

    van Mil, Marc H. W.; Boerwinkel, Dirk Jan; Waarlo, Arend Jan

    2013-01-01

    Although molecular-level details are part of the upper-secondary biology curriculum in most countries, many studies report that students fail to connect molecular knowledge to phenomena at the level of cells, organs and organisms. Recent studies suggest that students lack a framework to reason about complex systems to make this connection. In this…

  20. Deep Potential Molecular Dynamics: A Scalable Model with the Accuracy of Quantum Mechanics

    Science.gov (United States)

    Zhang, Linfeng; Han, Jiequn; Wang, Han; Car, Roberto; E, Weinan

    2018-04-01

    We introduce a scheme for molecular simulations, the deep potential molecular dynamics (DPMD) method, based on a many-body potential and interatomic forces generated by a carefully crafted deep neural network trained with ab initio data. The neural network model preserves all the natural symmetries in the problem. It is first-principles based in the sense that there are no ad hoc components aside from the network model. We show that the proposed scheme provides an efficient and accurate protocol in a variety of systems, including bulk materials and molecules. In all these cases, DPMD gives results that are essentially indistinguishable from the original data, at a cost that scales linearly with system size.

  1. Modelling of reverberation enhancement systems

    OpenAIRE

    ROUCH , Jeremy; Schmich , Isabelle; Galland , Marie-Annick

    2012-01-01

    International audience; Electroacoustic enhancement systems are increasingly specified by acoustic consultants to address the requests for a multi-purpose use of performance halls. However, there is still a lack of simple models to predict the effect induced by these systems on the acoustic field. Two models are introduced to establish the impulse responses of a room equipped with a reverberation enhancement system. These models are based on passive impulse responses according to the modified...

  2. MODELLING OF MATERIAL FLOW SYSTEMS

    OpenAIRE

    PÉTER TELEK

    2012-01-01

    Material flow systems are in generally very complex processes. During design, building and operation of complex systems there are many different problems. If these complex processes can be described in a simple model, the tasks will be clearer, better adaptable and easier solvable. As the material flow systems are very different, so using models is a very important aid to create uniform methods and solutions. This paper shows the details of the application possibilities of modelling in the ma...

  3. Dynamic Modeling of ALS Systems

    Science.gov (United States)

    Jones, Harry

    2002-01-01

    The purpose of dynamic modeling and simulation of Advanced Life Support (ALS) systems is to help design them. Static steady state systems analysis provides basic information and is necessary to guide dynamic modeling, but static analysis is not sufficient to design and compare systems. ALS systems must respond to external input variations and internal off-nominal behavior. Buffer sizing, resupply scheduling, failure response, and control system design are aspects of dynamic system design. We develop two dynamic mass flow models and use them in simulations to evaluate systems issues, optimize designs, and make system design trades. One model is of nitrogen leakage in the space station, the other is of a waste processor failure in a regenerative life support system. Most systems analyses are concerned with optimizing the cost/benefit of a system at its nominal steady-state operating point. ALS analysis must go beyond the static steady state to include dynamic system design. All life support systems exhibit behavior that varies over time. ALS systems must respond to equipment operating cycles, repair schedules, and occasional off-nominal behavior or malfunctions. Biological components, such as bioreactors, composters, and food plant growth chambers, usually have operating cycles or other complex time behavior. Buffer sizes, material stocks, and resupply rates determine dynamic system behavior and directly affect system mass and cost. Dynamic simulation is needed to avoid the extremes of costly over-design of buffers and material reserves or system failure due to insufficient buffers and lack of stored material.

  4. Modeling soft interface dominated systems

    NARCIS (Netherlands)

    Lamorgese, A.; Mauri, R.; Sagis, L.M.C.

    2017-01-01

    The two main continuum frameworks used for modeling the dynamics of soft multiphase systems are the Gibbs dividing surface model, and the diffuse interface model. In the former the interface is modeled as a two dimensional surface, and excess properties such as a surface density, or surface energy

  5. Molecular and supramolecular speciation of monoamide extractant systems

    International Nuclear Information System (INIS)

    Ferru, G.

    2012-01-01

    DEHiBA (N,N-di-(ethyl-2-hexyl)isobutyramide, a monoamide, was chosen as selective extractant for the recovery of uranium in the first cycle of the GANEX process, which aims to realize the grouped extraction of actinides in the second step of the process. The aim of this work is an improved description of monoamide organic solutions in alkane diluent after solutes extraction: water, nitric acid and uranyl nitrate. A parametric study was undertaken to characterize species at molecular scale (by IR spectroscopy, UV-visible spectroscopy, time-resolved laser-induced fluorescence spectroscopy, and electro-spray ionisation mass spectrometry) and at supramolecular scale (by vapor pressure osmometry and small angle X-ray scattering coupled to molecular dynamic simulations). Extraction isotherms were modelled taking into account the molecular and supramolecular speciation. These works showed that the organization of the organic solution depends on the amide concentration, the nature and the concentration of the extracted solute. Three regimes can be distinguished. 1/For extractant concentration less than 0.5 mol/L, monomers are predominate species. 2/ For extractant concentrations between 0.5 and 1 mol/L, small aggregates are formed containing 2 to 4 molecules of monoamide. 3/ For more concentrated solutions (greater than 1 mol/L), slightly larger species can be formed after water or nitric acid extraction. Concerning uranyl nitrate extraction, an important and strong organization of the organic phase is observed, which no longer allows the formation of well spherical defined aggregates. At molecular scale, complexes are not sensitive to the organization of the solution: the same species are observed, regardless of the solute and extractant concentrations in organic phase. (author) [fr

  6. From Numeric Models to Granular System Modeling

    Directory of Open Access Journals (Sweden)

    Witold Pedrycz

    2015-03-01

    To make this study self-contained, we briefly recall the key concepts of granular computing and demonstrate how this conceptual framework and its algorithmic fundamentals give rise to granular models. We discuss several representative formal setups used in describing and processing information granules including fuzzy sets, rough sets, and interval calculus. Key architectures of models dwell upon relationships among information granules. We demonstrate how information granularity and its optimization can be regarded as an important design asset to be exploited in system modeling and giving rise to granular models. With this regard, an important category of rule-based models along with their granular enrichments is studied in detail.

  7. Use of the confinement molecular model in the study of hydrogen under pressure. Comparison with the jellium model

    International Nuclear Information System (INIS)

    Castelluccio, G; Gervasoni, J; Cruz-Jimenez, S; Abriata, J

    2005-01-01

    The aim of this work is to present and compare the results of the model of molecular hydrogen in a dense system confinement by a penetrable barrier.It is used a simple localized orbital model which is represented by a floating spherical gaussian function with two parameters and an orbital center.The energy of the ground state of the molecule and its associated pressure are obtained for different barrier heights and nuclear radius.The values are compared with those obtained using the jellium model

  8. Thermal conductivity of ionic systems from equilibrium molecular dynamics.

    Science.gov (United States)

    Salanne, Mathieu; Marrocchelli, Dario; Merlet, Céline; Ohtori, Norikazu; Madden, Paul A

    2011-03-16

    Thermal conductivities of ionic compounds (NaCl, MgO, Mg(2)SiO(4)) are calculated from equilibrium molecular dynamics simulations using the Green-Kubo method. Transferable interaction potentials including many-body polarization effects are employed. Various physical conditions (solid and liquid states, high temperatures, high pressures) relevant to the study of the heat transport in the Earth's mantle are investigated, for which experimental measures are very challenging. By introducing a frequency-dependent thermal conductivity, we show that important coupled thermoelectric effects occur in the energy conduction mechanism in the case of liquid systems.

  9. High-pressure Brillouin scattering in a simple molecular system

    CERN Document Server

    Shimizu, H

    2002-01-01

    Recent developments in high-pressure in situ Brillouin spectroscopy of a simple molecular system are reviewed by demonstrating experimental and analytical methods for the study of acoustic velocities in any direction, adiabatic elastic constants, and elastic anisotropy. Detailed applications to solid argon (Ar) are presented, at pressures up to 70 GPa in a diamond anvil cell, using recently developed approaches that combine the method of in situ Brillouin spectroscopy, for a single crystal of Ar up to 4 GPa, and the envelope method applied to both longitudinal acoustic and transverse acoustic modes, for recrystallized Ar between 4 and 70 GPa.

  10. A complex systems approach to computational molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Lapedes, A. [Los Alamos National Lab., NM (United States)]|[Santa Fe Inst., NM (United States)

    1993-09-01

    We report on the containing research program at Santa Fe Institute that applies complex systems methodology to computational molecular biology. Two aspects are stressed here are the use of co-evolving adaptive neutral networks for determining predictable protein structure classifications, and the use of information theory to elucidate protein structure and function. A ``snapshot`` of the current state of research in these two topics is presented, representing the present state of two major research thrusts in the program of Genetic Data and Sequence Analysis at the Santa Fe Institute.

  11. Coastal Modeling System Advanced Topics

    Science.gov (United States)

    2012-06-18

    22 June 2012 - Day 5  Debugging and Problem solving  Model Calibration  Post-processing Coastal and Hydraulics Laboratory Focus of...Efficiently: • The setup process is fast and without wasted time or effort 3 Coastal and Hydraulics Laboratory 4 Coastal Modeling System (CMS) What...is the CMS? Integrated wave, current, and morphology change model in the Surface- water Modeling System (SMS). Why CMS? Operational at 10

  12. DCMS: A data analytics and management system for molecular simulation.

    Science.gov (United States)

    Kumar, Anand; Grupcev, Vladimir; Berrada, Meryem; Fogarty, Joseph C; Tu, Yi-Cheng; Zhu, Xingquan; Pandit, Sagar A; Xia, Yuni

    Molecular Simulation (MS) is a powerful tool for studying physical/chemical features of large systems and has seen applications in many scientific and engineering domains. During the simulation process, the experiments generate a very large number of atoms and intend to observe their spatial and temporal relationships for scientific analysis. The sheer data volumes and their intensive interactions impose significant challenges for data accessing, managing, and analysis. To date, existing MS software systems fall short on storage and handling of MS data, mainly because of the missing of a platform to support applications that involve intensive data access and analytical process. In this paper, we present the database-centric molecular simulation (DCMS) system our team developed in the past few years. The main idea behind DCMS is to store MS data in a relational database management system (DBMS) to take advantage of the declarative query interface ( i.e. , SQL), data access methods, query processing, and optimization mechanisms of modern DBMSs. A unique challenge is to handle the analytical queries that are often compute-intensive. For that, we developed novel indexing and query processing strategies (including algorithms running on modern co-processors) as integrated components of the DBMS. As a result, researchers can upload and analyze their data using efficient functions implemented inside the DBMS. Index structures are generated to store analysis results that may be interesting to other users, so that the results are readily available without duplicating the analysis. We have developed a prototype of DCMS based on the PostgreSQL system and experiments using real MS data and workload show that DCMS significantly outperforms existing MS software systems. We also used it as a platform to test other data management issues such as security and compression.

  13. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  14. Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

    Science.gov (United States)

    Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

    2016-01-20

    The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

  15. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. The overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  16. Safeguards system effectiveness modeling

    International Nuclear Information System (INIS)

    Bennett, H.A.; Boozer, D.D.; Chapman, L.D.; Daniel, S.L.; Engi, D.; Hulme, B.L.; Varnado, G.B.

    1976-01-01

    A general methodology for the comparative evaluation of physical protection system effectiveness at nuclear facilities is presently under development. The approach is applicable to problems of sabotage or theft at fuel cycle facilities. In this paper, the overall methodology and the primary analytic techniques used to assess system effectiveness are briefly outlined

  17. ePMV embeds molecular modeling into professional animation software environments.

    Science.gov (United States)

    Johnson, Graham T; Autin, Ludovic; Goodsell, David S; Sanner, Michel F; Olson, Arthur J

    2011-03-09

    Increasingly complex research has made it more difficult to prepare data for publication, education, and outreach. Many scientists must also wade through black-box code to interface computational algorithms from diverse sources to supplement their bench work. To reduce these barriers we have developed an open-source plug-in, embedded Python Molecular Viewer (ePMV), that runs molecular modeling software directly inside of professional 3D animation applications (hosts) to provide simultaneous access to the capabilities of these newly connected systems. Uniting host and scientific algorithms into a single interface allows users from varied backgrounds to assemble professional quality visuals and to perform computational experiments with relative ease. By enabling easy exchange of algorithms, ePMV can facilitate interdisciplinary research, smooth communication between broadly diverse specialties, and provide a common platform to frame and visualize the increasingly detailed intersection(s) of cellular and molecular biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Vibrational spectroscopy modeling of a drug in molecular solvents and enzymes

    Science.gov (United States)

    Devereux, Christian J.; Fulfer, Kristen D.; Zhang, Xiaoliu; Kuroda, Daniel G.

    2017-09-01

    Modeling of drugs in enzymes is of immensurable value to many areas of science. We present a theoretical study on the vibrational spectroscopy of Rilpivirine, a HIV reverse transcriptase inhibitor, in conventional solvents and in clinically relevant enzymes. The study is based on vibrational spectroscopy modeling of the drug using molecular dynamics simulations, DFT frequency maps, and theory. The modeling of the infrared lineshape shows good agreement with experimental data for the drug in molecular solvents where the local environment motions define the vibrational band lineshape. On the other hand, the theoretical description of the drug in the different enzymes does not match previous experimental findings indicating that the utilized methodology might not apply to heterogeneous environments. Our findings show that the lack of reproducibility might be associated with the development of the frequency map which does not contain all of the possible interactions observed in such systems.

  19. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  20. Fast Metabolic Response to Drug Intervention Through Analysis on a Miniaturized, Highly Integrated Molecular Imaging System

    OpenAIRE

    Wang, Jun; Hwang, Kiwook; Braas, Daniel; Dooraghi, Alex; Nathanson, David; Campbell, Dean O.; Gu, Yuchao; Sandberg, Troy; Mischel, Paul; Radu, Caius; Chatziioannou, Arion F.; Phelps, Michael E.; Christofk, Heather; Heath, James R.

    2013-01-01

    We report on a radiopharmaceutical imaging platform designed to capture the kinetics of cellular responses to drugs. Methods: A portable in vitro molecular imaging system comprising a microchip and a β-particle imaging camera permitted routine cell-based radioassays of small numbers of either suspended or adherent cells. We investigated the kinetics of responses of model lymphoma and glioblastoma cancer cell lines to ^(18)F-FDG uptake after drug exposure. Those responses were correlated with ...

  1. 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....

  2. A phenotypic culture system for the molecular analysis of CNS myelination in the spinal cord.

    Science.gov (United States)

    Davis, Hedvika; Gonzalez, Mercedes; Stancescu, Maria; Love, Rachal; Hickman, James J; Lambert, Stephen

    2014-10-01

    Studies of central nervous system myelination lack defined in vitro models which would effectively dissect molecular mechanisms of myelination that contain cells of the correct phenotype. Here we describe a co-culture of purified motoneurons and oligodendrocyte progenitor cells, isolated from rat embryonic spinal cord using a combination of immunopanning techniques. This model illustrates differentiation of oligodendrocyte progenitors into fully functional mature oligodendrocytes that myelinate axons. It also illustrates a contribution of axons to the rate of oligodendrocyte maturation and myelin gene expression. The defined conditions used allow molecular analysis of distinct stages of myelination and precise manipulation of inductive cues affecting axonal-oligodendrocyte interactions. This phenotypic in vitro myelination model can provide valuable insight into our understanding of demyelinating disorders, such as multiple sclerosis and traumatic diseases such as spinal cord injury where demyelination represents a contributing factor to the pathology of the disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Experimental models of communication at the molecular and microsystemic levels.

    Science.gov (United States)

    Fox, S. W.; Hsu, L.; Brooke, S.; Nakashima, T.; Lacey, J. C., Jr.

    1972-01-01

    Communication at both the macromolecular and the (supramacromolecular) microsystemic levels has been demonstrated in artificial polymers and artificial systems. These phenomena are models for communication in evolving and contemporary systems. The significance of a combination of communication at the two levels is emphasized.

  4. Molecular Thermodynamic Modeling of Fluctuation Solution Theory Properties

    DEFF Research Database (Denmark)

    O’Connell, John P.; Abildskov, Jens

    2013-01-01

    for densities and gas solubilities, including ionic liquids and complex mixtures such as coal liquids. The approach is especially useful in systems with strong nonidealities. This chapter describes successful application of such modeling to a wide variety of systems treated over several decades and suggests how...

  5. Modeling and analysis of the molecular basis of pain in sensory neurons.

    Directory of Open Access Journals (Sweden)

    Sang Ok Song

    Full Text Available Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons. The model architecture, which described 90 species connected by 162 interactions, was formulated by aggregating disparate molecular modules from literature. Unlike previous models, only mass action kinetics were used to describe the rate of molecular interactions. Thus, the majority of the 252 unknown model parameters were either association, dissociation or catalytic rate constants. Model parameters were estimated from nine independent data sets taken from multiple laboratories. The training data consisted of both dynamic and steady-state measurements. However, because of the complexity of the calcium network, we were unable to estimate unique model parameters. Instead, we estimated a family or ensemble of probable parameter sets using a multi-objective thermal ensemble method. Each member of the ensemble met an error criterion and was located along or near the optimal trade-off surface between the individual training data sets. The model quantitatively reproduced experimental measurements from dorsal root ganglion neurons as a function of extracellular ATP forcing. Hypothesized architecture linking phosphoinositide regulation with P2X receptor activity explained the inhibition of P2X-mediated current flow by activated metabotropic P2Y receptors. Sensitivity analysis using individual and the whole system outputs suggested which molecular subsystems were most important following P2 activation. Taken together, modeling and analysis of ATP-induced P2 mediated calcium signaling generated qualitative insight into the critical interactions controlling ATP induced calcium dynamics

  6. Bayesian comparison of Markov models of molecular dynamics with detailed balance constraint

    Science.gov (United States)

    Bacallado, Sergio; Chodera, John D.; Pande, Vijay

    2009-07-01

    Discrete-space Markov models are a convenient way of describing the kinetics of biomolecules. The most common strategies used to validate these models employ statistics from simulation data, such as the eigenvalue spectrum of the inferred rate matrix, which are often associated with large uncertainties. Here, we propose a Bayesian approach, which makes it possible to differentiate between models at a fixed lag time making use of short trajectories. The hierarchical definition of the models allows one to compare instances with any number of states. We apply a conjugate prior for reversible Markov chains, which was recently introduced in the statistics literature. The method is tested in two different systems, a Monte Carlo dynamics simulation of a two-dimensional model system and molecular dynamics simulations of the terminally blocked alanine dipeptide.

  7. International Conference on Intelligent Systems for Molecular Biology (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas; Komandurglayavilli, Ravikumar; Mahony, Shaun; Marinescu, Voichita; Mayrose, Itay; Minin, Vladimir; Neeman, Yossef; Nimrod, Guy; Novotny, Marian; Opiyo, Stephen; Portugaly, Elon; Sadka, Tali; Sakabe, Noboru; Sarkar, Indra; Schaub, Marc; Shafer, Paul; Shmygelska, Olena; Singer, Gregory; Song, Yun; Soumyaroop, Bhattacharya; Stadler, Michael; Strope, Pooja; Su, Rong; Tabach, Yuval; Tae, Hongseok; Taylor, Todd; Terribilini, Michael; Thomas, Asha; Tran, Nam; Tseng, Tsai-Tien; Vashist, Akshay; Vijaya, Parthiban; Wang, Kai; Wang, Ting; Wei, Lai; Woo, Yong; Wu, Chunlei; Yamanishi, Yoshihiro; Yan, Changhui; Yang, Jack; Yang, Mary; Ye, Ping; Zhang, Miao

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  8. Coarse Grained Molecular Dynamics Simulations of Transmembrane Protein-Lipid Systems

    Directory of Open Access Journals (Sweden)

    Peter Spijker

    2010-06-01

    Full Text Available Many biological cellular processes occur at the micro- or millisecond time scale. With traditional all-atom molecular modeling techniques it is difficult to investigate the dynamics of long time scales or large systems, such as protein aggregation or activation. Coarse graining (CG can be used to reduce the number of degrees of freedom in such a system, and reduce the computational complexity. In this paper the first version of a coarse grained model for transmembrane proteins is presented. This model differs from other coarse grained protein models due to the introduction of a novel angle potential as well as a hydrogen bonding potential. These new potentials are used to stabilize the backbone. The model has been validated by investigating the adaptation of the hydrophobic mismatch induced by the insertion of WALP-peptides into a lipid membrane, showing that the first step in the adaptation is an increase in the membrane thickness, followed by a tilting of the peptide.

  9. Venom Resistance as a Model for Understanding the Molecular Basis of Complex Coevolutionary Adaptations.

    Science.gov (United States)

    Holding, Matthew L; Drabeck, Danielle H; Jansa, Sharon A; Gibbs, H Lisle

    2016-11-01

    SynopsisVenom and venom resistance are molecular phenotypes widely considered to have diversified through coevolution between predators and prey. However, while evolutionary and functional studies on venom have been extensive, little is known about the molecular basis, variation, and complexity of venom resistance. We review known mechanisms of venom resistance and relate these mechanisms to their predicted impact on coevolutionary dynamics with venomous enemies. We then describe two conceptual approaches which can be used to examine venom/resistance systems. At the intraspecific level, tests of local adaptation in venom and resistance phenotypes can identify the functional mechanisms governing the outcomes of coevolution. At deeper evolutionary timescales, the combination of phylogenetically informed analyses of protein evolution coupled with studies of protein function promise to elucidate the mode and tempo of evolutionary change on potentially coevolving genes. We highlight case studies that use each approach to extend our knowledge of these systems as well as address larger questions about coevolutionary dynamics. We argue that resistance and venom are phenotypic traits which hold exceptional promise for investigating the mechanisms, dynamics, and outcomes of coevolution at the molecular level. Furthermore, extending the understanding of single gene-for-gene interactions to the whole resistance and venom phenotypes may provide a model system for examining the molecular and evolutionary dynamics of complex multi-gene interactions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  10. Electronic structure, transport, and collective effects in molecular layered systems

    Directory of Open Access Journals (Sweden)

    Torsten Hahn

    2017-10-01

    Full Text Available The great potential of organic heterostructures for organic device applications is exemplified by the targeted engineering of the electronic properties of phthalocyanine-based systems. The transport properties of two different phthalocyanine systems, a pure copper phthalocyanine (CoPc and a flourinated copper phthalocyanine–manganese phthalocyanine (F16CoPc/MnPc heterostructure, are investigated by means of density functional theory (DFT and the non-equilibrium Green’s function (NEGF approach. Furthermore, a master-equation-based approach is used to include electronic correlations beyond the mean-field-type approximation of DFT. We describe the essential theoretical tools to obtain the parameters needed for the master equation from DFT results. Finally, an interacting molecular monolayer is considered within a master-equation approach.

  11. Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

    Science.gov (United States)

    Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

    2017-05-01

    In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  12. Qualitative models for space system engineering

    Science.gov (United States)

    Forbus, Kenneth D.

    1990-01-01

    The objectives of this project were: (1) to investigate the implications of qualitative modeling techniques for problems arising in the monitoring, diagnosis, and design of Space Station subsystems and procedures; (2) to identify the issues involved in using qualitative models to enhance and automate engineering functions. These issues include representing operational criteria, fault models, alternate ontologies, and modeling continuous signals at a functional level of description; and (3) to develop a prototype collection of qualitative models for fluid and thermal systems commonly found in Space Station subsystems. Potential applications of qualitative modeling to space-systems engineering, including the notion of intelligent computer-aided engineering are summarized. Emphasis is given to determining which systems of the proposed Space Station provide the most leverage for study, given the current state of the art. Progress on using qualitative models, including development of the molecular collection ontology for reasoning about fluids, the interaction of qualitative and quantitative knowledge in analyzing thermodynamic cycles, and an experiment on building a natural language interface to qualitative reasoning is reported. Finally, some recommendations are made for future research.

  13. 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.

  14. Mechanical Systems, Classical Models

    CERN Document Server

    Teodorescu, Petre P

    2007-01-01

    All phenomena in nature are characterized by motion; this is an essential property of matter, having infinitely many aspects. Motion can be mechanical, physical, chemical or biological, leading to various sciences of nature, mechanics being one of them. Mechanics deals with the objective laws of mechanical motion of bodies, the simplest form of motion. In the study of a science of nature mathematics plays an important role. Mechanics is the first science of nature which was expressed in terms of mathematics by considering various mathematical models, associated to phenomena of the surrounding nature. Thus, its development was influenced by the use of a strong mathematical tool; on the other hand, we must observe that mechanics also influenced the introduction and the development of many mathematical notions. In this respect, the guideline of the present book is precisely the mathematical model of mechanics. A special accent is put on the solving methodology as well as on the mathematical tools used; vectors, ...

  15. Stochastic Modelling of Energy Systems

    DEFF Research Database (Denmark)

    Andersen, Klaus Kaae

    2001-01-01

    In this thesis dynamic models of typical components in Danish heating systems are considered. Emphasis is made on describing and evaluating mathematical methods for identification of such models, and on presentation of component models for practical applications. The thesis consists of seven...... of component models, such as e.g. heat exchanger and valve models, adequate for system simulations. Furthermore, the thesis demonstrates and discusses the advantages and disadvantages of using statistical methods in conjunction with physical knowledge in establishing adequate component models of heating...... research papers (case studies) together with a summary report. Each case study takes it's starting point in typical heating system components and both, the applied mathematical modelling methods and the application aspects, are considered. The summary report gives an introduction to the scope...

  16. 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.

  17. 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

  18. 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.

  19. PEP-II vacuum system pressure profile modeling using EXCEL

    International Nuclear Information System (INIS)

    Nordby, M.; Perkins, C.

    1994-06-01

    A generic, adaptable Microsoft EXCEL program to simulate molecular flow in beam line vacuum systems is introduced. Modeling using finite-element approximation of the governing differential equation is discussed, as well as error estimation and program capabilities. The ease of use and flexibility of the spreadsheet-based program is demonstrated. PEP-II vacuum system models are reviewed and compared with analytical models

  20. Phase equilibria and molecular interaction studies on (naphthols + vanillin) systems

    International Nuclear Information System (INIS)

    Gupta, Preeti; Agrawal, Tanvi; Das, Shiva Saran; Singh, Nakshatra Bahadur

    2012-01-01

    Highlights: ► Phase equilibria of (naphthol + vanillin) systems have been studied for the first time. ► Eutectic type phase diagrams are obtained. ► Eutectic mixtures show nonideal behaviour. ► There is a weak molecular interaction between the components in the eutectic mixtures. ► α-Naphthol–vanillin eutectic is more stable as compared to β-naphthol–vanillin. - Abstract: Phase equilibria between (α-naphthol + vanillin) and (β-naphthol + vanillin) systems have been studied by thaw-melt method and the results show the formation of simple eutectic mixtures. Crystallization velocities of components and eutectic mixtures were determined at different stages under cooling. With the help of differential scanning calorimeter (DSC), the enthalpy of fusion of components and eutectic mixtures was determined and from the values excess thermodynamic functions viz., excess Gibbs free energy (G E ), excess entropy (S E ), excess enthalpy (H E ) of hypo-, hyper- and eutectic mixtures were calculated. Flexural strength measurements were made in order to understand the non-ideal nature of eutectics. FT-IR spectral studies indicate the formation of hydrogen bond in the eutectic mixture. Anisotropic and isotropic microstructural studies of components, hypo-, hyper- and eutectic mixtures were made. Jackson’s roughness parameter was calculated and found to be greater than 2 suggesting the faceted morphology with irregular structures. The overall results have shown that there is a weak molecular interaction between the components in the eutectic mixtures and the (α-naphthol + vanillin) eutectic is more stable as compared to the (β-naphthol + vanillin) eutectic system.

  1. A multiscale modeling approach for biomolecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Bowling, Alan, E-mail: bowling@uta.edu; Haghshenas-Jaryani, Mahdi, E-mail: mahdi.haghshenasjaryani@mavs.uta.edu [The University of Texas at Arlington, Department of Mechanical and Aerospace Engineering (United States)

    2015-04-15

    This paper presents a new multiscale molecular dynamic model for investigating the effects of external interactions, such as contact and impact, during stepping and docking of motor proteins and other biomolecular systems. The model retains the mass properties ensuring that the result satisfies Newton’s second law. This idea is presented using a simple particle model to facilitate discussion of the rigid body model; however, the particle model does provide insights into particle dynamics at the nanoscale. The resulting three-dimensional model predicts a significant decrease in the effect of the random forces associated with Brownian motion. This conclusion runs contrary to the widely accepted notion that the motor protein’s movements are primarily the result of thermal effects. This work focuses on the mechanical aspects of protein locomotion; the effect ATP hydrolysis is estimated as internal forces acting on the mechanical model. In addition, the proposed model can be numerically integrated in a reasonable amount of time. Herein, the differences between the motion predicted by the old and new modeling approaches are compared using a simplified model of myosin V.

  2. 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...

  3. Charge migration and charge transfer in molecular systems

    Directory of Open Access Journals (Sweden)

    Hans Jakob Wörner

    2017-11-01

    Full Text Available The transfer of charge at the molecular level plays a fundamental role in many areas of chemistry, physics, biology and materials science. Today, more than 60 years after the seminal work of R. A. Marcus, charge transfer is still a very active field of research. An important recent impetus comes from the ability to resolve ever faster temporal events, down to the attosecond time scale. Such a high temporal resolution now offers the possibility to unravel the most elementary quantum dynamics of both electrons and nuclei that participate in the complex process of charge transfer. This review covers recent research that addresses the following questions. Can we reconstruct the migration of charge across a molecule on the atomic length and electronic time scales? Can we use strong laser fields to control charge migration? Can we temporally resolve and understand intramolecular charge transfer in dissociative ionization of small molecules, in transition-metal complexes and in conjugated polymers? Can we tailor molecular systems towards specific charge-transfer processes? What are the time scales of the elementary steps of charge transfer in liquids and nanoparticles? Important new insights into each of these topics, obtained from state-of-the-art ultrafast spectroscopy and/or theoretical methods, are summarized in this review.

  4. Model Reduction of Hybrid Systems

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza

    for model reduction of switched systems is based on the switching generalized gramians. The reduced order switched system is guaranteed to be stable for all switching signal in this method. This framework uses stability conditions which are based on switching quadratic Lyapunov functions which are less...... conservative than the stability conditions based on common quadratic Lyapunov functions. The stability conditions which are used for this method are very useful in model reduction and design problems because they have slack variables in the conditions. Similar conditions for a class of switched nonlinear......High-Technological solutions of today are characterized by complex dynamical models. A lot of these models have inherent hybrid/switching structure. Hybrid/switched systems are powerful models for distributed embedded systems design where discrete controls are applied to continuous processes...

  5. Molecular modeling studies of structural properties of polyvinyl alcohol: a comparative study using INTERFACE force field.

    Science.gov (United States)

    Radosinski, Lukasz; Labus, Karolina

    2017-10-05

    Polyvinyl alcohol (PVA) is a material with a variety of applications in separation, biotechnology, and biomedicine. Using combined Monte Carlo and molecular dynamics techniques, we present an extensive comparative study of second- and third-generation force fields Universal, COMPASS, COMPASS II, PCFF, and the newly developed INTERFACE, as applied to this system. In particular, we show that an INTERFACE force field provides a possibility of composing a reliable atomistic model to reproduce density change of PVA matrix in a narrow temperature range (298-348 K) and calculate a thermal expansion coefficient with reasonable accuracy. Thus, the INTERFACE force field may be used to predict mechanical properties of the PVA system, being a scaffold for hydrogels, with much greater accuracy than latter approaches. Graphical abstract Molecular Dynamics and Monte Carlo studies indicate that it is possible to predict properties of the PVA in narrow temperature range by using the INTERFACE force field.

  6. Neutron spectra and cross sections for ice and clathrate generated from the synthetic spectrum and synthetic model for molecular solids

    International Nuclear Information System (INIS)

    Petriw, S; Cantargi, F; Granada, R

    2006-01-01

    We present here a Synthetic Model for Molecular Solids, aimed at the description of the interaction of thermal neutrons with this kind of systems.Simple representations of the molecular dynamical modes are used, in order to produce a fair description of neutron scattering kernels and cross sections with a minimum set of input data. Using those spectra, we have generated thermal libraries for M C N P [es

  7. Tunneling of electrons via rotor–stator molecular interfaces: Combined ab initio and model study

    Energy Technology Data Exchange (ETDEWEB)

    Petreska, Irina, E-mail: irina.petreska@pmf.ukim.mk [Institute of Physics, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, PO Box 162, 1000 Skopje, Former Yugolav Republic of Macedonia, The (Macedonia, The Former Yugoslav Republic of); Ohanesjan, Vladimir [Institute of Physics, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University, PO Box 162, 1000 Skopje, Former Yugolav Republic of Macedonia, The (Macedonia, The Former Yugoslav Republic of); Pejov, Ljupčo [Institute of Chemistry, Department of Physical Chemistry, Ss. Cyril and Methodius University, Arhimedova 5, P.O. Box 162, 1000 Skopje, Former Yugolav Republic of Macedonia, The (Macedonia, The Former Yugoslav Republic of); Kocarev, Ljupčo [Macedonian Academy of Sciences and Arts, Krste Misirkov 2, PO Box 428, 1000 Skopje, Former Yugolav Republic of Macedonia, The (Macedonia, The Former Yugoslav Republic of); Faculty of Computer Science and Engineering, Ss. Cyril and Methodius University, Skopje, Former Yugolav Republic of Macedonia, The (Macedonia, The Former Yugoslav Republic of)

    2016-07-01

    Tunneling of electrons through rotor–stator anthracene aldehyde molecular interfaces is studied with a combined ab initio and model approach. Molecular electronic structure calculated from first principles is utilized to model different shapes of tunneling barriers. Together with a rectangular barrier, we also consider a sinusoidal shape that captures the effects of the molecular internal structure more realistically. Quasiclassical approach with the Simmons’ formula for current density is implemented. Special attention is paid on conformational dependence of the tunneling current. Our results confirm that the presence of the side aldehyde group enhances the interesting electronic properties of the pure anthracene molecule, making it a bistable system with geometry dependent transport properties. We also investigate the transition voltage and we show that conformation-dependent field emission could be observed in these molecular interfaces at realistically low voltages. The present study accompanies our previous work where we investigated the coherent transport via strongly coupled delocalized orbital by application of Non-equilibrium Green’s Function Formalism.

  8. Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

    Science.gov (United States)

    Petsev, Nikolai D.; Leal, L. Gary; Shell, M. Scott

    2017-12-01

    Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely resolved (e.g., molecular dynamics) and coarse-grained (e.g., continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 084115 (2016)], simulated using a particle-based continuum method known as smoothed dissipative particle dynamics. An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.

  9. 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.

  10. 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.

  11. Distribution system modeling and analysis

    CERN Document Server

    Kersting, William H

    2001-01-01

    For decades, distribution engineers did not have the sophisticated tools developed for analyzing transmission systems-often they had only their instincts. Things have changed, and we now have computer programs that allow engineers to simulate, analyze, and optimize distribution systems. Powerful as these programs are, however, without a real understanding of the operating characteristics of a distribution system, engineers using the programs can easily make serious errors in their designs and operating procedures. Distribution System Modeling and Analysis helps prevent those errors. It gives readers a basic understanding of the modeling and operating characteristics of the major components of a distribution system. One by one, the author develops and analyzes each component as a stand-alone element, then puts them all together to analyze a distribution system comprising the various shunt and series devices for power-flow and short-circuit studies. He includes the derivation of all models and includes many num...

  12. Animal models and therapeutic molecular targets of cancer: utility and limitations

    Directory of Open Access Journals (Sweden)

    Cekanova M

    2014-10-01

    Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

  13. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  14. Optical fiber-based photomechanical molecular delivery system

    Science.gov (United States)

    Nakano, Koki; Sato, Shunichi; Kawauchi, Satoko; Ashida, Hiroshi; Nishidate, Izumi

    2014-02-01

    Molecular delivery based on nanosecond pulsed laser-induced photomechanical waves (PMWs) enables endoscopic application by using an optical fiber for laser transmission. In our previous fiber system, a laser target, which was a black natural rubber film as a laser absorbing material covered with an optically transparent polyethylene terephthalate disk to confine the laser-induced plasma, was attached to the output end of a 1 mm core diameter quartz fiber. There were two problems in that system: 1) the outer diameter was large (~2.7 mm) and 2) available peak pressure rapidly decreased with increasing pulse number. In this study, we developed a new fiber delivery system to overcome these problems. As a laser absorbing material, we used a cap-type silicone rubber containing carbon black, into which the fiber output end can simply be inserted. The fiber end surface works to confine the laser-induced plasma. The outer diameter of the fiber system was reduced to ~1.4 mm. At an output laser fluence of 1.2 J/cm2, peak pressure of the first PMW pulse exceeded ~40 MPa. With successive 10 laser pulses, decreasing rate of the peak pressure was 22%, which was considerably lower than that with the previous fiber system (82%), enabling generation of at least successive 30 pulses of PMW with the same cap-type target. With this fiber system, we attempted transfer of plasmid DNA encoding EGFP (enhanced green fluorescence protein) to the rat skin as a test tissue in vivo, showing site-selective efficient gene expression.

  15. Hydronic distribution system computer model

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, J.W.; Strasser, J.J.

    1994-10-01

    A computer model of a hot-water boiler and its associated hydronic thermal distribution loop has been developed at Brookhaven National Laboratory (BNL). It is intended to be incorporated as a submodel in a comprehensive model of residential-scale thermal distribution systems developed at Lawrence Berkeley. This will give the combined model the capability of modeling forced-air and hydronic distribution systems in the same house using the same supporting software. This report describes the development of the BNL hydronics model, initial results and internal consistency checks, and its intended relationship to the LBL model. A method of interacting with the LBL model that does not require physical integration of the two codes is described. This will provide capability now, with reduced up-front cost, as long as the number of runs required is not large.

  16. Effect of attenuation models on communication system design

    Science.gov (United States)

    Shimabukuro, Fred I.

    1995-01-01

    The atmosphere has a significant impact on the design of a global communication system operating at 20 GHz. The system under consideration has a total atmospheric link attenuation budget that is less than 6 dB. For this relatively small link margin, rain, cloud, and molecular attenuation have to be taken into account. For an assessment of system performance on a global basis, attenuation models are utilized. There is concern whether current models can adequately describe the atmospheric effects such that a system planner can properly allocate his resources for superior overall system performance. The atmospheric attenuation as predicted by models will be examined.

  17. Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

    Science.gov (United States)

    Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

    2015-12-15

    Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to

  18. Animal models and therapeutic molecular targets of cancer: utility and limitations.

    Science.gov (United States)

    Cekanova, Maria; Rathore, Kusum

    2014-01-01

    Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients.

  19. Modeling and molecular dynamics simulation of PR-1 protein from ...

    African Journals Online (AJOL)

    Pathogenesis-related (PR) proteins are considered as major weapons in plant's defense tactics against pathogens. The PR-1protein of Solanum tuberosum forms an integral part of the host defense system. We present here the 3D structure of PR-1 protein of S. tuberosum based on homology modeling technique.

  20. Bicanonical ab Initio Molecular Dynamics for Open Systems.

    Science.gov (United States)

    Frenzel, Johannes; Meyer, Bernd; Marx, Dominik

    2017-08-08

    Performing ab initio molecular dynamics simulations of open systems, where the chemical potential rather than the number of both nuclei and electrons is fixed, still is a challenge. Here, drawing on bicanonical sampling ideas introduced two decades ago by Swope and Andersen [ J. Chem. Phys. 1995 , 102 , 2851 - 2863 ] to calculate chemical potentials of liquids and solids, an ab initio simulation technique is devised, which introduces a fictitious dynamics of two superimposed but otherwise independent periodic systems including full electronic structure, such that either the chemical potential or the average fractional particle number of a specific chemical species can be kept constant. As proof of concept, we demonstrate that solvation free energies can be computed from these bicanonical ab initio simulations upon directly superimposing pure bulk water and the respective aqueous solution being the two limiting systems. The method is useful in many circumstances, for instance for studying heterogeneous catalytic processes taking place on surfaces where the chemical potential of reactants rather than their number is controlled and opens a pathway toward ab initio simulations at constant electrochemical potential.

  1. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

    Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

  2. An Atomistic Carbide-Derived Carbon Model Generated Using ReaxFF-Based Quenched Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Matthew W. Thompson

    2017-10-01

    Full Text Available We report a novel atomistic model of carbide-derived carbons (CDCs, which are nanoporous carbons with high specific surface areas, synthesis-dependent degrees of graphitization, and well-ordered, tunable porosities. These properties make CDCs viable substrates in several energy-relevant applications, such as gas storage media, electrochemical capacitors, and catalytic supports. These materials are heterogenous, non-ideal structures and include several important parameters that govern their performance. Therefore, a realistic model of the CDC structure is needed in order to study these systems and their nanoscale and macroscale properties with molecular simulation. We report the use of the ReaxFF reactive force field in a quenched molecular dynamics routine to generate atomistic CDC models. The pair distribution function, pore size distribution, and adsorptive properties of this model are reported and corroborated with experimental data. Simulations demonstrate that compressing the system after quenching changes the pore size distribution to better match the experimental target. Ring size distributions of this model demonstrate the prevalence of non-hexagonal carbon rings in CDCs. These effects may contrast the properties of CDCs against those of activated carbons with similar pore size distributions and explain higher energy densities of CDC-based supercapacitors.

  3. Intrusion detection: systems and models

    Science.gov (United States)

    Sherif, J. S.; Dearmond, T. G.

    2002-01-01

    This paper puts forward a review of state of the art and state of the applicability of intrusion detection systems, and models. The paper also presents a classfication of literature pertaining to intrusion detection.

  4. Plant and safety system model

    International Nuclear Information System (INIS)

    Beltracchi, Leo

    1999-01-01

    The design and development of a digital computer-based safety system for a nuclear power plant is a complex process. The process of design and product development must result in a final product free of critical errors; operational safety of nuclear power plants must not be compromised. This paper focuses on the development of a safety system model to assist designers, developers, and regulators in establishing and evaluating requirements for a digital computer-based safety system. The model addresses hardware, software, and human elements for use in the requirements definition process. The purpose of the safety system model is to assist and serve as a guide to humans in the cognitive reasoning process of establishing requirements. The goals in the use of the model are to: (1) enhance the completeness of the requirements and (2) reduce the number of errors associated with the requirements definition phase of a project

  5. 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...

  6. Molecular dynamics simulations of water, solution, and clay mineral-water systems (Invited)

    Science.gov (United States)

    Kawamura, K.

    2009-12-01

    Clays and clay minerals together with zeolites are major mineral components in the earth's surface environment. These minerals interact with the atmosphere, natural water, inorganic and organic components in soils, etc. Physicochemical processes in the surface region are generally complex and difficult to understand because of the complicated "molecular" structures and the ambient conditions under wet circumstances. We have investigated the structure and physical/dynamical properties of the mineral-gas/liquid systems by means of molecular simulation methods; molecular dynamics and Metropolis Monte Carlo methods. Swelling of smectite and adsorption of inorganic molecules in clay minerals and zeolites, etc. were simulated and analyzed on the basis of the atomic and molecular processes. We have developed atomic and molecular interaction models of inorganic systems. The models compose of electrostatic, short range repulsive, van der Waals and covalent (radial and angular) terms with respect to all the elements appeared in the mineral-water systems. All of our molecular dynamics simulations (MD) were performed with full degree of freedom of atom motions. Using the model for H2O molecule, the structure and physical properties such as density, diffusion coefficients, etc. of ice polymorphs and water are well reproduced. Alkaliharide aqueous solutions and gas hydrates and their (hydrophobic) solutions are also reasonably simulated. Clay mineral-water interactions are particularly important to understand the mechanical and chemical processes in the environments, in order to develop nano-composite materials, and to use clays in engineering applications. Absorption and swelling are the most remarkable properties of clay minerals, specially smectite. We have investigate these properties by means of molecular simulation methods using various clay minerals-water/solution systems. The swelling curves, the relation between humidity and the basal spacings, were reproduced

  7. Molecular tailoring of interfaces for thin film on substrate systems

    Science.gov (United States)

    Grady, Martha Elizabeth

    Thin film on substrate systems appear most prevalently within the microelectronics industry, which demands that devices operate in smaller and smaller packages with greater reliability. The reliability of these multilayer film systems is strongly influenced by the adhesion of each of the bimaterial interfaces. During use, microelectronic components undergo thermo-mechanical cycling, which induces interfacial delaminations leading to failure of the overall device. The ability to tailor interfacial properties at the molecular level provides a mechanism to improve thin film adhesion, reliability and performance. This dissertation presents the investigation of molecular level control of interface properties in three thin film-substrate systems: photodefinable polyimide films on passivated silicon substrates, self-assembled monolayers at the interface of Au films and dielectric substrates, and mechanochemically active materials on rigid substrates. For all three materials systems, the effect of interfacial modifications on adhesion is assessed using a laser-spallation technique. Laser-induced stress waves are chosen because they dynamically load the thin film interface in a precise, noncontacting manner at high strain rates and are suitable for both weak and strong interfaces. Photodefinable polyimide films are used as dielectrics in flip chip integrated circuit packages to reduce the stress between silicon passivation layers and mold compound. The influence of processing parameters on adhesion is examined for photodefinable polyimide films on silicon (Si) substrates with three different passivation layers: silicon nitride (SiNx), silicon oxynitride (SiOxNy), and the native silicon oxide (SiO2). Interfacial strength increases when films are processed with an exposure step as well as a longer cure cycle. Additionally, the interfacial fracture energy is assessed using a dynamic delamination protocol. The high toughness of this interface (ca. 100 J/m2) makes it difficult

  8. Mathematical modeling of aeroelastic systems

    Science.gov (United States)

    Velmisov, Petr A.; Ankilov, Andrey V.; Semenova, Elizaveta P.

    2017-12-01

    In the paper, the stability of elastic elements of a class of designs that are in interaction with a gas or liquid flow is investigated. The definition of the stability of an elastic body corresponds to the concept of stability of dynamical systems by Lyapunov. As examples the mathematical models of flowing channels (models of vibration devices) at a subsonic flow and the mathematical models of protective surface at a supersonic flow are considered. Models are described by the related systems of the partial differential equations. An analytic investigation of stability is carried out on the basis of the construction of Lyapunov-type functionals, a numerical investigation is carried out on the basis of the Galerkin method. The various models of the gas-liquid environment (compressed, incompressible) and the various models of a deformable body (elastic linear and elastic nonlinear) are considered.

  9. Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

    Science.gov (United States)

    Engleman, Eric A; Katner, Simon N; Neal-Beliveau, Bethany S

    2016-01-01

    Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission

  10. ABSTRACT MODELS FOR SYSTEM VIRTUALIZATION

    Directory of Open Access Journals (Sweden)

    M. G. Koveshnikov

    2015-05-01

    Full Text Available The paper is dedicated to issues of system objects securing (system files and user system or application configuration files against unauthorized access including denial of service attacks. We have suggested the method and developed abstract system virtualization models, which are used toresearch attack scenarios for different virtualization modes. Estimation for system tools virtualization technology effectiveness is given. Suggested technology is based on redirection of access requests to system objects shared among access subjects. Whole and partial system virtualization modes have been modeled. The difference between them is the following: in the whole virtualization mode all copies of access system objects are created whereon subjects’ requests are redirected including corresponding application objects;in the partial virtualization mode corresponding copies are created only for part of a system, for example, only system objects for applications. Alternative solutions effectiveness is valued relating to different attack scenarios. We consider proprietary and approved technical solution which implements system virtualization method for Microsoft Windows OS family. Administrative simplicity and capabilities of correspondingly designed system objects security tools are illustrated on this example. Practical significance of the suggested security method has been confirmed.

  11. Aerodynamic and Mechanical System Modelling

    DEFF Research Database (Denmark)

    Jørgensen, Martin Felix

    This thesis deals with mechanical multibody-systems applied to the drivetrain of a 500 kW wind turbine. Particular focus has been on gearbox modelling of wind turbines. The main part of the present project involved programming multibody systems to investigate the connection between forces, moments...

  12. Molecular analysis of acute and chronic reactive astrocytes in the pilocarpine model of temporal lobe epilepsy.

    Science.gov (United States)

    Clasadonte, Jerome; Morel, Lydie; Barrios-Camacho, Camila M; Chiang, Ming Sum R; Zhang, Jinhua; Iyer, Lakshmanan; Haydon, Philip G; Yang, Yongjie

    2016-07-01

    Astroglia, the most abundant glial cells in the mammalian central nervous system (CNS), are considered an emerging key player in seizure induction and progression. Although astrocytes undergo reactive gliosis in temporal lobe epilepsy (TLE) with dramatic morphological and molecular changes, specific astrocyte targets/molecular pathways that contribute to the induction and progression of seizure remain largely unknown. By combining translating ribosomal affinity purification (TRAP) with the pilocarpine model of TLE in BAC aldh1l1 TRAP mice, we profiled translating mRNAs from hippocampal or cortical astrocytes at different phases (3days, 30days, and 60days post-pilocarpine injections) of pilocarpine-induced epilepsy models. Our results found that hippocampal (but not cortical) astrocytes undergo early and unique molecular changes at 3days post-pilocarpine injections. These changes indicate a potentially primary pathogenic role of hippocampal astrocytes in seizure induction and progression and provide new insights about the involvement of specific astrocytic pathways/targets in epilepsy. In particular, we validated expression changes of ocrl and aeg1 in pilocarpine models. Follow-up studies on these genes may reveal new roles of hippocampal astrocytes in TLE. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. 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…

  14. Hidden Markov models and other machine learning approaches in computational molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, P. [California Inst. of Tech., Pasadena, CA (United States)

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Computational tools are increasingly needed to process the massive amounts of data, to organize and classify sequences, to detect weak similarities, to separate coding from non-coding regions, and reconstruct the underlying evolutionary history. The fundamental problem in machine learning is the same as in scientific reasoning in general, as well as statistical modeling: to come up with a good model for the data. In this tutorial four classes of models are reviewed. They are: Hidden Markov models; artificial Neural Networks; Belief Networks; and Stochastic Grammars. When dealing with DNA and protein primary sequences, Hidden Markov models are one of the most flexible and powerful alignments and data base searches. In this tutorial, attention is focused on the theory of Hidden Markov Models, and how to apply them to problems in molecular biology.

  15. Computational models to assign biopharmaceutics drug disposition classification from molecular structure.

    Science.gov (United States)

    Khandelwal, Akash; Bahadduri, Praveen M; Chang, Cheng; Polli, James E; Swaan, Peter W; Ekins, Sean

    2007-12-01

    We applied in silico methods to automatically classify drugs according to the Biopharmaceutics Drug Disposition Classification System (BDDCS). Models were developed using machine learning methods including recursive partitioning (RP), random forest (RF) and support vector machine (SVM) algorithms with ChemDraw, clogP, polar surface area, VolSurf and MolConnZ descriptors. The dataset consisted of 165 training and 56 test set molecules. RF model 3, RP model 1, and SVM model 1 can correctly predict 73.1, 63.6 and 78.6% test compounds in classes 1, 2 and 3, respectively. Both RP and SVM models can be used for class 4 prediction. The inclusion of consensus analysis resulted in improved test set predictions for class 2 and 4 drugs. The models can be used to predict BDDCS class for new compounds from molecular structure using readily available molecular descriptors and software, representing an area where in silico approaches could aid the pharmaceutical industry in speeding drugs to the patient and reducing costs. This could have significant applications in drug discovery to identify molecules that may have future developability issues.

  16. Workflow Management Systems for Molecular Dynamics on Leadership Computers

    Science.gov (United States)

    Wells, Jack; Panitkin, Sergey; Oleynik, Danila; Jha, Shantenu

    Molecular Dynamics (MD) simulations play an important role in a range of disciplines from Material Science to Biophysical systems and account for a large fraction of cycles consumed on computing resources. Increasingly science problems require the successful execution of ''many'' MD simulations as opposed to a single MD simulation. There is a need to provide scalable and flexible approaches to the execution of the workload. We present preliminary results on the Titan computer at the Oak Ridge Leadership Computing Facility that demonstrate a general capability to manage workload execution agnostic of a specific MD simulation kernel or execution pattern, and in a manner that integrates disparate grid-based and supercomputing resources. Our results build upon our extensive experience of distributed workload management in the high-energy physics ATLAS project using PanDA (Production and Distributed Analysis System), coupled with recent conceptual advances in our understanding of workload management on heterogeneous resources. We will discuss how we will generalize these initial capabilities towards a more production level service on DOE leadership resources. This research is sponsored by US DOE/ASCR and used resources of the OLCF computing facility.

  17. Preface: the hydra model system.

    Science.gov (United States)

    Galliot, Brigitte

    2012-01-01

    The freshwater Hydra polyp emerged as a model system in 1741 when Abraham Trembley not only discovered its amazing regenerative potential, but also demonstrated that experimental manipulations pave the way to research in biology. Since then, Hydra flourished as a potent and fruitful model system to help answer questions linked to cell and developmental biology, as such as the setting up of an organizer to regenerate a complex missing structure, the establishment and maintainance of polarity in a multicellular organism, the development of mathematical models to explain the robust developmental rules observed in this animal, the maintainance of stemness and multipotency in a highly dynamic environment, the plasticity of differentiated cells, to name but a few. However the Hydra model system is not restricted to cell and developmental biology; during the past 270 years it has also been heavily used to investigate the relationships between Hydra and its environment, opening new horizons concerning neurophysiology, innate immunity, ecosystems, ecotoxicology, symbiosis...

  18. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  19. Elements of a dynamic systems model of canopy photosynthesis.

    Science.gov (United States)

    Zhu, Xin-Guang; Song, Qingfeng; Ort, Donald R

    2012-06-01

    Improving photosynthesis throughout the full canopy rather than photosynthesis of only the top leaves of the canopy is central to improving crop yields. Many canopy photosynthesis models have been developed from physiological and ecological perspectives, however most do not consider heterogeneities of microclimatic factors inside a canopy, canopy dynamics and associated energetics, or competition among different plants, and most models lack a direct linkage to molecular processes. Here we described the rationale, elements, and approaches necessary to build a dynamic systems model of canopy photosynthesis. A systems model should integrate metabolic processes including photosynthesis, respiration, nitrogen metabolism, resource re-mobilization and photosynthate partitioning with canopy level light, CO(2), water vapor distributions and heat exchange processes. In so doing a systems-based canopy photosynthesis model will enable studies of molecular ecology and dramatically improve our insight into engineering crops for improved canopy photosynthetic CO(2) uptake, resource use efficiencies and yields. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Multiscale modeling of complex molecular structure and dynamics with MBN Explorer

    CERN Document Server

    Solov’yov, Ilia A; Solov’yov, Andrey V

    2017-01-01

    This book introduces readers to MesoBioNano (MBN) Explorer – a multi-purpose software package designed to model molecular systems at various levels of size and complexity. In addition, it presents a specially designed multi-task toolkit and interface – the MBN Studio – which enables the set-up of input files, controls the simulations, and supports the subsequent visualization and analysis of the results obtained. The book subsequently provides a systematic description of the capabilities of this universal and powerful software package within the framework of computational molecular science, and guides readers through its applications in numerous areas of research in bio- and chemical physics and material science – ranging from the nano- to the meso-scale. MBN Explorer is particularly suited to computing the system’s energy, to optimizing molecular structure, and to exploring the various facets of molecular and random walk dynamics. The package allows the use of a broad variety of interatomic potenti...

  1. System Convergence in Transport Modelling

    DEFF Research Database (Denmark)

    Rich, Jeppe; Nielsen, Otto Anker; Cantarella, Guilio E.

    2010-01-01

    A fundamental premise of most applied transport models is the existence and uniqueness of an equilibrium solution that balances demand x(t) and supply t(x). The demand consists of the people that travel in the transport system and on the defined network, whereas the supply consists of the resulting...... level-of-service attributes (e.g., travel time and cost) offered to travellers. An important source of complexity is the congestion, which causes increasing demand to affect travel time in a non-linear way. Transport models most often involve separate models for traffic assignment and demand modelling...

  2. Biomimetic polymers of plant cutin: An approach from molecular modeling

    OpenAIRE

    San-Miguel, M. A.; Oviedo, Jaime; Heredia-Guerrero, José A.; Heredia, Antonio; Benítez, José J.

    2014-01-01

    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 ...

  3. 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.

  4. Molecular basis of structural make-up of feeds in relation to nutrient absorption in ruminants, revealed with advanced molecular spectroscopy: A review on techniques and models

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Md. Mostafizar [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Yu, Peiqiang [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    2017-01-31

    Progress in ruminant feed research is no more feasible only based on wet chemical analysis, which is merely able to provide information on chemical composition of feeds regardless of their digestive features and nutritive value in ruminants. Studying internal structural make-up of functional groups/feed nutrients is often vital for understanding the digestive behaviors and nutritive values of feeds in ruminant because the intrinsic structure of feed nutrients is more related to its overall absorption. In this article, the detail information on the recent developments in molecular spectroscopic techniques to reveal microstructural information of feed nutrients and the use of nutrition models in regards to ruminant feed research was reviewed. The emphasis of this review was on (1) the technological progress in the use of molecular spectroscopic techniques in ruminant feed research; (2) revealing spectral analysis of functional groups of biomolecules/feed nutrients; (3) the use of advanced nutrition models for better prediction of nutrient availability in ruminant systems; and (4) the application of these molecular techniques and combination of nutrient models in cereals, co-products and pulse crop research. The information described in this article will promote better insight in the progress of research on molecular structural make-up of feed nutrients in ruminants.

  5. 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.

  6. 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.

  7. Modeling molecular effects on plasmon transport: Silver nanoparticles with tartrazine

    Science.gov (United States)

    Arntsen, Christopher; Lopata, Kenneth; Wall, Michael R.; Bartell, Lizette; Neuhauser, Daniel

    2011-02-01

    Modulation of plasmon transport between silver nanoparticles by a yellow fluorophore, tartrazine, is studied theoretically. The system is studied by combining a finite-difference time-domain Maxwell treatment of the electric field and the plasmons with a time-dependent parameterized method number 3 simulation of the tartrazine, resulting in an effective Maxwell/Schrödinger (i.e., classical/quantum) method. The modeled system has three linearly arranged small silver nanoparticles with a radius of 2 nm and a center-to-center separation of 4 nm; the molecule is centered between the second and third nanoparticles. We initiate an x-polarized current on the first nanoparticle and monitor the transmission through the system. The molecule rotates much of the x-polarized current into the y-direction and greatly reduces the overall transmission of x-polarized current.

  8. 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.

  9. A model of early formation of uranium molecular oxides in laser-ablated plasmas

    Science.gov (United States)

    Finko, Mikhail; Curreli, Davide; Azer, Magdi; Weisz, David; Crowhurst, Jonathan; Rose, Timothy; Koroglu, Batikan; Radousky, Harry; Zaug, Joseph; Armstrong, Mike

    2017-10-01

    An important problem within the field of nuclear forensics is fractionation: the formation of post-detonation nuclear debris whose composition does not reflect that of the source weapon. We are investigating uranium fractionation in rapidly cooling plasma using a combined experimental and modeling approach. In particular, we use laser ablation of uranium metal samples to produce a low-temperature plasma with physical conditions similar to a condensing nuclear fireball. Here we present a first plasma-chemistry model of uranium molecular species formation during the early stage of laser ablated plasma evolution in atmospheric oxygen. The system is simulated using a global kinetic model with rate coefficients calculated according to literature data and the application of reaction rate theory. The model allows for a detailed analysis of the evolution of key uranium molecular species and represents the first step in producing a uranium fireball model that is kinetically validated against spatially and temporally resolved spectroscopy measurements. This project was sponsored by the DoD, Defense Threat Reduction Agency, Grant HDTRA1-16- 1-0020. This work was performed in part under the auspices of the U.S. DoE by Lawrence Livermore National Laboratory under Contract DE-AC52- 07NA27344.

  10. 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

  11. The ultimate complex system: networks in molecular biology

    Science.gov (United States)

    Schreiber, Andreas W.

    2010-07-01

    This contribution provides a brief survey of networks as they occur in molecular biology. It is intended as an introduction for a physics audience with no prior knowledge of molecular biology. References to key papers and reviews are included for the reader who wishes to explore this fascinating area further.

  12. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Directory of Open Access Journals (Sweden)

    Maria Victoria Maliandi

    2011-01-01

    Full Text Available The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  13. High resolution color raster computer animation of space filling molecular models

    International Nuclear Information System (INIS)

    Max, N.L.

    1981-01-01

    The ATOMLLL system efficiently produces realistic photographs of ball-and-stick or space-filling molecular models, with color shading, highlights, shadows, and transparency. The hidden surface problem for a scene composed of intersecting spheres and cylinders is solved on a CDC-7600, which outputs onto magnetic tape the outlines of the visible parts of each object. The outlines are then rendered, at up to 4096 x 4096 resolution, by a Dicomed D-48 color film recorder, controlled by a Varian V-75 minicomputer. The Varian computes the shading and highlights for each pixel in a fast microcoded loop. Recent modifications to give shadows and transparency are described

  14. Executive Information Systems' Multidimensional Models

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

  15. 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

  16. Numerical Modeling of Microelectrochemical Systems

    DEFF Research Database (Denmark)

    Adesokan, Bolaji James

    for the reactants in the bulk electrolyte that are traveling waves. The first paper presents the mathematical model which describes an electrochemical system and simulates an electroanalytical technique called cyclic voltammetry. The model is governed by a system of advection–diffusion equations with a nonlinear...... reaction term at the boundary. We investigate the effect of flow rates, scan rates, and concentration on the cyclic voltammetry. We establish that high flow rates lead to the reduced hysteresis in the cyclic voltammetry curves and increasing scan rates lead to more pronounced current peaks. The final part...... of the paper shows that the response current in a cyclic voltammetry increases proportionally to the electrolyte concentration. In the second paper we present an experiment of an electrochemical system in a microfluidc system and compare the result to the numerical solutions. We investigate how the position...

  17. System Code Models and Capabilities

    International Nuclear Information System (INIS)

    Bestion, D.

    2008-01-01

    System thermalhydraulic codes such as RELAP, TRACE, CATHARE or ATHLET are now commonly used for reactor transient simulations. The whole methodology of code development is described including the derivation of the system of equations, the analysis of experimental data to obtain closure relation and the validation process. The characteristics of the models are briefly presented starting with the basic assumptions, the system of equations and the derivation of closure relationships. An extensive work was devoted during the last three decades to the improvement and validation of these models, which resulted in some homogenisation of the different codes although separately developed. The so called two-fluid model is the common basis of these codes and it is shown how it can describe both thermal and mechanical nonequilibrium. A review of some important physical models allows to illustrate the main capabilities and limitations of system codes. Attention is drawn on the role of flow regime maps, on the various methods for developing closure laws, on the role of interfacial area and turbulence on interfacial and wall transfers. More details are given for interfacial friction laws and their relation with drift flux models. Prediction of chocked flow and CFFL is also addressed. Based on some limitations of the present generation of codes, perspectives for future are drawn.

  18. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...... insight. It is based on a sensitivity approach that is useful for choice of model structure, for experiment design, and for accuracy verification. The method is implemented in the Matlab toolkit Senstools. The method and the presentation have been developed with generally preferred learning styles in mind...

  19. Fragment molecular orbital calculations on large scale systems containing heavy metal atom

    Science.gov (United States)

    Ishikawa, Takeshi; Mochizuki, Yuji; Nakano, Tatsuya; Amari, Shinji; Mori, Hirotoshi; Honda, Hiroaki; Fujita, Takatoshi; Tokiwa, Hiroaki; Tanaka, Shigenori; Komeiji, Yuto; Fukuzawa, Kaori; Tanaka, Kiyoshi; Miyoshi, Eisaku

    2006-08-01

    We have realized a fully quantum mechanical treatment of large scale systems containing heavy metal atom, by introducing the model core potential (MCP) technique into the fragment molecular orbital (FMO) scheme. The scalar relativistic effects are incorporated by the use of MCP. This FMO/MCP method was applied to the divalent mercury ion hydrated with 256 water molecules at the second-order Møller-Plesset (MP2) perturbation level. The complex between cisplatin and DNA was also calculated with MP2, where about a thousand of water molecules and dozens of sodium ions were employed for the explicit treatment of hydration.

  20. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Bañares, Rafael; Nevens, Frederik; Larsen, Fin Stolze

    2013-01-01

    Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189...... sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event...

  1. 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.

  2. System geometry optimization for molecular breast tomosynthesis with focusing multi-pinhole collimators.

    Science.gov (United States)

    van Roosmalen, Jarno; Beekman, Freek J; Goorden, Marlies C

    2017-12-19

    Imaging of 99m Tc-labelled tracers is gaining popularity for detecting breast tumours. Recently, we proposed a novel design for molecular breast tomosynthesis (MBT) based on two sliding focusing multi-pinhole collimators that scan a modestly compressed breast. Simulation studies indicate that MBT has the potential to improve the tumour-to-background contrast-to-noise ratio significantly over state-of-the-art planar molecular breast imaging. The aim of the present paper is to optimize the collimator-detector geometry of MBT. Using analytical models, we first optimized sensitivity at different fixed system resolutions (ranging from 5 to 12 mm) by tuning the pinhole diameters and the distance between breast and detector for a whole series of automatically generated multi-pinhole designs. We evaluated both MBT with a conventional continuous crystal detector with 3.2 mm intrinsic resolution and with a pixelated detector with 1.6 mm pixels. Subsequently, full system simulations of a breast phantom containing several lesions were performed for the optimized geometry at each system resolution for both types of detector. From these simulations, we found that tumour-to-background contrast-to-noise ratio was highest for systems in the 7 mm-10 mm system resolution range over which it hardly varied. No significant differences between the two detector types were found.

  3. ESTIMATION OF HYDROLYSIS RATE CONSTANTS OF CARBOXYLIC ACID ESTER AND PHOSPHATE ESTER COMPOUNDS IN AQUEOUS SYSTEMS FROM MOLECULAR STRUCTURE BY SPARC

    Science.gov (United States)

    SPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity models were extended to calculate hydrolysis rate constants for carboxylic acid ester and phosphate ester compounds in aqueous non- aqueous and systems strictly from molecular structure. The energy diffe...

  4. Fully atomistic molecular-mechanical model of liquid alkane oils: Computational validation.

    Science.gov (United States)

    Zahariev, Tsvetan K; Slavchov, Radomir I; Tadjer, Alia V; Ivanova, Anela N

    2014-04-15

    Fully atomistic molecular dynamics simulations were performed on liquid n-pentane, n-hexane, and n-heptane to derive an atomistic model for middle-chain-length alkanes. All simulations were based on existing molecular-mechanical parameters for alkanes. The computational protocol was optimized, for example, in terms of thermo- and barostat, to reproduce properly the properties of the liquids. The model was validated by comparison of thermal, structural, and dynamic properties of the normal alkane liquids to experimental data. Two different combinations of temperature and pressure coupling algorithms were tested. A simple differential approach was applied to evaluate fluctuation-related properties with sufficient accuracy. Analysis of the data reveals a satisfactory representation of the hydrophobic systems behavior. Thermodynamic parameters are close to the experimental values and exhibit correct temperature dependence. The observed intramolecular geometry corresponds to extended conformations domination, whereas the intermolecular structure demonstrates all characteristics of liquid systems. Cavity size distribution function was calculated from coordinates analysis and was applied to study the solubility of gases in hexane and heptane oils. This study provides a platform for further in-depth research on hydrophobic solutions and multicomponent systems. Copyright © 2014 Wiley Periodicals, Inc.

  5. Smart Sensing Based on DNA-Metal Interaction Enables a Label-Free and Resettable Security Model of Electrochemical Molecular Keypad Lock.

    Science.gov (United States)

    Du, Yan; Han, Xu; Wang, Chenxu; Li, Yunhui; Li, Bingling; Duan, Hongwei

    2018-01-26

    Recently, molecular keypad locks have received increasing attention. As a new subgroup of smart biosensors, they show great potential for protecting information as a molecular security data processor, rather than merely molecular recognition and quantitation. Herein, label-free electrochemically transduced Ag + and cysteine (Cys) sensors were developed. A molecular keypad lock model with reset function was successfully realized based on the balanced interaction of metal ion with its nucleic acid and chemical ligands. The correct input of "1-2-3" (i.e., "Ag + -Cys-cDNA") is the only password of such molecular keypad lock. Moreover, the resetting process of either correct or wrong input order could be easily made by Cys, buffer, and DI water treatment. Therefore, our system provides an even smarter system of molecular keypad lock, which could inhibit illegal access of unauthorized users, holding great promise in information protection at the molecular level.

  6. Theoretical study on the molecular tautomerism of the 3-hydroxy-pyridin-4-one system

    Science.gov (United States)

    Zborowski, Krzysztof K.; Mohammadpour, Mehrdad; Sadeghi, Amir; Proniewicz, Leonard M.

    2013-04-01

    3-hydroxy-pyridin-4-one is a parent molecule for the family of hydroxypyridinones that are known in coordination chemistry as efficient metal ions chelators. In this work, relative stabilities of some possible tautomers were investigated using several quantum chemical methods: CBS (complete basis set methods), Gn, DFT (density functional theory), Hartree-Fock and MP2. Performed calculations show that the system under consideration exists as a mixture of two tautomers with comparable energies. Among them, the hydroxypyridinone structure of the studied molecular system seems to be a bit more stable than the o-dihydroxypyridine one, by a few kJ/mol only. Aromaticity and intra-molecular hydrogen bonding are the main effects influencing the stability of the studied tautomeric structures. Consequently, aromatic effects were calculated using several indices of aromaticity: HOMA (harmonic oscillator model of aromaticity), NICS (nucleus independent chemical shift), H, PDI (para delocalisation index), MCI (multi-centre index) and ASE (aromatic stabilisation energy). The strength of possible intra-molecular hydrogen bonds (H-bonds) was determined by means of the AIM (atoms-in-molecules) method and by calculating enthalpies for theoretical reactions that do or do not involve H-bonds. The AIM method was employed to understand how variations in atomic energies influence the stability of different tautomeric structures.

  7. Large-scale theoretical calculations in molecular science - design of a large computer system for molecular science and necessary conditions for future computers

    International Nuclear Information System (INIS)

    Kashiwagi, H.

    1982-01-01

    A large computer system was designed and established for molecular science under the leadership of molecular scientists. Features of the computer system are an automated operation system and an open self-service system. Large-scale theoretical calculations have been performed to solve many problems in molecular science, using the computer system. Necessary conditions for future computers are discussed on the basis of this experience. (orig.)

  8. Reverse engineering systems models of regulation: discovery, prediction and mechanisms.

    Science.gov (United States)

    Ashworth, Justin; Wurtmann, Elisabeth J; Baliga, Nitin S

    2012-08-01

    Biological systems can now be understood in comprehensive and quantitative detail using systems biology approaches. Putative genome-scale models can be built rapidly based upon biological inventories and strategic system-wide molecular measurements. Current models combine statistical associations, causative abstractions, and known molecular mechanisms to explain and predict quantitative and complex phenotypes. This top-down 'reverse engineering' approach generates useful organism-scale models despite noise and incompleteness in data and knowledge. Here we review and discuss the reverse engineering of biological systems using top-down data-driven approaches, in order to improve discovery, hypothesis generation, and the inference of biological properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Multi-scale Modeling of Compressible Single-phase Flow in Porous Media using Molecular Simulation

    KAUST Repository

    Saad, Ahmed Mohamed

    2016-05-01

    In this study, an efficient coupling between Monte Carlo (MC) molecular simulation and Darcy-scale flow in porous media is presented. The cell-centered finite difference method with a non-uniform rectangular mesh were used to discretize the simulation domain and solve the governing equations. To speed up the MC simulations, we implemented a recently developed scheme that quickly generates MC Markov chains out of pre-computed ones, based on the reweighting and reconstruction algorithm. This method astonishingly reduces the required computational time by MC simulations from hours to seconds. In addition, the reweighting and reconstruction scheme, which was originally designed to work with the LJ potential model, is extended to work with a potential model that accounts for the molecular quadrupole moment of fluids with non-spherical molecules such as CO2. The potential model was used to simulate the thermodynamic equilibrium properties for single-phase and two-phase systems using the canonical ensemble and the Gibbs ensemble, respectively. Comparing the simulation results with the experimental data showed that the implemented model has an excellent fit outperforming the standard LJ model. To demonstrate the strength of the proposed coupling in terms of computational time efficiency and numerical accuracy in fluid properties, various numerical experiments covering different compressible single-phase flow scenarios were conducted. The novelty in the introduced scheme is in allowing an efficient coupling of the molecular scale and Darcy scale in reservoir simulators. This leads to an accurate description of the thermodynamic behavior of the simulated reservoir fluids; consequently enhancing the confidence in the flow predictions in porous media.

  10. Understanding DNA Under Oxidative Stress and Sensitization: The Role of Molecular Modeling

    Directory of Open Access Journals (Sweden)

    Antonio eMonari

    2015-07-01

    Full Text Available DNA is constantly exposed to damaging threats coming from oxidative stress, i.e. from the presence of free radicals and reactive oxygen species. Sensitization from exogenous and endogenous compounds that strongly enhance the frequency of light-induced lesions also plays an important role. The experimental determination of DNA lesions, though a difficult subject, is somehow well established and allows to elucidate even extremely rare DNA lesions. In parallel, molecular modeling has become fundamental to clearly understand the fine mechanisms related to DNA defects induction. Indeed, it offers an unprecedented possibility to get access to an atomistic or even electronic resolution. Ab initio molecular dynamics may also describe the time-evolution of the molecular system and its reactivity. Yet the modeling of DNA (photo-reactions does necessitate elaborate multi-scale methodologies to tackle a damage induction reactivity that takes place in a complex environment. The double-stranded DNA environment is first characterized by a very high flexibility, that dynamical effects are to be taken into account, but also a strongly inhomogeneous electrostatic embedding. Additionally, one aims at capturing more subtle effects, such as the sequence selectivity which is of critical important for DNA damage. The structure and dynamics of the DNA/sensitizers complexes, as well as the photo-induced electron- and energy-transfer phenomena taking place upon sensitization, should be carefully modeled. Finally the factors inducing different repair ratios for different lesions should also be rationalized.In this review we will critically analyze the different computational strategies used to model DNA lesions. A clear picture of the complex interplay between reactivity and structural factors will be sketched. The use of proper multi-scale modeling leads to the in-depth comprehension of DNA lesions mechanism and also to the rational design of new chemo-therapeutic agents.

  11. 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

  12. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    Science.gov (United States)

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

  13. 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

  14. 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

  15. Parametric Modeling for Fluid Systems

    Science.gov (United States)

    Pizarro, Yaritzmar Rosario; Martinez, Jonathan

    2013-01-01

    Fluid Systems involves different projects that require parametric modeling, which is a model that maintains consistent relationships between elements as is manipulated. One of these projects is the Neo Liquid Propellant Testbed, which is part of Rocket U. As part of Rocket U (Rocket University), engineers at NASA's Kennedy Space Center in Florida have the opportunity to develop critical flight skills as they design, build and launch high-powered rockets. To build the Neo testbed; hardware from the Space Shuttle Program was repurposed. Modeling for Neo, included: fittings, valves, frames and tubing, between others. These models help in the review process, to make sure regulations are being followed. Another fluid systems project that required modeling is Plant Habitat's TCUI test project. Plant Habitat is a plan to develop a large growth chamber to learn the effects of long-duration microgravity exposure to plants in space. Work for this project included the design and modeling of a duct vent for flow test. Parametric Modeling for these projects was done using Creo Parametric 2.0.

  16. Molecular photoionization studies of nucleobases and correlated systems

    Energy Technology Data Exchange (ETDEWEB)

    Poliakoff, Erwin D. [Louisiana State Univ., Baton Rouge, LA (United States)

    2015-03-11

    We proposed molecular photoionization studies in order to probe correlated events in fundamental scattering phenomena. In particular, we suggested that joint theoretical-experimental studies would provide a window into the microscopic aspects that are of central importance in AMO and chemical physics generally, and would generate useful data for wide array of important DOE topics, such as ultrafast dynamics, high harmonic generation, and probes of nonadiabatic processes. The unifying theme is that correlations between electron scattering dynamics and molecular geometry highlight inherently molecular aspects of the photoelectron behavior.

  17. Biliary System Architecture: Experimental Models and Visualization Techniques

    Czech Academy of Sciences Publication Activity Database

    Sarnová, Lenka; Gregor, Martin

    2017-01-01

    Roč. 66, č. 3 (2017), s. 383-390 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604; GA ČR GA15-23858S Institutional support: RVO:68378050 Keywords : Biliary system * Mouse model * Cholestasis * Visualisation * Morphology Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 1.461, year: 2016

  18. Model checking embedded system designs

    NARCIS (Netherlands)

    Brinksma, Hendrik; Mader, Angelika H.

    2002-01-01

    Model checking has established itself as a successful tool supported technique for the verification and debugging of various hardware and software systems [16]. Not only in academia, but also by industry this technique is increasingly being regarded as a promising and practical proposition,

  19. GENERIC model for multiphase systems

    NARCIS (Netherlands)

    Sagis, L.M.C.

    2010-01-01

    GENERIC is a nonequilibrium thermodynamic formalism in which the dynamic behavior of a system is described by a single compact equation involving two types of brackets: a Poisson bracket and a dissipative bracket. This formalism has proved to be a very powerful instrument to model the dynamic

  20. An extensible analysable system model

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, Rene Rydhof

    2008-01-01

    Analysing real-world systems for vulnerabilities with respect to security and safety threats is a difficult undertaking, not least due to a lack of availability of formalisations for those systems. While both formalisations and analyses can be found for artificial systems such as software......, this does not hold for real physical systems. Approaches such as threat modelling try to target the formalisation of the real-world domain, but still are far from the rigid techniques available in security research. Many currently available approaches to assurance of critical infrastructure security...... are based on (quite successful) ad-hoc techniques. We believe they can be significantly improved beyond the state-of-the-art by pairing them with static analyses techniques. In this paper we present an approach to both formalising those real-world systems, as well as providing an underlying semantics, which...

  1. Molecular Genetic and Gene Therapy Studies of the Musculoskeletal System

    National Research Council Canada - National Science Library

    Baylink, David

    2004-01-01

    The primary goal of the proposed work is to apply several state of the art molecular genetic and gene therapy technologies to address fundamental questions in bone biology with a particular emphasis on attempting: l...

  2. Systems modeling for laser IFE

    Science.gov (United States)

    Meier, W. R.; Raffray, A. R.; Sviatoslavsky, I. N.

    2006-06-01

    A systems model of a laser-driven IFE power plant is being developed to assist in design trade-offs and optimization. The focus to date has been on modeling the fusion chamber, blanket and power conversion system. A self-consistent model has been developed to determine key chamber and thermal cycle parameters (e.g., chamber radius, structure and coolant temperatures, cycle efficiency, etc.) as a function of the target yield and pulse repetition rate. Temperature constraints on the tungsten armor, ferritic steel wall, and structure/coolant interface are included in evaluating the potential design space. Results are presented for a lithium cooled first wall coupled with a Brayton power cycle. LLNL work performed under the auspices of the US Department of Energy by the University of California LLNL under Contract W-7405-Eng-48.

  3. The chloroplast thylakoid membrane system is a molecular conveyor belt.

    Science.gov (United States)

    Critchley, C

    1988-10-01

    Light drives photosynthesis, but paradoxically light is also the most variable environmental factor influencing photosynthesis both qualitatively and quantitatively. The photosynthetic apparatus of higher plants is adaptable in the extreme, as exemplified by its capacity for acclimation to very bright sunny or deeply shaded conditions. It can also respond to rapid changes in light such as sunflecks. In this paper I offer a model that i) explains the thylakoid membrane organisation into grana stacks and stroma lamellae, ii) proposes a role for rapid D1 protein turnover and LHCII phosphorylation, and iii) suggests a mechanism for photoinhibition. I argue that the photosynthetic membrane system is dynamic in three dimensions, so much so that, in the light, it is in constant motion and operates in a manner somewhat analogous to a conveyor belt. D1 protein degradation is proposed to be the motor that drives this system. Photoinhibition is suggested to be due to the arrest of D1 protein turnover.

  4. Molecular Mechanisms Used bySalmonellato Evade the Immune System.

    Science.gov (United States)

    Bernal-Bayard, Joaquín; Ramos-Morales, Francisco

    2018-01-01

    Human and animal pathogens are able to circumvent, at least temporarily, the sophisticated immune defenses of their hosts. Several serovars of the Gram-negative bacterium Salmonella enterica have been used as models for the study of pathogen-host interactions. In this review we discuss the strategies used by Salmonella to evade or manipulate three levels of host immune defenses: physical barriers, innate immunity and adaptive immunity. During its passage through the digestive system, Salmonella has to face the acidic pH of the stomach, bile and antimicrobial peptides in the intestine, as well as the competition with resident microbiota. After host cell invasion, Salmonella manipulates inflammatory pathways and the autophagy process. Finally, Salmonella evades the adaptive immune system by interacting with dendritic cells, and T and B lymphocytes. Mechanisms allowing the establishment of persistent infections are also discussed.

  5. Cotangent Models for Integrable Systems

    Science.gov (United States)

    Kiesenhofer, Anna; Miranda, Eva

    2017-03-01

    We associate cotangent models to a neighbourhood of a Liouville torus in symplectic and Poisson manifolds focusing on b-Poisson/ b-symplectic manifolds. The semilocal equivalence with such models uses the corresponding action-angle theorems in these settings: the theorem of Liouville-Mineur-Arnold for symplectic manifolds and an action-angle theorem for regular Liouville tori in Poisson manifolds (Laurent- Gengoux et al., IntMath Res Notices IMRN 8: 1839-1869, 2011). Our models comprise regular Liouville tori of Poisson manifolds but also consider the Liouville tori on the singular locus of a b-Poisson manifold. For this latter class of Poisson structures we define a twisted cotangent model. The equivalence with this twisted cotangent model is given by an action-angle theorem recently proved by the authors and Scott (Math. Pures Appl. (9) 105(1):66-85, 2016). This viewpoint of cotangent models provides a new machinery to construct examples of integrable systems, which are especially valuable in the b-symplectic case where not many sources of examples are known. At the end of the paper we introduce non-degenerate singularities as lifted cotangent models on b-symplectic manifolds and discuss some generalizations of these models to general Poisson manifolds.

  6. A hybrid particle–field molecular dynamics approach: a route toward efficient coarse-grained models for biomembranes

    International Nuclear Information System (INIS)

    Milano, Giuseppe; De Nicola, Antonio; Kawakatsu, Toshihiro

    2013-01-01

    This paper gives an overview of the coarse-grained models of phospholipids recently developed by the authors in the frame of a hybrid particle–field molecular dynamics technique. This technique employs a special class of coarse-grained models that are gaining popularity because they allow simulations of large scale systems and, at the same time, they provide sufficiently detailed chemistry for the mapping scheme adopted. The comparison of the computational costs of our approach with standard molecular dynamics simulations is a function of the system size and the number of processors employed in the parallel calculations. Due to the low amount of data exchange, the larger the number of processors, the better are the performances of the hybrid particle–field models. This feature makes these models very promising ones in the exploration of several problems in biophysics. (paper)

  7. Molecular dynamics for ion-tuned wettability in oil/brine/rock systems

    Directory of Open Access Journals (Sweden)

    Huanhuan Tian

    2017-12-01

    Full Text Available The dependence of wettability on brine ionic composition in oil/brine/rock systems, which is denoted as ion-tuned wettability, has important applications in geoscience. Due to the involvement of non-continuum effects, molecular dynamics (MD simulation is necessary to improve understanding of its mechanism. This work establishes a reliable molecular dynamics (MD framework to study ion-tuned wettability. We prove that our model system can well represent the wettability of the real oil/brine/rock system, and that the wettability alteration from the MD results is qualitatively consistent with the EDL repulsion theory when ion-binding does not exist. In the process to establish the MD framework, our work suggests that adding counter ions to balance interface charges is good for studying concentration effect on wettability, and the contact angle defined from mass center coordinates is effective to measure the wettability of the nano-scale MD system. This work provides the basis for on-going studies using MD simulation to reveal the mechanism of ion-tuned wettability.

  8. Molecular dynamics for ion-tuned wettability in oil/brine/rock systems

    Science.gov (United States)

    Tian, Huanhuan; Wang, Moran

    2017-12-01

    The dependence of wettability on brine ionic composition in oil/brine/rock systems, which is denoted as ion-tuned wettability, has important applications in geoscience. Due to the involvement of non-continuum effects, molecular dynamics (MD) simulation is necessary to improve understanding of its mechanism. This work establishes a reliable molecular dynamics (MD) framework to study ion-tuned wettability. We prove that our model system can well represent the wettability of the real oil/brine/rock system, and that the wettability alteration from the MD results is qualitatively consistent with the EDL repulsion theory when ion-binding does not exist. In the process to establish the MD framework, our work suggests that adding counter ions to balance interface charges is good for studying concentration effect on wettability, and the contact angle defined from mass center coordinates is effective to measure the wettability of the nano-scale MD system. This work provides the basis for on-going studies using MD simulation to reveal the mechanism of ion-tuned wettability.

  9. FAMSD: A powerful protein modeling platform that combines alignment methods, homology modeling, 3D structure quality estimation and molecular dynamics.

    Science.gov (United States)

    Kanou, Kazuhiko; Iwadate, Mitsuo; Hirata, Tomoko; Terashi, Genki; Umeyama, Hideaki; Takeda-Shitaka, Mayuko

    2009-12-01

    The prediction of a protein three-dimensional (3D) structure is one of the most important challenges in computational structural biology. We have developed an automatic protein 3D structure prediction method called FAMSD. FAMSD is based on a comparative modeling method which consists of the following four steps: (1) generating and selecting sequence alignments between target and template proteins; (2) constructing 3D structure models based on each selected alignment; (3) selecting the best 3D structure model and (4) refining the selected model. In the FAMSD method, sequence alignment programs such as a series of BLAST programs, SP3 and SPARKS2 programs, the homology modeling program FAMS (Full Automatic Modeling System), the model quality estimation program CIRCLE and the molecular dynamics program APRICOT were used in combination to construct high quality protein models. To assess the FAMSD method we have participated in the 8th Critical Assessment of Techniques for Protein Structure Prediction (CASP8) experiment. The results of our original assessment indicate that the FAMSD method offers excellent capability in packing side-chains with the correct torsion angles while avoiding the formation of atom-atom collisions. Since side-chain packing plays a significant role in defining the biological function of proteins, this method is a valuable resource in biological, pharmaceutical and medicinal research efforts.

  10. Thermal conductivity of molten salt mixtures: Theoretical model supported by equilibrium molecular dynamics simulations

    Science.gov (United States)

    Gheribi, Aïmen E.; Chartrand, Patrice

    2016-02-01

    A theoretical model for the description of thermal conductivity of molten salt mixtures as a function of composition and temperature is presented. The model is derived by considering the classical kinetic theory and requires, for its parametrization, only information on thermal conductivity of pure compounds. In this sense, the model is predictive. For most molten salt mixtures, no experimental data on thermal conductivity are available in the literature. This is a hindrance for many industrial applications (in particular for thermal energy storage technologies) as well as an obvious barrier for the validation of the theoretical model. To alleviate this lack of data, a series of equilibrium molecular dynamics (EMD) simulations has been performed on several molten chloride systems in order to determine their thermal conductivity in the entire range of composition at two different temperatures: 1200 K and 1300 K. The EMD simulations are first principles type, as the potentials used to describe the interactions have been parametrized on the basis of first principle electronic structure calculations. In addition to the molten chlorides system, the model predictions are also compared to a recent similar EMD study on molten fluorides and with the few reliable experimental data available in the literature. The accuracy of the proposed model is within the reported numerical and/or experimental errors.

  11. Thermal conductivity of molten salt mixtures: Theoretical model supported by equilibrium molecular dynamics simulations.

    Science.gov (United States)

    Gheribi, Aïmen E; Chartrand, Patrice

    2016-02-28

    A theoretical model for the description of thermal conductivity of molten salt mixtures as a function of composition and temperature is presented. The model is derived by considering the classical kinetic theory and requires, for its parametrization, only information on thermal conductivity of pure compounds. In this sense, the model is predictive. For most molten salt mixtures, no experimental data on thermal conductivity are available in the literature. This is a hindrance for many industrial applications (in particular for thermal energy storage technologies) as well as an obvious barrier for the validation of the theoretical model. To alleviate this lack of data, a series of equilibrium molecular dynamics (EMD) simulations has been performed on several molten chloride systems in order to determine their thermal conductivity in the entire range of composition at two different temperatures: 1200 K and 1300 K. The EMD simulations are first principles type, as the potentials used to describe the interactions have been parametrized on the basis of first principle electronic structure calculations. In addition to the molten chlorides system, the model predictions are also compared to a recent similar EMD study on molten fluorides and with the few reliable experimental data available in the literature. The accuracy of the proposed model is within the reported numerical and/or experimental errors.

  12. Molecular mechanics and quantum mechanical modeling of hexane soot structure and interactions with pyrene

    Directory of Open Access Journals (Sweden)

    Kubicki JD

    2000-09-01

    Full Text Available Molecular simulations (energy minimizations and molecular dynamics of an n-hexane soot model developed by Smith and co-workers (M. S. Akhter, A. R. Chughtai and D. M. Smith, Appl. Spectrosc., 1985, 39, 143; ref. 1 were performed. The MM+ (N. L. Allinger, J. Am. Chem. Soc., 1977, 395, 157; ref. 2 and COMPASS (H. Sun, J. Phys. Chem., 1998, 102, 7338; ref. 3 force fields were tested for their ability to produce realistic soot nanoparticle structure. The interaction of pyrene with the model soot was simulated. Quantum mechanical calculations on smaller soot fragments were carried out. Starting from an initial 2D structure, energy minimizations are not able to produce the observed layering within soot with either force field. Results of molecular dynamics simulations indicate that the COMPASS force field does a reasonably accurate job of reproducing observations of soot structure. Increasing the system size from a 683 to a 2732 atom soot model does not have a significant effect on predicted structures. Neither does the addition of water molecules surrounding the soot model. Pyrene fits within the soot structure without disrupting the interlayer spacing. Polycyclic aromatic hydrocarbons (PAH, such as pyrene, may strongly partition into soot and have slow desorption kinetics because the PAH-soot bonding is similar to soot–soot interactions. Diffusion of PAH into soot micropores may allow the PAH to be irreversibly adsorbed and sequestered so that they partition slowly back into an aqueous phase causing dis-equilibrium between soil organic matter and porewater.

  13. Molecular Dynamics Simulation of Coarse-Grain Model of Silicon Functionalized Graphene

    Directory of Open Access Journals (Sweden)

    Hui Zhixin

    2015-01-01

    Full Text Available The electronic transport, the storage capacity and the service life of the anode material for lithium ion batteries will be reduced seriously in the event of the material layering or cracking, so the anode material must have strong mechanical reliability. Firstly, in view of the traditional molecular dynamics (MD limited by the geometric scales of the model of Silicon functionalized graphenen (SFG as lithium ion batteries anode material, some full atomic models of SFG were established using Tersoff potential and Lennard-Jones potential, and used to calculate the modulus and the adhesion properties. What’s more, the assertion of mechanical equilibrium condition and energy conservation between full atomic and coarse-grain models through elastic strain energy were enforced to arrive at model parameters. The model of SFG coarse-grain bead-spring elements and its system energy function were obtained via full atomic simulations. Finally, the validity of the SFG coarse-grain model was verified by comparing the tensile property of coarse-grain model with full atoms model.

  14. 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,

  15. Graph modeling systems and methods

    Science.gov (United States)

    Neergaard, Mike

    2015-10-13

    An apparatus and a method for vulnerability and reliability modeling are provided. The method generally includes constructing a graph model of a physical network using a computer, the graph model including a plurality of terminating vertices to represent nodes in the physical network, a plurality of edges to represent transmission paths in the physical network, and a non-terminating vertex to represent a non-nodal vulnerability along a transmission path in the physical network. The method additionally includes evaluating the vulnerability and reliability of the physical network using the constructed graph model, wherein the vulnerability and reliability evaluation includes a determination of whether each terminating and non-terminating vertex represents a critical point of failure. The method can be utilized to evaluate wide variety of networks, including power grid infrastructures, communication network topologies, and fluid distribution systems.

  16. Photochemical reactions of various model protocell systems

    Science.gov (United States)

    Folsome, C. E.

    1986-01-01

    Models for the emergence of cellular life on the primitive Earth, and for physical environments of that era have been studied that embody these assumptions: (1) pregenetic cellular forms were phase-bounded systems primarily photosynthetic in nature, and (2) the early Earth environment was anoxic (lacking appreciable amounts of free hydrogen). It was found that organic structures can also be formed under anoxic conditions (N2, CO3=, H2O) by protracted longwavelength UV radiation. Apparently these structures form initially as organic layers upon CaCO3 crystalloids. The question remains as to whether the UV photosynthetic ability of such phase bounded structures is a curiosity, or a general property of phase bounded systems which is of direct interest to the emergence of cellular life. The question of the requirement and sailient features of a phase boundary for UV photosynthetic abilities was addressed by searching for similar general physical properties which might be manifest in a variety of other simple protocell-like structures. Since it has been shown that laboratory protocell models can effect the UV photosynthesis of low molecular weight compounds, this reaction is being used as an assay to survey other types of structures for similar UV photosynthetic reactions. Various kinds of structures surveyed are: (1) proteinoids; (2) liposomes; (3) reconstituted cell membrane spheroids; (4) coacervates; and (5) model protocells formed under anoxic conditions.

  17. Probabilistic models for feedback systems.

    Energy Technology Data Exchange (ETDEWEB)

    Grace, Matthew D.; Boggs, Paul T.

    2011-02-01

    In previous work, we developed a Bayesian-based methodology to analyze the reliability of hierarchical systems. The output of the procedure is a statistical distribution of the reliability, thus allowing many questions to be answered. The principal advantage of the approach is that along with an estimate of the reliability, we also can provide statements of confidence in the results. The model is quite general in that it allows general representations of all of the distributions involved, it incorporates prior knowledge into the models, it allows errors in the 'engineered' nodes of a system to be determined by the data, and leads to the ability to determine optimal testing strategies. In this report, we provide the preliminary steps necessary to extend this approach to systems with feedback. Feedback is an essential component of 'complexity' and provides interesting challenges in modeling the time-dependent action of a feedback loop. We provide a mechanism for doing this and analyze a simple case. We then consider some extensions to more interesting examples with local control affecting the entire system. Finally, a discussion of the status of the research is also included.

  18. Animal models and therapeutic molecular targets of cancer: utility and limitations

    Science.gov (United States)

    Cekanova, Maria; Rathore, Kusum

    2014-01-01

    Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. PMID:25342884

  19. Stochastic Modelling of Hydrologic Systems

    DEFF Research Database (Denmark)

    Jonsdottir, Harpa

    2007-01-01

    In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains an introduct......In this PhD project several stochastic modelling methods are studied and applied on various subjects in hydrology. The research was prepared at Informatics and Mathematical Modelling at the Technical University of Denmark. The thesis is divided into two parts. The first part contains...... an introduction and an overview of the papers published. Then an introduction to basic concepts in hydrology along with a description of hydrological data is given. Finally an introduction to stochastic modelling is given. The second part contains the research papers. In the research papers the stochastic methods...... are described, as at the time of publication these methods represent new contribution to hydrology. The second part also contains additional description of software used and a brief introduction to stiff systems. The system in one of the papers is stiff....

  20. Discrete modelling of drapery systems

    Science.gov (United States)

    Thoeni, Klaus; Giacomini, Anna

    2016-04-01

    Drapery systems are an efficient and cost-effective measure in preventing and controlling rockfall hazards on rock slopes. The simplest form consists of a row of ground anchors along the top of the slope connected to a horizontal support cable from which a wire mesh is suspended down the face of the slope. Such systems are generally referred to as simple or unsecured draperies (Badger and Duffy 2012). Variations such as secured draperies, where a pattern of ground anchors is incorporated within the field of the mesh, and hybrid systems, where the upper part of an unsecured drapery is elevated to intercept rockfalls originating upslope of the installation, are becoming more and more popular. This work presents a discrete element framework for simulation of unsecured drapery systems and its variations. The numerical model is based on the classical discrete element method (DEM) and implemented into the open-source framework YADE (Šmilauer et al., 2010). The model takes all relevant interactions between block, drapery and slope into account (Thoeni et al., 2014) and was calibrated and validated based on full-scale experiments (Giacomini et al., 2012).The block is modelled as a rigid clump made of spherical particles which allows any shape to be approximated. The drapery is represented by a set of spherical particle with remote interactions. The behaviour of the remote interactions is governed by the constitutive behaviour of the wire and generally corresponds to a piecewise linear stress-strain relation (Thoeni et al., 2013). The same concept is used to model wire ropes. The rock slope is represented by rigid triangular elements where material properties (e.g., normal coefficient of restitution, friction angle) are assigned to each triangle. The capabilities of the developed model to simulate drapery systems and estimate the residual hazard involved with such systems is shown. References Badger, T.C., Duffy, J.D. (2012) Drapery systems. In: Turner, A.K., Schuster R

  1. Preface - From molecules to molecular materials, biological molecular systems and nanostructures: A collection of contributions presented at the XIIIth International Conference on Molecular Spectroscopy

    Science.gov (United States)

    Ratajczak, Henryk; Drozd, Marek; Fausto, Rui

    2016-12-01

    This volume contains a series of selected contributions presented at the XIIIth International Conference on Molecular Spectroscopy (ICMS): "From Molecules to Molecular Materials, Biological Molecular Systems and Nanostructures" held in Wrocław, Poland, 9-12 September 2015, under the auspices of the Mayor of Wrocław and the European Academy of Sciences, Arts and Humanities. Wrocław was chosen not accidentally as venue for the conference. With more than a thousand years of history, Wrocław is the location of one of the oldest universities in Central Europe. Being a place where education and science play major roles in the daily life of its inhabitants, Wrocław is also a privileged center for spectroscopy in Poland.

  2. High-performance modeling of CO2 sequestration by coupling reservoir simulation and molecular dynamics

    KAUST Repository

    Bao, Kai

    2013-01-01

    The present work describes a parallel computational framework for CO2 sequestration simulation by coupling reservoir simulation and molecular dynamics (MD) on massively parallel HPC systems. In this framework, a parallel reservoir simulator, Reservoir Simulation Toolbox (RST), solves the flow and transport equations that describe the subsurface flow behavior, while the molecular dynamics simulations are performed to provide the required physical parameters. Numerous technologies from different fields are employed to make this novel coupled system work efficiently. One of the major applications of the framework is the modeling of large scale CO2 sequestration for long-term storage in the subsurface geological formations, such as depleted reservoirs and deep saline aquifers, which has been proposed as one of the most attractive and practical solutions to reduce the CO2 emission problem to address the global-warming threat. To effectively solve such problems, fine grids and accurate prediction of the properties of fluid mixtures are essential for accuracy. In this work, the CO2 sequestration is presented as our first example to couple the reservoir simulation and molecular dynamics, while the framework can be extended naturally to the full multiphase multicomponent compositional flow simulation to handle more complicated physical process in the future. Accuracy and scalability analysis are performed on an IBM BlueGene/P and on an IBM BlueGene/Q, the latest IBM supercomputer. Results show good accuracy of our MD simulations compared with published data, and good scalability are observed with the massively parallel HPC systems. The performance and capacity of the proposed framework are well demonstrated with several experiments with hundreds of millions to a billion cells. To our best knowledge, the work represents the first attempt to couple the reservoir simulation and molecular simulation for large scale modeling. Due to the complexity of the subsurface systems

  3. Low-Volatility Model Demonstrates Humidity Affects Environmental Toxin Deposition on Plastics at a Molecular Level.

    Science.gov (United States)

    Hankett, Jeanne M; Collin, William R; Yang, Pei; Chen, Zhan; Duhaime, Melissa

    2016-02-02

    Despite the ever-increasing prevalence of plastic debris and endocrine disrupting toxins in aquatic ecosystems, few studies describe their interactions in freshwater environments. We present a model system to investigate the deposition/desorption behaviors of low-volatility lake ecosystem toxins on microplastics in situ and in real time. Molecular interactions of gas-phase nonylphenols (NPs) with the surfaces of two common plastics, poly(styrene) and poly(ethylene terephthalate), were studied using quartz crystal microbalance and sum frequency generation vibrational spectroscopy. NP point sources were generated under two model environments: plastic on land and plastic on a freshwater surface. We found the headspace above calm water provides an excellent environment for NP deposition and demonstrate significant NP deposition on plastic within minutes at relevant concentrations. Further, NP deposits and orders differently on both plastics under humid versus dry environments. We attributed the unique deposition behaviors to surface energy changes from increased water content during the humid deposition. Lastly, nanograms of NP remained on microplastic surfaces hours after initial NP introduction and agitating conditions, illustrating feasibility for plastic-bound NPs to interact with biota and surrounding matter. Our model studies reveal important interactions between low-volatility environmental toxins and microplastics and hold potential to correlate the environmental fate of endocrine disrupting toxins in the Great Lakes with molecular behaviors.

  4. Comparing selected morphological models of hydrated Nafion using large scale molecular dynamics simulations

    Science.gov (United States)

    Knox, Craig K.

    Experimental elucidation of the nanoscale structure of hydrated Nafion, the most popular polymer electrolyte or proton exchange membrane (PEM) to date, and its influence on macroscopic proton conductance is particularly challenging. While it is generally agreed that hydrated Nafion is organized into distinct hydrophilic domains or clusters within a hydrophobic matrix, the geometry and length scale of these domains continues to be debated. For example, at least half a dozen different domain shapes, ranging from spheres to cylinders, have been proposed based on experimental SAXS and SANS studies. Since the characteristic length scale of these domains is believed to be ˜2 to 5 nm, very large molecular dynamics (MD) simulations are needed to accurately probe the structure and morphology of these domains, especially their connectivity and percolation phenomena at varying water content. Using classical, all-atom MD with explicit hydronium ions, simulations have been performed to study the first-ever hydrated Nafion systems that are large enough (~2 million atoms in a ˜30 nm cell) to directly observe several hydrophilic domains at the molecular level. These systems consisted of six of the most significant and relevant morphological models of Nafion to-date: (1) the cluster-channel model of Gierke, (2) the parallel cylinder model of Schmidt-Rohr, (3) the local-order model of Dreyfus, (4) the lamellar model of Litt, (5) the rod network model of Kreuer, and (6) a 'random' model, commonly used in previous simulations, that does not directly assume any particular geometry, distribution, or morphology. These simulations revealed fast intercluster bridge formation and network percolation in all of the models. Sulfonates were found inside these bridges and played a significant role in percolation. Sulfonates also strongly aggregated around and inside clusters. Cluster surfaces were analyzed to study the hydrophilic-hydrophobic interface. Interfacial area and cluster volume

  5. 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

  6. Optimization of fuel ethanol recovery systems using molecular sieves

    International Nuclear Information System (INIS)

    Scheller, W.A.

    1989-01-01

    The use of molecular sieves for the dehydration of rectified fuel ethanol requires only about 58% of the energy required by azeotropic distillation, the usual commercial process. Recently molecular sieve prices have become low enough that their use can be economically competitive with azeotropic distillation. This paper contains results of mass and energy balances to determine the water content of the rectified ethanol (6.15 weight percent) that will result in the minimum energy requirement for producing anhydrous ethanol with the molecular sieve process and byproduct distillers soluble syrup from fermented corn mash containing 7.23 weight percent ethanol. In this paper results of economic evaluations to determine the water content of the rectified ethanol (7.58 weight percent) which results in a minimum investment and operating cost are presented

  7. Environmental Molecular Sciences Laboratory Operations System: Version 4.0 - system requirements specification

    Energy Technology Data Exchange (ETDEWEB)

    Kashporenko, D.

    1996-07-01

    This document is intended to provide an operations standard for the Environmental Molecular Sciences Laboratory OPerations System (EMSL OPS). It is directed toward three primary audiences: (1) Environmental Molecular Sciences Laboratory (EMSL) facility and operations personnel; (2) laboratory line managers and staff; and (3) researchers, equipment operators, and laboratory users. It is also a statement of system requirements for software developers of EMSL OPS. The need for a finely tuned, superior research environment as provided by the US Department of Energy`s (DOE) Environmental Molecular Sciences Laboratory has never been greater. The abrupt end of the Cold War and the realignment of national priorities caused major US and competing overseas laboratories to reposition themselves in a highly competitive research marketplace. For a new laboratory such as the EMSL, this means coming into existence in a rapidly changing external environment. For any major laboratory, these changes create funding uncertainties and increasing global competition along with concomitant demands for higher standards of research product quality and innovation. While more laboratories are chasing fewer funding dollars, research ideas and proposals, especially for molecular-level research in the materials and biological sciences, are burgeoning. In such an economically constrained atmosphere, reduced costs, improved productivity, and strategic research project portfolio building become essential to establish and maintain any distinct competitive advantage. For EMSL, this environment and these demands require clear operational objectives, specific goals, and a well-crafted strategy. Specific goals will evolve and change with the evolution of the nature and definition of DOE`s environmental research needs. Hence, EMSL OPS is designed to facilitate migration of these changes with ease into every pertinent job function, creating a facile {open_quotes}learning organization.{close_quotes}

  8. 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.

  9. Molecular profiles to biology and pathways: a systems biology approach.

    Science.gov (United States)

    Van Laere, Steven; Dirix, Luc; Vermeulen, Peter

    2016-06-16

    Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters.

  10. Soft Phonon and Central Peak Scattering in Molecular Crystal System

    DEFF Research Database (Denmark)

    Ellenson, W. D.; Kjems, Jørgen

    1977-01-01

    Elastic and inelastic neutron scattering has been used to study the continuous structural transition in chloranil at Tc=90.3 K. The transition results in a doubling of the monoclinic unit cell along the c axis and the molecular displacements correspond to a staggered rotation, ϕ, about axes...... perpendicular to the molecular planes. The temperature dependence of the order parameter, ϕ, has been determined from superlattice Bragg intensities with the result ϕ∝ (Tc−T)0.33±0.02 for 0.005

  11. Study of melting of molecular crystals by a modified Pople-Karasz model

    Science.gov (United States)

    Yazıcı, Mustafa; Özgan, Şükrü; Keskin, Mustafa

    2005-02-01

    A new modified model that combines the modified models of Chandrasekhar et al. with those of Keskin and Özgan, which are based on the Pople-Karasz theory, is applied to study the thermodynamics of melting and solid-solid transitions of molecular crystals. The thermodynamic properties of the disordered system are evaluated relative to those of the perfectly ordered one using the lowest approximation of the cluster-variation method, which is identical to the mean-field approximation. A good agreement is found between the present modified theory and the available experimental data. For melting transitions the agreement is excellent and much better than with the calculations of the Pople-Karasz theory and its previous modified theories. Approximate agreement is obtained for the solid-solid transitions. However, for these transition the experimental agreement with the present modified theory is still better than previous modified theories except at zero and low pressures.

  12. Computational models of complex systems

    CERN Document Server

    Dabbaghian, Vahid

    2014-01-01

    Computational and mathematical models provide us with the opportunities to investigate the complexities of real world problems. They allow us to apply our best analytical methods to define problems in a clearly mathematical manner and exhaustively test our solutions before committing expensive resources. This is made possible by assuming parameter(s) in a bounded environment, allowing for controllable experimentation, not always possible in live scenarios. For example, simulation of computational models allows the testing of theories in a manner that is both fundamentally deductive and experimental in nature. The main ingredients for such research ideas come from multiple disciplines and the importance of interdisciplinary research is well recognized by the scientific community. This book provides a window to the novel endeavours of the research communities to present their works by highlighting the value of computational modelling as a research tool when investigating complex systems. We hope that the reader...

  13. Model reduction of parametrized systems

    CERN Document Server

    Ohlberger, Mario; Patera, Anthony; Rozza, Gianluigi; Urban, Karsten

    2017-01-01

    The special volume offers a global guide to new concepts and approaches concerning the following topics: reduced basis methods, proper orthogonal decomposition, proper generalized decomposition, approximation theory related to model reduction, learning theory and compressed sensing, stochastic and high-dimensional problems, system-theoretic methods, nonlinear model reduction, reduction of coupled problems/multiphysics, optimization and optimal control, state estimation and control, reduced order models and domain decomposition methods, Krylov-subspace and interpolatory methods, and applications to real industrial and complex problems. The book represents the state of the art in the development of reduced order methods. It contains contributions from internationally respected experts, guaranteeing a wide range of expertise and topics. Further, it reflects an important effor t, carried out over the last 12 years, to build a growing research community in this field. Though not a textbook, some of the chapters ca...

  14. 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

  15. 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…

  16. Chapter 5: Quantum Dynamics in Dissipative Molecular Systems

    Science.gov (United States)

    Zhang, Hou-Dao; Xu, J.; Xu, Rui-Xue; Yan, Y. J.

    2014-04-01

    The following sections are included: * Introduction * HEOM versus Path Integral Formalism: Background * Generic form and terminology of HEOM * Statistical mechanics description of bath influence * Feynman-Vernon influence functional formalism * General comments * Memory-Frequency Decomposition of Bath Correlation Functions * PSD of Bose function * Brownian oscillators decomposition of bath spectral density function * Optimized HEOM Theory With Accuracy Control * Construction of HEOM via path integral formalism * Accuracy control on white-noise residue ansatz * Efficient HEOM propagator: Numerical filtering and indexing algorithm * HEOM in Quantum Mechanics for Open Systems * The HEOM space and the Schrödinger picture * HEOM in the Heisenberg picture * Mixed Heisenberg-Schrödinger block-matrix dynamics in nonlinear optical response functions * Two-Dimensional Spectroscopy: Model Calculations * Concluding Remarks * Acknowledgments * References

  17. Phases of polymer systems in solution studied via molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Joshua Allen [Iowa State Univ., Ames, IA (United States)

    2009-05-01

    Polymers are amazingly versatile molecules with a tremendous range of applications. Our lives would be very different without them. There would be no multitudes of plastic encased electronic gizmos, no latex paint on the walls and no rubber tires, just to name a few of the many commonplace polymer materials. In fact, life as we know it wouldn’t exist without polymers as two of the most essential types of molecules central to cellular life, Proteins and DNA, are both polymers! [1] With their wide range of application to a variety of uses, polymers are still a very active field in basic research. Of particular current interest is the idea of combining polymers with inorganic particles to form novel composite materials. [2] As computers are becoming faster, they are becoming all the more powerful tools for modeling and simulating real systems. With recent advances in computing on graphics processing units (GPUs) [3–7], questions can now be answered via simulation that could not even be asked before. This thesis focuses on the use of computer simulations to model novel polymerinorganic composite systems in order to predict what possible phases can form and under what conditions. The goal is to provide some direction for future experiments and to gain a deeper understanding of the fundamental physics involved. Along the way, there are some interesting and essential side-tracks in the areas of equilibrating complicated phases and accelerating the available computer power with GPU computing, both of which are necessary steps to enable the study of polymer nanocomposites.

  18. Molecular materials and devices: developing new functional systems based on the coordination chemistry approach

    Directory of Open Access Journals (Sweden)

    Toma Henrique E.

    2003-01-01

    Full Text Available At the onset of the nanotechnology age, molecular designing of materials and single molecule studies are opening wide possibilities of using molecular systems in electronic and photonic devices, as well as in technological applications based on molecular switching or molecular recognition. In this sense, inorganic chemists are privileged by the possibility of using the basic strategies of coordination chemistry to build up functional supramolecular materials, conveying the remarkable chemical properties of the metal centers and the characteristics of the ancillary ligands. Coordination chemistry also provides effective self-assembly strategies based on specific metal-ligand affinity and stereochemistry. Several molecular based materials, derived from inorganic and metal-organic compounds are focused on this article, with emphasis on new supramolecular porphyrins and porphyrazines, metal-clusters and metal-polyimine complexes. Such systems are also discussed in terms of their applications in catalysis, sensors and molecular devices.

  19. Modeling software systems by domains

    Science.gov (United States)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  20. MolabIS--an integrated information system for storing and managing molecular genetics data.

    Science.gov (United States)

    Truong, Cong V C; Groeneveld, Linn F; Morgenstern, Burkhard; Groeneveld, Eildert

    2011-10-31

    Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org.

  1. PPARγ: A Molecular Link between systemic metabolic disease and benign prostate hyperplasia

    Science.gov (United States)

    Jiang, Ming; Strand, Douglas W.; Franco, Omar E.; Clark, Peter E.; Hayward, Simon W.

    2011-01-01

    The emergent epidemic of metabolic syndrome and its complex list of sequelae mandate a more thorough understanding of benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) in the context of systemic metabolic disease. Here we discuss the nature and origins of BPH, examine its role as a component of LUTS and review retrospective clinical studies that have drawn associations between BPH/LUTS and type II diabetes, inflammation and dyslipidemia. PPARγ signaling, which sits at the nexus of systemic metabolic disease and BPH/LUTS through its regulation of inflammation and insulin resistance is proposed as a candidate for molecular manipulation in regard to BPH/LUTS. Finally, we introduce new cell and animal models that are being used to study the consequences of obesity, diabetes and inflammation on benign prostatic growth. PMID:21645960

  2. Combined Temperature/Momentum Boundary Conditions for Molecular Dynamics Simulations of Flow in Nanofluidic Systems

    Science.gov (United States)

    Templeton, Jeremy; Jones, Reese

    2012-11-01

    Molecular dynamics (MD) is a useful technique for scientific investigations of nanofluidic processes as it explicitly represents the dynamics of every atom in a system. In order to model systems of interest, e.g. nanochannels, it is necessary to constrain atomic motions to conform to conditions corresponding to large-scale information, e.g. thermodynamic variables. However, many engineered configurations involve complex interactions between the system and its environment, and take place in non-trivial geometries. To accurately simulate these phenomena, methods to apply boundary conditions to MD systems are required that simultaneously regulate the temperature (i.e., energy) and momentum of the atoms in a local manner. This work uses an atomistic-to-continuum formulation to generate boundary conditions by using finite elements (FE) and their associated shape functions to define ``boundaries'' for a particle system. By projecting onto the FE basis, coarse-scale observables are identified for regulation based on separating the mean and fluctuating velocity components defining the momentum and temperature. Regulating the MD system is achieved by applying constraints posed on the coarse-grained variables. The method is illustrated by application to several nanofluidic systems. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE.

  3. Human endotoxemia as a model of systemic inflammation

    DEFF Research Database (Denmark)

    Krabbe, K.S.; Krogh-Madsen, R.; Taudorf, S.

    2008-01-01

    Systemic inflammation is a pathogenetic component in a vast number of acute and chronic diseases such as sepsis, trauma, type 2 diabetes, atherosclerosis, and Alzheimer's disease, all of which are associated with a substantial morbidity and mortality. However, the molecular mechanisms...... and physiological significance of the systemic inflammatory response are still not fully understood. The human endotoxin model, an in vivo model of systemic inflammation in which lipopolysaccharide is injected or infused intravenously in healthy volunteers, may be helpful in unravelling these issues. The present...

  4. 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...

  5. 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

  6. 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…

  7. Integrative pathway knowledge bases as a tool for systems molecular medicine.

    Science.gov (United States)

    Liang, Mingyu

    2007-08-20

    There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

  8. Molecular Mechanisms of the Whole DNA Repair System: A Comparison of Bacterial and Eukaryotic Systems

    Directory of Open Access Journals (Sweden)

    Rihito Morita

    2010-01-01

    Full Text Available DNA is subjected to many endogenous and exogenous damages. All organisms have developed a complex network of DNA repair mechanisms. A variety of different DNA repair pathways have been reported: direct reversal, base excision repair, nucleotide excision repair, mismatch repair, and recombination repair pathways. Recent studies of the fundamental mechanisms for DNA repair processes have revealed a complexity beyond that initially expected, with inter- and intrapathway complementation as well as functional interactions between proteins involved in repair pathways. In this paper we give a broad overview of the whole DNA repair system and focus on the molecular basis of the repair machineries, particularly in Thermus thermophilus HB8.

  9. 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...

  10. Modeling human risk: Cell & molecular biology in context

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response.

  11. Modeling human risk: Cell ampersand molecular biology in context

    International Nuclear Information System (INIS)

    1997-06-01

    It is anticipated that early in the next century manned missions into outer space will occur, with a mission to Mars scheduled between 2015 and 2020. However, before such missions can be undertaken, a realistic estimation of the potential risks to the flight crews is required. One of the uncertainties remaining in this risk estimation is that posed by the effects of exposure to the radiation environment of outer space. Although the composition of this environment is fairly well understood, the biological effects arising from exposure to it are not. The reasons for this are three-fold: (1) A small but highly significant component of the radiation spectrum in outer space consists of highly charged, high energy (HZE) particles which are not routinely experienced on earth, and for which there are insufficient data on biological effects; (2) Most studies on the biological effects of radiation to date have been high-dose, high dose-rate, whereas in space, with the exception of solar particle events, radiation exposures will be low-dose, low dose-rate; (3) Although it has been established that the virtual absence of gravity in space has a profound effect on human physiology, it is not clear whether these effects will act synergistically with those of radiation exposure. A select panel will evaluate the utilizing experiments and models to accurately predict the risks associated with exposure to HZE particles. Topics of research include cellular and tissue response, health effects associated with radiation damage, model animal systems, and critical markers of Radiation response

  12. On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Garrido, J. M. [Departamento de Ingeniería Química, Universidad de Concepción, POB 160-C Concepción (Chile); Algaba, J.; Blas, F. J., E-mail: felipe@uhu.es [Laboratorio de Simulación Molecular y Química Computacional, CIQSO-Centro de Investigación en Química Sostenible and Departamento de Física Aplicada, Universidad de Huelva, 21007 Huelva (Spain); Míguez, J. M. [Laboratoire des Fluides Complexes et Leurs Reservoirs, Université de Pau et des Pays de l’Adour, CNRS, TOTAL–UMR 5150, Avenue de l’Université, B.P. 1155, Pau F-64013 (France); Departamento de Física Aplicada, Universidade de Vigo, E36310 Vigo (Spain); Mendiboure, B. [Laboratoire des Fluides Complexes et Leurs Reservoirs, Université de Pau et des Pays de l’Adour, CNRS, TOTAL–UMR 5150, Avenue de l’Université, B.P. 1155, Pau F-64013 (France); Moreno-Ventas Bravo, A. I. [Laboratorio de Simulación Molecular y Química Computacional, CIQSO-Centro de Investigación en Química Sostenible and Departamento de Geología, Universidad de Huelva, 21007 Huelva (Spain); Piñeiro, M. M. [Departamento de Física Aplicada, Universidade de Vigo, E36310 Vigo (Spain)

    2016-04-14

    We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with

  13. Single-site Lennard-Jones models via polynomial chaos surrogates of Monte Carlo molecular simulation

    KAUST Repository

    Kadoura, Ahmad Salim

    2016-06-01

    In this work, two Polynomial Chaos (PC) surrogates were generated to reproduce Monte Carlo (MC) molecular simulation results of the canonical (single-phase) and the NVT-Gibbs (two-phase) ensembles for a system of normalized structureless Lennard-Jones (LJ) particles. The main advantage of such surrogates, once generated, is the capability of accurately computing the needed thermodynamic quantities in a few seconds, thus efficiently replacing the computationally expensive MC molecular simulations. Benefiting from the tremendous computational time reduction, the PC surrogates were used to conduct large-scale optimization in order to propose single-site LJ models for several simple molecules. Experimental data, a set of supercritical isotherms, and part of the two-phase envelope, of several pure components were used for tuning the LJ parameters (ε, σ). Based on the conducted optimization, excellent fit was obtained for different noble gases (Ar, Kr, and Xe) and other small molecules (CH4, N2, and CO). On the other hand, due to the simplicity of the LJ model used, dramatic deviations between simulation and experimental data were observed, especially in the two-phase region, for more complex molecules such as CO2 and C2 H6.

  14. Finite lattice model for molecular aggregation equilibria. Boolean statistics, analytical approximations, and the macroscopic limit.

    Science.gov (United States)

    Rankin, Blake M; Ben-Amotz, Dor; Widom, B

    2015-09-14

    Molecular processes, ranging from hydrophobic aggregation and protein binding to mesoscopic self-assembly, are typically driven by a delicate balance of energetic and entropic non-covalent interactions. Here, we focus on a broad class of such processes in which multiple ligands bind to a central solute molecule as a result of solute-ligand (direct) and/or ligand-ligand (cooperative) interaction energies. Previously, we described a weighted random mixing (WRM) mean-field model for such processes and compared the resulting adsorption isotherms and aggregate size distributions with exact finite lattice (FL) predictions, for lattices with up to n = 20 binding sites. Here, we compare FL predictions obtained using both Bethe-Guggenheim (BG) and WRM approximations, and find that the latter two approximations are complementary, as they are each most accurate in different aggregation regimes. Moreover, we describe a computationally efficient method for exhaustively counting nearest neighbors in FL configurations, thus making it feasible to obtain FL predictions for systems with up n = 48 binding sites, whose properties approach the thermodynamic (infinite lattice) limit. We further illustrate the applicability of our results by comparing lattice model and molecular dynamics simulation predictions pertaining to the aggregation of methane around neopentane.

  15. 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.

  16. Long-range force and moment calculations in multiresolution simulations of molecular systems

    Science.gov (United States)

    Poursina, Mohammad; Anderson, Kurt S.

    2012-08-01

    Multiresolution simulations of molecular systems such as DNAs, RNAs, and proteins are implemented using models with different resolutions ranging from a fully atomistic model to coarse-grained molecules, or even to continuum level system descriptions. For such simulations, pairwise force calculation is a serious bottleneck which can impose a prohibitive amount of computational load on the simulation if not performed wisely. Herein, we approximate the resultant force due to long-range particle-body and body-body interactions applicable to multiresolution simulations. Since the resultant force does not necessarily act through the center of mass of the body, it creates a moment about the mass center. Although this potentially important torque is neglected in many coarse-grained models which only use particle dynamics to formulate the dynamics of the system, it should be calculated and used when coarse-grained simulations are performed in a multibody scheme. Herein, the approximation for this moment due to far-field particle-body and body-body interactions is also provided.

  17. 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.

  18. A model for studying molecular plant-bacteria interactions in the flight experimet

    Science.gov (United States)

    Kovtunovych, G.; Lar, O.; Kovalchuk, M.; Negrutska, V.; Rogutski, I.; Kozyrovska, N.; Kordyum, V.

    The ability to grow plants in space self-perpetuating gardens is actual for providing an advanced life support system for humans during extended missions. Nevertheless, studies of molecular mechanisms of plant-bacteria interactions in the flight experiments are still in their infancy. Space factors affect cell microenvironment and signal transduction through membranes, and it may result in induction in bacteria of some genes regulated by the systems, sensing environmental signals. In space a risk of genetic rearrangements is increased, and some changes in bacterial DNA expected. As a consequence, bacteria may exhibit novel characters, e.g., pathogenicity. During the previous our experience we have determined an increase of internal colonisation of the rice roots with bacteria in space flight. It is important to characterise molecular-genetic plant-bacteria interactions influenced with physical factors. Genes coding for bacterial pectinases provide a suitable model for studies of well integrated objectives, concerning plant-bacteria interactions. From examining a mode of expression of pectinases encoding genes of a plant-associated bacterium and nucleotide polymorphism within pectate lyase- and polygalacturonase encoding genes in microcosm experiments in earth and space flight we get new knowledges about understanding some physical factors as the environmental signals and the possible risk of changes in interactions of bacteria with the plant.

  19. The challenges for molecular nutrition research 4: the "nutritional systems biology level"

    NARCIS (Netherlands)

    Ommen, B. van; Cavallieri, D.; Roche, H.M.; Klein, U.I.; Daniel, H.

    2008-01-01

    Nutritional systems biology may be defined as the ultimate goal of molecular nutrition research, where all relevant aspects of regulation of metabolism in health and disease states at all levels of its complexity are taken into account to describe the molecular physiology of nutritional processes.

  20. Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

    Science.gov (United States)

    Weiss, J.; Egea-Cortines, M.

    2008-01-01

    We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

  1. Electrochemistry of single molecules and biomolecules, molecular scale nanostructures, and low-dimensional systems

    DEFF Research Database (Denmark)

    Nazmutdinov, Renat R.; Zinkicheva, Tamara T.; Zinkicheva, Tamara T.

    2018-01-01

    Electrochemistry at ultra-small scales, where even the single molecule or biomolecule can be characterized and manipulated, is on the way to a consolidated status. At the same time molecular electrochemistry is expanding into other areas of sophisticated nano- and molecular scale systems including...

  2. Molecular Modeling of Aerospace Polymer Matrices Including Carbon Nanotube-Enhanced Epoxy

    Science.gov (United States)

    Radue, Matthew S.

    -functionalresins) are simulated with embedded CNT to understand how the affinity to nanoparticles affects the mechanical response. Multiscale modeling techniques are then employed to translate the molecular phenomena observed to predict the behavior of realistic composites. The effective stiffness of hybrid composites are predicted for CNT/epoxy composites with randomly oriented CNTs, for CF/CNT/epoxy systems with aligned CFs and randomly oriented CNTs, and for woven CF/CNT/epoxy fabric with randomly oriented CNTs. The results indicate that in the CNT/epoxy systems the epoxy type has a significant influence on the elastic properties. For the CF/CNT/epoxy hybrid composites, the axial modulus is highly influenced by CF concentration, while the transverse modulus is primarily affected by the CNT weight fraction.

  3. Cognitive models embedded in system simulation models

    International Nuclear Information System (INIS)

    Siegel, A.I.; Wolf, J.J.

    1982-01-01

    If we are to discuss and consider cognitive models, we must first come to grips with two questions: (1) What is cognition; (2) What is a model. Presumably, the answers to these questions can provide a basis for defining a cognitive model. Accordingly, this paper first places these two questions into perspective. Then, cognitive models are set within the context of computer simulation models and a number of computer simulations of cognitive processes are described. Finally, pervasive issues are discussed vis-a-vis cognitive modeling in the computer simulation context

  4. Thermodynamic modeling of complex systems

    DEFF Research Database (Denmark)

    Liang, Xiaodong

    . Contrary to earlier theories, the oil is not only present on the surface, but also in great volumes both in the water column and on the seafloor, which indicates that we do not know enough about how oil behaves in water and interacts with it. Sonar detection is one of the most important and necessary...... after an oil spill. Engineering thermodynamics could be applied in the state-of-the-art sonar products through advanced artificial technology, if the speed of sound, solubility and density of oil-seawater systems could be satisfactorily modelled. The addition of methanol or glycols into unprocessed well...... streams during subsea pipelines is necessary to inhibit gas hydrate formation, and the offshore reservoirs often mean complicated temperature and pressure conditions. Accurate description of the phase behavior and thermalphysical properties of complex systems containing petroleum fluids and polar...

  5. Studies of Catalytic Model Systems

    DEFF Research Database (Denmark)

    Holse, Christian

    of the Cu/ZnO nanoparticles is highly relevant to industrial methanol synthesis for which the direct interaction of Cu and ZnO nanocrystals synergistically boost the catalytic activity. The dynamical behavior of the nanoparticles under reducing and oxidizing environments were studied by means of ex situ X...... as the nanoparticles are reduced. The Cu/ZnO nanoparticles are tested on a  µ-reactor platform and prove to be active towards methanol synthesis, making it an excellent model system for further investigations into activity depended morphology changes....

  6. Molecular Modeling and Simulation Tools in the Development of Peptide-Based Biosensors for Mycotoxin Detection: Example of Ochratoxin

    Directory of Open Access Journals (Sweden)

    Aby A. Thyparambil

    2017-12-01

    Full Text Available Mycotoxin contamination of food and feed is now ubiquitous. Exposures to mycotoxin via contact or ingestion can potentially induce adverse health outcomes. Affordable mycotoxin-monitoring systems are highly desired but are limited by (a the reliance on technically challenging and costly molecular recognition by immuno-capture technologies; and (b the lack of predictive tools for directing the optimization of alternative molecular recognition modalities. Our group has been exploring the development of ochratoxin detection and monitoring systems using the peptide NFO4 as the molecular recognition receptor in fluorescence, electrochemical and multimodal biosensors. Using ochratoxin as the model mycotoxin, we share our perspective on addressing the technical challenges involved in biosensor fabrication, namely: (a peptide receptor design; and (b performance evaluation. Subsequently, the scope and utility of molecular modeling and simulation (MMS approaches to address the above challenges are described. Informed and enabled by phage display, the subsequent application of MMS approaches can rationally guide subsequent biomolecular engineering of peptide receptors, including bioconjugation and bioimmobilization approaches to be used in the fabrication of peptide biosensors. MMS approaches thus have the potential to reduce biosensor development cost, extend product life cycle, and facilitate multi-analyte detection of mycotoxins, each of which positively contributes to the overall affordability of mycotoxin biosensor monitoring systems.

  7. 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.

  8. A Panchromatic Study of Molecular Gas in the Protoplanetary System RY Lupi

    Science.gov (United States)

    Arulanantham, Nicole; France, Kevin; Hoadley, Keri

    2018-01-01

    To understand how planet formation occurs in protoplanetary disks, we must first characterize the behavior of material within 10 AU of the central star. We present a study of molecular gas at these radii in the disk around the young star RY Lupi, through spectra from HST-COS, HST-STIS, and VLT-CRIRES. We model the radial distribution of flux from hot (T ~ 2000 K) molecular gas in a surface layer between r = 0.1-10 AU, as traced by LyA-pumped H2. The result indicates that the H2 emission originates in a narrow ring centered at 1 AU, with a sharp decline in flux at r statistically better fit to the H2 emission lines than the single-component model of a smooth disk. This two-component profile includes broad (FWHMbroad, H2 = 105 +/- 15 km/s) and narrow (FWHMnarrow, H2 = 43 +/- 13 km/s) lines, corresponding to average gas radii of ~ 0.4 AU and ~ 3 AU. An analysis of the spatial origin of 4.7 micron 12CO emission shows that this population of warm (T ~ 1500 K) gas also produces two-component emission line profiles ( ~ 0.4 AU, ~ 15 AU), indicating again that the inner disk is radially stratified. Despite the evidence that this is a transitional disk system, we detect UV CO absorption that is not typically seen in more evolved systems. We model these features along with IR CO absorptions to constrain the properties of the cooler (T ~ 100-300 K) disk atmosphere.

  9. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations.

    Science.gov (United States)

    Jain, Vaibhav; Maiti, Prabal K; Bharatam, Prasad V

    2016-09-28

    Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH 2 ) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH 2 ) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH 2 ) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

  10. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations

    Science.gov (United States)

    Jain, Vaibhav; Maiti, Prabal K.; Bharatam, Prasad V.

    2016-09-01

    Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details. For this purpose, possible inclusion complexes of model drug Nateglinide (Ntg) (antidiabetic, belongs to Biopharmaceutics Classification System class II) with amine- and acetyl-terminated G4 poly(amidoamine) (G4 PAMAM(NH2) and G4 PAMAM(Ac)) dendrimers at neutral and low pH conditions are explored in this work. MD simulation analysis on dendrimer-drug complexes revealed that the drug encapsulation efficiency of G4 PAMAM(NH2) and G4 PAMAM(Ac) dendrimers at neutral pH was 6 and 5, respectively, while at low pH it was 12 and 13, respectively. Center-of-mass distance analysis showed that most of the drug molecules are located in the interior hydrophobic pockets of G4 PAMAM(NH2) at both the pH; while in the case of G4 PAMAM(Ac), most of them are distributed near to the surface at neutral pH and in the interior hydrophobic pockets at low pH. Structural properties such as radius of gyration, shape, radial density distribution, and solvent accessible surface area of dendrimer-drug complexes were also assessed and compared with that of the drug unloaded dendrimers. Further, binding energy calculations using molecular mechanics Poisson-Boltzmann surface area approach revealed that the location of drug molecules in the dendrimer is not the decisive factor for the higher and lower binding affinity of the complex, but the charged state of dendrimer and drug, intermolecular interactions, pH-induced conformational changes, and surface groups of dendrimer do play an

  11. 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....

  12. Multi-scenario modelling of uncertainty in stochastic chemical systems

    International Nuclear Information System (INIS)

    Evans, R. David; Ricardez-Sandoval, Luis A.

    2014-01-01

    Uncertainty analysis has not been well studied at the molecular scale, despite extensive knowledge of uncertainty in macroscale systems. The ability to predict the effect of uncertainty allows for robust control of small scale systems such as nanoreactors, surface reactions, and gene toggle switches. However, it is difficult to model uncertainty in such chemical systems as they are stochastic in nature, and require a large computational cost. To address this issue, a new model of uncertainty propagation in stochastic chemical systems, based on the Chemical Master Equation, is proposed in the present study. The uncertain solution is approximated by a composite state comprised of the averaged effect of samples from the uncertain parameter distributions. This model is then used to study the effect of uncertainty on an isomerization system and a two gene regulation network called a repressilator. The results of this model show that uncertainty in stochastic systems is dependent on both the uncertain distribution, and the system under investigation. -- Highlights: •A method to model uncertainty on stochastic systems was developed. •The method is based on the Chemical Master Equation. •Uncertainty in an isomerization reaction and a gene regulation network was modelled. •Effects were significant and dependent on the uncertain input and reaction system. •The model was computationally more efficient than Kinetic Monte Carlo

  13. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    Science.gov (United States)

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  14. Reservoir Model Information System: REMIS

    Science.gov (United States)

    Lee, Sang Yun; Lee, Kwang-Wu; Rhee, Taehyun; Neumann, Ulrich

    2009-01-01

    We describe a novel data visualization framework named Reservoir Model Information System (REMIS) for the display of complex and multi-dimensional data sets in oil reservoirs. It is aimed at facilitating visual exploration and analysis of data sets as well as user collaboration in an easier way. Our framework consists of two main modules: the data access point module and the data visualization module. For the data access point module, the Phrase-Driven Grammar System (PDGS) is adopted for helping users facilitate the visualization of data. It integrates data source applications and external visualization tools and allows users to formulate data query and visualization descriptions by selecting graphical icons in a menu or on a map with step-by-step visual guidance. For the data visualization module, we implemented our first prototype of an interactive volume viewer named REMVR to classify and to visualize geo-spatial specific data sets. By combining PDGS and REMVR, REMIS assists users better in describing visualizations and exploring data so that they can easily find desired data and explore interesting or meaningful relationships including trends and exceptions in oil reservoir model data.

  15. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos

    2003-01-01

    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  16. 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…

  17. In situ sensing and modeling of molecular events at the cellular level

    Science.gov (United States)

    Yang, Ruiguo

    We developed the Atomic Force Microscopy (AFM) based nanorobot in combination with other nanomechanical sensors for the investigation of cell signaling pathways. The AFM nanorobotics hinge on the superior spatial resolution of AFM in imaging and extends it into the measurement of biological processes and manipulation of biological matters. A multiple input single output control system was designed and implemented to solve the issues of nanomanipulation of biological materials, feedback, response frequency and nonlinearity. The AFM nanorobotic system therefore provide the human-directed position, velocity and force control with high frequency feedback, and more importantly it can feed the operator with the real-time imaging of manipulation result from the fast-imaging based local scanning. The use of the system has taken the study of cellular process at the molecular scale into a new level. The cellular response to the physiological conditions can be significantly manifested in cellular mechanics. Dynamic mechanical property has been regarded as biomarkers, sometimes even regulators of the signaling and physiological processes, thus the name mechanobiology. We sought to characterize the relationship between the structural dynamics and the molecular dynamics and the role of them in the regulation of cell behavior. We used the AFM nanorobotics to investigate the mechanical properties in real-time of cells that are stimulated by different chemical species. These reagents could result in similar ion channel responses but distinctive mechanical behaviors. We applied these measurement results to establish a model that describes the cellular stimulation and the mechanical property change, a "two-hit" model that comprises the loss of cell adhesion and the initiation of cell apoptosis. The first hit was verified by functional experiments: depletion of Calcium and nanosurgery to disrupt the cellular adhesion. The second hit was tested by a labeling of apoptotic markers that

  18. Materials learning from life: concepts for active, adaptive and autonomous molecular systems.

    Science.gov (United States)

    Merindol, Rémi; Walther, Andreas

    2017-09-18

    Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: cells keep track of time, communicate, move, adapt, evolve and replicate continuously. Stirred by the understanding of biological principles, artificial out-of-equilibrium systems are emerging in many fields of soft matter science. Here we put in perspective the molecular mechanisms driving biological functions with the ones driving synthetic molecular systems. Focusing on principles that enable new levels of functionalities (temporal control, autonomous structures, motion and work generation, information processing) rather than on specific material classes, we outline key cross-disciplinary concepts that emerge in this challenging field. Ultimately, the goal is to inspire and support new generations of autonomous and adaptive molecular devices fueled by self-regulating chemistry.

  19. Molecular-beam epitaxial growth and ion-beam analysis systems for functional materials research

    International Nuclear Information System (INIS)

    Takeshita, H.; Aoki, Y.; Yamamoto, S.; Naramoto, H.

    1992-01-01

    Experimental systems for molecular beam epitaxial growth and ion beam analysis have been designed and constructed for the research of inorganic functional materials such as thin films and superlattices. (author)

  20. Interactions of mercury with different molecular weight fractions of humic substances in aquatic systems.

    Digital Repository Service at National Institute of Oceanography (India)

    Chakraborty, P.; Yao, K.M.; Chennuri, K.; Vudamala, K.; Babu, P.V.R.

    Interactions of mercury (Hg) with different molecular weight fractions of humic substances (HS) play an important role in controlling distribution, diffusion, speciation, and bioavailability of Hg in natural systems. This study suggests that Hg...

  1. Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

    Science.gov (United States)

    EPA announced the release of the final report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology. This report describes new approaches that are faster, less resource intensive, and more robust that can help ...

  2. Pulse radiolysis studies of fast reactions in molecular systems. Progress report, November 1976--October 1977

    International Nuclear Information System (INIS)

    Dorfman, L.M.

    1977-01-01

    Results from research in the following two areas are given: formation, properties, and reactivity of molecular ionic species in irradiated liquid systems; and pulse radiolysis of elementary reactions in protein function

  3. Bond graph modeling of centrifugal compression systems

    OpenAIRE

    Uddin, Nur; Gravdahl, Jan Tommy

    2015-01-01

    A novel approach to model unsteady fluid dynamics in a compressor network by using a bond graph is presented. The model is intended in particular for compressor control system development. First, we develop a bond graph model of a single compression system. Bond graph modeling offers a different perspective to previous work by modeling the compression system based on energy flow instead of fluid dynamics. Analyzing the bond graph model explains the energy flow during compressor surge. Two pri...

  4. Structuring Problem Analysis for Embedded Systems Modelling

    NARCIS (Netherlands)

    Marincic, J.; Mader, Angelika H.; Wieringa, Roelf J.; Lucas, Yan

    Our interest is embedded systems validation as part of the model-driven approach. To design a model, the modeller needs to obtain knowledge about the system and decide what is relevant to model and how. A part of the modelling activities is inherently informal - it cannot be formalised in such a way

  5. Mixed 2D molecular systems: Mechanic, thermodynamic and dielectric properties

    Energy Technology Data Exchange (ETDEWEB)

    Beno, Juraj [Department of Physics, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovicova 3, 812 19-SK Bratislava (Slovakia); Weis, Martin [Department of Physics, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovicova 3, 812 19-SK Bratislava (Slovakia)], E-mail: Martin.Weis@stuba.sk; Dobrocka, Edmund [Department of Physics, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovicova 3, 812 19-SK Bratislava (Slovakia); Institute of Electrical Engineering, Slovak Academy of Sciences, Dubravska cesta 9, 841 04-SK Bratislava (Slovakia); Hasko, Daniel [International Laser Centre, Ilkovicova 3, 812 19-SK Bratislava (Slovakia)

    2008-08-15

    Study of Langmuir monolayers consisting of stearic acid (SA) and dipalmitoylphosphatidylcholine (DPPC) molecules was done by surface pressure-area isotherms ({pi}-A), the Maxwell displacement current (MDC) measurement, X-ray reflectivity (XRR) and atomic force microscopy (AFM) to investigate the selected mechanic, thermodynamic and dielectric properties based on orientational structure of monolayers. On the base of {pi}-A isotherms analysis we explain the creation of stable structures and found optimal monolayer composition. The dielectric properties represented by MDC generated monolayers were analyzed in terms of excess dipole moment, proposing the effect of dipole-dipole interaction. XRR and AFM results illustrate deposited film structure and molecular ordering.

  6. Few-body physics with ultracold atomic and molecular systems in traps.

    Science.gov (United States)

    Blume, D

    2012-04-01

    Few-body physics has played a prominent role in atomic, molecular and nuclear physics since the early days of quantum mechanics. It is now possible-thanks to tremendous progress in cooling, trapping and manipulating ultracold samples-to experimentally study few-body phenomena in trapped atomic and molecular systems with unprecedented control. This review summarizes recent studies of few-body phenomena in trapped atomic and molecular gases, with an emphasis on small trapped systems. We start by introducing the free-space scattering properties and then investigate what happens when two particles, bosons or fermions, are placed in an external confinement. Next, various three-body systems are treated analytically in limiting cases. Our current understanding of larger two-component Fermi systems and Bose systems is reviewed, and connections with the corresponding bulk systems are established. Lastly, future prospects and challenges are discussed. Throughout this review, commonalities with other systems such as nuclei or quantum dots are highlighted.

  7. Tetrahedra system Cudaca: high-temperature manifold of molecular configurations governing low-temperature properties

    OpenAIRE

    Zaharko, O.; Mesot, J.; Salguero, L. A.; Valenti, R.; Zbiri, M.; Johnson, M.; Filinchuk, Y.; Klemke, B.; Kiefer, K.; Mys'kiv, M.; Straessle, T.; Mutka, H.

    2008-01-01

    The Cudaca system composed of isolated Cu2+ S=1/2 tetrahedra with antiferromagnetic exchange should exhibit properties of a frustrated quantum spin system. ab initio density functional theory calculations for electronic structure and molecular dynamics computations suggest a complex interplay between magnetic exchange, electron delocalization and molecular vibrations. Yet, extensive experimental characterization of Cudaca by means of synchrotron x-ray diffraction, magnetization, specific heat...

  8. A molecular dynamic model for analyzing concentrations of electrolytes: Fractional molar dependences of microstructure properties

    Science.gov (United States)

    Khalansky, D.; Popova, E.; Gladyshev, P.; Dushanov, E.; Kholmurodov, Kh.

    2014-12-01

    Aqueous electrolyte solutions play an important role in many electrophysical and chemical processes in aerospace technology and industrial applications. As noncovalent interactions, the interactions between ions are crucially important for biomolecular structures as well (protein structure folding, molecular level processes followed by ionic pair correlations, the formation of flexible hydrate shells, and so on). Specifically, ions (cations and anions with the same valence charges) can form stable pairs if their sizes match. The formation of ionic pairs can substantially affect the thermodynamic stabilities of proteins in the alkali salts physiologically present in the human body. Research aims and problems impose severe demands on readjustments of the ionic force fields and potential parameters developed to describe aqueous solutions and electrolytic systems. Ionic solutions and their interaction with biomolecules have been observed for over 100 years [1], but the behavior of such solutions remains poorly studied today. New data obtained in this work deals with parameterization strategies and adjustments for the ionic force fields of the alkali cations and halide anions that should be helpful in biomolecular research. Using molecular dynamics (MD) models, four electrolytic systems (HCl-H2O, LiCl-H2O, NaCl-H2O, and KCl-H2O) are investigated as binary mixtures of water and cations and anions, respectively. The intermolecular interaction parameters are varied for two of the four model electrolytes (HCl-H2O and NaCl-H2O) to simulate the possibility of different ionic shells forming during interaction with water. It is found that varying the potential parameters strongly affects the dynamic and structural characteristics of electrolyte systems. MD simulations are performed in the temperature range of 300 to 600 K with a step of 50 K. MD simulations for all electrolyte models (HCl-H2O, LiCl-H2O, NaCl-H2O, KCl-H2O) are also conducted for different molar fractions of

  9. Raman spectroscopy on simple molecular systems at very high density

    International Nuclear Information System (INIS)

    Schiferl, D.; LeSar, R.S.; Moore, D.S.

    1988-01-01

    We present an overview of how Raman spectroscopy is done on simple molecular substances at high pressures. Raman spectroscopy is one of the most powerful tools for studying these substances. It is often the quickest means to explore changes in crystal and molecular structures, changes in bond strength, and the formation of new chemical species. Raman measurements have been made at pressures up to 200 GPa (2 Mbar). Even more astonishing is the range of temperatures (4-5200/degree/K) achieved in various static and dynamic (shock-wave) pressure experiments. One point we particularly wish to emphasize is the need for a good theoretical understanding to properly interpret and use experimental results. This is particularly true at ultra-high pressures, where strong crystal field effects can be misinterpreted as incipient insulator-metal transitions. We have tried to point out apparatus, techniques, and results that we feel are particularly noteworthy. We have also included some of the /open quotes/oral tradition/close quotes/ of high pressure Raman spectroscopy -- useful little things that rarely or never appear in print. Because this field is rapidly expanding, we discuss a number of exciting new techniques that have been informally communicated to us, especially those that seem to open new possibilities. 58 refs., 18 figs

  10. A logic-based dynamic modeling approach to explicate the evolution of the central dogma of molecular biology.

    Science.gov (United States)

    Jafari, Mohieddin; Ansari-Pour, Naser; Azimzadeh, Sadegh; Mirzaie, Mehdi

    It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

  11. Small animal optoacoustic tomography system for molecular imaging of contrast agents

    Science.gov (United States)

    Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

    2016-03-01

    We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

  12. Possible signatures of nuclear-molecular formation in O+C systems

    International Nuclear Information System (INIS)

    Tighe, R.J.; Kolata, J.J.; Belbot, M.; Aguilera, E.F.

    1993-01-01

    The interplay between the elastic, quasielastic, and fusion reaction channels at energies from just above to well below the Coulomb barrier is investigated for O+C systems. Elastic-scattering and quasielastic-scattering angular distributions were measured using the kinematic coincidence technique. Fusion yields were obtained by direct detection of the evaporation residues using a time-of-flight energy spectrometer, at energies from just above to well below the Coulomb barrier. The fusion yields differ significantly from previous work, but the present measurements give barrier parameters consistent with systematics. Comparisons with two-center shell model and coupled-channels predictions show possible indications of nuclear-molecular formation in the elastic, inelastic, and single-neutron transfer channels

  13. Molecular solid-state inverter-converter system

    Science.gov (United States)

    Birchenough, A. G.

    1973-01-01

    A modular approach for aerospace electrical systems has been developed, using lightweight high efficiency pulse width modulation techniques. With the modular approach, a required system is obtained by paralleling modules. The modular system includes the inverters and converters, a paralleling system, and an automatic control and fault-sensing protection system with a visual annunciator. The output is 150 V dc, or a low distortion three phase sine wave at 120 V, 400 Hz. Input power is unregulated 56 V dc. Each module is rated 2.5 kW or 3.6 kVA at 0.7 power factor.

  14. Modeling evolution and immune system by cellular automata

    International Nuclear Information System (INIS)

    Bezzi, M.

    2001-01-01

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

  15. Model reduction in mathematical pharmacology : Integration, reduction and linking of PBPK and systems biology models.

    Science.gov (United States)

    Snowden, Thomas J; van der Graaf, Piet H; Tindall, Marcus J

    2018-03-26

    In this paper we present a framework for the reduction and linking of physiologically based pharmacokinetic (PBPK) models with models of systems biology to describe the effects of drug administration across multiple scales. To address the issue of model complexity, we propose the reduction of each type of model separately prior to being linked. We highlight the use of balanced truncation in reducing the linear components of PBPK models, whilst proper lumping is shown to be efficient in reducing typically nonlinear systems biology type models. The overall methodology is demonstrated via two example systems; a model of bacterial chemotactic signalling in Escherichia coli and a model of extracellular regulatory kinase activation mediated via the extracellular growth factor and nerve growth factor receptor pathways. Each system is tested under the simulated administration of three hypothetical compounds; a strong base, a weak base, and an acid, mirroring the parameterisation of pindolol, midazolam, and thiopental, respectively. Our method can produce up to an 80% decrease in simulation time, allowing substantial speed-up for computationally intensive applications including parameter fitting or agent based modelling. The approach provides a straightforward means to construct simplified Quantitative Systems Pharmacology models that still provide significant insight into the mechanisms of drug action. Such a framework can potentially bridge pre-clinical and clinical modelling - providing an intermediate level of model granularity between classical, empirical approaches and mechanistic systems describing the molecular scale.

  16. Emergent quantum phases in a heteronuclear molecular Bose-Einstein condensate model

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, Melissa [Centre for Mathematical Physics, School of Physical Sciences, University of Queensland, Brisbane 4072 (Australia); Foerster, Angela [Instituto de Fisica da UFRGS, Av. Bento Goncalves 9500, Porto Alegre, RS (Brazil); Links, Jon [Centre for Mathematical Physics, School of Physical Sciences, University of Queensland, Brisbane 4072 (Australia)]. E-mail: jrl@maths.uq.edu.au; Mattei, Eduardo [Instituto de Fisica da UFRGS, Av. Bento Goncalves 9500, Porto Alegre, RS (Brazil); Oelkers, Norman [Centre for Mathematical Physics, School of Physical Sciences, University of Queensland, Brisbane 4072 (Australia); Tonel, Arlei Prestes [Centro de Ciencias Exatas e Tecnologicas, Universidade Federal de Pelotas/UniPampa, Rua Carlos Barbosa, SN, Bage, RS (Brazil)

    2007-04-09

    We study a three-mode Hamiltonian modelling a heteronuclear molecular Bose-Einstein condensate. Two modes are associated with two distinguishable atomic constituents, which can combine to form a molecule represented by the third mode. Beginning with a semi-classical analogue of the model, we conduct an analysis to determine the phase space fixed points of the system. Bifurcations of the fixed points naturally separate the coupling parameter space into different regions. Two distinct scenarios are found, dependent on whether the imbalance between the number operators for the atomic modes is zero or non-zero. This result suggests the ground-state properties of the model exhibit an unusual sensitivity on the atomic imbalance. We then test this finding for the quantum mechanical model. Specifically we use Bethe ansatz methods, ground-state expectation values, the character of the quantum dynamics, and ground-state wavefunction overlaps to clarify the nature of the ground-state phases. The character of the transition is smoothed due to quantum fluctuations, but we may nonetheless identify the emergence of a quantum phase boundary in the limit of zero atomic imbalance.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. A molecular thermodynamic approach to predict the secondary structure of homopolypeptides in aqueous systems.

    Science.gov (United States)

    Chen, C C; Zhu, Y; King, J A; Evans, L B

    1992-10-01

    Under physiological conditions, many polypeptide chains spontaneously fold into discrete and tightly packed three-dimensional structures. The folded polypeptide chain conformation is believed to represent a minimum Gibbs energy of the system, governed by the weak interactions that operate between the amino acid residues and between the residues and the solvent. A semiempirical molecular thermodynamic model is proposed to represent the Gibbs energy of folding of aqueous homopolypeptide systems. The model takes into consideration both the entropy contribution and the enthalpy contribution of folding homopolypeptide chains in aqueous solutions. The entropy contribution is derived from the Flory-Huggins expression for the entropy of mixing. It accounts for the entropy loss in folding a random-coiled polypeptide chain into a specific polypeptide conformation. The enthalpy contribution is derived from a molecular segment-based Non-Random Two Liquid (NRTL) local composition model [H. Renon and J. M. Prausnitz (1968) AIChE J., Vol. 14, pp. 135-142; C.-C. Chen and L. B. Evans (1986) AIChE J., Vol. 32, pp. 444-454], which takes into consideration of the residue-residue, residue-solvent, and solvent-solvent binary physical interactions along with the local compositions of amino acid residues in aqueous homopolypeptides. The UNIFAC group contribution method [A. Fredenslund, R. L. Jones, and J. M. Prausnitz (1975) AIChE J., 21, 1086-1099; A. Fredenslund, J. Gmehling, and P. Rasmussen (1977) Vapor-Liquid Equilibrium Using UNIFAC, Elsevier Scientific Publishing Company, Amsterdam], developed originally to estimate the excess Gibbs energy of solutions of small molecules, was used to estimate the NRTL binary interaction parameters. The model yields a hydrophobicity scale for the 20 amino acid side chains, which compares favorably with established scales [Y. Nozaki and C. Tanford (1971) Journal of Biological Chemistry, Vol. 46, pp. 2211-2217; E. B. Leodidis and T. A. Hatton (1990

  2. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  3. 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....

  4. Probing molecular adsorbates with core-level spectroscopies: Electronic structure and bonding models

    Science.gov (United States)

    Fohlisch, Alexander

    Resonantly excited X-ray emission spectroscopy has been applied to study the valence electronic structure of molecular adsorbates in an atom specific and orbital symmetry selective manner. In combination with ab initio cluster calculations, electronic structure and bonding models have been derived. Existing models of surface chemical bonding have been reviewed and partially revised. Most notably, the bonding mechanism of carbon monoxide (CO) on transition and noble metals has been revised and is found to be the result of a strong covalent interaction between the CO orbitals and the metal bands within each orbital symmetry. A characteristic allylic configuration is found in the π system and strong polarization within the σ system. The equilibrium properties of adsorbed CO are the direct result of a balance between the repulsive σ-interaction and the attractive π-interaction both in terms of the total energy and the local bond properties. The bonding of ammonia (NH3) on the Cu(110) surface is found to be dominated by a large covalent interaction, which contrasts the previous model of a strong electrostatic interaction. Furthermore, adsorbate-adsorbate interaction leads to a tilted adsorption geometry. Ethylene (C2H4) on Cu(110) is adsorbed in the di-σ configuration, according to the generally accepted Dewar Chatt Duncanson model for hydrocarbon adsorption. The application and interpretation of resonantly excited X-ray emission on these systems also required a thorough discussion of the spectroscopic process. Another topic was the vibrational fine structure in the X-ray photoemission core-level main lines of adsorbed molecules. The observation of the vibrational fine structure in molecular adsorbates is remarkable, as it was previously thought impossible to observe due to solid state broadening contributions. A detailed analysis of the vibrational fine structure and the line profile makes it possible to study the electronic and geometric properties of the core

  5. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  6. 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.

  7. 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

    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

  8. Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application.

    Science.gov (United States)

    Rahman, Mahabubur; Watabe, Hiroshi

    2018-05-01

    Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid

  9. Modelling protocells the emergent synchronization of reproduction and molecular replication

    CERN Document Server

    Serra, Roberto

    2017-01-01

    The monograph discusses models of synthetic protocells, which are cell-like structures obtained from non-living matter endowed with some rudimentary kind of metabolism and genetics, but much simpler than biological cells. They should grow and proliferate, generating offsprings that resemble in some way the parent protocells with some variation, so that selection may take place. Sustainable protocell populations have not yet been obtained experimentally and mathematical models are therefore extremely important to address key questions concerning their synthesis and behavior. Different protocell “architectures” have been proposed and high-level abstract models like those that are presented in this book are particularly relevant to gain a better understanding of the different properites. These models are able to treat all the major dynamical phenomena in a unified framework, so they can be seen as “virtual laboratories” for protocell research. Particular attention is paid to the problem of synchronizatio...

  10. Molecular dynamics modelling of EGCG clusters on ceramide bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Jingjie; Cheng, Yuan; Li, Weifeng; Zhang, Yong-Wei [Institute of High Performance Computing, A*STAR, 138632 (Singapore)

    2015-12-31

    A novel method of atomistic modelling and characterization of both pure ceramide and mixed lipid bilayers is being developed, using only the General Amber ForceField. Lipid bilayers modelled as pure ceramides adopt hexagonal packing after equilibration, and the area per lipid and bilayer thickness are consistent with previously reported theoretical results. Mixed lipid bilayers are modelled as a combination of ceramides, cholesterol, and free fatty acids. This model is shown to be stable after equilibration. Green tea extract, also known as epigallocatechin-3-gallate, is introduced as a spherical cluster on the surface of the mixed lipid bilayer. It is demonstrated that the cluster is able to bind to the bilayers as a cluster without diffusing into the surrounding water.

  11. From molecular modelling to nanotechnology and clean energy

    Czech Academy of Sciences Publication Activity Database

    Kupka, T.; Stachów, M.; Nieradka, M.; Radula-Janik, K.; Stobinski, L.; Kaminský, Jakub; Sauer, S. P. A.

    2014-01-01

    Roč. 68, č. 4 (2014), s. 288-295 ISSN 0009-2886 Grant - others:GA MŠk(CZ) LM2010005 Keywords : mollecular modelling * nanocarbons * fullerene * DFT * nanotubes Subject RIV: CF - Physical ; Theoretical Chemistry

  12. 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...

  13. Visual computing model for immune system and medical system.

    Science.gov (United States)

    Gong, Tao; Cao, Xinxue; Xiong, Qin

    2015-01-01

    Natural immune system is an intelligent self-organizing and adaptive system, which has a variety of immune cells with different types of immune mechanisms. The mutual cooperation between the immune cells shows the intelligence of this immune system, and modeling this immune system has an important significance in medical science and engineering. In order to build a comprehensible model of this immune system for better understanding with the visualization method than the traditional mathematic model, a visual computing model of this immune system was proposed and also used to design a medical system with the immune system, in this paper. Some visual simulations of the immune system were made to test the visual effect. The experimental results of the simulations show that the visual modeling approach can provide a more effective way for analyzing this immune system than only the traditional mathematic equations.

  14. Molecular weight​/branching distribution modeling of low-​density-​polyethylene accounting for topological scission and combination termination in continuous stirred tank reactor

    NARCIS (Netherlands)

    Yaghini, N.; Iedema, P.D.

    2014-01-01

    We present a comprehensive model to predict the molecular weight distribution (MWD),(1) and branching distribution of low-density polyethylene (IdPE),(2) for free radical polymerization system in a continuous stirred tank reactor (CSTR).(3) The model accounts for branching, by branching moment or

  15. A grass molecular identification system for forensic botany: a critical evaluation of the strengths and limitations.

    Science.gov (United States)

    Ward, Jodie; Gilmore, Simon R; Robertson, James; Peakall, Rod

    2009-11-01

    Plant material is frequently encountered in criminal investigations but often overlooked as potential evidence. We designed a DNA-based molecular identification system for 100 Australian grasses that consisted of a series of polymerase chain reaction assays that enabled the progressive identification of grasses to different taxonomic levels. The identification system was based on DNA sequence variation at four chloroplast and two mitochondrial loci. Seventeen informative indels and 68 single-nucleotide polymorphisms were utilized as molecular markers for subfamily to species-level identification. To identify an unknown sample to subfamily level required a minimum of four markers or nine markers for species identification. The accuracy of the system was confirmed by blind tests. We have demonstrated "proof of concept" of a molecular identification system for trace botanical samples. Our evaluation suggests that the adoption of a system that combines this approach with DNA sequencing could assist the morphological identification of grasses found as forensic evidence.

  16. Model Information Exchange System (MIXS).

    Science.gov (United States)

    2013-08-01

    Many travel demand forecast models operate at state, regional, and local levels. While they share the same physical network in overlapping geographic areas, they use different and uncoordinated modeling networks. This creates difficulties for models ...

  17. Two sustainable energy system analysis models

    DEFF Research Database (Denmark)

    Lund, Henrik; Goran Krajacic, Neven Duic; da Graca Carvalho, Maria

    2005-01-01

    This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy.......This paper presents a comparative study of two energy system analysis models both designed with the purpose of analysing electricity systems with a substantial share of fluctuating renewable energy....

  18. Models for multimegawatt space power systems

    Energy Technology Data Exchange (ETDEWEB)

    Edenburn, M.W.

    1990-06-01

    This report describes models for multimegawatt, space power systems which Sandia's Advanced Power Systems Division has constructed to help evaluate space power systems for SDI's Space Power Office. Five system models and models for associated components are presented for both open (power system waste products are exhausted into space) and closed (no waste products) systems: open, burst mode, hydrogen cooled nuclear reactor -- turboalternator system; open, hydrogen-oxygen combustion turboalternator system; closed, nuclear reactor powered Brayton cycle system; closed, liquid metal Rankine cycle system; and closed, in-core, reactor therminonic system. The models estimate performance and mass for the components in each of these systems. 17 refs., 8 figs., 15 tabs.

  19. The methylazoxymethanol acetate (MAM-E17) rat model: molecular and functional effects in the hippocampus.

    Science.gov (United States)

    Hradetzky, Eva; Sanderson, Thomas M; Tsang, Tsz M; Sherwood, John L; Fitzjohn, Stephen M; Lakics, Viktor; Malik, Nadia; Schoeffmann, Stephanie; O'Neill, Michael J; Cheng, Tammy Mk; Harris, Laura W; Rahmoune, Hassan; Guest, Paul C; Sher, Emanuele; Collingridge, Graham L; Holmes, Elaine; Tricklebank, Mark D; Bahn, Sabine

    2012-01-01

    Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission, as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia.

  20. Multipole correction of atomic monopole models of molecular charge distribution. I. Peptides

    Science.gov (United States)

    Sokalski, W. A.; Keller, D. A.; Ornstein, R. L.; Rein, R.

    1993-01-01

    The defects in atomic monopole models of molecular charge distribution have been analyzed for several model-blocked peptides and compared with accurate quantum chemical values. The results indicate that the angular characteristics of the molecular electrostatic potential around functional groups capable of forming hydrogen bonds can be considerably distorted within various models relying upon isotropic atomic charges only. It is shown that these defects can be corrected by augmenting the atomic point charge models by cumulative atomic multipole moments (CAMMs). Alternatively, sets of off-center atomic point charges could be automatically derived from respective multipoles, providing approximately equivalent corrections. For the first time, correlated atomic multipoles have been calculated for N-acetyl, N'-methylamide-blocked derivatives of glycine, alanine, cysteine, threonine, leucine, lysine, and serine using the MP2 method. The role of the correlation effects in the peptide molecular charge distribution are discussed.