Sample records for chemical exchange protein-ligand

  1. Auto-FACE: an NMR based binding site mapping program for fast chemical exchange protein-ligand systems.

    Directory of Open Access Journals (Sweden)

    Janarthanan Krishnamoorthy

    Full Text Available BACKGROUND: Nuclear Magnetic Resonance (NMR spectroscopy offers a variety of experiments to study protein-ligand interactions at atomic resolution. Among these experiments, 15N Heteronuclear Single Quantum Correlation (HSQCexperiment is simple, less time consuming and highly informative in mapping the binding site of the ligand. The interpretation of 15N HSQC becomes ambiguous when the chemical shift perturbations are caused by non-specific interactions like allosteric changes and local structural rearrangement. Under such cases, detailed chemical exchange analysis based on chemical shift perturbation will assist in locating the binding site accurately. METHODOLOGY/PRINCIPAL FINDINGS: We have automated the mapping of binding sites for fast chemical exchange systems using information obtained from 15N HSQC spectra of protein serially titrated with ligand of increasing concentrations. The automated program Auto-FACE (Auto-FAst Chemical Exchange analyzer determines the parameters, e.g. rate of change of perturbation, binding equilibrium constant and magnitude of chemical shift perturbation to map the binding site residues.Interestingly, the rate of change of perturbation at lower ligand concentration is highly sensitive in differentiating the binding site residues from the non-binding site residues. To validate this program, the interaction between the protein hBcl(XL and the ligand BH3I-1 was studied. Residues in the hydrophobic BH3 binding groove of hBcl(XL were easily identified to be crucial for interaction with BH3I-1 from other residues that also exhibited perturbation. The geometrically averaged equilibrium constant (3.0 x 10(4 calculated for the residues present at the identified binding site is consistent with the values obtained by other techniques like isothermal calorimetry and fluorescence polarization assays (12.8 x 10(4. Adjacent to the primary site, an additional binding site was identified which had an affinity of 3.8 times weaker

  2. Mapping Protein-Ligand Interactions with Proteolytic Fragmentation, Hydrogen/Deuterium Exchange-Mass Spectrometry. (United States)

    Gallagher, Elyssia S; Hudgens, Jeffrey W


    Biological processes are the result of noncovalent, protein-ligand interactions, where the ligands range from small organic and inorganic molecules to lipids, nucleic acids, peptides, and proteins. Amide groups within proteins constantly exchange protons with water. When immersed in heavy water (D2O), mass spectrometry (MS) can measure the change of mass associated with the hydrogen to deuterium exchange (HDX). Protein-ligand interactions modify the hydrogen exchange rates of amide protons, and the measurement of the amide exchange rates can provide rich information regarding the dynamical structure of the protein-ligand complex. This chapter describes a protocol for conducting bottom-up, continuous uptake, proteolytic fragmentation HDX-MS experiments that can help identify and map the interacting peptides of a protein-ligand interface. This tutorial outlines the fundamental theory governing hydrogen exchange; provides practical information regarding the preparation of protein samples and solutions; and describes the exchange reaction, reaction quenching, enzymatic digestion, chromatographic separation, and peptide analysis by MS. Tables list representative combinations of fluidic components used by HDX-MS researchers and summarize the available HDX-MS analysis software packages. Additionally, two HDX-MS case studies are used to illustrate protein-ligand interactions involving: (1) a continuous sequence of interacting residues and (2) a set of discontinuously numbered residues, residing spatially near each other.

  3. Protein-Ligand Binding Potential of Mean Force Calculations with Hamiltonian Replica Exchange on Alchemical Interaction Grids

    CERN Document Server

    Minh, David D L


    A binding potential of mean force (BPMF) is a free energy of noncovalent association in which one binding partner is flexible and the other is rigid. I have developed a method to calculate BPMFs for protein-ligand systems. The method is based on replica exchange sampling from multiple thermodynamic states at different temperatures and protein-ligand interaction strengths. Protein-ligand interactions are represented by interpolating precomputed electrostatic and van der Waals grids. Using a simple estimator for thermodynamic length, thermodynamic states are initialized at approximately equal intervals. The method is demonstrated on the Astex diverse set, a database of 85 protein-ligand complexes relevant to pharmacy or agriculture. Fifteen independent simulations of each complex were started using poses from crystallography, docking, or the lowest-energy pose observed in the other simulations. Benchmark simulations completed within three days on a single processor. Overall, protocols initialized using the ther...

  4. Protein-ligand docking using hamiltonian replica exchange simulations with soft core potentials. (United States)

    Luitz, Manuel P; Zacharias, Martin


    Molecular dynamics (MD) simulations in explicit solvent allow studying receptor-ligand binding processes including full flexibility of the binding partners and an explicit inclusion of solvation effects. However, in MD simulations, the search for an optimal ligand-receptor complex geometry is frequently trapped in locally stable non-native binding geometries. A Hamiltonian replica-exchange (H-REMD)-based protocol has been designed to enhance the sampling of putative ligand-receptor complexes. It is based on softening nonbonded ligand-receptor interactions along the replicas and one reference replica under the control of the original force field. The efficiency of the method has been evaluated on two receptor-ligand systems and one protein-peptide complex. Starting from misplaced initial docking geometries, the H-REMD method reached in each case the known binding geometry significantly faster than a standard MD simulation. The approach could also be useful to identify and evaluate alternative binding geometries in a given binding region with small relative differences in binding free energy.

  5. In Silico Generation of Peptides by Replica Exchange Monte Carlo: Docking-Based Optimization of Maltose-Binding-Protein Ligands.

    Directory of Open Access Journals (Sweden)

    Anna Russo

    Full Text Available Short peptides can be designed in silico and synthesized through automated techniques, making them advantageous and versatile protein binders. A number of docking-based algorithms allow for a computational screening of peptides as binders. Here we developed ex-novo peptides targeting the maltose site of the Maltose Binding Protein, the prototypical system for the study of protein ligand recognition. We used a Monte Carlo based protocol, to computationally evolve a set of octapeptides starting from a polialanine sequence. We screened in silico the candidate peptides and characterized their binding abilities by surface plasmon resonance, fluorescence and electrospray ionization mass spectrometry assays. These experiments showed the designed binders to recognize their target with micromolar affinity. We finally discuss the obtained results in the light of further improvement in the ex-novo optimization of peptide based binders.

  6. Analyzing protein-ligand interactions by dynamic NMR spectroscopy. (United States)

    Mittermaier, Anthony; Meneses, Erick


    Nuclear magnetic resonance (NMR) spectroscopy can provide detailed information on protein-ligand interactions that is inaccessible using other biophysical techniques. This chapter focuses on NMR-based approaches for extracting affinity and rate constants for weakly binding transient protein complexes with lifetimes of less than about a second. Several pulse sequences and analytical techniques are discussed, including line-shape simulations, spin-echo relaxation dispersion methods (CPMG), and magnetization exchange (EXSY) experiments.

  7. Heat Exchanger Lab for Chemical Engineering Undergraduates (United States)

    Rajala, Jonathan W.; Evans, Edward A.; Chase, George G.


    Third year chemical engineering undergraduate students at The University of Akron designed and fabricated a heat exchanger for a stirred tank as part of a Chemical Engineering Laboratory course. The heat exchanger portion of this course was three weeks of the fifteen week long semester. Students applied concepts of scale-up and dimensional…

  8. Measurement of protein-ligand complex formation. (United States)

    Lowe, Peter N; Vaughan, Cara K; Daviter, Tina


    Experimental approaches to detect, measure, and quantify protein-ligand binding, along with their theoretical bases, are described. A range of methods for detection of protein-ligand interactions is summarized. Specific protocols are provided for a nonequilibrium procedure pull-down assay, for an equilibrium direct binding method and its modification into a competition-based measurement and for steady-state measurements based on the effects of ligands on enzyme catalysis.

  9. Lead Generation and Optimization Based on Protein-Ligand Complementarity

    Directory of Open Access Journals (Sweden)

    Koji Ogata


    Full Text Available This work proposes a computational procedure for structure-based lead generation and optimization, which relies on the complementarity of the protein-ligand interactions. This procedure takes as input the known structure of a protein-ligand complex. Retaining the positions of the ligand heavy atoms in the protein binding site it designs structurally similar compounds considering all possible combinations of atomic species (N, C, O, CH3, NH,etc. Compounds are ranked based on a score which incorporates energetic contributions evaluated using molecular mechanics force fields. This procedure was used to design new inhibitor molecules for three serine/threonine protein kinases (p38 MAP kinase, p42 MAP kinase (ERK2, and c-Jun N-terminal kinase 3 (JNK3. For each enzyme, the calculations produce a set of potential inhibitors whose scores are in agreement with IC50 data and Ki values. Furthermore, the native ligands for each protein target, scored within the five top-ranking compounds predicted by our method, one of the top-ranking compounds predicted to inhibit JNK3 was synthesized and his inhibitory activity confirmed against ATP hydrolysis. Our computational procedure is therefore deemed to be a useful tool for generating chemically diverse molecules active against known target proteins.

  10. Ultrafast two dimensional infrared chemical exchange spectroscopy (United States)

    Fayer, Michael


    The method of ultrafast two dimensional infrared (2D IR) vibrational echo spectroscopy is described. Three ultrashort IR pulses tuned to the frequencies of the vibrational transitions of interest are directed into the sample. The interaction of these pulses with the molecular vibrational oscillators produces a polarization that gives rise to a fourth pulse, the vibrational echo. The vibrational echo pulse is combined with another pulse, the local oscillator, for heterodyne detection of the signal. For fixed time between the second and third pulses, the waiting time, the first pulse is scanned. Two Fourier transforms of the data yield a 2D IR spectrum. The waiting time is increased, and another spectrum is obtained. The change in the 2D IR spectra with increased waiting time provides information on the time evolution of the structure of the molecular system under observation. In a 2D IR chemical exchange experiment, two species A and B, are undergoing chemical exchange. A's are turning into B's, and B's are turning into A's, but the overall concentrations of the species are not changing. The kinetics of the chemical exchange on the ground electronic state under thermal equilibrium conditions can be obtained 2D IR spectroscopy. A vibration that has a different frequency for the two species is monitored. At very short time, there will be two peaks on the diagonal of the 2D IR spectrum, one for A and one for B. As the waiting time is increased, chemical exchange causes off-diagonal peaks to grow in. The time dependence of the growth of these off-diagonal peaks gives the chemical exchange rate. The method is applied to organic solute-solvent complex formation, orientational isomerization about a carbon-carbon single bond, migration of a hydrogen bond from one position on a molecule to another, protein structural substate interconversion, and water hydrogen bond switching between ions and water molecules. This work was supported by the Air Force Office of Scientific

  11. Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies. (United States)

    Bryce, Richard A


    The ability to accurately predict the interaction of a ligand with its receptor is a key limitation in computer-aided drug design approaches such as virtual screening and de novo design. In this article, we examine current strategies for a physics-based approach to scoring of protein-ligand affinity, as well as outlining recent developments in force fields and quantum chemical techniques. We also consider advances in the development and application of simulation-based free energy methods to study protein-ligand interactions. Fuelled by recent advances in computational algorithms and hardware, there is the opportunity for increased integration of physics-based scoring approaches at earlier stages in computationally guided drug discovery. Specifically, we envisage increased use of implicit solvent models and simulation-based scoring methods as tools for computing the affinities of large virtual ligand libraries. Approaches based on end point simulations and reference potentials allow the application of more advanced potential energy functions to prediction of protein-ligand binding affinities. Comprehensive evaluation of polarizable force fields and quantum mechanical (QM)/molecular mechanical and QM methods in scoring of protein-ligand interactions is required, particularly in their ability to address challenging targets such as metalloproteins and other proteins that make highly polar interactions. Finally, we anticipate increasingly quantitative free energy perturbation and thermodynamic integration methods that are practical for optimization of hits obtained from screened ligand libraries.

  12. Synthesizing Novel Anthraquinone Natural Product-Like Compounds to Investigate Protein-Ligand Interactions in Both an in Vitro and in Vivo Assay: An Integrated Research-Based Third-Year Chemical Biology Laboratory Course (United States)

    McKenzie, Nancy; McNulty, James; McLeod, David; McFadden, Meghan; Balachandran, Naresh


    A new undergraduate program in chemical biology was launched in 2008 to provide a unique learning experience for those students interested in this interdisciplinary science. An innovative undergraduate chemical biology laboratory course at the third-year level was developed as a key component of the curriculum. The laboratory course introduces…

  13. Spin-locking versus chemical exchange saturation transfer MRI for investigating chemical exchange process between water and labile metabolite protons. (United States)

    Jin, Tao; Autio, Joonas; Obata, Takayuki; Kim, Seong-Gi


    Chemical exchange saturation transfer (CEST) and spin-locking (SL) experiments were both able to probe the exchange process between protons of nonequivalent chemical environments. To compare the characteristics of the CEST and SL approaches in the study of chemical exchange effects, we performed CEST and SL experiments at varied pH and concentrated metabolite phantoms with exchangeable amide, amine, and hydroxyl protons at 9.4 T. Our results show that: (i) on-resonance SL is most sensitive to chemical exchanges in the intermediate-exchange regime and is able to detect hydroxyl and amine protons on a millimolar concentration scale. Off-resonance SL and CEST approaches are sensitive to slow-exchanging protons when an optimal SL or saturation pulse power matches the exchanging rate, respectively. (ii) Offset frequency-dependent SL and CEST spectra are very similar and can be explained well with an SL model recently developed by Trott and Palmer (J Magn Reson 2002;154:157-160). (iii) The exchange rate and population of metabolite protons can be determined from offset-dependent SL or CEST spectra or from on-resonance SL relaxation dispersion measurements. (iv) The asymmetry of the magnetization transfer ratio (MTR(asym)) is highly dependent on the choice of saturation pulse power. In the intermediate-exchange regime, MTR(asym) becomes complicated and should be interpreted with care.

  14. Comparison of molecular mechanics, semi-empirical quantum mechanical, and density functional theory methods for scoring protein-ligand interactions. (United States)

    Yilmazer, Nusret Duygu; Korth, Martin


    Correctly ranking protein-ligand interactions with respect to overall free energy of binding is a grand challenge for virtual drug design. Here we compare the performance of various quantum chemical approaches for tackling this so-called "scoring" problem. Relying on systematically generated benchmark sets of large protein/ligand model complexes based on the PDBbind database, we show that the performance depends first of all on the general level of theory. Comparing classical molecular mechanics (MM), semiempirical quantum mechanical (SQM), and density functional theory (DFT) based methods, we find that enhanced SQM approaches perform very similar to DFT methods and substantially different from MM potentials.

  15. Steered molecular dynamics simulations of protein-ligand interactions

    Institute of Scientific and Technical Information of China (English)

    XU; Yechun; SHEN; Jianhua; LUO; Xiaomin; SHEN; Xu; CHEN; Ka


    Studies of protein-ligand interactions are helpful to elucidating the mechanisms of ligands, providing clues for rational drug design. The currently developed steered molecular dynamics (SMD) is a complementary approach to experimental techniques in investigating the biochemical processes occurring at microsecond or second time scale, thus SMD may provide dynamical and kinetic processes of ligand-receptor binding and unbinding, which cannot be accessed by the experimental methods. In this article, the methodology of SMD is described, and the applications of SMD simulations for obtaining dynamic insights into protein-ligand interactions are illustrated through two of our own examples. One is associated with the simulations of binding and unbinding processes between huperzine A and acetylcholinesterase, and the other is concerned with the unbinding process of α-APA from HIV-1 reverse transcriptase.

  16. A statistical mechanics handbook for protein-ligand binding simulation. (United States)

    Rocchia, Walter; Bonella, Sara


    In this work, the fundamental elements of statistical mechanics underlying the simulation of the protein-ligand binding process, such as statistical ensembles and the concept of microscopic estimators of macroscopic observables and free energy, are summarized in a self consistent fashion. Particular attention is then devoted to the introduction of some mathematical tools that are used in atomistic simulations aimed at estimating binding affinities and free energy profiles, and to the illustration of the origins of the difficulties encountered in this endeavor.

  17. Stochastic Simulation of Chemical Exchange in Two Dimensional Infrared Spectroscopy

    CERN Document Server

    Sanda, F; Sanda, Frantisek; Mukamel, Shaul


    The stochastic Liouville equations are employed to investigate the combined signatures of chemical exchange (two-state-jump) and spectral diffusion (coupling to an overdamped Brownian oscillator) in the coherent response of an anharmonic vibration to three femtosecond infrared pulses. Simulations reproduce the main features recently observed in the OD stretch of phenol in benzene.

  18. Separation of the isotopes of boron by chemical exchange reactions

    Energy Technology Data Exchange (ETDEWEB)

    McCandless, F.P.; Herbst, R.S.


    The isotopes of boron, {sup 10}B and {sup 11}B, are separated by means of a gas-liquid chemical exchange reaction involving the isotopic equilibrium between gaseous BF{sub 3} and a liquid BF{sub 3} donor molecular addition complex formed between BF{sub 3} gas and a donor chosen from the group consisting of: nitromethane, acetone, methyl isobutyl ketone, or diisobutyl ketone. 1 Fig.

  19. Glucans monomer-exchange dynamics as an open chemical network

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Riccardo, E-mail:; Esposito, Massimiliano, E-mail: [Complex Systems and Statistical Mechanics, Physics and Materials Science Research Unit, University of Luxembourg, L-1511 Luxembourg (Luxembourg); Lacoste, David [Laboratoire de Physico-Chimie Théorique, UMR CNRS Gulliver 7083, ESPCI - 10 rue Vauquelin, F-75231 Paris (France)


    We describe the oligosaccharides-exchange dynamics performed by the so-called D-enzymes on polysaccharides. To mimic physiological conditions, we treat this process as an open chemical network by assuming some of the polymer concentrations fixed (chemostatting). We show that three different long-time behaviors may ensue: equilibrium states, nonequilibrium steady states, and continuous growth states. We dynamically and thermodynamically characterize these states and emphasize the crucial role of conservation laws in identifying the chemostatting conditions inducing them.

  20. Glucans monomer-exchange dynamics as an open chemical network

    CERN Document Server

    Rao, Riccardo; Esposito, Massimiliano


    We describe the oligosaccharides-exchange dynamics performed by so-called D-enzymes on polysaccharides. To mimic physiological conditions, we treat this process as an open chemical network by assuming some of the polymer concentrations fixed (chemostatting). We show that three different long-time behaviors may ensue: equilibrium states, nonequilibrium steady states, and continuous growth states. We dynamically and thermodynamically characterize these states and emphasize the crucial role of conservation laws in identifying the chemostatting conditions inducing them.

  1. Protein-Directed Dynamic Combinatorial Chemistry: A Guide to Protein Ligand and Inhibitor Discovery

    Directory of Open Access Journals (Sweden)

    Renjie Huang


    Full Text Available Protein-directed dynamic combinatorial chemistry is an emerging technique for efficient discovery of novel chemical structures for binding to a target protein. Typically, this method relies on a library of small molecules that react reversibly with each other to generate a combinatorial library. The components in the combinatorial library are at equilibrium with each other under thermodynamic control. When a protein is added to the equilibrium mixture, and if the protein interacts with any components of the combinatorial library, the position of the equilibrium will shift and those components that interact with the protein will be amplified, which can then be identified by a suitable biophysical technique. Such information is useful as a starting point to guide further organic synthesis of novel protein ligands and enzyme inhibitors. This review uses literature examples to discuss the practicalities of applying this method to inhibitor discovery, in particular, the set-up of the combinatorial library, the reversible reactions that may be employed, and the choice of detection methods to screen protein ligands from a mixture of reversibly forming molecules.

  2. Cloud computing for protein-ligand binding site comparison. (United States)

    Hung, Che-Lun; Hua, Guan-Jie


    The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

  3. Cloud Computing for Protein-Ligand Binding Site Comparison

    Directory of Open Access Journals (Sweden)

    Che-Lun Hung


    Full Text Available The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

  4. Protein-Ligand Docking Based on Beta-Shape (United States)

    Kim, Chong-Min; Won, Chung-In; Kim, Jae-Kwan; Ryu, Joonghyun; Bhak, Jong; Kim, Deok-Soo

    Protein-ligand docking is to predict the location and orientation of a ligand with respect to a protein within its binding site, and has been known to be essential for the development of new drugs. The protein-ligand docking problem is usually formulated as an energy minimization problem to identify the docked conformation of the ligand. A ligand usually docks around a depressed region, called a pocket, on the surface of a protein. Presented in this paper is a docking method, called BetaDock, based on the newly developed geometric construct called the β-shape and the β-complex. To cope with the computational intractability, the global minimum of the potential energy function is searched using the genetic algorithm. The proposed algorithm first locates initial chromosomes at some locations within the pocket recognized according to the local shape of the β-shape. Then, the algorithm proceeds generations by taking advantage of powerful properties of the β-shape to achieve an extremely fast and good solution. We claim that the proposed method is much faster than other popular docking softwares including AutoDock.

  5. Transverse relaxation in the rotating frame induced by chemical exchange (United States)

    Michaeli, Shalom; Sorce, Dennis J.; Idiyatullin, Djaudat; Ugurbil, Kamil; Garwood, Michael


    In the presence of radiofrequency irradiation, relaxation of magnetization aligned with the effective magnetic field is characterized by the time constant T1 ρ. On the other hand, the time constant T2 ρ characterizes the relaxation of magnetization that is perpendicular to the effective field. Here, it is shown that T2 ρ can be measured directly with Carr-Purcell sequences composed of a train of adiabatic full-passage (AFP) pulses. During adiabatic rotation, T2 ρ characterizes the relaxation of the magnetization, which under adiabatic conditions remains approximately perpendicular to the time-dependent effective field. Theory is derived to describe the influence of chemical exchange on T2 ρ relaxation in the fast-exchange regime, with time constant defined as T2 ρ,ex . The derived theory predicts the rate constant R 2ρ, ex (=1/T 2ρ, ex) to be dependent on the choice of amplitude- and frequency-modulation functions used in the AFP pulses. Measurements of R2 ρ,ex of the water/ethanol exchanging system confirm the predicted dependence on modulation functions. The described theoretical framework and adiabatic methods represent new tools to probe exchanging systems.

  6. Charge Exchange and Chemical Reactions with Trapped Th$^{3+}$

    CERN Document Server

    Churchill, L R; Chapman, M S


    We have measured the reaction rates of trapped, buffer gas cooled Th$^{3+}$ and various gases and have analyzed the reaction products using trapped ion mass spectrometry techniques. Ion trap lifetimes are usually limited by reactions with background molecules, and the high electron affinity of multiply charged ions such as Th$^{3+}$ make them more prone to loss. Our results show that reactions of Th$^{3+}$ with carbon dioxide, methane, and oxygen all occur near the classical Langevin rate, while reaction rates with argon, hydrogen, and nitrogen are orders of magnitude lower. Reactions of Th$^{3+}$ with oxygen and methane proceed primarily via charge exchange, while simultaneous charge exchange and chemical reaction occurs between Th$^{3+}$ and carbon dioxide. Loss rates of Th$^{3+}$ in helium are consistent with reaction with impurities in the gas. Reaction rates of Th$^{3+}$ with nitrogen and argon depend on the internal electronic configuration of the Th$^{3+}$.

  7. Advances in boron-10 isotope separation by chemical exchange distillation

    Energy Technology Data Exchange (ETDEWEB)

    Song Shuang, E-mail: [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Mu Yujun; Li Xiaofeng; Bai Peng [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China)


    Advances in boron-10 isotope separation by chemical exchange distillation are reviewed in this article. With a brief introduction of the principle of the separation, the progress on the research of this method and the problems relating to the separation coefficient are discussed. Several new donors, including nitromethane, acetone, methyl isobutyl ketone (MIBK) and diisobutyl ketone (DIBK), which have large separation factors are introduced. The complexes of these new donors and boron trifluoride (BF{sub 3}) are more stable than those of using the donors examined before. Among these new donors nitromethane could be a promising substitute for donors in present use to develop new technology of separating boron-10.

  8. Advantages of chemical exchange-sensitive spin-lock (CESL) over chemical exchange saturation transfer (CEST) for hydroxyl- and amine-water proton exchange studies. (United States)

    Jin, Tao; Kim, Seong-Gi


    The chemical exchange (CE) rate of endogenous hydroxyl and amine protons with water is often comparable to the difference in their chemical shifts. These intermediate exchange processes have been imaged by the CE saturation transfer (CEST) approach with low-power and long-duration irradiation. However, the sensitivity is not optimal and, more importantly, the signal is contaminated by slow magnetization transfer processes. Here, the properties of CEST signals are compared with those of a CE-sensitive spin-lock (CESL) technique irradiating at the labile proton frequency. First, using a higher power and shorter irradiation in CE-MRI, we obtain: (i) an increased selectivity to faster CE rates via a higher sensitivity to faster CEs and a lower sensitivity to slower CEs and magnetization transfer processes; and (ii) a decreased in vivo asymmetric magnetization transfer contrast measured at ±15 ppm. The sensitivity gain of CESL over CEST is higher for a higher power and shorter irradiation. Unlike CESL, CEST signals oscillate at a very high power and short irradiation. Second, time-dependent CEST and CESL signals are well modeled by analytical solutions of CE-MRI with an asymmetric population approximation, which can be used for quantitative CE-MRI and validated by simulations of Bloch-McConnell equations and phantom experiments. Finally, the in vivo amine-water proton exchange contrast measured at 2.5 ppm with ω1 = 500 Hz is 18% higher in sensitivity for CESL than CEST at 9.4 T. Overall, CESL provides better exchange rate selectivity and sensitivity than CEST; therefore, CESL is more suitable for CE-MRI of intermediate exchange protons.

  9. Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI. (United States)

    Li, Jikun; Feng, Xinxin; Zhu, Wei; Oskolkov, Nikita; Zhou, Tianhui; Kim, Boo Kyung; Baig, Noman; McMahon, Michael T; Oldfield, Eric


    Diamagnetic chemical exchange saturation transfer (CEST) contrast agents offer an alternative to Gd(3+) -based contrast agents for MRI. They are characterized by containing protons that can rapidly exchange with water and it is advantageous to have these protons resonate in a spectral window that is far removed from water. Herein, we report the first results of DFT calculations of the (1) H nuclear magnetic shieldings in 41 CEST agents, finding that the experimental shifts can be well predicted (R(2) =0.882). We tested a subset of compounds with the best MRI properties for toxicity and for activity as uncouplers, then obtained mice kidney CEST MRI images for three of the most promising leads finding 16 (2,4-dihydroxybenzoic acid) to be one of the most promising CEST MRI contrast agents to date. Overall, the results are of interest since they show that (1) H NMR shifts for CEST agents-charged species-can be well predicted, and that several leads have low toxicity and yield good in vivo MR images.

  10. Determination of protein-ligand interactions using accelerator mass spectrometry: modified crosslinking assay. (United States)

    Hah, Sang Soo


    A highly sensitive detection method for the determination of protein-ligand interactions has been developed. Radiocarbon-labeled 17beta-estradiol was incubated with estrogen receptor-alpha; as a selective binding partner, and covalently attached using crosslinking agents, to form covalently linked protein-ligand complexes. After separation using a denaturing gel, the (14)C content in the sliced gels was identified by accelerator mass spectrometry. The obtained data demonstrated specific binding of the small molecule to its binding partner. In theory, this method can be applied to most protein-ligand interaction studies.

  11. Tailoring exchange bias through chemical order in epitaxial FePt3 films (United States)

    Saerbeck, T.; Zhu, H.; Lott, D.; Lee, H.; LeClair, P. R.; Mankey, G. J.; Stampfl, A. P. J.; Klose, F.


    Intentional introduction of chemical disorder into mono-stoichiometric epitaxial FePt3 films allows to create a ferro-/antiferromagnetic two-phase system, which shows a pronounced and controllable exchange bias effect. In contrast to conventional exchange bias systems, granular magnetic interfaces are created within the same crystallographic structure by local variation of chemical order. The amount of the exchange bias can be controlled by the relative amount and size of ferromagnetic and antiferromagnetic volume fractions and the interface between them. The tailoring of the magnetic composition alone, without affecting the chemical and structural compositions, opens the way to study granular magnetic exchange bias concepts separated from structural artifacts.

  12. Multivalent drug design and inhibition of cholera toxin by specific and transient protein-ligand interactions. (United States)

    Liu, Jiyun; Begley, Darren; Mitchell, Daniel D; Verlinde, Christophe L M J; Varani, Gabriele; Fan, Erkang


    Multivalent inhibitors of the cholera toxin B pentamer are potential therapeutic drugs for treating cholera and serve as models for demonstrating multivalent ligand effects through a structure-based approach. A crucial yet often overlooked aspect of multivalent drug design is the length, rigidity and chemical composition of the linker used to connect multiple binding moieties. To specifically study the role of chemical linkers in multivalent ligand design, we have synthesized a series of compounds with one and two binding motifs connected by several different linkers. These compounds have affinity for and potency against the cholera toxin B pentamer despite the fact that none can simultaneously bind two toxin receptor sites. Results from saturation transfer difference NMR reveal transient, non-specific interactions between the cholera toxin and linker groups contribute significantly to overall binding affinity of monovalent compounds. However, the same random protein-ligand interactions do not appear to affect binding of bivalent molecules. Moreover, the binding affinities and potencies of these 'non-spanning' bivalent ligands appear to be wholly independent of linker length. Our detailed analysis identifies multiple effects that account for the improved inhibitory potencies of bivalent ligands and suggest approaches to further improve the activity of this class of compounds.

  13. Structural interaction fingerprint (SIFt): a novel method for analyzing three-dimensional protein-ligand binding interactions. (United States)

    Deng, Zhan; Chuaqui, Claudio; Singh, Juswinder


    Representing and understanding the three-dimensional (3D) structural information of protein-ligand complexes is a critical step in the rational drug discovery process. Traditional analysis methods are proving inadequate and inefficient in dealing with the massive amount of structural information being generated from X-ray crystallography, NMR, and in silico approaches such as structure-based docking experiments. Here, we present SIFt (structural interaction fingerprint), a novel method for representing and analyzing 3D protein-ligand binding interactions. Key to this approach is the generation of an interaction fingerprint that translates 3D structural binding information from a protein-ligand complex into a one-dimensional binary string. Each fingerprint represents the "structural interaction profile" of the complex that can be used to organize, analyze, and visualize the rich amount of information encoded in ligand-receptor complexes and also to assist database mining. We have applied SIFt to tackle three common tasks in structure-based drug design. The first involved the analysis and organization of a typical set of results generated from a docking study. Using SIFt, docking poses with similar binding modes were identified, clustered, and subsequently compared with conventional scoring function information. A second application of SIFt was to analyze approximately 90 known X-ray crystal structures of protein kinase-inhibitor complexes obtained from the Protein Databank. Using SIFt, we were able to organize the structures and reveal striking similarities and diversity between their small molecule binding interactions. Finally, we have shown how SIFt can be used as an effective molecular filter during the virtual chemical library screening process to select molecules with desirable binding mode(s) and/or desirable interaction patterns with the protein target. In summary, SIFt shows promise to fully leverage the wealth of information being generated in rational

  14. Proton Exchange in a Paramagnetic Chemical Exchange Saturation Transfer Agent from Experimental Studies and ab Initio Metadynamics Simulation. (United States)

    Pollet, Rodolphe; Bonnet, Célia S; Retailleau, Pascal; Durand, Philippe; Tóth, Éva


    The proton-exchange process between water and a carbamate has been studied experimentally and theoretically in a lanthanide-based paramagnetic chemical exchange saturation transfer agent endowed with potential multimodality detection capabilities (optical imaging, or T1 MRI for the Gd(III) analogue). In addition to an in-depth structural analysis by a combined approach (using X-ray crystallography, NMR, and molecular dynamics), our ab initio simulation in aqueous solution sheds light on the reaction mechanism for this proton exchange, which involves structural Grotthuss diffusion.

  15. 10 CFR Appendix E to Part 110 - Illustrative List of Chemical Exchange or Ion Exchange Enrichment Plant Equipment and Components... (United States)


    ... purification and electrolytic cells for reducing the uranium U+6 or U+4 to U+3. These systems produce uranium... designed or prepared electrochemical reduction cells to reduce uranium from one valence state to another for uranium enrichment using the chemical exchange process. The cell materials in contact with...

  16. Predicting protein-ligand affinity with a random matrix framework. (United States)

    Lee, Alpha A; Brenner, Michael P; Colwell, Lucy J


    Rapid determination of whether a candidate compound will bind to a particular target receptor remains a stumbling block in drug discovery. We use an approach inspired by random matrix theory to decompose the known ligand set of a target in terms of orthogonal "signals" of salient chemical features, and distinguish these from the much larger set of ligand chemical features that are not relevant for binding to that particular target receptor. After removing the noise caused by finite sampling, we show that the similarity of an unknown ligand to the remaining, cleaned chemical features is a robust predictor of ligand-target affinity, performing as well or better than any algorithm in the published literature. We interpret our algorithm as deriving a model for the binding energy between a target receptor and the set of known ligands, where the underlying binding energy model is related to the classic Ising model in statistical physics.

  17. A sequence-based dynamic ensemble learning system for protein ligand-binding site prediction

    KAUST Repository

    Chen, Peng


    Background: Proteins have the fundamental ability to selectively bind to other molecules and perform specific functions through such interactions, such as protein-ligand binding. Accurate prediction of protein residues that physically bind to ligands is important for drug design and protein docking studies. Most of the successful protein-ligand binding predictions were based on known structures. However, structural information is not largely available in practice due to the huge gap between the number of known protein sequences and that of experimentally solved structures

  18. Staff exchange with Chemical Waste Management. Final project report

    Energy Technology Data Exchange (ETDEWEB)

    Harrer, B.J.; Barak, D.W.


    Original objective was transfer of PNL technology and expertise in computational chemistry and waste flow/treatment modeling to CWM. Identification and characterization of a broader portfolio of PNL`s environmental remediation technologies with high potential for rapid application became the focus of the exchange, which included E-mail exchanges. Of the 14 technologies discussed, the following were identified as being of high interest to CWM: six phase soil heating (in-situ heating), high energy electrical corona, RAAS/ReOpt{trademark} (remedial, expert system), TEES{trademark} (catalytic production of methane from biological wastes), PST (process for treating petroleum sludge). CWM`s reorganization and downsizing reduced the potential benefits to industry, but a proposal for transfer and application of PST to Wheelabrator was made.

  19. Calculation of two-dimensional infrared spectra of ultrafast chemical exchange with numerical Langevin simulations

    NARCIS (Netherlands)

    Jansen, Thomas la Cour; Knoester, Jasper


    We combine numerical Langevin simulations with numerical integration of the Schrodinger equation to calculate two-dimensional infrared spectra of ultrafast chemical exchange. This provides a tool to model and interpret such spectra of molecules undergoing chemical processes, such as isomerization an

  20. VS-APPLE: A Virtual Screening Algorithm Using Promiscuous Protein-Ligand Complexes. (United States)

    Okuno, Tatsuya; Kato, Koya; Terada, Tomoki P; Sasai, Masaki; Chikenji, George


    As the number of structurally resolved protein-ligand complexes increases, the ligand-binding pockets of many proteins have been found to accommodate multiple different compounds. Effective use of these structural data is important for developing virtual screening (VS) methods that identify bioactive compounds. Here, we introduce a VS method, VS-APPLE (Virtual Screening Algorithm using Promiscuous Protein-Ligand complExes), based on promiscuous protein-ligand binding structures. In VS-APPLE, multiple ligands bound to a pocket are combined into a query template for screening. Both the structural match between a test compound and the multiple-ligand template and the possible collisions between the test compound and the target protein are evaluated by an efficient geometric hashing method. The performance of VS-APPLE was examined on a filtered, clustered version of the Directory of Useful Decoys data set. In Area Under the Curve analyses of this data set, VS-APPLE outperformed several popular screening programs. Judging from the performance of VS-APPLE, the structural data of promiscuous protein-ligand bindings could be further analyzed and exploited for developing VS methods.

  1. A new test set for validating predictions of protein-ligand interaction. (United States)

    Nissink, J Willem M; Murray, Chris; Hartshorn, Mike; Verdonk, Marcel L; Cole, Jason C; Taylor, Robin


    We present a large test set of protein-ligand complexes for the purpose of validating algorithms that rely on the prediction of protein-ligand interactions. The set consists of 305 complexes with protonation states assigned by manual inspection. The following checks have been carried out to identify unsuitable entries in this set: (1) assessing the involvement of crystallographically related protein units in ligand binding; (2) identification of bad clashes between protein side chains and ligand; and (3) assessment of structural errors, and/or inconsistency of ligand placement with crystal structure electron density. In addition, the set has been pruned to assure diversity in terms of protein-ligand structures, and subsets are supplied for different protein-structure resolution ranges. A classification of the set by protein type is available. As an illustration, validation results are shown for GOLD and SuperStar. GOLD is a program that performs flexible protein-ligand docking, and SuperStar is used for the prediction of favorable interaction sites in proteins. The new CCDC/Astex test set is freely available to the scientific community (

  2. Preliminary Assessment of Mercury Atmosphere-Surface Exchange Parameterizations for Incorporation into Chemical Transport Models (United States)

    Khan, T.; Agnan, Y.; Obrist, D.; Selin, N. E.; Urban, N. R.; Wu, S.; Perlinger, J. A.


    Inadequate representation of process-based mechanisms of exchange behavior of elemental mercury (Hg0) and decoupled treatment of deposition and emission are two major limitations of parameterizations of atmosphere-surface exchange flux commonly incorporated into chemical transport models (CTMs). Of nineteen CTMs for Hg0 exchange we reviewed (ten global, nine regional), eight global and seven regional models have decoupled treatment of Hg0 deposition and emission, two global models include no parameterization to account for emission, and the remaining two regional models include coupled deposition and emission parameterizations (i.e., net atmosphere-surface exchange). The performance of atmosphere-surface exchange parameterizations in CTMs depends on parameterization uncertainty (in terms of both accuracy and precision) and feasibility of implementation. We provide a comparison of the performance of three available parameterizations of net atmosphere-surface exchange. To evaluate parameterization accuracy, we compare predicted exchange fluxes to field measurements conducted over a variety of surfaces compiled in a recently developed global database of terrestrial Hg0 surface-atmosphere exchange flux measurements. To assess precision, we estimate the sensitivity of predicted fluxes to the imprecision in parameter input values, and compare this sensitivity to that derived from analysis of the global Hg0 flux database. Feasibility of implementation is evaluated according to the availability of input parameters, computational requirements, and the adequacy of uncertainty representation. Based on this assessment, we provide suggestions for improved treatment of Hg0 net exchange processes in CTMs.

  3. A comparison of various optimization algorithms of protein-ligand docking programs by fitness accuracy. (United States)

    Guo, Liyong; Yan, Zhiqiang; Zheng, Xiliang; Hu, Liang; Yang, Yongliang; Wang, Jin


    In protein-ligand docking, an optimization algorithm is used to find the best binding pose of a ligand against a protein target. This algorithm plays a vital role in determining the docking accuracy. To evaluate the relative performance of different optimization algorithms and provide guidance for real applications, we performed a comparative study on six efficient optimization algorithms, containing two evolutionary algorithm (EA)-based optimizers (LGA, DockDE) and four particle swarm optimization (PSO)-based optimizers (SODock, varCPSO, varCPSO-ls, FIPSDock), which were implemented into the protein-ligand docking program AutoDock. We unified the objective functions by applying the same scoring function, and built a new fitness accuracy as the evaluation criterion that incorporates optimization accuracy, robustness, and efficiency. The varCPSO and varCPSO-ls algorithms show high efficiency with fast convergence speed. However, their accuracy is not optimal, as they cannot reach very low energies. SODock has the highest accuracy and robustness. In addition, SODock shows good performance in efficiency when optimizing drug-like ligands with less than ten rotatable bonds. FIPSDock shows excellent robustness and is close to SODock in accuracy and efficiency. In general, the four PSO-based algorithms show superior performance than the two EA-based algorithms, especially for highly flexible ligands. Our method can be regarded as a reference for the validation of new optimization algorithms in protein-ligand docking.

  4. Assessing protein-ligand docking for the binding of organometallic compounds to proteins. (United States)

    Ortega-Carrasco, Elisabeth; Lledós, Agusti; Maréchal, Jean-Didier


    Organometallic compounds are increasingly used as molecular scaffolds in drug development projects; their structural and electronic properties offering novel opportunities in protein-ligand complementarities. Interestingly, while protein-ligand dockings have long become a spearhead in computer assisted drug design, no benchmarking nor optimization have been done for their use with organometallic compounds. Pursuing our efforts to model metal mediated recognition processes, we herein present a systematic study of the capabilities of the program GOLD to predict the interactions of protein with organometallic compounds. The study focuses on inert systems for which no alteration of the first coordination sphere of the metal occurs upon binding. Several scaffolds are used as test systems with different docking schemes and scoring functions. We conclude that ChemScore is the most robust scoring function with ASP and ChemPLP providing with good results too and GoldScore slightly underperforming. This study shows that current state-of-the-art protein-ligand docking techniques are reliable for the docking of inert organometallic compounds binding to protein.

  5. Proteins and Their Interacting Partners: An Introduction to Protein-Ligand Binding Site Prediction Methods. (United States)

    Roche, Daniel Barry; Brackenridge, Danielle Allison; McGuffin, Liam James


    Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein-ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein-ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein-ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

  6. Coarse-grained molecular dynamics simulations of protein-ligand binding. (United States)

    Negami, Tatsuki; Shimizu, Kentaro; Terada, Tohru


    Coarse-grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein-ligand binding processes. We chose two protein-ligand systems, the levansucrase-sugar (glucose or sucrose), and LinB-1,2-dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand-binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse-grained (CG) ligand molecules revealed potential ligand-binding sites on the protein surfaces other than the real ligand-binding sites. The ligands bound most strongly to the real ligand-binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase-sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand-binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein-ligand binding processes.

  7. PSOVina: The hybrid particle swarm optimization algorithm for protein-ligand docking. (United States)

    Ng, Marcus C K; Fong, Simon; Siu, Shirley W I


    Protein-ligand docking is an essential step in modern drug discovery process. The challenge here is to accurately predict and efficiently optimize the position and orientation of ligands in the binding pocket of a target protein. In this paper, we present a new method called PSOVina which combined the particle swarm optimization (PSO) algorithm with the efficient Broyden-Fletcher-Goldfarb-Shannon (BFGS) local search method adopted in AutoDock Vina to tackle the conformational search problem in docking. Using a diverse data set of 201 protein-ligand complexes from the PDBbind database and a full set of ligands and decoys for four representative targets from the directory of useful decoys (DUD) virtual screening data set, we assessed the docking performance of PSOVina in comparison to the original Vina program. Our results showed that PSOVina achieves a remarkable execution time reduction of 51-60% without compromising the prediction accuracies in the docking and virtual screening experiments. This improvement in time efficiency makes PSOVina a better choice of a docking tool in large-scale protein-ligand docking applications. Our work lays the foundation for the future development of swarm-based algorithms in molecular docking programs. PSOVina is freely available to non-commercial users at .

  8. Dual temperature dual pressure water-hydrogen chemical exchange for water detritiation

    Energy Technology Data Exchange (ETDEWEB)

    Sugiyama, Takahiko, E-mail: [Faculty of Engineering, Nagoya University, Fro-cho 1, Chikusa-ku, Nagoya 464-8603 (Japan); Takada, Akito; Morita, Youhei [Faculty of Engineering, Nagoya University, Fro-cho 1, Chikusa-ku, Nagoya 464-8603 (Japan); Kotoh, Kenji [Graduate School of Engineering, Kyushu University, Moto-oka 744, Nishi-ku, Fukuoka 819-0395 (Japan); Munakata, Kenzo [Faculty of Engineering and Resource Science, Akita University, Tegata-gakuen-machi 1-1, Akita 010-8502 (Japan); Taguchi, Akira [Hydrogen Isotope Research Center, University of Toyama, Gofuku 3190, Toyama 930-8555 (Japan); Kawano, Takao; Tanaka, Masahiro; Akata, Naofumi [National Institute for Fusion Science, Oroshi-cho 322-6, Toki, Gifu 509-5292 (Japan)


    Experimental and analytical studies on hydrogen-tritium isotope separation by a dual temperature dual pressure catalytic exchange (DTDP-CE) with liquid phase chemical exchange columns were carried out in order to apply it to a part of the water detritiation system for DEMO fuel cycle. A prototype DTDP-CE apparatus was successfully operated and it was confirmed that tritium was separated by the apparatus as significantly distinguishable. A calculation code was developed based on the channeling stage model. The values of separation factors and the effects of some operating parameters were well predicted by the separative analyses with the code.

  9. Mass Spectrometry-Based Monitoring of Millisecond Protein-Ligand Binding Dynamics Using an Automated Microfluidic Platform

    Energy Technology Data Exchange (ETDEWEB)

    Cong, Yongzheng; Katipamula, Shanta; Trader, Cameron D.; Orton, Daniel J.; Geng, Tao; Baker, Erin Shammel; Kelly, Ryan T.


    Characterizing protein-ligand binding dynamics is crucial for understanding protein function and developing new therapeutic agents. We have developed a novel microfluidic platform that features rapid mixing of protein and ligand solutions, variable incubation times, and on-chip electrospray ionization to perform label-free, solution-based monitoring of protein-ligand binding dynamics. This platform offers many advantages including automated processing, rapid mixing, and low sample consumption.


    Energy Technology Data Exchange (ETDEWEB)

    Boltz, J.C. (ed.)


    EXCHANGE is published monthly by the Idaho National Engineering Laboratory (INEL), a multidisciplinary facility operated for the US Department of Energy (DOE). The purpose of EXCHANGE is to inform computer users about about recent changes and innovations in both the mainframe and personal computer environments and how these changes can affect work being performed at DOE facilities.

  11. Interaction Entropy: A New Paradigm for Highly Efficient and Reliable Computation of Protein-Ligand Binding Free Energy. (United States)

    Duan, Lili; Liu, Xiao; Zhang, John Z H


    Efficient and reliable calculation of protein-ligand binding free energy is a grand challenge in computational biology and is of critical importance in drug design and many other molecular recognition problems. The main challenge lies in the calculation of entropic contribution to protein-ligand binding or interaction systems. In this report, we present a new interaction entropy method which is theoretically rigorous, computationally efficient, and numerically reliable for calculating entropic contribution to free energy in protein-ligand binding and other interaction processes. Drastically different from the widely employed but extremely expensive normal mode method for calculating entropy change in protein-ligand binding, the new method calculates the entropic component (interaction entropy or -TΔS) of the binding free energy directly from molecular dynamics simulation without any extra computational cost. Extensive study of over a dozen randomly selected protein-ligand binding systems demonstrated that this interaction entropy method is both computationally efficient and numerically reliable and is vastly superior to the standard normal mode approach. This interaction entropy paradigm introduces a novel and intuitive conceptual understanding of the entropic effect in protein-ligand binding and other general interaction systems as well as a practical method for highly efficient calculation of this effect.

  12. Forging the Basis for Developing Protein-Ligand Interaction Scoring Functions. (United States)

    Liu, Zhihai; Su, Minyi; Han, Li; Liu, Jie; Yang, Qifan; Li, Yan; Wang, Renxiao


    In structure-based drug design, scoring functions are widely used for fast evaluation of protein-ligand interactions. They are often applied in combination with molecular docking and de novo design methods. Since the early 1990s, a whole spectrum of protein-ligand interaction scoring functions have been developed. Regardless of their technical difference, scoring functions all need data sets combining protein-ligand complex structures and binding affinity data for parametrization and validation. However, data sets of this kind used to be rather limited in terms of size and quality. On the other hand, standard metrics for evaluating scoring function used to be ambiguous. Scoring functions are often tested in molecular docking or even virtual screening trials, which do not directly reflect the genuine quality of scoring functions. Collectively, these underlying obstacles have impeded the invention of more advanced scoring functions. In this Account, we describe our long-lasting efforts to overcome these obstacles, which involve two related projects. On the first project, we have created the PDBbind database. It is the first database that systematically annotates the protein-ligand complexes in the Protein Data Bank (PDB) with experimental binding data. This database has been updated annually since its first public release in 2004. The latest release (version 2016) provides binding data for 16 179 biomolecular complexes in PDB. Data sets provided by PDBbind have been applied to many computational and statistical studies on protein-ligand interaction and various subjects. In particular, it has become a major data resource for scoring function development. On the second project, we have established the Comparative Assessment of Scoring Functions (CASF) benchmark for scoring function evaluation. Our key idea is to decouple the "scoring" process from the "sampling" process, so scoring functions can be tested in a relatively pure context to reflect their quality. In our

  13. Fast automated placement of polar hydrogen atoms in protein-ligand complexes

    Directory of Open Access Journals (Sweden)

    Lippert Tobias


    Full Text Available Abstract Background Hydrogen bonds play a major role in the stabilization of protein-ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side-chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted. Results We have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein-ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach. Conclusion Our results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation.

  14. Proteochemometric modeling of the bioactivity spectra of HIV-1 protease inhibitors by introducing protein-ligand interaction fingerprint.

    Directory of Open Access Journals (Sweden)

    Qi Huang

    Full Text Available HIV-1 protease is one of the main therapeutic targets in HIV. However, a major problem in treatment of HIV is the rapid emergence of drug-resistant strains. It should be particularly helpful to clinical therapy of AIDS if one method can be used to predict antivirus capability of compounds for different variants. In our study, proteochemometric (PCM models were created to study the bioactivity spectra of 92 chemical compounds with 47 unique HIV-1 protease variants. In contrast to other PCM models, which used Multiplication of Ligands and Proteins Descriptors (MLPD as cross-term, one new cross-term, i.e. Protein-Ligand Interaction Fingerprint (PLIF was introduced in our modeling. With different combinations of ligand descriptors, protein descriptors and cross-terms, nine PCM models were obtained, and six of them achieved good predictive abilities (Q(2(test>0.7. These results showed that the performance of PCM models could be improved when ligand and protein descriptors were complemented by the newly introduced cross-term PLIF. Compared with the conventional cross-term MLPD, the newly introduced PLIF had a better predictive ability. Furthermore, our best model (GD & P & PLIF: Q(2(test = 0.8271 could select out those inhibitors which have a broad antiviral activity. As a conclusion, our study indicates that proteochemometric modeling with PLIF as cross-term is a potential useful way to solve the HIV-1 drug-resistant problem.

  15. Transfer Rate Edited experiment for the selective detection of Chemical Exchange via Saturation Transfer (TRE-CEST). (United States)

    Friedman, Joshua I; Xia, Ding; Regatte, Ravinder R; Jerschow, Alexej


    Chemical Exchange Saturation Transfer (CEST) magnetic resonance experiments have become valuable tools in magnetic resonance for the detection of low concentration solutes with far greater sensitivity than direct detection methods. Accurate measures of rates of chemical exchange provided by CEST are of particular interest to biomedical imaging communities where variations in chemical exchange can be related to subtle variations in biomarker concentration, temperature and pH within tissues using MRI. Despite their name, however, traditional CEST methods are not truly selective for chemical exchange and instead detect all forms of magnetization transfer including through-space NOE. This ambiguity crowds CEST spectra and greatly complicates subsequent data analysis. We have developed a Transfer Rate Edited CEST experiment (TRE-CEST) that uses two different types of solute labeling in order to selectively amplify signals of rapidly exchanging proton species while simultaneously suppressing 'slower' NOE-dominated magnetization transfer processes. This approach is demonstrated in the context of both NMR and MRI, where it is used to detect the labile amide protons of proteins undergoing chemical exchange (at rates⩾30s(-1)) while simultaneously eliminating signals originating from slower (∼5s(-1)) NOE-mediated magnetization transfer processes. TRE-CEST greatly expands the utility of CEST experiments in complex systems, and in-vivo, in particular, where it is expected to improve the quantification of chemical exchange and magnetization transfer rates while enabling new forms of imaging contrast.

  16. Impact of sediment-seawater cation exchange on Himalayan chemical weathering fluxes (United States)

    Lupker, Maarten; France-Lanord, Christian; Lartiges, Bruno


    Continental-scale chemical weathering budgets are commonly assessed based on the flux of dissolved elements carried by large rivers to the oceans. However, the interaction between sediments and seawater in estuaries can lead to additional cation exchange fluxes that have been very poorly constrained so far. We constrained the magnitude of cation exchange fluxes from the Ganga-Brahmaputra river system based on cation exchange capacity (CEC) measurements of riverine sediments. CEC values of sediments are variable throughout the river water column as a result of hydrological sorting of minerals with depth that control grain sizes and surface area. The average CEC of the integrated sediment load of the Ganga-Brahmaputra is estimated ca. 6.5 meq 100 g-1. The cationic charge of sediments in the river is dominated by bivalent ions Ca2+ (76 %) and Mg2+ (16 %) followed by monovalent K+ (6 %) and Na+ (2 %), and the relative proportion of these ions is constant among all samples and both rivers. Assuming a total exchange of exchangeable Ca2+ for marine Na+ yields a maximal additional Ca2+ flux of 28 × 109 mol yr-1 of calcium to the ocean, which represents an increase of ca. 6 % of the actual river dissolved Ca2+ flux. In the more likely event that only a fraction of the adsorbed riverine Ca2+ is exchanged, not only for marine Na+ but also Mg2+ and K+, estuarine cation exchange for the Ganga-Brahmaputra is responsible for an additional Ca2+ flux of 23 × 109 mol yr-1, while ca. 27 × 109 mol yr-1 of Na+, 8 × 109 mol yr-1 of Mg2+ and 4 × 109 mol yr-1 of K+ are re-absorbed in the estuaries. This represents an additional riverine Ca2+ flux to the ocean of 5 % compared to the measured dissolved flux. About 15 % of the dissolved Na+ flux, 8 % of the dissolved K+ flux and 4 % of the Mg2+ are reabsorbed by the sediments in the estuaries. The impact of estuarine sediment-seawater cation exchange appears to be limited when evaluated in the context of the long-term carbon cycle and

  17. SirX: a selective inversion recovery experiment on X-nuclei for the determination of the exchange rate of slow chemical exchanges between two sites. (United States)

    Xie, Xiulan; Bönisch, Friedrich


    Nuclear magnetic resonance spectroscopy has proven to be powerful for the study of dynamic processes. A new pulse sequence, SirX, is designed to provide boundary conditions that simplify the McConnell equations. Both an initial rate approximation and a whole curve fitting to the time course of magnetization can be used to calculate the exchange rate. These methods were used to study the exchange kinetics of N,N-dimethylacetamide. As compared with the well-established exchange spectroscopy suitable to studies of slow exchange, SirX has the advantage of being less time consuming and capable of providing more reliable kinetic data. Furthermore, by setting the observation on X-nuclei with larger chemical shift dispersion as compared with an observation on (1)H resonance, SirX extends the upper limit of a reliable determination of exchange rates.

  18. Charge Exchange Reaction in Dopant-Assisted Atmospheric Pressure Chemical Ionization and Atmospheric Pressure Photoionization. (United States)

    Vaikkinen, Anu; Kauppila, Tiina J; Kostiainen, Risto


    The efficiencies of charge exchange reaction in dopant-assisted atmospheric pressure chemical ionization (DA-APCI) and dopant-assisted atmospheric pressure photoionization (DA-APPI) mass spectrometry (MS) were compared by flow injection analysis. Fourteen individual compounds and a commercial mixture of 16 polycyclic aromatic hydrocarbons were chosen as model analytes to cover a wide range of polarities, gas-phase ionization energies, and proton affinities. Chlorobenzene was used as the dopant, and methanol/water (80/20) as the solvent. In both techniques, analytes formed the same ions (radical cations, protonated molecules, and/or fragments). However, in DA-APCI, the relative efficiency of charge exchange versus proton transfer was lower than in DA-APPI. This is suggested to be because in DA-APCI both dopant and solvent clusters can be ionized, and the formed reagent ions can react with the analytes via competing charge exchange and proton transfer reactions. In DA-APPI, on the other hand, the main reagents are dopant-derived radical cations, which favor ionization of analytes via charge exchange. The efficiency of charge exchange in both DA-APPI and DA-APCI was shown to depend heavily on the solvent flow rate, with best efficiency seen at lowest flow rates studied (0.05 and 0.1 mL/min). Both DA-APCI and DA-APPI showed the radical cation of chlorobenzene at 0.05-0.1 mL/min flow rate, but at increasing flow rate, the abundance of chlorobenzene M(+.) decreased and reagent ion populations deriving from different gas-phase chemistry were recorded. The formation of these reagent ions explains the decreasing ionization efficiency and the differences in charge exchange between the techniques. Graphical Abstract ᅟ.

  19. Towards full Quantum-Mechanics-based Protein-Ligand Binding Affinities. (United States)

    Ehrlich, Stephan; Göller, Andreas H; Grimme, Stefan


    Computational methods play a key role in modern drug design in the pharmaceutical industry but are mostly based on force fields, which are limited in accuracy when describing non-classical binding effects, proton transfer, or metal coordination. Here, we propose a general fully quantum mechanical (QM) scheme for the computation of protein-ligand affinities. It works on a single protein cutout (of about 1000 atoms) and evaluates all contributions (interaction energy, solvation, thermostatistical) to absolute binding free energy on the highest feasible QM level. The methodology is tested on two different protein targets: activated serine protease factor X (FXa) and tyrosine-protein kinase 2 (TYK2). We demonstrate that the geometry of the model systems can be efficiently energy-minimized by using general purpose graphics processing units, resulting in structures that are close to the co-crystallized protein-ligand structures. Our best calculations at a hybrid DFT level (PBEh-3c composite method) for the FXa ligand set result in an overall mean absolute deviation as low as 2.1 kcal mol(-1) . Though very encouraging, an analysis of outliers indicates that the structure optimization level, conformational sampling, and solvation treatment require further improvement.

  20. Alignment-free ultra-high-throughput comparison of druggable protein-ligand binding sites. (United States)

    Weill, Nathanaël; Rognan, Didier


    Inferring the biological function of a protein from its three-dimensional structure as well as explaining why a drug may bind to various targets is of crucial importance to modern drug discovery. Here we present a generic 4833-integer vector describing druggable protein-ligand binding sites that can be applied to any protein and any binding cavity. The fingerprint registers counts of pharmacophoric triplets from the Calpha atomic coordinates of binding-site-lining residues. Starting from a customized data set of diverse protein-ligand binding site pairs, the most appropriate metric and a similarity threshold could be defined for similar binding sites. The method (FuzCav) has been used in various scenarios: (i) screening a collection of 6000 binding sites for similarity to different queries; (ii) classifying protein families (serine endopeptidases, protein kinases) by binding site diversity; (iii) discriminating adenine-binding cavities from decoys. The fingerprint generation and comparison supports ultra-high throughput (ca. 1000 measures/s), does not require prior alignment of protein binding sites, and is able to detect local similarity among subpockets. It is thus particularly well suited to the functional annotation of novel genomic structures with low sequence identity to known X-ray templates.

  1. A microfluidic linear node array for the study of protein-ligand interactions. (United States)

    Li, Cheuk-Wing; Yu, Guodong; Jiang, Jingyun; Lee, Simon Ming-Yuen; Yi, Changqing; Yue, Wanqing; Yang, Mengsu


    We have developed a microfluidic device for the continuous separation of small molecules from a protein mixture and demonstrated its practical use in the study of protein-ligand binding, a crucial aspect in drug discovery. Our results demonstrated dose-dependent binding between bovine serum albumin (BSA) and its small-molecule site marker, Eosin Y (EY), and found that the binding reached a plateau when the BSA : EY ratio was above 1, which agreed with the eosin binding capacity of BSA reported in literature. By streamline control using a combination of two fundamental building blocks (R and L nodes) with a microdevice operated at a high flow rate (up to 1300 μL h(-1)), a solution barrier was created to "filter" off protein/protein-ligand complexes such that the small unbound molecules were isolated and quantified easily. The percentage decrease of small molecules with increasing protein concentration indicated the presence of binding events. Several fluorophores with different molecular weights were used to test the performance of the microfluidic "filter", which was tunable by 1) the total flow rate, and/or 2) the flow distribution ratio between the two device inlets; both were easily controllable by changing the syringe pump settings. Since the microdevice was operated at a relatively high flow rate, aliquots were easily recovered from the device outlets to facilitate off-chip detection. This microfluidic design is a novel and promising tool for preliminary drug screening.

  2. Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods. (United States)

    Yilmazer, Nusret Duygu; Korth, Martin


    We review the first successes and failures of a "new wave" of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of "enhanced", dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects.

  3. Challenges, applications, and recent advances of protein-ligand docking in structure-based drug design. (United States)

    Grinter, Sam Z; Zou, Xiaoqin


    The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions.

  4. Diverse, high-quality test set for the validation of protein-ligand docking performance. (United States)

    Hartshorn, Michael J; Verdonk, Marcel L; Chessari, Gianni; Brewerton, Suzanne C; Mooij, Wijnand T M; Mortenson, Paul N; Murray, Christopher W


    A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered according to the protein sequences, and clusters have been discarded if they do not represent proteins thought to be of direct interest to the pharmaceutical or agrochemical industry. Rules have been used to exclude complexes containing non-drug-like ligands. One complex from each cluster has been selected where a structure of sufficient quality was available. The final Astex diverse set contains 85 diverse, relevant protein-ligand complexes, which have been prepared in a format suitable for docking and are to be made freely available to the entire research community ( The performance of the docking program GOLD against the new set is assessed using a variety of protocols. Relatively unbiased protocols give success rates of approximately 80% for redocking into native structures, but it is possible to get success rates of over 90% with some protocols.

  5. pK(a) based protonation states and microspecies for protein-ligand docking. (United States)

    ten Brink, Tim; Exner, Thomas E


    In this paper we present our reworked approach to generate ligand protonation states with our structure preparation tool SPORES (Structure PrOtonation and REcognition System). SPORES can be used for the preprocessing of proteins and protein-ligand complexes as e.g. taken from the Protein Data Bank as well as for the setup of 3D ligand databases. It automatically assigns atom and bond types, generates different protonation, tautomeric states as well as different stereoisomers. In the revised version, pKa calculations with the ChemAxon software MARVIN are used either to determine the likeliness of a combinatorial generated protonation state or to determine the titrable atoms used in the combinatorial approach. Additionally, the MARVIN software is used to predict microspecies distributions of ligand molecules. Docking studies were performed with our recently introduced program PLANTS (Protein-Ligand ANT System) on all protomers resulting from the three different selection methods for the well established CCDC/ASTEX clean data set demonstrating the usefulness of especially the latter approach.

  6. A D3R prospective evaluation of machine learning for protein-ligand scoring (United States)

    Sunseri, Jocelyn; Ragoza, Matthew; Collins, Jasmine; Koes, David Ryan


    We assess the performance of several machine learning-based scoring methods at protein-ligand pose prediction, virtual screening, and binding affinity prediction. The methods and the manner in which they were trained make them sufficiently diverse to evaluate the utility of various strategies for training set curation and binding pose generation, but they share a novel approach to classification in the context of protein-ligand scoring. Rather than explicitly using structural data such as affinity values or information extracted from crystal binding poses for training, we instead exploit the abundance of data available from high-throughput screening to approach the problem as one of discriminating binders from non-binders. We evaluate the performance of our various scoring methods in the 2015 D3R Grand Challenge and find that although the merits of some features of our approach remain inconclusive, our scoring methods performed comparably to a state-of-the-art scoring function that was fit to binding affinity data.

  7. Challenges, Applications, and Recent Advances of Protein-Ligand Docking in Structure-Based Drug Design

    Directory of Open Access Journals (Sweden)

    Sam Z. Grinter


    Full Text Available The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions.

  8. Quantitative chemical exchange saturation transfer (qCEST) MRI--RF spillover effect-corrected omega plot for simultaneous determination of labile proton fraction ratio and exchange rate. (United States)

    Sun, Phillip Zhe; Wang, Yu; Dai, ZhuoZhi; Xiao, Gang; Wu, Renhua


    Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute proteins and peptides as well as microenvironmental properties. However, the complexity of the CEST MRI effect, which varies with the labile proton content, exchange rate and experimental conditions, underscores the need for developing quantitative CEST (qCEST) analysis. Towards this goal, it has been shown that omega plot is capable of quantifying paramagnetic CEST MRI. However, the use of the omega plot is somewhat limited for diamagnetic CEST (DIACEST) MRI because it is more susceptible to direct radio frequency (RF) saturation (spillover) owing to the relatively small chemical shift. Recently, it has been found that, for dilute DIACEST agents that undergo slow to intermediate chemical exchange, the spillover effect varies little with the labile proton ratio and exchange rate. Therefore, we postulated that the omega plot analysis can be improved if RF spillover effect could be estimated and taken into account. Specifically, simulation showed that both labile proton ratio and exchange rate derived using the spillover effect-corrected omega plot were in good agreement with simulated values. In addition, the modified omega plot was confirmed experimentally, and we showed that the derived labile proton ratio increased linearly with creatine concentration (p exchange rate (p = 0.32). In summary, our study extends the conventional omega plot for quantitative analysis of DIACEST MRI.

  9. Ceramic Heat Exchangers and Chemical Reactors with Micro-Scale Features for In-Situ Resource Processing Project (United States)

    National Aeronautics and Space Administration — It is proposed to develop compact and lightweight ceramic heat exchangers and chemical reactors suitable for high temperature processes. These devices will have...

  10. Simplified quantification of labile proton concentration-weighted chemical exchange rate (k(ws) ) with RF saturation time dependent ratiometric analysis (QUESTRA): normalization of relaxation and RF irradiation spillover effects for improved quantitative chemical exchange saturation transfer (CEST) MRI. (United States)

    Sun, Phillip Zhe


    Chemical exchange saturation transfer MRI is an emerging imaging technique capable of detecting dilute proteins/peptides and microenvironmental properties, with promising in vivo applications. However, chemical exchange saturation transfer MRI contrast is complex, varying not only with the labile proton concentration and exchange rate, but also with experimental conditions such as field strength and radiofrequency (RF) irradiation scheme. Furthermore, the optimal RF irradiation power depends on the exchange rate, which must be estimated in order to optimize the chemical exchange saturation transfer MRI experiments. Although methods including numerical fitting with modified Bloch-McConnell equations, quantification of exchange rate with RF saturation time and power (QUEST and QUESP), have been proposed to address this relationship, they require multiple-parameter non-linear fitting and accurate relaxation measurement. Our work extended the QUEST algorithm with ratiometric analysis (QUESTRA) that normalizes the magnetization transfer ratio at labile and reference frequencies, which effectively eliminates the confounding relaxation and RF spillover effects. Specifically, the QUESTRA contrast approaches its steady state mono-exponentially at a rate determined by the reverse exchange rate (k(ws) ), with little dependence on bulk water T(1) , T(2) , RF power and chemical shift. The proposed algorithm was confirmed numerically, and validated experimentally using a tissue-like phantom of serially titrated pH compartments.

  11. Design and optimization of pulsed Chemical Exchange Saturation Transfer MRI using a multiobjective genetic algorithm. (United States)

    Yoshimaru, Eriko S; Randtke, Edward A; Pagel, Mark D; Cárdenas-Rodríguez, Julio


    Pulsed Chemical Exchange Saturation Transfer (CEST) MRI experimental parameters and RF saturation pulse shapes were optimized using a multiobjective genetic algorithm. The optimization was carried out for RF saturation duty cycles of 50% and 90%, and results were compared to continuous wave saturation and Gaussian waveform. In both simulation and phantom experiments, continuous wave saturation performed the best, followed by parameters and shapes optimized by the genetic algorithm and then followed by Gaussian waveform. We have successfully demonstrated that the genetic algorithm is able to optimize pulse CEST parameters and that the results are translatable to clinical scanners.

  12. In Pursuit of Fully Flexible Protein-Ligand Docking: Modeling the Bilateral Mechanism of Binding. (United States)

    Henzler, Angela M; Rarey, Matthias


    Modern structure-based drug design aims at accounting for the intrinsic flexibility of therapeutic relevant targets. Over the last few years a considerable amount of docking approaches that encounter this challenging problem has emerged. Here we provide the readership with an overview of established methods for fully flexible protein-ligand docking and current developments in the field. All methods are based on one of two fundamental models which describe the dynamic behavior of proteins upon ligand binding. Methods for ensemble docking (ED) model the protein conformational change before the ligand is placed, whereas induced-fit docking (IFD) optimizes the protein structure afterwards. A third category of docking approaches is formed by recent approaches that follow both concepts. This categorization allows to comprehensively discover strengths and weaknesses of the individual processes and to extract information for their applicability in real world docking scenarios.

  13. Composition of Overlapping Protein-Protein and Protein-Ligand Interfaces.

    Directory of Open Access Journals (Sweden)

    Ruzianisra Mohamed

    Full Text Available Protein-protein interactions (PPIs play a major role in many biological processes and they represent an important class of targets for therapeutic intervention. However, targeting PPIs is challenging because often no convenient natural substrates are available as starting point for small-molecule design. Here, we explored the characteristics of protein interfaces in five non-redundant datasets of 174 protein-protein (PP complexes, and 161 protein-ligand (PL complexes from the ABC database, 436 PP complexes, and 196 PL complexes from the PIBASE database and a dataset of 89 PL complexes from the Timbal database. In all cases, the small molecule ligands must bind at the respective PP interface. We observed similar amino acid frequencies in all three datasets. Remarkably, also the characteristics of PP contacts and overlapping PL contacts are highly similar.

  14. WONKA: objective novel complex analysis for ensembles of protein-ligand structures. (United States)

    Bradley, A R; Wall, I D; von Delft, F; Green, D V S; Deane, C M; Marsden, B D


    WONKA is a tool for the systematic analysis of an ensemble of protein-ligand structures. It makes the identification of conserved and unusual features within such an ensemble straightforward. WONKA uses an intuitive workflow to process structural co-ordinates. Ligand and protein features are summarised and then presented within an interactive web application. WONKA's power in consolidating and summarising large amounts of data is described through the analysis of three bromodomain datasets. Furthermore, and in contrast to many current methods, WONKA relates analysis to individual ligands, from which we find unusual and erroneous binding modes. Finally the use of WONKA as an annotation tool to share observations about structures is demonstrated. WONKA is freely available to download and install locally or can be used online at

  15. Influence of Alkylammonium Acetate Buffers on Protein-Ligand Noncovalent Interactions Using Native Mass Spectrometry (United States)

    Zhuang, Xiaoyu; Gavriilidou, Agni F. M.; Zenobi, Renato


    We investigate the influence of three volatile alkylammonium acetate buffers on binding affinities for protein-ligand interactions determined by native electrospray ionization-mass spectrometry (ESI-MS). Four different types of proteins were chosen for this study. A charge-reduction effect was observed for all the cases studied, in comparison to the ions formed in ammonium acetate solution. When increasing the collision energy, the complexes of trypsin and the ligand were found to be more stable when sprayed from alkylammonium acetate buffers than from ammonium acetate. The determined dissociation constant (Kd) also exhibited a drop (up to 40%) when ammonium acetate was replaced by alkylammonium acetate buffers for the case of lysozyme and the ligand. The prospective uses of these ammonium acetate analogs in native ESI-MS are discussed in this paper as well.

  16. Thermodynamics calculation of protein-ligand interactions by QM/MM polarizable charge parameters. (United States)

    Wang, Jinan; Shao, Qiang; Cossins, Benjamin P; Shi, Jiye; Chen, Kaixian; Zhu, Weiliang


    The calculation of protein-ligand binding free energy (ΔG) is of great importance for virtual screening and drug design. Molecular dynamics (MD) simulation has been an attractive tool to investigate this scientific problem. However, the reliability of such approach is affected by many factors including electrostatic interaction calculation. Here, we present a practical protocol using quantum mechanics/molecular mechanics (QM/MM) calculations to generate polarizable QM protein charge (QMPC). The calculated QMPC of some atoms in binding pockets was obviously different from that calculated by AMBER ff03, which might significantly affect the calculated ΔG. To evaluate the effect, the MD simulations and MM/GBSA calculation with QMPC for 10 protein-ligand complexes, and the simulation results were then compared to those with the AMBER ff03 force field and experimental results. The correlation coefficient between the calculated ΔΔG using MM/GBSA under QMPC and the experimental data is .92, while that with AMBER ff03 force field is .47 for the complexes formed by streptavidin or its mutants and biotin. Moreover, the calculated ΔΔG with QMPC for the complexes formed by ERβ and five ligands is positively related to experimental result with correlation coefficient of .61, while that with AMBER ff03 charge is negatively related to experimental data with correlation coefficient of .42. The detailed analysis shows that the electrostatic polarization introduced by QMPC affects the electrostatic contribution to the binding affinity and thus, leads to better correlation with experimental data. Therefore, this approach should be useful to virtual screening and drug design.

  17. Chemical vapor transport and solid-state exchange synthesis of new copper selenite bromides (United States)

    Charkin, Dmitri O.; Kayukov, Roman A.; Zagidullin, Karim A.; Siidra, Oleg I.


    A new dimorphic copper selenite bromide, Cu5(SeO3)4Br2 was obtained via chemical transport reactions. α-Cu5(SeO3)4Br2, monoclinic (1m) and β-Cu5(SeO3)4Br2, triclinic (1a) polymorphs were produced simultaneously upon reaction of amorphous, partially dehydrated copper selenite and copper bromide. 1m is similar to Cu5(SeO3)4Cl2, whereas 1a is distantly related to Ni5(SeO3)4Br2 and Co5(SeO3)4Br2. Attempts to reproduce synthesis of 1a via exchange reaction between Na2SeO3 and CuBr2 resulted in a new Na2[Cu7O2](SeO3)4Br4 (2). Current study demonstrates for the first time, that both chemical vapor and exchange reactions can be employed in preparation of new selenite halides.

  18. Effect of chemical exchange on radiation damping in aqueous solutions of the osmolyte glycine. (United States)

    Rodríguez, Juan Carlos; Jennings, Patricia A; Melacini, Giuseppe


    Radiation damping is of central relevance in NMR spectroscopy especially with the advent of ultrahigh-field magnets and of supersensitive probes. Furthermore, the recent realization that the combined effect of the distant dipole field and of radiation damping causes the resurrection of undesired crushed water magnetization emphasizes the need for a thorough understanding of all the factors affecting radiation damping. While the effects of pulsed-field gradients and of active feedback have been extensively investigated, the consequences on radiation damping of chemical exchange between water and co-solutes is not as well understood. Here it is demonstrated that the rate of water radiation damping is significantly affected by free glycine (Gly), a representative of an important class of biocompatible osmolytes often used at molar concentrations as protein stabilizers. The pH and temperature dependencies of this effect were investigated and rationalized in terms of radiation damping attenuation caused by incoherent dephasing occurring in the intermediate exchange regime. For instance, at pH 6.0 and at a temperature of 313 K the Gly NH3+/water exchange has the same dramatic effect on radiation damping as a series of repeated weak PFGs, increasing the water inversion-recovery zero-crossing delay from approximately 30 ms to approximately 2.3 s. In addition, under these conditions, the Gly NH3+/water exchange suppresses the resurrection of unwanted crushed water magnetization. When used in combination with PFGs and water flip-back schemes, glycine is therefore expected to tame chaotic dynamics and improve the reproducibility of the NMR experiments affected by it.

  19. Study of multi-site chemical exchange in solution state by NMR: 1D experiments with multiply selective excitation

    Indian Academy of Sciences (India)

    Samanwita Pal


    Chemical exchange in solution state has been investigated traditionally by both 1D and 2D NMR, permitting the extraction of kinetic parameters (e.g. the spin-lattice relaxation time 1, the exchange rate constant and the activation parameters). This work demonstrates a simple 1D NMR approach employing multiply selective excitation to study multi-site exchange processes in solution, applying it to systems that exhibit three-site exchange. This approach involves simultaneous excitation of all - or a chosen subset of - the exchanging sites by using an appropriately modulated shaped radiofrequency pulse. The pulse sequence, as well as analysis is summarized. Significant features of the experiment, which relies on sign labelling of the exchanging sites, include considerably shorter experiment time compared to standard 2D exchange work, clear definition of the exchange time window and uniform pulse non-ideality effects for all the exchanging sites. Complete kinetic information is reported in the study of dynamic processes in superacid solutions of two weak bases, studied by 1H NMR. An analytical solution, leading to the determination of four rate parameters, is presented for proton exchange studies on these systems, which involve a mixture of two weak bases in arbitrary concentration ratio, and stoichiometric excess of the superacid.

  20. Protein-ligand binding affinity determination by the waterLOGSY method: An optimised approach considering ligand rebinding (United States)

    Huang, Renjie; Bonnichon, Arnaud; Claridge, Timothy D. W.; Leung, Ivanhoe K. H.


    WaterLOGSY is a popular ligand-observed NMR technique to screen for protein-ligand interactions, yet when applied to measure dissociation constants (KD) through ligand titration, the results were found to be strongly dependent on sample conditions. Herein, we show that accurate KDs can be obtained by waterLOGSY with optimised experimental setup.

  1. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations (United States)

    Pedro, Liliana; Van Voorhis, Wesley C.; Quinn, Ronald J.


    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase ( PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.

  2. Complementary Spectroscopic Assays for Investigating Protein-Ligand Binding Activity: A Project for the Advanced Chemistry Laboratory (United States)

    Mascotti, David P.; Waner, Mark J.


    A protein-ligand binding, guided-inquiry laboratory project with potential application across the advanced undergraduate curriculum is described. At the heart of the project are fluorescence and spectrophotometric assays utilizing biotin-4-fluorescein and streptavidin. The use of the same stock solutions for an assay that may be examined by two…

  3. Microbial, Physical and Chemical Drivers of COS and 18O-CO2 Exchange in Soils (United States)

    Meredith, L. K.; Boye, K.; Whelan, M.; Pang, E.; von Sperber, C.; Brueggemann, N.; Berry, J. A.; Welander, P. V.


    Carbonyl sulfide (COS) and the oxygen isotope composition (δ18O) of CO2 are potential tools for differentiating the contributions of photosynthesis and respiration to the balance of global carbon cycling. These processes are coupled at the leaf level via the enzyme carbonic anhydrase (CA), which hydrolyzes CO2 in the first biochemical step of the photosynthetic pathway (CO2 + H2O ⇌ HCO3- + H+) and correspondingly structural analogue COS (COS + H2O → CO2 + H2S). CA also accelerates the exchange of oxygen isotopes between CO2 and H2O leading to a distinct isotopic imprint [1]. The biogeochemical cycles of these tracers include significant, yet poorly characterized soil processes that challenge their utility for probing the carbon cycle. In soils, microbial CA also hydrolyze COS and accelerate O isotope exchange between CO2 and soil water. Soils have been observed to emit COS by undetermined processes. To account for these soil processes, measurements are needed to identify the key microbial, chemical, and physical factors. In this study, we survey COS and δ18O exchange in twenty different soils spanning a variety of biomes and soil properties. By comparing COS fluxes and δ18O-CO2 values emitted from moist soils we investigate whether the same types of CA catalyze these two processes. Additionally, we seek to identify the potential chemical drivers of COS emissions by measuring COS fluxes in dry soils. These data are compared with soil physical (bulk density, volumetric water content, texture), chemical (pH, elemental analysis, sulfate, sulfur K-edge XANES), and microbial measurements (biomass and phylogeny). Furthermore, we determine the abundance and diversity of CA-encoding genes to directly link CA with measured soil function. This work will define the best predictors for COS fluxes and δ18O-CO2 values from our suite of biogeochemical measurements. The suitability of identified predictor variables can be tested in follow-up studies and applied for modeling

  4. Dual Exchange in PCN-333: A Facile Strategy to Chemically Robust Mesoporous Chromium Metal-Organic Framework with Functional Groups. (United States)

    Park, Jihye; Feng, Dawei; Zhou, Hong-Cai


    A facile preparation of a mesoporous Cr-MOF, PCN-333(Cr) with functional group, has been demonstrated through a dual exchange strategy, involving a sequential ligand exchange and metal metathesis process. After optimization of the exchange system, the functionalized PCN-333(Cr), N3-PCN-333(Cr) shows well maintained crystallinity, porosity, as well as much improved chemical stability. Because of the exceptionally large pores (∼5.5 nm) in PCN-333(Cr), a secondary functional moiety, Zn-TEPP with a size of 18 Å × 18 Å, has been successfully clicked into the framework. In this article, we have also analyzed kinetics and thermodynamics during dual exchange process, showing our attempts to interpret the exchange event in the PCN-333. Our findings not only provide a highly stable mesoporous Cr-MOF platform for expanding MOF-based applications, but also suggest a route to functionalized Cr-MOF which may have not been achievable through conventional approaches.

  5. Ion Exchange Equilibrium and Kinetic Properties of Polyacrylate Films and Applications to Chemical Analysis and Environmental Decontamination (United States)

    Tanner, Stephen P.


    One of the goals of the original proposal was to study how cross-linking affects the properties of an ion exchange material(IEM) developed at Lewis Research Center. However, prior to the start of this work, other workers at LERC investigated the effect of cross-linking on the properties of this material. Other than variation in the ion exchange capacity, the chemical characteristics were shown to be independent of the cross-linking agent, and the degree of cross-linking. New physical forms of the film were developed (film, supported film, various sizes of beads, and powder). All showed similar properties with respect to ion exchange equilibria but the kinetics of ion exchange depended on the surface area per unit mass; the powder form of the IEM exchanging much more rapidly than the other forms. The research performed under this grant was directed towards the application of the IEM to the analysis of metal ions at environmental concentrations.

  6. Influence of Sulfolane on ESI-MS Measurements of Protein-Ligand Affinities (United States)

    Yao, Yuyu; Richards, Michele R.; Kitova, Elena N.; Klassen, John S.


    The results of an investigation into the influence of sulfolane, a commonly used supercharging agent, on electrospray ionization mass spectrometry (ESI-MS) measurements of protein-ligand affinities are described. Binding measurements carried out on four protein-carbohydrate complexes, lysozyme with β- d-GlcNAc-(1→4)-β- d-GlcNAc-(1→4)-β- d-GlcNAc-(1→4)- d-GlcNAc, a single chain variable fragment and α- d-Gal-(1→2)-[α- d-Abe-(1→3)]-α- d-Man-OCH3, cholera toxin B subunit homopentamer with β- d-Gal-(1→3)-β- d-GalNAc-(1→4)[α- d-Neu5Ac-(2→3)]-β- d-Gal-(1→4)-β- d-Glc, and a fragment of galectin 3 and α- l-Fuc-(1→2)-β- d-Gal-(1→3)-β- d-GlcNAc-(1→3)-β- d-Gal-(1→4)-β- d-Glc, revealed that sulfolane generally reduces the apparent (as measured by ESI-MS) protein-ligand affinities. To establish the origin of this effect, a detailed study was undertaken using the lysozyme-tetrasaccharide interaction as a model system. Measurements carried out using isothermal titration calorimetry (ITC), circular dichroism, and nuclear magnetic resonance spectroscopies reveal that sulfolane reduces the binding affinity in solution but does not cause any significant change in the higher order structure of lysozyme or to the intermolecular interactions. These observations confirm that changes to the structure of lysozyme in bulk solution are not responsible for the supercharging effect induced by sulfolane. Moreover, the agreement between the ESI-MS and ITC-derived affinities indicates that there is no dissociation of the complex during ESI or in the gas phase (i.e., in-source dissociation). This finding suggests that supercharging of lysozyme by sulfolane is not related to protein unfolding during the ESI process. Binding measurements performed using liquid sample desorption ESI-MS revealed that protein supercharging with sulfolane can be achieved without a reduction in affinity.

  7. Separation of selected stable isotopes by liquid-phase thermal diffusion and by chemical exchange (United States)

    Rutherford, W. M.; Jepson, B. E.; Michaels, E. D.

    Useful applications of enriched stable nuclides are unduly restricted by high cost and limited availability. Recent research on liquid phase thermal diffusion (LTD) has resulted in practical processes for separating S34, CL35, and CL37 in significant quantities (100 to 500 g/yr) at costs much lower than those associated with the electromagnetic (Calutron) process. The separation of the isotopes of bromine by LTD is now in progress and BR79 is being produced in relatively simple equivalent at a rate on the order of 0.5 g/day. The results of recent measurements show that the isotopes of Zn can be separated by LTD of zinc alkyls. The isotopes of calcium can be separated by LTD and by chemical exchange. The LTD process is based on the use of aqueous Ca(NO3)2 as a working fluid.

  8. Ultrasensitive anion detection by NMR spectroscopy: a supramolecular strategy based on modulation of chemical exchange rate. (United States)

    Perruchoud, Loïse H; Hadzovic, Alen; Zhang, Xiao-An


    NMR spectroscopy is a powerful tool for monitoring molecular interactions and is widely used to characterize supramolecular systems at the atomic level. NMR is limited for sensing purposes, however, due to low sensitivity. Dynamic processes such as conformational changes or binding events can induce drastic effects on NMR spectra in response to variations in chemical exchange (CE) rate, which can lead to new strategies in the design of supramolecular sensors through the control and monitoring of CE rate. Here, we present an indirect NMR anion sensing technique in which increased CE rate, due to anion-induced conformational flexibility of a relatively rigid structure of a novel sensor, allows ultrasensitive anion detection as low as 120 nM.

  9. Lactate Chemical Exchange Saturation Transfer (LATEST) Imaging in vivo A Biomarker for LDH Activity. (United States)

    DeBrosse, Catherine; Nanga, Ravi Prakash Reddy; Bagga, Puneet; Nath, Kavindra; Haris, Mohammad; Marincola, Francesco; Schnall, Mitchell D; Hariharan, Hari; Reddy, Ravinder


    Non-invasive imaging of lactate is of enormous significance in cancer and metabolic disorders where glycolysis dominates. Here, for the first time, we describe a chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method (LATEST), based on the exchange between lactate hydroxyl proton and bulk water protons to image lactate with high spatial resolution. We demonstrate the feasibility of imaging lactate with LATEST in lactate phantoms under physiological conditions, in a mouse model of lymphoma tumors, and in skeletal muscle of healthy human subjects pre- and post-exercise. The method is validated by measuring LATEST changes in lymphoma tumors pre- and post-infusion of pyruvate and correlating them with lactate determined from multiple quantum filtered proton magnetic resonance spectroscopy (SEL-MQC (1)H-MRS). Similarly, dynamic LATEST changes in exercising human skeletal muscle are correlated with lactate determined from SEL-MQC (1)H-MRS. The LATEST method does not involve injection of radioactive isotopes or labeled metabolites. It has over two orders of magnitude higher sensitivity compared to conventional (1)H-MRS. It is anticipated that this technique will have a wide range of applications including diagnosis and evaluation of therapeutic response of cancer, diabetes, cardiac, and musculoskeletal diseases. The advantages of LATEST over existing methods and its potential challenges are discussed.

  10. Kinetic bottlenecks to chemical exchange rates for deep-sea animals – Part 1: Oxygen

    Directory of Open Access Journals (Sweden)

    E. T. Peltzer


    Full Text Available Ocean warming will reduce dissolved oxygen concentrations which can pose challenges to marine life. Oxygen limits are traditionally reported simply as a static concentration thresholds with no temperature, pressure or flow rate dependency. Here we treat the oceanic oxygen supply potential for heterotrophic consumption as a dynamic molecular exchange problem analogous to familiar gas exchange processes at the sea surface. A combination of the purely physico-chemical oceanic properties temperature, hydrostatic pressure, and oxygen concentration defines the ability of the ocean to supply oxygen to any given animal. This general oceanic oxygen supply potential is modulated by animal specific properties such as the diffusive boundary layer thickness to define and limit maximal oxygen supply rates. Here we combine all these properties into formal, mechanistic equations defining novel oceanic properties that subsume various relevant classical oceanographic parameters to better visualize, map, comprehend, and predict the impact of ocean deoxygenation on aerobic life. By explicitly including temperature and hydrostatic pressure into our quantities, various ocean regions ranging from the cold deep-sea to warm, coastal seas can be compared. We define purely physico-chemical quantities to describe the oceanic oxygen supply potential, but also quantities that contain organism-specific properties which in a most generalized way describe general concepts and dependencies. We apply these novel quantities to example oceanic profiles around the world and find that temperature and pressure dependencies of diffusion and partial pressure create zones of greatest physical constriction on oxygen supply typically at around 1000 m depth, which coincides with oxygen concentration minimum zones. In these zones, which comprise the bulk of the world ocean, ocean warming and deoxygenation have a clear negative effect for aerobic life. In some shallow and warm waters the

  11. Influence of protonation, tautomeric, and stereoisomeric states on protein-ligand docking results. (United States)

    ten Brink, Tim; Exner, Thomas E


    In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and Recognition System). First, the most probable protonations, as defined by this rule based system, were compared to the ones stored in the well-known, manually revised CCDC/ASTEX data set. Then, to investigate the influence of the ligand protonation state on the docking results, different protonation states were created. Redocking and virtual screening experiments were conducted demonstrating that both docking programs have problems in identifying the correct protomer for each complex. Therefore, a preselection of plausible protomers or the improvement of the scoring functions concerning their ability to rank different molecules/states is needed. Additionally, ligand stereoisomers were tested for a subset of the CCDC/ASTEX set, showing similar problems regarding the ranking of these stereoisomers as the ranking of the protomers.

  12. Empirical scoring functions for advanced protein-ligand docking with PLANTS. (United States)

    Korb, Oliver; Stützle, Thomas; Exner, Thomas E


    In this paper we present two empirical scoring functions, PLANTS(CHEMPLP) and PLANTS(PLP), designed for our docking algorithm PLANTS (Protein-Ligand ANT System), which is based on ant colony optimization (ACO). They are related, regarding their functional form, to parts of already published scoring functions and force fields. The parametrization procedure described here was able to identify several parameter settings showing an excellent performance for the task of pose prediction on two test sets comprising 298 complexes in total. Up to 87% of the complexes of the Astex diverse set and 77% of the CCDC/Astex clean listnc (noncovalently bound complexes of the clean list) could be reproduced with root-mean-square deviations of less than 2 A with respect to the experimentally determined structures. A comparison with the state-of-the-art docking tool GOLD clearly shows that this is, especially for the druglike Astex diverse set, an improvement in pose prediction performance. Additionally, optimized parameter settings for the search algorithm were identified, which can be used to balance pose prediction reliability and search speed.

  13. Specific noncovalent interactions at protein-ligand interface: implications for rational drug design. (United States)

    Zhou, P; Huang, J; Tian, F


    Specific noncovalent interactions that are indicative of attractive, directional intermolecular forces have always been of key interest to medicinal chemists in their search for the "glue" that holds drugs and their targets together. With the rapid increase in the number of solved biomolecular structures as well as the performance enhancement of computer hardware and software in recent years, it is now possible to give more comprehensive insight into the geometrical characteristics and energetic landscape of certain sophisticated noncovalent interactions present at the binding interface of protein receptors and small ligands based on accumulated knowledge gaining from the combination of two quite disparate but complementary approaches: crystallographic data analysis and quantum-mechanical ab initio calculation. In this perspective, we survey massive body of published works relating to structural characterization and theoretical investigation of three kinds of strong, specific, direct, enthalpy-driven intermolecular forces, including hydrogen bond, halogen bond and salt bridge, involved in the formation of protein-ligand complex architecture in order to characterize their biological functions in conferring affinity and specificity for ligand recognition by host protein. In particular, the biomedical implications of raised knowledge are discussed with respect to potential applications in rational drug design.

  14. Cation exchange on the nanoscale: an emerging technique for new material synthesis, device fabrication, and chemical sensing. (United States)

    Rivest, Jessy B; Jain, Prashant K


    Cation exchange is an age-old technique for the chemical conversion of liquids or extended solids by place-exchanging the cations in an ionic material with a different set of cations. The technique is undergoing a major revival with the advent of high-quality nanocrystals: researchers are now able to overcome the limitations in bulk systems and fully exploit cation exchange for materials synthesis and discovery via rapid, low-temperature transformations in the solid state. In this tutorial review, we discuss cation exchange as a promising materials synthesis and discovery tool. Exchange on the nanoscale exhibits some unique attributes: rapid kinetics at room temperature (orders of magnitude faster than in the bulk) and the tuning of reactivity via control of nanocrystal size, shape, and surface faceting. These features make cation exchange a convenient tool for accessing nanocrystal compositions and morphologies for which conventional synthesis may not be established. A simple exchange reaction allows extension of nanochemistry to a larger part of the periodic table, beyond the typical gamut of II-VI, IV-VI, and III-V materials. Cation exchange transformations in nanocrystals can be topotactic and size- and shape-conserving, allowing nanocrystals synthesized by conventional methods to be used as templates for production of compositionally novel, multicomponent, or doped nanocrystals. Since phases and compositions resulting from an exchange reaction can be kinetically controlled, rather than governed by the phase diagram, nanocrystals of metastable and hitherto inaccessible compositions are attainable. Outside of materials synthesis, applications for cation exchange exist in water purification, chemical staining, and sensing. Since nanoscale cation exchange occurs rapidly at room temperature, it can be integrated with sensitive environments such as those in biological systems. Cation exchange is already allowing access to a variety of new materials and processes

  15. Label-free detection of protein-ligand interactions in real time using micromachined bulk acoustic resonators (United States)

    Zhang, Hao; Pang, Wei; Marma, Mong S.; Lee, Chuang-Yuan; Kamal-Bahl, Sanat; Kim, Eun Sok; McKenna, Charles E.


    In this paper, we present a micromachined film bulk acoustic resonator (FBAR) to detect protein-ligand interactions in real-time. The surface of the FBAR device has a thin layer of gold deposited on it to immobilize thiol-modified biotin. The resonant frequency of the biotin modified FBAR was measured to decrease by 170 ppm when exposed to streptavidin solution with a concentration of 5×10-7 M, corresponding to an added mass of 120 pg on the FBAR surface due to the biotin-streptavidin interaction. Consequently, the biotin modified FBAR can be used to observe in real time the biotin-streptavidin interaction without the use of labeling or molecular tags. The FBAR can be used in a variety of protein-ligand systems, and be designed for testing in array formats to give high throughput screening for drug discovery.

  16. A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach. (United States)

    Estrada, T; Zhang, B; Cicotti, P; Armen, R S; Taufer, M


    We present a scalable and accurate method for classifying protein-ligand binding geometries in molecular docking. Our method is a three-step process: the first step encodes the geometry of a three-dimensional (3D) ligand conformation into a single 3D point in the space; the second step builds an octree by assigning an octant identifier to every single point in the space under consideration; and the third step performs an octree-based clustering on the reduced conformation space and identifies the most dense octant. We adapt our method for MapReduce and implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in MapReduce allow screening of very large conformation spaces not approachable with traditional clustering methods. We analyze results for docking trials for 23 protein-ligand complexes for HIV protease, 21 protein-ligand complexes for Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze cross docking trials for 24 ligands, each docking into 24 protein conformations of the HIV protease, and receptor ensemble docking trials for 24 ligands, each docking in a pool of HIV protease receptors. Our method demonstrates significant improvement over energy-only scoring for the accurate identification of native ligand geometries in all these docking assessments. The advantages of our clustering approach make it attractive for complex applications in real-world drug design efforts. We demonstrate that our method is particularly useful for clustering docking results using a minimal ensemble of representative protein conformational states (receptor ensemble docking), which is now a common strategy to address protein flexibility in molecular docking.

  17. Calculating protein-ligand binding affinities with MMPBSA: Method and error analysis. (United States)

    Wang, Changhao; Nguyen, Peter H; Pham, Kevin; Huynh, Danielle; Le, Thanh-Binh Nancy; Wang, Hongli; Ren, Pengyu; Luo, Ray


    Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) methods have become widely adopted in estimating protein-ligand binding affinities due to their efficiency and high correlation with experiment. Here different computational alternatives were investigated to assess their impact to the agreement of MMPBSA calculations with experiment. Seven receptor families with both high-quality crystal structures and binding affinities were selected. First the performance of nonpolar solvation models was studied and it was found that the modern approach that separately models hydrophobic and dispersion interactions dramatically reduces RMSD's of computed relative binding affinities. The numerical setup of the Poisson-Boltzmann methods was analyzed next. The data shows that the impact of grid spacing to the quality of MMPBSA calculations is small: the numerical error at the grid spacing of 0.5 Å is already small enough to be negligible. The impact of different atomic radius sets and different molecular surface definitions was further analyzed and weak influences were found on the agreement with experiment. The influence of solute dielectric constant was also analyzed: a higher dielectric constant generally improves the overall agreement with experiment, especially for highly charged binding pockets. The data also showed that the converged simulations caused slight reduction in the agreement with experiment. Finally the direction of estimating absolute binding free energies was briefly explored. Upon correction of the binding-induced rearrangement free energy and the binding entropy lost, the errors in absolute binding affinities were also reduced dramatically when the modern nonpolar solvent model was used, although further developments were apparently necessary to further improve the MMPBSA methods. © 2016 Wiley Periodicals, Inc.

  18. Consistent two-dimensional visualization of protein-ligand complex series

    Directory of Open Access Journals (Sweden)

    Stierand Katrin


    Full Text Available Abstract Background The comparative two-dimensional graphical representation of protein-ligand complex series featuring different ligands bound to the same active site offers a quick insight in their binding mode differences. In comparison to arbitrary orientations of the residue molecules in the individual complex depictions a consistent placement improves the legibility and comparability within the series. The automatic generation of such consistent layouts offers the possibility to apply it to large data sets originating from computer-aided drug design methods. Results We developed a new approach, which automatically generates a consistent layout of interacting residues for a given series of complexes. Based on the structural three-dimensional input information, a global two-dimensional layout for all residues of the complex ensemble is computed. The algorithm incorporates the three-dimensional adjacencies of the active site residues in order to find an universally valid circular arrangement of the residues around the ligand. Subsequent to a two-dimensional ligand superimposition step, a global placement for each residue is derived from the set of already placed ligands. The method generates high-quality layouts, showing mostly overlap-free solutions with molecules which are displayed as structure diagrams providing interaction information in atomic detail. Application examples document an improved legibility compared to series of diagrams whose layouts are calculated independently from each other. Conclusions The presented method extends the field of complex series visualizations. A series of molecules binding to the same protein active site is drawn in a graphically consistent way. Compared to existing approaches these drawings substantially simplify the visual analysis of large compound series.

  19. Design of protein-ligand binding based on the molecular-mechanics energy model. (United States)

    Boas, F Edward; Harbury, Pehr B


    While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruct the coordinates of various binding sites with an average root-mean-square error of 0.61 A and to reproduce known ligand-induced side-chain conformational shifts. Within a series of 34 mutants, the calculation can always distinguish between weak (K(d)>1 mM) and tight (K(d)mechanics potential is used to redesign a ribose-binding site. Out of a search space of 2 x 10(12) sequences, the calculation selects a point mutant of the native protein as the top solution (experimental K(d)=17 microM) and the native protein as the second best solution (experimental K(d)=210 nM). The quality of the predictions depends on the accuracy of the generalized Born electrostatics model, treatment of protonation equilibria, high-resolution rotamer sampling, a final local energy minimization step, and explicit modeling of the bound, unbound, and unfolded states. The application of unmodified molecular-mechanics potentials to protein design links two fields in a mutually beneficial way. Design provides a new avenue for testing molecular-mechanics energy functions, and future improvements in these energy functions will presumably lead to more accurate design results.

  20. Exploring the composition of protein-ligand binding sites on a large scale.

    Directory of Open Access Journals (Sweden)

    Nickolay A Khazanov

    Full Text Available The residue composition of a ligand binding site determines the interactions available for diffusion-mediated ligand binding, and understanding general composition of these sites is of great importance if we are to gain insight into the functional diversity of the proteome. Many structure-based drug design methods utilize such heuristic information for improving prediction or characterization of ligand-binding sites in proteins of unknown function. The Binding MOAD database if one of the largest curated sets of protein-ligand complexes, and provides a source of diverse, high-quality data for establishing general trends of residue composition from currently available protein structures. We present an analysis of 3,295 non-redundant proteins with 9,114 non-redundant binding sites to identify residues over-represented in binding regions versus the rest of the protein surface. The Binding MOAD database delineates biologically-relevant "valid" ligands from "invalid" small-molecule ligands bound to the protein. Invalids are present in the crystallization medium and serve no known biological function. Contacts are found to differ between these classes of ligands, indicating that residue composition of biologically relevant binding sites is distinct not only from the rest of the protein surface, but also from surface regions capable of opportunistic binding of non-functional small molecules. To confirm these trends, we perform a rigorous analysis of the variation of residue propensity with respect to the size of the dataset and the content bias inherent in structure sets obtained from a large protein structure database. The optimal size of the dataset for establishing general trends of residue propensities, as well as strategies for assessing the significance of such trends, are suggested for future studies of binding-site composition.

  1. Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.

    Directory of Open Access Journals (Sweden)

    Noah Ollikainen

    Full Text Available Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein-ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i prediction of enzyme specificity altering mutations and (ii prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art "fixed backbone" design methods perform poorly on these tests, we develop a new "coupled moves" design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein-ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution.

  2. Chemical exchange saturation transfer MR imaging of Parkinson's disease at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chunmei; Peng, Shuai; Wang, Rui; Chen, Min [Beijing Hospital, Department of Radiology, Beijing (China); Chen, Haibo; Su, Wen [Beijing Hospital, Department of Neurology, Beijing (China); Zhao, Xuna [Peking University, Center for MRI Research and Beijing City Key Lab for Medical Physics and Engineering, Beijing (China); Zhou, Jinyuan [Johns Hopkins University, Department of Radiology, Baltimore, MD (United States)


    To demonstrate the feasibility of using chemical exchange saturation transfer (CEST) imaging to detect Parkinson's disease (PD) in patients at 3 Tesla. Twenty-seven PD patients (17 men and 10 women; age range, 54-77 years) and 22 age-matched normal controls (13 men and 9 women; age range, 55-73 years) were examined on a 3-Tesla MRI system. Magnetization transfer spectra with 31 different frequency offsets (-6 to 6 ppm) were acquired at two transverse slices of the head, including the basal ganglia and midbrain. One-way analysis of variance tests was used to compare the differences in CEST imaging signals between PD patients and normal controls. Total CEST signal between the offsets of 0 and 4 ppm in the substantia nigra was significantly lower in PD patients than in normal controls (P = 0.006), which could be associated with the loss of dopaminergic neurons. Protein-based CEST imaging signals at the offset of 3.5 ppm in the globus pallidus, putamen and caudate were significantly increased in PD patients, compared to normal controls (P < 0.001, P = 0.003, P < 0.001, respectively). CEST imaging signals could potentially serve as imaging biomarkers to aid in the non-invasive molecular diagnosis of PD. (orig.)

  3. Nuclear overhauser enhancement mediated chemical exchange saturation transfer imaging at 7 Tesla in glioblastoma patients.

    Directory of Open Access Journals (Sweden)

    Daniel Paech

    Full Text Available BACKGROUND AND PURPOSE: Nuclear Overhauser Enhancement (NOE mediated chemical exchange saturation transfer (CEST is a novel magnetic resonance imaging (MRI technique on the basis of saturation transfer between exchanging protons of tissue proteins and bulk water. The purpose of this study was to evaluate and compare the information provided by three dimensional NOE mediated CEST at 7 Tesla (7T and standard MRI in glioblastoma patients. PATIENTS AND METHODS: Twelve patients with newly diagnosed histologically proven glioblastoma were enrolled in this prospective ethics committee-approved study. NOE mediated CEST contrast was acquired with a modified three-dimensional gradient-echo sequence and asymmetry analysis was conducted at 3.3 ppm (B1 = 0.7 µT to calculate the magnetization transfer ratio asymmetry (MTR(asym. Contrast enhanced T1 (CE-T1 and T2-weighted images were acquired at 3T and used for data co-registration and comparison. RESULTS: Mean NOE mediated CEST signal based on MTR(asym values over all patients was significantly increased (p<0.001 in CE-T1 tumor (-1.99 ± 1.22%, tumor necrosis (-1.36 ± 1.30% and peritumoral CEST hyperintensities (PTCH within T2 edema margins (-3.56 ± 1.24% compared to contralateral normal appearing white matter (-8.38 ± 1.19%. In CE-T1 tumor (p = 0.015 and tumor necrosis (p<0.001 mean MTR(asym values were significantly higher than in PTCH. Extent of the surrounding tumor hyperintensity was smaller in eight out of 12 patients on CEST than on T2-weighted images, while four displayed at equal size. In all patients, isolated high intensity regions (0.40 ± 2.21% displayed on CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted images. CONCLUSION: NOE mediated CEST Imaging at 7 T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2

  4. Novel Chemically Stable Er3+-Yb3+ Codopded Phosphate Glass for Ion-Exchanged Active Waveguide Devices

    Institute of Scientific and Technical Information of China (English)

    陈宝玉; 赵士龙; 胡丽丽


    A novel Er3+-Yb3+ codoped phosphate glass,which combines good chemical durability with good spectroscopic properties,is developed for the ion-exchange process.The relevant properties of this glass are presented for reference in the design and modelling of ion-exchanged active waveguide devices.The weight-loss rate of this glass is 1.45 × 10-5 in boiling water,which is comparable to that of Kigre's Q-246 silicate glass.The emission cross section of Er3+ in this glass is calculated to be 0.72 × 10-20 cm2 using the McCumber theory.It is found that a planar waveguide with three modes at 632.8 nm is readily realized in this glass from our primary ion-exchange experiments.

  5. Ion Exchange Processed CdS Nanorods in Powder Form Using Cadmium Hydroxide Nanowires By Wet Chemical Route

    Directory of Open Access Journals (Sweden)

    Savita L. Patil


    Full Text Available Simple, inexpensive and soft chemical route (wet chemical method was employed for the synthesis of bulk forms of cadmium hydroxide [Cd(OH2] nanowires bundles and their conversion to cadmium sulphide [CdS] nanorods at room temperature by simple anion exchange route. Due to difference in solubility product and diffusion rates of the Cd(OH2 and CdS, the anion exchange reaction was taken place and CdS nanorods were formed. CdS nanorods were characterized by X-ray diffraction (XRD, and scanning electron microscopy (SEM, energy-dispersive X-ray (EDX analysis. Since CdS is semi-conducting material, it has variety of potential applications, this work demonstrates a cost effective method for the synthesis of CdS nanorods in bulk form like CNT.

  6. Chemical assessment of ballast water exchange compliance: Implementation in North America and New Zealand

    Directory of Open Access Journals (Sweden)

    Monaca eNoble


    Full Text Available Fluorescence by naturally occurring dissolved organic matter (FDOM is a sensitive indicator of ballast water source, with high FDOM in coastal ballast water decreasing typically dramatically when replaced by oceanic seawater during ballast water exchange. In this study, FDOM was measured in 92 ships arriving at Pacific ports on the US west coast and in New Zealand, and used to assess their compliance with ballast water regulations that required 95% replacement of port water to minimize invasive species risks. Fluorescence in many ships that reported ballast water exchange was significantly higher than is usual for oceanic seawater, and in several cases, significantly higher than in other ships with similar provenance and ballast water management. Pre-exchange source port conditions represented the largest source of uncertainty in the analysis, because residual coastal FDOM when highly fluorescent can significantly influence the fluorescence signature of exchanged ballast water. A meta-analysis comparing the intensities of FDOM in un-exchanged ballast tanks with calculated pre-exchange intensities assuming that ships all correctly implemented and reported ballast water exchange revealed notable discrepancies. Thus, the incidence of high-FDOM port waters was seven times lower in reality than would be expected on the basis of these calculations. The results suggest that a significant rate of reporting errors occur due to a combination of factors that may include inadequate ballast water exchange and unintentional or deliberate misreporting of ballast water management.

  7. Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Novel Protease Inhibitors: Design, Synthesis, Protein-Ligand X-ray Structure and Biological Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Takayama, Jun; Rao, Kalapala Venkateswar; Ratia, Kiira; Chaudhuri, Rima; Mulhearn, Debbie C.; Lee, Hyun; Nichols, Daniel B.; Baliji, Surendranath; Baker, Susan C.; Johnson, Michael E.; Mesecar, Andrew D. (Purdue); (UC); (UIC)


    The design, synthesis, X-ray crystal structure, molecular modeling, and biological evaluation of a series of new generation SARS-CoV PLpro inhibitors are described. A new lead compound 3 (6577871) was identified via high-throughput screening of a diverse chemical library. Subsequently, we carried out lead optimization and structure-activity studies to provide a series of improved inhibitors that show potent PLpro inhibition and antiviral activity against SARS-CoV infected Vero E6 cells. Interestingly, the (S)-Me inhibitor 15h (enzyme IC{sub 50} = 0.56 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) and the corresponding (R)-Me 15g (IC{sub 50} = 0.32 {mu}M; antiviral EC{sub 50} = 9.1 {mu}M) are the most potent compounds in this series, with nearly equivalent enzymatic inhibition and antiviral activity. A protein-ligand X-ray structure of 15g-bound SARS-CoV PLpro and a corresponding model of 15h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions.

  8. Improved measurement of labile proton concentration-weighted chemical exchange rate (k(ws)) with experimental factor-compensated and T(1) -normalized quantitative chemical exchange saturation transfer (CEST) MRI. (United States)

    Wu, Renhua; Liu, Charng-Ming; Liu, Philip K; Sun, Phillip Zhe


    Chemical exchange saturation transfer (CEST) MRI enables measurement of dilute CEST agents and microenvironment properties such as pH and temperature, holding great promise for in vivo applications. However, because of confounding concomitant radio frequency (RF) irradiation and relaxation effects, the CEST-weighted MRI contrast may not fully characterize the underlying CEST phenomenon. We postulated that the accuracy of quantitative CEST MRI could be improved if the experimental factors (labeling efficiency and RF spillover effect) were estimated and taken into account. Specifically, the experimental factor was evaluated as a function of exchange rate and CEST agent concentration ratio, which remained relatively constant for intermediate RF irradiation power levels. Hence, the experimental factors can be calculated based on the reasonably estimated exchange rate and labile proton concentration ratio, which significantly improved quantification. The simulation was confirmed with creatine phantoms of serially varied concentration titrated to the same pH, whose reverse exchange rate (k(ws)) was found to be linearly correlated with the concentration. In summary, the proposed solution provides simplified yet reasonably accurate quantification of the underlying CEST system, which may help guide the ongoing development of quantitative CEST MRI.

  9. Assessment of chemical exchange in tryptophan–albumin solution through {sup 19}F multicomponent transverse relaxation dispersion analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ping-Chang, E-mail: [Howard University, Department of Radiology, College of Medicine (United States)


    A number of NMR methods possess the capability of probing chemical exchange dynamics in solution. However, certain drawbacks limit the applications of these NMR approaches, particularly, to a complex system. Here, we propose a procedure that integrates the regularized nonnegative least squares (NNLS) analysis of multiexponential T{sub 2} relaxation into Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion experiments to probe chemical exchange in a multicompartmental system. The proposed procedure was validated through analysis of {sup 19}F T{sub 2} relaxation data of 6-fluoro-DL-tryptophan in a two-compartment solution with and without bovine serum albumin. Given the regularized NNLS analysis of a T{sub 2} relaxation curve acquired, for example, at the CPMG frequency υ{sub CPMG} = 125, the nature of two distinct peaks in the associated T{sub 2} distribution spectrum indicated 6-fluoro-DL-tryptophan either retaining the free state, with geometric mean */multiplicative standard deviation (MSD) = 1851.2 ms */1.51, or undergoing free/albumin-bound interconversion, with geometric mean */MSD = 236.8 ms */1.54, in the two-compartment system. Quantities of the individual tryptophan species were accurately reflected by the associated T{sub 2} peak areas, with an interconversion state-to-free state ratio of 0.45 ± 0.11. Furthermore, the CPMG relaxation dispersion analysis estimated the exchange rate between the free and albumin-bound states in this fluorinated tryptophan analog and the corresponding dissociation constant of the fluorinated tryptophan–albumin complex in the chemical-exchanging, two-compartment system.

  10. Reliable Determinations of Protein-Ligand Interactions by Direct ESI-MS Measurements. Are We There Yet? (United States)

    Kitova, Elena N.; El-Hawiet, Amr; Schnier, Paul D.; Klassen, John S.


    The association-dissociation of noncovalent interactions between protein and ligands, such as other proteins, carbohydrates, lipids, DNA, or small molecules, are critical events in many biological processes. The discovery and characterization of these interactions is essential to a complete understanding of biochemical reactions and pathways and to the design of novel therapeutic agents that may be used to treat a variety of diseases and infections. Over the last 20 y, electrospray ionization mass spectrometry (ESI-MS) has emerged as a versatile tool for the identification and quantification of protein-ligand interactions in vitro. Here, we describe the implementation of the direct ESI-MS assay for the determination of protein-ligand binding stoichiometry and affinity. Additionally, we outline common sources of error encountered with these measurements and various strategies to overcome them. Finally, we comment on some of the outstanding challenges associated with the implementation of the assay and highlight new areas where direct ESI-MS measurements are expected to make significant contributions in the future.

  11. Development of a protein-ligand-binding site prediction method based on interaction energy and sequence conservation. (United States)

    Tsujikawa, Hiroto; Sato, Kenta; Wei, Cao; Saad, Gul; Sumikoshi, Kazuya; Nakamura, Shugo; Terada, Tohru; Shimizu, Kentaro


    We present a new method for predicting protein-ligand-binding sites based on protein three-dimensional structure and amino acid conservation. This method involves calculation of the van der Waals interaction energy between a protein and many probes placed on the protein surface and subsequent clustering of the probes with low interaction energies to identify the most energetically favorable locus. In addition, it uses amino acid conservation among homologous proteins. Ligand-binding sites were predicted by combining the interaction energy and the amino acid conservation score. The performance of our prediction method was evaluated using a non-redundant dataset of 348 ligand-bound and ligand-unbound protein structure pairs, constructed by filtering entries in a ligand-binding site structure database, LigASite. Ligand-bound structure prediction (bound prediction) indicated that 74.0 % of predicted ligand-binding sites overlapped with real ligand-binding sites by over 25 % of their volume. Ligand-unbound structure prediction (unbound prediction) indicated that 73.9 % of predicted ligand-binding residues overlapped with real ligand-binding residues. The amino acid conservation score improved the average prediction accuracy by 17.0 and 17.6 points for the bound and unbound predictions, respectively. These results demonstrate the effectiveness of the combined use of the interaction energy and amino acid conservation in the ligand-binding site prediction.

  12. A Novel Ion Exchange System to Purify Mixed ISS Waste Water Brines for Chemical Production and Enhanced Water Recovery (United States)

    Lunn, Griffin; Spencer, LaShelle; Ruby, Anna-Maria; McCaskill, Andrew


    Current International Space Station water recovery regimes produce a sizable portion of waste water brine. This brine is highly toxic and water recovery is poor: a highly wasteful proposition. With new biological techniques that do not require waste water chemical pretreatment, the resulting brine would be chromium-free and nitrate rich which can allow possible fertilizer recovery for future plant systems. Using a system of ion exchange resins we can remove hardness, sulfate, phosphate and nitrate from these brines to leave only sodium and potassium chloride. At this point modern chlor-alkali cells can be utilized to produce a low salt stream as well as an acid and base stream. The first stream can be used to gain higher water recovery through recycle to the water separation stage while the last two streams can be used to regenerate the ion exchange beds used here, as well as other ion exchange beds in the ISS. Conveniently these waste products from ion exchange regeneration would be suitable as plant fertilizer. In this report we go over the performance of state of the art resins designed for high selectivity of target ions under brine conditions. Using ersatz ISS waste water we can evaluate the performance of specific resins and calculate mass balances to determine resin effectiveness and process viability. If this system is feasible then we will be one step closer to closed loop environmental control and life support systems (ECLSS) for current or future applications.

  13. Mixed IR/Vis two-dimensional spectroscopy: chemical exchange beyond the vibrational lifetime and sub-ensemble selective photochemistry. (United States)

    van Wilderen, Luuk J G W; Messmer, Andreas T; Bredenbeck, Jens


    Two-dimensional exchange spectroscopy (2D EXSY) is a powerful method to study the interconversion (chemical exchange) of molecular species in equilibrium. This method has recently been realized in femtosecond 2D-IR spectroscopy, dramatically increasing the time resolution. However, current implementations allow the EXSY signal (and therefore the chemical process of interest) only to be tracked during the lifetime (T1 ) of the observed spectroscopic transition. This is a severe limitation, as typical vibrational T1 are only a few ps. An IR/Vis pulse sequence is presented that overcomes this limit and makes the EXSY signal independent of T1 . The same pulse sequence allows to collect time-resolved IR spectra after electronic excitation of a particular chemical species in a mixture of species with strongly overlapping UV/Vis spectra. Different photoreaction pathways and dynamics of coexisting isomers or of species involved in different intermolecular interactions can thus be revealed, even if the species cannot be isolated because they are in rapid equilibrium.

  14. A computational study of the protein-ligand interactions in CDK2 inhibitors: using quantum mechanics/molecular mechanics interaction energy as a predictor of the biological activity. (United States)

    Alzate-Morales, Jans H; Contreras, Renato; Soriano, Alejandro; Tuñon, Iñaki; Silla, Estanislao


    We report a combined quantum mechanics/molecular mechanics (QM/MM) study to determine the protein-ligand interaction energy between CDK2 (cyclin-dependent kinase 2) and five inhibitors with the N(2)-substituted 6-cyclohexyl-methoxy-purine scaffold. The computational results in this work show that the QM/MM interaction energy is strongly correlated to the biological activity and can be used as a predictor, at least within a family of substrates. A detailed analysis of the protein-ligand structures obtained from molecular dynamics simulations shows specific interactions within the active site that, in some cases, have not been reported before to our knowledge. The computed interaction energy gauges the strength of protein-ligand interactions. Finally, energy decomposition and multiple regression analyses were performed to check the contribution of the electrostatic and van der Waals energies to the total interaction energy and to show the capabilities of the computational model to identify new potent inhibitors.

  15. Magnetic isotope effect and theory of atomic orbital hybridization to predict a mechanism of chemical exchange reactions. (United States)

    Epov, Vladimir N


    A novel approach is suggested to investigate the mechanisms of chemical complexation reactions based on the results of Fujii with co-workers; they have experimentally observed that several metals and metalloids demonstrate mass-independent isotope fractionation during the reactions with the DC18C6 crown ether using solvent-solvent extraction. In this manuscript, the isotope fractionation caused by the magnetic isotope effect is used to understand the mechanisms of chemical exchange reactions. Due to the rule that reactions are allowed for certain electron spin states, and forbidden for others, magnetic isotopes show chemical anomalies during these reactions. Mass-independent fractionation is suggested to take place due to the hyperfine interaction of the nuclear spin with the electron spin of the intermediate product. Moreover, the sign of the mass-independent fractionation is found to be dependent on the element and its species, which is also explained by the magnetic isotope effect. For example, highly negative mass-independent isotope fractionation of magnetic isotopes was observed for reactions of DC18C6 with SnCl(2) species and with several Ru(III) chloro-species, and highly positive for reactions of this ether with TeCl(6)(2-), and with several Cd(II) and Pd(II) species. The atomic radius of an element is also a critical parameter for the reaction with crown ether, particularly the element ions with [Kr]4d(n)5s(m) electron shell fits the best with the DC18C6 crown ring. It is demonstrated that the magnetic isotope effect in combination with the theory of orbital hybridization can help to understand the mechanism of complexation reactions. The suggested approach is also applied to explain previously published mass-independent fractionation of Hg isotopes in other types of chemical exchange reactions.

  16. Protein ligand-tethered synthetic calcium indicator for localization control and spatiotemporal calcium imaging in plant cells. (United States)

    Takaoka, Yousuke; Shigenaga, Miyuki; Imai, Masaki; Nukadzuka, Yuuki; Ishimaru, Yasuhiro; Saito, Kei; Yokoyama, Ryusuke; Nishitani, Kazuhiko; Ueda, Minoru


    In plant biology, calcium ions are involved in a variety of intriguing biological phenomena as a secondary messenger. However, most conventional calcium indicators are not applicable for plant cells because of the difficulty with their localization control in plant cells. We here introduce a method to monitor spatiotemporal Ca(2+) dynamics in living plant cells based on linking the synthetic calcium indicator Calcium Green-1 to a natural product-based protein ligand. In a proof-of-concept study using cultured BY-2 cells overexpressing the target protein for the ligand, the ligand-tethered probe accumulated in the cytosol and nucleus, and enabled real-time monitoring of the cytosolic and nucleus Ca(2+) dynamics under the physiological condition. The present strategy using ligand-tethered fluorescent sensors may be successfully applied to reveal the spatiotemporal dynamics of calcium ions in living plant cells.

  17. Lectin-like oxidized low-density lipoprotein receptor-1: protein,ligands, expression and pathophysiological significance

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiu-ping; DU Guan-hua


    Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)including its protein, ligands, expression and pathophysiological significance.Data sources Information included in this article was identified by searching of PUBMED (1997-2006) online resources using the key term LOX-1.Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected.Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed.Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.

  18. Computational biotechnology: prediction of competitive substrate inhibition of enzymes by buffer compounds with protein-ligand docking. (United States)

    Schomburg, Karen T; Ardao, Inés; Götz, Katharina; Rieckenberg, Fabian; Liese, Andreas; Zeng, An-Ping; Rarey, Matthias


    In vitro enzymatic activity highly depends on the reaction medium. One of the most important parameters is the buffer used to keep the pH stable. The buffering compound prevents a severe pH-change and therefore a possible denaturation of the enzyme. However buffer agents can also have negative effects on the enzymatic activity, such as competitive substrate inhibition. We assess this effect with a computational approach based on a protein-ligand docking method and the HYDE scoring function. Our method predicts competitive binding of the buffer compound to the active site of the enzyme. Using data from literature and new experimental data, the procedure is evaluated on nine different enzymatic reactions. The method predicts buffer-enzyme interactions and is able to score these interactions with the correct trend of enzymatic activities. Using the new method, possible buffers can be selected or discarded prior to laboratory experiments.

  19. General expressions for R1ρ relaxation for N-site chemical exchange and the special case of linear chains (United States)

    Koss, Hans; Rance, Mark; Palmer, Arthur G.


    Exploration of dynamic processes in proteins and nucleic acids by spin-locking NMR experiments has been facilitated by the development of theoretical expressions for the R1ρ relaxation rate constant covering a variety of kinetic situations. Herein, we present a generalized approximation to the chemical exchange, Rex, component of R1ρ for arbitrary kinetic schemes, assuming the presence of a dominant major site population, derived from the negative reciprocal trace of the inverse Bloch-McConnell evolution matrix. This approximation is equivalent to first-order truncation of the characteristic polynomial derived from the Bloch-McConnell evolution matrix. For three- and four-site chemical exchange, the first-order approximations are sufficient to distinguish different kinetic schemes. We also introduce an approach to calculate R1ρ for linear N-site schemes, using the matrix determinant lemma to reduce the corresponding 3N × 3N Bloch-McConnell evolution matrix to a 3 × 3 matrix. The first- and second order-expansions of the determinant of this 3 × 3 matrix are closely related to previously derived equations for two-site exchange. The second-order approximations for linear N-site schemes can be used to obtain more accurate approximations for non-linear N-site schemes, such as triangular three-site or star four-site topologies. The expressions presented herein provide powerful means for the estimation of Rex contributions for both low (CEST-limit) and high (R1ρ-limit) radiofrequency field strengths, provided that the population of one state is dominant. The general nature of the new expressions allows for consideration of complex kinetic situations in the analysis of NMR spin relaxation data.

  20. Imaging in Vivo Extracellular pH with a Single Paramagnetic Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent

    Directory of Open Access Journals (Sweden)

    Guanshu Liu


    Full Text Available The measurement of extracellular pH (pHe has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST was designed to measure tumor pHe throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb3+-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 10-o-aminoanilide (Yb-DO3A-oAA suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.

  1. Evidence of chemical exchange in recombinant Major Urinary Protein and quenching thereof upon pheromone binding

    Energy Technology Data Exchange (ETDEWEB)

    Perazzolo, Chiara, E-mail:; Verde, Mariachiara [Ecole Polytechnique Federale de Lausanne, Institut des Sciences et Ingenierie Chimiques (Switzerland); Homans, Steve W. [University of Leeds, Institute of Molecular and Cellular Biology (United Kingdom); Bodenhausen, Geoffrey [Ecole Polytechnique Federale de Lausanne, Institut des Sciences et Ingenierie Chimiques (Switzerland)


    The internal dynamics of recombinant Major Urinary Protein (rMUP) have been investigated by monitoring transverse nitrogen-15 relaxation using multiple-echo Carr-Purcell-Meiboom-Gill (CPMG) experiments. While the ligand-free protein (APO-rMUP) features extensive evidence of motions on the milliseconds time scale, the complex with 2-methoxy-3-isobutylpyrazine (HOLO-rMUP) appears to be much less mobile on this time scale. At 308 K, exchange rates k{sub ex} = 500-2000 s{sup -1} were typically observed in APO-rMUP for residues located adjacent to a {beta}-turn comprising residues 83-87. These residues occlude an entry to the binding pocket and have been proposed to be a portal for ligand entry in other members of the lipocalin family, such as the retinol binding protein and the human fatty-acid binding protein. Exchange rates and populations are largely uncorrelated, suggesting local 'breathing' motions rather than a concerted global conformational change.

  2. Structural insights, protein-ligand interactions and spectroscopic characterization of isoformononetin (United States)

    Srivastava, Anubha; Singh, Harshita; Mishra, Rashmi; Dev, Kapil; Tandon, Poonam; Maurya, Rakesh


    Isoformononetin, a methoxylated isoflavone present in medicinal plants, has non-estrogenic bone forming effect via differential mitogen-activated protein kinase (MAPK) signaling. Spectroscopic (FT-Raman, FT-IR, UV-vis and NMR spectra) and quantum chemical calculations using density functional theory (DFT) and 6-311++G(d,p) as a large basis set have been employed to study the structural and electronic properties of isoformononetin. A detailed conformational analysis is performed to determine the stability among conformers and the various possibilities of intramolecular hydrogen bonding formation. Molecular docking studies with different protein kinases were performed on isoformononetin and previously studied isoflavonoid, formononetin in order to understand their inhibitory nature and the effect of functional groups on osteogenic or osteoporosis associated proteins. It is found that the oxygen atoms of methoxy, hydroxyl groups attached to phenyl rings R1, R3 and carbonyl group attached to pyran ring R2, play a major role in binding with the protein kinases that is responsible for the osteoporosis; however, no hydrophobic interactions are observed between rings of ligand and protein. The electronic properties such as HOMO and LUMO energies were determined by time-dependent TD-DFT which predict that conformer II is a little bit more stable and chemically low reactive than conformer I of isoformononetin. To estimate the structure-activity relationship, the molecular electrostatic potential (MEP) surface map, and reactivity descriptors are calculated from the optimized geometry of the molecule. From these results, it is also found that isoformononetin is kinetically more stable, less toxic, weak electrophile and chemically less reactive than formononetin. The atoms in molecules and natural bond orbital analysis are applied for the detailed analysis of intra and intermolecular hydrogen bonding interactions.

  3. A new concept for multidimensional selection of ligand conformations (MultiSelect) and multidimensional scoring (MultiScore) of protein-ligand binding affinities

    DEFF Research Database (Denmark)

    Terp, G E; Johansen, B N; Christensen, I T


    the best candidate between different docked conformations of an inhibitor (MultiSelect) and (2) to quantify the protein-ligand binding affinity (MultiScore). By use of the docking program GOLD, 40 different inhibitors were docked into the active site of three matrix metalloproteinases (MMP's), yielding...

  4. New avenues to efficient chemical synthesis of exchange coupled hard/soft nanocomposite magnet. (United States)

    Lee, Don Keun; Cha, Hyun Gil; Kim, Young Hwan; Kim, Chang Woo; Ji, Eun Sun; Kang, Young Soo


    Nd-Fe-B ultrafine amorphous alloy particles were prepared by reaction of metal ions with borohydride in aqueous solution. Monodispersed Fe nanoparticles were synthesized under an argon atmosphere via thermal decomposition of Fe(2+)-oleate2. Exchange coupled Nd2Fe14B/Fe nanocomposite magnets have been prepared by self-assembly using surfactant. The crystal structure of the synthesized nanoparticles was identified by using X-ray powder diffraction (XRD). The size and shape of nanoparticles were obtained by transmission electron microscope (TEM). Thermogravimetry using a microbalance with magnetic field gradient positioned below the sample was used for the measurement of a thermomagnetic analysis (TMA) curve showing the downward magnetic force versus temperature.

  5. The radiolytic and chemical degradation of organic ion exchange resins under alkaline conditions: effect on radionuclide speciation

    Energy Technology Data Exchange (ETDEWEB)

    Loon, L. van; Hummel, W. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)


    The formation of water soluble organic ligands by the radiolytic and chemical degradation of several ion exchange resins was investigated under conditions close to those of the near field of a cementitious repository. The most important degradation products were characterised and their role on radionuclide speciation evaluated thoroughly. Irradiation of strong acidic cation exchange resins (Powdex PCH and Lewatite S-100) resulted in the formation of mainly sulphate and dissolved organic carbon. A small part of the carbon (10-20%) could be identified as oxalate. The identity of the remainder is unknown. Complexation studies with Cu{sup 2+} and Ni{sup 2+} showed the presence of two ligands: oxalate and ligand X. Although ligand X could not be identified, it could be characterised by its concentration, a deprotonation constant and a complexation constant for the NiX complex. The influence of oxalate and ligand X on the speciation of radionuclides is examined in detail. For oxalate no significant influence on the speciation of radionuclides is expected. The stronger complexing ligand X may exert some influence depending on its concentration and the values of other parameters. These critical parameters are discussed and limiting values are evaluated. In absence of irradiation, no evidence for the formation of ligands was found. Irradiation of strong basic anion exchange resins (Powdex PAO and Lewatite M-500) resulted in the formation of mainly ammonia, amines and dissolved organic carbon. Up to 50% of the carbon could be identified as methyl-, dimethyl- and trimethylamine. Complexation studies with Eu{sup 3+} showed that the complexing capacity under near field conditions was negligible. The speciation of cations such as Ag, Ni, Cu and Pd can be influenced by the presence of amins. The strongest amine-complexes are formed with Pd and therefore, as an example, the aqueous Pd-ammonia system is examined in great detail. (author) 30 figs., 10 tabs., refs.

  6. Modelling static and dynamic behaviour of proton exchange membrane fuel cells on the basis of electro-chemical description (United States)

    Ceraolo, M.; Miulli, C.; Pozio, A.

    A simplified dynamical model of a fuel cell of the proton exchange membrane (PEM) type, based on physical-chemical knowledge of the phenomena occurring inside the cell has been developed by the authors. The model has been implemented in the MATLAB/SIMULINK environment. Lab tests have been carried out at ENEA's laboratories; and a good agreement has been found between tests and simulations, both in static and dynamic conditions. In a previous study [M. Ceraolo, R. Giglioli, C. Miulli, A. Pozio, in: Proceedings of the 18th International Electric Fuel Cell and Hybrid Vehicle Symposium (EVS18), Berlin, 20-24 October 2001, p. 306] the basic ideas of the model, as well as its experimental validation have been published. In the present paper, the full implementation of the model is reported in detail. Moreover, a procedure for evaluating all the needed numerical parameters is presented.

  7. Bacterial spore detection and analysis using hyperpolarized (129)Xe chemical exchange saturation transfer (Hyper-CEST) NMR. (United States)

    Bai, Yubin; Wang, Yanfei; Goulian, Mark; Driks, Adam; Dmochowski, Ivan J


    Previously, we reported hyperpolarized (129)Xe chemical exchange saturation transfer (Hyper-CEST) NMR techniques for the ultrasensitive (i.e., 1 picomolar) detection of xenon host molecules known as cryptophane. Here, we demonstrate a more general role for Hyper-CEST NMR as a spectroscopic method for probing nanoporous structures, without the requirement for cryptophane or engineered xenon-binding sites. Hyper-CEST (129)Xe NMR spectroscopy was employed to detect Bacillus anthracis and Bacillus subtilis spores in solution, and interrogate the layers that comprise their structures. (129)Xe-spore samples were selectively irradiated with radiofrequency pulses; the depolarized (129)Xe returned to aqueous solution and depleted the (129)Xe-water signal, providing measurable contrast. Removal of the outermost spore layers in B. anthracis and B. subtilis (the exosporium and coat, respectively) enhanced (129)Xe exchange with the spore interior. Notably, the spores were invisible to hyperpolarized (129)Xe NMR direct detection methods, highlighting the lack of high-affinity xenon-binding sites, and the potential for extending Hyper-CEST NMR structural analysis to other biological and synthetic nanoporous structures.

  8. Chemical fractionation and speciation modelling for optimization of ion-exchange processes to recover palladium from industrial wastewater. (United States)

    Folens, K; Van Hulle, S; Vanhaecke, F; Du Laing, G


    Palladium is used in several industrial applications and, given its high intrinsic value, intense efforts are made to recover the element. In this hydrometallurgic perspective, ion-exchange (IEX) technologies are principal means. Yet, without incorporating the chemical and physical properties of the Pd present in real, plant-specific conditions, the recovery cannot reach its technical nor economic optimum. This study characterized a relevant Pd-containing waste stream of a mirror manufacturer to provide input for a speciation model, predicting the Pd speciation as a function of pH and chloride concentration. Besides the administered neutral PdCl2 form, both positively and negatively charged [PdCln](2-n) species occur depending on the chloride concentration in solution. Purolite C100 and Relite 2AS IEX resins were selected and applied in combination with other treatment steps to optimize the Pd recovery. A combination of the cation and anion exchange resins was found successful to quantitatively recover Pd. Given the fact that Pd was also primarily associated with particles, laboratory-scale experiments focused on physical removal of the Pd-containing flow were conducted, which showed that particle-bound Pd can already be removed by physical pre-treatment prior to IEX, while the ionic fraction remains fully susceptible to the IEX mechanism.

  9. Evaluating the use of a continuous approximation for model-based quantification of pulsed chemical exchange saturation transfer (CEST) (United States)

    Tee, Y. K.; Khrapitchev, A. A.; Sibson, N. R.; Payne, S. J.; Chappell, M. A.


    Many potential clinical applications of chemical exchange saturation transfer (CEST) have been studied in recent years. However, due to various limitations such as specific absorption rate guidelines and scanner hardware constraints, most of the proposed applications have yet to be translated into routine diagnostic tools. Currently, pulsed CEST which uses multiple short pulses to perform the saturation is the only viable irradiation scheme for clinical translation. However, performing quantitative model-based analysis on pulsed CEST is time consuming because it is necessary to account for the time dependent amplitude of the saturation pulses. As a result, pulsed CEST is generally treated as continuous CEST by finding its equivalent average field or power. Nevertheless, theoretical analysis and simulations reveal that the resulting magnetization is different when the different irradiation schemes are applied. In this study, the quantification of important model parameters such as the amine proton exchange rate from a pulsed CEST experiment using quantitative model-based analyses were examined. Two model-based approaches were considered - discretized and continuous approximation to the time dependent RF irradiation pulses. The results showed that the discretized method was able to fit the experimental data substantially better than its continuous counterpart, but the smaller fitted error of the former did not translate to significantly better fit for the important model parameters. For quantification of the endogenous CEST effect, such as in amide proton transfer imaging, a model-based approach using the average power equivalent saturation can thus be used in place of the discretized approximation.

  10. Kinetic bottlenecks to chemical exchange rates for deep-sea animals II: Carbon dioxide (United States)

    Hofmann, A. F.; Peltzer, E. T.; Brewer, P. G.


    Increased ocean acidification from fossil fuel CO2 invasion, from temperature-driven changes in respiration, and from possible leakage from sub-seabed geologic CO2 disposal has aroused concern over the impacts of elevated CO2 concentrations on marine life. Discussion of these impacts has so far focused only on changes in the oceanic bulk fluid properties (ΔpH, Δ[∑CO2] etc.) as the critical variable and with a major focus on carbonate shell dissolution. Here we describe the rate problem for animals that must export CO2 at about the same rate at which O2 is consumed. We analyze the basic properties controlling CO2 export within the diffusive boundary layer around marine animals in an ocean changing in temperature (T) and CO2 concentration in order to compare the challenges posed by O2 uptake under stress with the equivalent problem of CO2 expulsion. The problem is more complex than that for a non-reactive gas since, as with gas exchange of CO2 at the air-sea interface, the influence of the ensemble of reactions within the CO2-HCO3--CO32- acid-base system needs to be considered. These reactions significantly facilitate CO2 efflux compared to O2 intake at equal temperature, pressure and flow rate under typical oceanic concentrations.The effect of these reactions can be described by an enhancement factor. For organisms, this means mechanically increasing flow over their surface to thin the boundary layer as is required to alleviate O2 stress seems not necessary to facilitate CO2 efflux. Nevertheless the elevated pCO2 cost most likely is non-zero. Regionally as with O2 the combination of T, P, and pH/pCO2 creates a zone of maximum CO2 stress at around 1000 m depth. But the net result is that, for the problem of gas exchange with the bulk ocean, the combination of an increasing T combined with declining O2 poses a greater challenge to marine life than does increasing CO2. The relationships developed here allow a more accurate prediction of the impacts on marine life

  11. Assessing Soil Available Potassium by Cation Exchange Membrane and COnventional Chemical Extractions

    Institute of Scientific and Technical Information of China (English)



    Four testing methods using cation exchange membrane (CEM),ammonium acetate,ASI(0.25mol L-1 NaHCO3+0.01mol L-1 EDTA +0.01 molL-1 NH4F) and 1.0molL-1 boiling nitric acid,respectively,were used to evaluate soil available K.The soil K tested by CEM was significantly correlated with that by the other (conventional)methods(r2=0.43**-0.95***).The soil K tested by CEM saturated with NH4HCO3(15min extraction)was most closely correlated with that by the other methods(r2=0.60**-0.95***),Potassium availability,as predicted by soil test,was comparable to actual K uptake by canola and wheat grown on the soils in growth chamber.Regression analyses showed that plant K uptake was more closely correlated wiht K extracted by CEM(r2=0.56**-0.81***)than that by the conventional methods(r2=0.46***-0.81***),most colsely correlated with that by NH4HCO3-saturated CEM for 15 min (r2=0.81***).and worst correlated with that by HNO3(r2=0.45**-0.72***)

  12. D3R grand challenge 2015: Evaluation of protein-ligand pose and affinity predictions (United States)

    Gathiaka, Symon; Liu, Shuai; Chiu, Michael; Yang, Huanwang; Stuckey, Jeanne A.; Kang, You Na; Delproposto, Jim; Kubish, Ginger; Dunbar, James B.; Carlson, Heather A.; Burley, Stephen K.; Walters, W. Patrick; Amaro, Rommie E.; Feher, Victoria A.; Gilson, Michael K.


    The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challenges for both target datasets were conducted in two stages, with the first stage testing pose predictions and the capacity to rank compounds by affinity with minimal structural data; and the second stage testing methods for ranking compounds with knowledge of at least a subset of the ligand-protein poses. An additional sub-challenge provided small groups of chemically similar HSP90 compounds amenable to alchemical calculations of relative binding free energy. Unlike previous blinded Challenges, we did not provide cognate receptors or receptors prepared with hydrogens and likewise did not require a specified crystal structure to be used for pose or affinity prediction in Stage 1. Given the freedom to select from over 200 crystal structures of HSP90 in the PDB, participants employed workflows that tested not only core docking and scoring technologies, but also methods for addressing water-mediated ligand-protein interactions, binding pocket flexibility, and the optimal selection of protein structures for use in docking calculations. Nearly 40 participating groups submitted over 350 prediction sets for Grand Challenge 2015. This overview describes the datasets and the organization of the challenge components, summarizes the results across all submitted predictions, and considers broad conclusions that may be drawn from this collaborative community endeavor.

  13. Kinetic bottlenecks to chemical exchange rates for deep-sea animals II: Carbon dioxide

    Directory of Open Access Journals (Sweden)

    A. F. Hofmann


    Full Text Available Increased ocean acidification from fossil fuel CO2 invasion, from temperature-driven changes in respiration, and from possible leakage from sub-seabed geologic CO2 disposal has aroused concern over the impacts of elevated CO2 concentrations on marine life. Discussion of these impacts has so far focused only on changes in the oceanic bulk fluid properties (ΔpH, Δ[∑CO2] etc. as the critical variable and with a major focus on carbonate shell dissolution. Here we describe the rate problem for animals that must export CO2 at about the same rate at which O2 is consumed. We analyze the basic properties controlling CO2 export within the diffusive boundary layer around marine animals in an ocean changing in temperature (T and CO2 concentration in order to compare the challenges posed by O2 uptake under stress with the equivalent problem of CO2 expulsion. The problem is more complex than that for a non-reactive gas since, as with gas exchange of CO2 at the air-sea interface, the influence of the ensemble of reactions within the CO2-HCO3-CO32– acid-base system needs to be considered. These reactions significantly facilitate CO2 efflux compared to O2 intake at equal temperature, pressure and flow rate under typical oceanic concentrations.The effect of these reactions can be described by an enhancement factor. For organisms, this means mechanically increasing flow over their surface to thin the boundary layer as is required to alleviate O2 stress seems not necessary to facilitate CO2 efflux. Nevertheless the elevated pCO2 cost most likely is non-zero. Regionally as with O2 the combination of T, P, and pH/pCO2 creates a zone of maximum CO2 stress at around

  14. Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity (United States)

    Ollikainen, Noah; de Jong, René M.; Kortemme, Tanja


    Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein–ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i) prediction of enzyme specificity altering mutations and (ii) prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art “fixed backbone” design methods perform poorly on these tests, we develop a new “coupled moves” design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein – ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution. PMID:26397464

  15. Automated identification of protein-ligand interaction features using Inductive Logic Programming: a hexose binding case study

    Directory of Open Access Journals (Sweden)

    A Santos Jose C


    Full Text Available Abstract Background There is a need for automated methods to learn general features of the interactions of a ligand class with its diverse set of protein receptors. An appropriate machine learning approach is Inductive Logic Programming (ILP, which automatically generates comprehensible rules in addition to prediction. The development of ILP systems which can learn rules of the complexity required for studies on protein structure remains a challenge. In this work we use a new ILP system, ProGolem, and demonstrate its performance on learning features of hexose-protein interactions. Results The rules induced by ProGolem detect interactions mediated by aromatics and by planar-polar residues, in addition to less common features such as the aromatic sandwich. The rules also reveal a previously unreported dependency for residues cys and leu. They also specify interactions involving aromatic and hydrogen bonding residues. This paper shows that Inductive Logic Programming implemented in ProGolem can derive rules giving structural features of protein/ligand interactions. Several of these rules are consistent with descriptions in the literature. Conclusions In addition to confirming literature results, ProGolem’s model has a 10-fold cross-validated predictive accuracy that is superior, at the 95% confidence level, to another ILP system previously used to study protein/hexose interactions and is comparable with state-of-the-art statistical learners.

  16. ABS-Scan: In silico alanine scanning mutagenesis for binding site residues in protein-ligand complex. (United States)

    Anand, Praveen; Nagarajan, Deepesh; Mukherjee, Sumanta; Chandra, Nagasuma


    Most physiological processes in living systems are fundamentally regulated by protein-ligand interactions. Understanding the process of ligand recognition by proteins is a vital activity in molecular biology and biochemistry. It is well known that the residues present at the binding site of the protein form pockets that provide a conducive environment for recognition of specific ligands. In many cases, the boundaries of these sites are not well defined. Here, we provide a web-server to systematically evaluate important residues in the binding site of the protein that contribute towards the ligand recognition through in silico alanine-scanning mutagenesis experiments. Each of the residues present at the binding site is computationally mutated to alanine. The ligand interaction energy is computed for each mutant and the corresponding ΔΔG values are calculated by comparing it to the wild type protein, thus evaluating individual residue contributions towards ligand interaction. The server will thus provide a ranked list of residues to the user in order to obtain loss-of-function mutations. This web-tool can be freely accessed through the following address:

  17. Quantitative chemical exchange saturation transfer (qCEST) MRI - omega plot analysis of RF-spillover-corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate. (United States)

    Wu, Renhua; Xiao, Gang; Zhou, Iris Yuwen; Ran, Chongzhao; Sun, Phillip Zhe


    Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST-weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P exchange rate followed a dominantly base-catalyzed exchange relationship (P exchange rate in a relatively complex in vitro CEST system.

  18. Chemical-Specific Representation of Air-Soil Exchange and Soil Penetration in Regional Multimedia Models

    Energy Technology Data Exchange (ETDEWEB)

    McKone, T.E.; Bennett, D.H.


    In multimedia mass-balance models, the soil compartment is an important sink as well as a conduit for transfers to vegetation and shallow groundwater. Here a novel approach for constructing soil transport algorithms for multimedia fate models is developed and evaluated. The resulting algorithms account for diffusion in gas and liquid components; advection in gas, liquid, or solid phases; and multiple transformation processes. They also provide an explicit quantification of the characteristic soil penetration depth. We construct a compartment model using three and four soil layers to replicate with high reliability the flux and mass distribution obtained from the exact analytical solution describing the transient dispersion, advection, and transformation of chemicals in soil with fixed properties and boundary conditions. Unlike the analytical solution, which requires fixed boundary conditions, the soil compartment algorithms can be dynamically linked to other compartments (air, vegetation, ground water, surface water) in multimedia fate models. We demonstrate and evaluate the performance of the algorithms in a model with applications to benzene, benzo(a)pyrene, MTBE, TCDD, and tritium.

  19. Predicting Electrophoretic Mobility of Protein-Ligand Complexes for Ligands from DNA-Encoded Libraries of Small Molecules. (United States)

    Bao, Jiayin; Krylova, Svetlana M; Cherney, Leonid T; Hale, Robert L; Belyanskaya, Svetlana L; Chiu, Cynthia H; Shaginian, Alex; Arico-Muendel, Christopher C; Krylov, Sergey N


    Selection of target-binding ligands from DNA-encoded libraries of small molecules (DELSMs) is a rapidly developing approach in drug-lead discovery. Methods of kinetic capillary electrophoresis (KCE) may facilitate highly efficient homogeneous selection of ligands from DELSMs. However, KCE methods require accurate prediction of electrophoretic mobilities of protein-ligand complexes. Such prediction, in turn, requires a theory that would be applicable to DNA tags of different structures used in different DELSMs. Here we present such a theory. It utilizes a model of a globular protein connected, through a single point (small molecule), to a linear DNA tag containing a combination of alternating double-stranded and single-stranded DNA (dsDNA and ssDNA) regions of varying lengths. The theory links the unknown electrophoretic mobility of protein-DNA complex with experimentally determined electrophoretic mobilities of the protein and DNA. Mobility prediction was initially tested by using a protein interacting with 18 ligands of various combinations of dsDNA and ssDNA regions, which mimicked different DELSMs. For all studied ligands, deviation of the predicted mobility from the experimentally determined value was within 11%. Finally, the prediction was tested for two proteins and two ligands with a DNA tag identical to those of DELSM manufactured by GlaxoSmithKline. Deviation between the predicted and experimentally determined mobilities did not exceed 5%. These results confirm the accuracy and robustness of our model, which makes KCE methods one step closer to their practical use in selection of drug leads, and diagnostic probes from DELSMs.

  20. Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders (United States)

    DeBrosse, Catherine; Nanga, Ravi Prakash Reddy; Wilson, Neil; D’Aquilla, Kevin; Elliott, Mark; Yan, Felicia; Wade, Kristin; Nguyen, Sara; Worsley, Diana; Parris-Skeete, Chevonne; McCormick, Elizabeth; Xiao, Rui; Cunningham, Zuela Zolkipli; Fishbein, Lauren; Nathanson, Katherine L.; Lynch, David R.; Stallings, Virginia A.; Yudkoff, Marc; Falk, Marni J.; Reddy, Ravinder; McCormack, Shana E.


    Systemic mitochondrial energy deficiency is implicated in the pathophysiology of many age-related human diseases. Currently available tools to estimate mitochondrial oxidative phosphorylation (OXPHOS) capacity in skeletal muscle in vivo lack high anatomic resolution. Muscle groups vary with respect to their contractile and metabolic properties. Therefore, muscle group–specific estimates of OXPHOS would be advantageous. To address this need, a noninvasive creatine chemical exchange saturation transfer (CrCEST) MRI technique has recently been developed, which provides a measure of free creatine. After exercise, skeletal muscle can be imaged with CrCEST in order to make muscle group–specific measurements of OXPHOS capacity, reflected in the recovery rate (τCr) of free Cr. In this study, we found that individuals with genetic mitochondrial diseases had significantly (P = 0.026) prolonged postexercise τCr in the medial gastrocnemius muscle, suggestive of less OXPHOS capacity. Additionally, we observed that lower resting CrCEST was associated with prolonged τPCr, with a Pearson’s correlation coefficient of –0.42 (P = 0.046), consistent with previous hypotheses predicting that resting creatine levels may correlate with 31P magnetic resonance spectroscopy–based estimates of OXPHOS capacity. We conclude that CrCEST can noninvasively detect changes in muscle creatine content and OXPHOS capacity, with high anatomic resolution, in individuals with mitochondrial disorders. PMID:27812541

  1. Eu(III) complexes as anion-responsive luminescent sensors and paramagnetic chemical exchange saturation transfer agents. (United States)

    Hammell, Jacob; Buttarazzi, Leandro; Huang, Ching-Hui; Morrow, Janet R


    The Eu(III) complex of (1S,4S,7S,10S)-1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (S-THP) is studied as a sensor for biologically relevant anions. Anion interactions produce changes in the luminescence emission spectrum of the Eu(III) complex, in the (1)H NMR spectrum, and correspondingly, in the PARACEST spectrum of the complex (PARACEST = paramagnetic chemical exchange saturation transfer). Direct excitation spectroscopy and luminescence lifetime studies of Eu(S-THP) give information about the speciation and nature of anion interactions including carbonate, acetate, lactate, citrate, phosphate, and methylphosphate at pH 7.2. Data is consistent with the formation of both innersphere and outersphere complexes of Eu(S-THP) with acetate, lactate, and carbonate. These anions have weak dissociation constants that range from 19 to 38 mM. Citrate binding to Eu(S-THP) is predominantly innersphere with a dissociation constant of 17 μM. Luminescence emission peak changes upon addition of anion to Eu(S-THP) show that there are two distinct binding events for phosphate and methylphosphate with dissociation constants of 0.3 mM and 3.0 mM for phosphate and 0.6 mM and 9.8 mM for methyl phosphate. Eu(THPC) contains an appended carbostyril derivative as an antenna to sensitize Eu(III) luminescence. Eu(THPC) binds phosphate and citrate with dissociation constants that are 10-fold less than that of the Eu(S-THP) parent, suggesting that functionalization through a pendent group disrupts the anion binding site. Eu(S-THP) functions as an anion responsive PARACEST agent through exchange of the alcohol protons with bulk water. The alcohol proton resonances of Eu(S-THP) shift downfield in the presence of acetate, lactate, citrate, and methylphosphate, giving rise to distinct PARACEST peaks. In contrast, phosphate binds to Eu(S-THP) to suppress the PARACEST alcohol OH peak and carbonate does not markedly change the alcohol peak at 5 mM Eu(S-THP), 15 mM carbonate at p

  2. A Potential Magnetic Resonance Imaging Technique Based on Chemical Exchange Saturation Transfer for In Vivo γ-Aminobutyric Acid Imaging (United States)

    Yan, Gen; Zhang, Tao; Dai, Zhuozhi; Yi, Meizhi; Jia, Yanlong; Nie, Tingting; Zhang, Handi; Xiao, Gang; Wu, Renhua


    Purpose We developed a novel magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer (CEST) for GABA imaging and investigated the concentration-dependent CEST effect ofGABA in a rat model of brain tumor with blood—brain barrier (BBB) disruption. Materials and Methods All MRI studies were performed using a 7.0-T Agilent MRI scanner. Z-spectra for GABA were acquired at 7.0 T, 37°C, and a pH of 7.0 using varying B1 amplitudes. CEST images of phantoms with different concentrations of GABA solutions (pH, 7.0) and other metabolites (glutamine, myoinositol, creatinine, and choline) were collected to investigate the concentration-dependent CEST effect of GABA and the potential contribution from other brain metabolites. CEST maps for GABA in rat brains with tumors were collected at baseline and 50 min, 1.5 h, and 2.0 h after the injection of GABA solution. Results The CEST effect of GABA was observed at approximately 2.75 parts per million(ppm) downfield from bulk water, and this effect increased with an increase in the B1 amplitude and remained steady after the B1 amplitude reached 6.0 μT (255 Hz). The CEST effect of GABA was proportional to the GABA concentration in vitro. CEST imaging of GABA in a rat brain with a tumor and compromised BBB showed a gradual increase in the CEST effect after GABA injection. Conclusion The findings of this study demonstrate the feasibility and potential of CEST MRI with the optimal B1 amplitude, which exhibits excellent spatial and temporal resolutions, to map changes in GABA. PMID:27711138

  3. Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results

    Energy Technology Data Exchange (ETDEWEB)

    Schleich, Christoph; Mueller-Lutz, Anja; Zimmermann, Lisa; Boos, Johannes; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk [Department of Diagnostic and Interventional Radiology, University Dusseldorf, Medical Faculty, Dusseldorf (Germany); Schmitt, Benjamin [Siemens Ltd. Australia, Healthcare Sector, Macquarie Park, NSW (Australia)


    To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. Forty-two cervical intervertebral discs of seven healthy volunteers (four females, three males; mean age: 21.4 ± 1.4 years; range: 19-24 years) were examined at a 3T MRI scanner in this prospective study. The MRI protocol comprised standard morphological, sagittal T2 weighted (T2w) images to assess the magnetic resonance imaging (MRI) based grading system for cervical intervertebral disc degeneration (IVD) and biochemical imaging with gagCEST to calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). GagCEST of cervical IVDs was technically successful at 3T with significant higher gagCEST values in NP compared to AF (1.17 % ± 1.03 % vs. 0.79 % ± 1.75 %; p = 0.005). We found topological differences of gagCEST values of the cervical spine with significant higher gagCEST effects in lower IVDs (r = 1; p = 0). We could demonstrate a significant, negative correlation between gagCEST values and cervical disc degeneration of NP (r = -0.360; p = 0.019). Non-degenerated IVDs had significantly higher gagCEST effects compared to degenerated IVDs in NP (1.76 % ± 0.92 % vs. 0.52 % ± 1.17 %; p < 0.001). Biochemical imaging of cervical IVDs is feasible at 3T. GagCEST analysis demonstrated a topological GAG distribution of the cervical spine. The depletion of GAG in the NP with increasing level of morphological degeneration can be assessed using gagCEST imaging. (orig.)

  4. Chemical exchange saturation transfer (CEST) MR technique for in-vivo liver imaging at 3.0 tesla

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shu-Zhong; Deng, Min; Wang, Yi-Xiang J. [Chinese University of Hong Kong, Prince of Wales Hospital, Department of Imaging and Interventional Radiology, Faculty of Medicine (China); Yuan, Jing [Hong Kong Sanatorium and Hospital, Medical Physics and Research Department, Happy Valley, Hong Kong (China); Wei, Juan [Philips Healthcare Asia, Shanghai (China); Zhou, Jinyuan [Johns Hopkins University, Department of Radiology, Baltimore, MD (United States); Kennedy Krieger Institute, F.M. Kirby Research Center for Functional Brain Imaging, Baltimore, MD (United States)


    To evaluate Chemical Exchange Saturation Transfer (CEST) MRI for liver imaging at 3.0-T. Images were acquired at offsets (n = 41, increment = 0.25 ppm) from -5 to 5 ppm using a TSE sequence with a continuous rectangular saturation pulse. Amide proton transfer-weighted (APTw) and GlycoCEST signals were quantified as the asymmetric magnetization transfer ratio (MTR{sub asym}) at 3.5 ppm and the total MTR{sub asym} integrated from 0.5 to 1.5 ppm, respectively, from the corrected Z-spectrum. Reproducibility was assessed for rats and humans. Eight rats were devoid of chow for 24 hours and scanned before and after fasting. Eleven rats were scanned before and after one-time CCl4 intoxication. For reproducibility, rat liver APTw and GlycoCEST measurements had 95 % limits of agreement of -1.49 % to 1.28 % and -0.317 % to 0.345 %. Human liver APTw and GlycoCEST measurements had 95 % limits of agreement of -0.842 % to 0.899 % and -0.344 % to 0.164 %. After 24 hours, fasting rat liver APTw and GlycoCEST signals decreased from 2.38 ± 0.86 % to 0.67 ± 1.12 % and from 0.34 ± 0.26 % to -0.18 ± 0.37 % respectively (p < 0.05). After CCl4 intoxication rat liver APTw and GlycoCEST signals decreased from 2.46 ± 0.48 % to 1.10 ± 0.77 %, and from 0.34 ± 0.23 % to -0.16 ± 0.51 % respectively (p < 0.05). CEST liver imaging at 3.0-T showed high sensitivity for fasting as well as CCl4 intoxication. (orig.)

  5. Balanced Steady-State Free Precession (bSSFP) from an effective field perspective: Application to the detection of chemical exchange (bSSFPX) (United States)

    Zhang, Shu; Liu, Zheng; Grant, Aaron; Keupp, Jochen; Lenkinski, Robert E.; Vinogradov, Elena


    Chemical exchange saturation transfer (CEST) is a novel contrast mechanism and it is gaining increasing popularity as many promising applications have been proposed and investigated. Fast and quantitative CEST imaging techniques are further needed in order to increase the applicability of CEST for clinical use as well as to derive quantitative physiological and biological information. Steady-state methods for fast CEST imaging have been reported recently. Here, we observe that an extreme case of these methods is a balanced steady-state free precession (bSSFP) sequence. The bSSFP in itself is sensitive to the exchange processes; hence, no additional saturation or preparation is needed for CEST-like data acquisition. The bSSFP experiment can be regarded as observation during saturation, without separate saturation and acquisition modules as used in standard CEST and similar experiments. One of the differences from standard CEST methods is that the bSSFP spectrum is an XY-spectrum not a Z-spectrum. As the first proof-of-principle step, we have implemented the steady-state bSSFP sequence for chemical exchange detection (bSSFPX) and verified its feasibility in phantom studies. These studies have shown that bSSFPX can achieve exchange-mediated contrast comparable to the standard CEST experiment. Therefore, the bSSFPX method has a potential for fast and quantitative CEST data acquisition.

  6. Electrical conductivity and oxygen exchange kinetics of La2NiO4+delta thin films grown by chemical vapor deposition

    DEFF Research Database (Denmark)

    Garcia, G.; Burriel, M.; Bonanos, Nikolaos


    Epitaxial c-axis oriented La2NiO4+delta films were deposited onto SrTiO3 and NdGaO3 substrates by the pulsed injection metal organic chemical vapor deposition technique. Experimental conditions were optimized in order to accurately control the composition, thickness, and texture of the layers. X...... by the electrical conductivity relaxation technique, from which the surface exchange coefficient was determined. (C) 2008 The Electrochemical Society....

  7. The role of a novel protein ligand hMSH 2 in Vγ9δ2 T cell-mediated anti-cervix cancer immunity

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the role of hMSH2,a novel endogenous tumor-associated protein ligand recognized by Vγ9δ2 T cells,in innate anti-cervix cancer immunity.Methods hMSH2 that expressed on the surface of cervical cancer cell line HeLa cells was blocked by specific antibody.Then the differences in their effects on Vγ9δ2T cells before and after antibody blockage were evaluated by cytotoxicity of Vγ9δ2 T cells and cytokines secretion.

  8. Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI. (United States)

    Tietze, Anna; Blicher, Jakob; Mikkelsen, Irene Klaerke; Østergaard, Leif; Strother, Megan K; Smith, Seth A; Donahue, Manus J


    Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton transfer (APT) MRI has shown promise in animal studies for the prediction of infarction risk in ischemic tissue. Here, APT MRI was translated to patients with acute stroke (1-24 h post-symptom onset), and assessments of APT contrast, perfusion, diffusion, disability and final infarct volume (23-92 days post-stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute onset of symptoms (0-4 h, n = 7; uncertain onset diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery (FLAIR) and CEST. Traditional asymmetry and a Lorentzian-based APT index were calculated in the infarct core, at-risk tissue (time-to-peak, TTP; lengthening) and final infarct volume. On average (mean ± standard deviation), control white matter APT values (asymmetry, 0.019 ± 0.005; Lorentzian, 0.045 ± 0.006) were not significantly different (p > 0.05) from APT values in normal-appearing white matter (NAWM) of patients (asymmetry, 0.022 ± 0.003; Lorentzian, 0.048 ± 0.003); however, ischemic regions in patients showed reduced (p = 0.03) APT effects compared with NAWM. Representative cases are presented, whereby the APT contrast is compared quantitatively with contrast from other imaging modalities. The findings vary between patients; in some patients, a trend for a reduction in the APT signal in the final infarct region compared with at-risk tissue was observed, consistent with tissue acidosis. However, in other patients, no relationship was observed in the infarct core and final infarct volume. Larger clinical studies, in combination with focused efforts on sequence development at clinically available field strengths (e.g. 3.0 T), are necessary to fully understand the potential of APT imaging for guiding the hyperacute management of patients.

  9. Combined quantum mechanics/molecular mechanics (QM/MM) simulations for protein-ligand complexes: free energies of binding of water molecules in influenza neuraminidase. (United States)

    Woods, Christopher J; Shaw, Katherine E; Mulholland, Adrian J


    The applicability of combined quantum mechanics/molecular mechanics (QM/MM) methods for the calculation of absolute binding free energies of conserved water molecules in protein/ligand complexes is demonstrated. Here, we apply QM/MM Monte Carlo simulations to investigate binding of water molecules to influenza neuraminidase. We investigate five different complexes, including those with the drugs oseltamivir and peramivir. We investigate water molecules in two different environments, one more hydrophobic and one hydrophilic. We calculate the free-energy change for perturbation of a QM to MM representation of the bound water molecule. The calculations are performed at the BLYP/aVDZ (QM) and TIP4P (MM) levels of theory, which we have previously demonstrated to be consistent with one another for QM/MM modeling. The results show that the QM to MM perturbation is significant in both environments (greater than 1 kcal mol(-1)) and larger in the more hydrophilic site. Comparison with the same perturbation in bulk water shows that this makes a contribution to binding. The results quantify how electronic polarization differences in different environments affect binding affinity and also demonstrate that extensive, converged QM/MM free-energy simulations, with good levels of QM theory, are now practical for protein/ligand complexes.

  10. Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations. (United States)

    Wang, Bo; Li, Liwei; Hurley, Thomas D; Meroueh, Samy O


    End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal·mol(-1) highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10), but larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the nonpolar and entropy components, rather than a better representation of the electrostatics. The SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal-mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo, and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by prescoring

  11. A general approach for developing system-specific functions to score protein-ligand docked complexes using support vector inductive logic programming. (United States)

    Amini, Ata; Shrimpton, Paul J; Muggleton, Stephen H; Sternberg, Michael J E


    Despite the increased recent use of protein-ligand and protein-protein docking in the drug discovery process due to the increases in computational power, the difficulty of accurately ranking the binding affinities of a series of ligands or a series of proteins docked to a protein receptor remains largely unsolved. This problem is of major concern in lead optimization procedures and has lead to the development of scoring functions tailored to rank the binding affinities of a series of ligands to a specific system. However, such methods can take a long time to develop and their transferability to other systems remains open to question. Here we demonstrate that given a suitable amount of background information a new approach using support vector inductive logic programming (SVILP) can be used to produce system-specific scoring functions. Inductive logic programming (ILP) learns logic-based rules for a given dataset that can be used to describe properties of each member of the set in a qualitative manner. By combining ILP with support vector machine regression, a quantitative set of rules can be obtained. SVILP has previously been used in a biological context to examine datasets containing a series of singular molecular structures and properties. Here we describe the use of SVILP to produce binding affinity predictions of a series of ligands to a particular protein. We also for the first time examine the applicability of SVILP techniques to datasets consisting of protein-ligand complexes. Our results show that SVILP performs comparably with other state-of-the-art methods on five protein-ligand systems as judged by similar cross-validated squares of their correlation coefficients. A McNemar test comparing SVILP to CoMFA and CoMSIA across the five systems indicates our method to be significantly better on one occasion. The ability to graphically display and understand the SVILP-produced rules is demonstrated and this feature of ILP can be used to derive hypothesis for

  12. High-throughput calculation of protein-ligand binding affinities: modification and adaptation of the MM-PBSA protocol to enterprise grid computing. (United States)

    Brown, Scott P; Muchmore, Steven W


    We have developed a system for performing computations on an enterprise grid using a freely available package for grid computing that allows us to harvest unused CPU cycles off of employee desktop computers. By modifying the traditional formulation of Molecular Mechanics with Poisson-Boltzmann Surface Area (MM-PBSA) methodology, in combination with a coarse-grain parallelized implementation suitable for deployment onto our enterprise grid, we show that it is possible to produce rapid physics-based estimates of protein-ligand binding affinities that have good correlation to experimental data. This is demonstrated by examining the correlation of our calculated binding affinities to experimental data and also by comparison to the correlation obtained from the binding-affinity calculations using traditional MM-PBSA that are reported in the literature.

  13. Optimization and application of atmospheric pressure chemical and photoionization hydrogen-deuterium exchange mass spectrometry for speciation of oxygen-containing compounds. (United States)

    Acter, Thamina; Kim, Donghwi; Ahmed, Arif; Jin, Jang Mi; Yim, Un Hyuk; Shim, Won Joon; Kim, Young Hwan; Kim, Sunghwan


    This paper presents a detailed investigation of the feasibility of optimized positive and negative atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) and atmospheric pressure photoionization (APPI) MS coupled to hydrogen-deuterium exchange (HDX) for structural assignment of diverse oxygen-containing compounds. The important parameters for optimization of HDX MS were characterized. The optimized techniques employed in the positive and negative modes showed satisfactory HDX product ions for the model compounds when dichloromethane and toluene were employed as a co-solvent in APCI- and APPI-HDX, respectively. The evaluation of the mass spectra obtained from 38 oxygen-containing compounds demonstrated that the extent of the HDX of the ions was structure-dependent. The combination of information provided by different ionization techniques could be used for better speciation of oxygen-containing compounds. For example, (+) APPI-HDX is sensitive to compounds with alcohol, ketone, or aldehyde substituents, while (-) APPI-HDX is sensitive to compounds with carboxylic functional groups. In addition, the compounds with alcohol can be distinguished from other compounds by the presence of exchanged peaks. The combined information was applied to study chemical compositions of degraded oils. The HDX pattern, double bond equivalent (DBE) distribution, and previously reported oxidation products were combined to predict structures of the compounds produced from oxidation of oil. Overall, this study shows that APCI- and APPI-HDX MS are useful experimental techniques that can be applied for the structural analysis of oxygen-containing compounds.

  14. Nonfitting protein-ligand interaction scoring function based on first-principles theoretical chemistry methods: development and application on kinase inhibitors. (United States)

    Rao, Li; Zhang, Igor Ying; Guo, Wenping; Feng, Li; Meggers, Eric; Xu, Xin


    Targeted therapy is currently a hot topic in the fields of cancer research and drug design. An important requirement for this approach is the development of potent and selective inhibitors for the identified target protein. However, current ways to estimate inhibitor efficacy rely on empirical protein-ligand interaction scoring functions which, suffering from their heavy parameterizations, often lead to a low accuracy. In this work, we develop a nonfitting scoring function, which consists of three terms: (1) gas-phase protein-ligand binding enthalpy obtained by the eXtended ONIOM hybrid method based on an integration of density functional theory (DFT) methods (XYG3 and ωB97X-D) and the semiempirical PM6 method, (2) solvation free energy based on DFT-SMD solvation model, and (3) entropy effect estimated by using DFT frequency analysis. The new scoring function is tested on a cyclin-dependent kinase 2 (CDK2) inhibitor database including 76 CDK2 protein inhibitors and a p21-activated kinase 1 (PAK1) inhibitor database including 20 organometallic PAK1 protein inhibitors. From the results, good correlations are found between the calculated scores and the experimental inhibitor efficacies with the square of correlation coefficient R(2) of 0.76-0.88. This suggests a good predictive power of this scoring function. To the best of our knowledge, this is the first high level theory-based nonfitting scoring function with such a good level of performance. This scoring function is recommended to be used in the final screening of lead structure derivatives.

  15. Effect of resin charged functional group, porosity, and chemical matrix on the long-term pharmaceutical removal mechanism by conventional ion exchange resins. (United States)

    Wang, Wei; Li, Xiaofeng; Yuan, Shengliu; Sun, Jian; Zheng, Shaokui


    This study attempted to clarify the long-term pharmaceutical removal mechanism from sewage treatment plant effluent during the cyclical adsorption-regeneration operation of 5 commercial resin-based fixed-bed reactors with the simultaneous occurrence of electrostatic interactions and complex non-electrostatic interactions. It examined 12 pharmaceuticals belonging to 10 therapeutic classes with different predominant existing forms and hydrophobicities. Furthermore, the effect of the resin charged functional group (strong-base vs. strong-acid vs. non-ionic), porosity (macroporous vs. gel), and chemical matrix (polystyrenic vs. polyacrylic) on the mechanism was investigated to optimize resin properties and achieve higher pharmaceutical removal. The results reported herein indicate the importance of non-electrostatic interactions between pharmaceuticals and the resin backbone during short-term cyclical operation (i.e., the 1st adsorption-regeneration cycle). With the development of cyclical operation, however, non-electrostatic interaction-induced pharmaceutical removal generally decreased and even disappeared when equilibrium was achieved between the influent and the resin. Despite pharmaceutical therapeutic class or hydrophilicity, anion (or cation) exchange resin preferentially removed those pharmaceuticals that were predominantly present as organic anions (or cations) by ion exchange process during long-term cyclical operation (i.e., ≥6 adsorption-regeneration cycles). Besides pharmaceuticals predominantly present as undissociated molecules, some amphoteric pharmaceuticals containing large amounts of zwitterions were also difficult to remove by ion exchange resin. Additionally, neither resin porosity nor chemical matrix had any significant effect on the long-term pharmaceutical removal mechanism.

  16. 1H and 15N NMR Analyses on Heparin, Heparan Sulfates and Related Monosaccharides Concerning the Chemical Exchange Regime of the N-Sulfo-Glucosamine Sulfamate Proton

    Directory of Open Access Journals (Sweden)

    Vitor H. Pomin


    Full Text Available Heparin and heparan sulfate are structurally related glycosaminoglycans (GAGs. Both GAGs present, although in different concentrations, N-sulfo-glucosamine (GlcNS as one of their various composing units. The conditional fast exchange property of the GlcNS sulfamate proton in these GAGs has been pointed as the main barrier to its signal detection via NMR experiments, especially 1H-15N HSQC. Here, a series of NMR spectra is collected on heparin, heparan sulfate and related monosaccharides. The N-acetyl glucosamine-linked uronic acid types of these GAGs were properly assigned in the 1H-15N HSQC spectra. Dynamic nuclear polarization (DNP was employed in order to facilitate 1D spectral acquisition of the sulfamate 15N signal of free GlcNS. Analyses on the multiplet pattern of scalar couplings of GlcNS 15N has helped to understand the chemical properties of the sulfamate proton in solution. The singlet peak observed for GlcNS happens due to fast chemical exchange of the GlcNS sulfamate proton in solution. Analyses on kinetics of alpha-beta anomeric mutarotation via 1H NMR spectra have been performed in GlcNS as well as other glucose-based monosaccharides. 1D 1H and 2D 1H-15N HSQC spectra recorded at low temperature for free GlcNS dissolved in a proton-rich solution showed signals from all exchangeable protons, including those belonging to the sulfamate group. This work suits well to the current grand celebration of one-century-anniversary of the discovery of heparin.

  17. Cleaning chemical and mechanical of heat exchangers in french nuclear plants; Limpieza mecanica y quimica de intercambiadores de calor en centrales nucleares francesas

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, J. t.; Guerra, P.; Carreres, C.


    This project was carried out under the frame of the approval of LAINSA as a supplier of EDF in France. The inspection performed on systems called the moisture separator reheaters (GSS) of CPO series reactor of EDF nuclear power plants has shown evidence of significant clogging due to deposits of magnetite inside the tubes of tube bundle. The pressure drop between inlet and outlet of the heating was close to maximum design criterion. This effect could result in equipment damage and loss of plant productivity. The aim of the work was the design, development, approval and implementation of a procedure for un blocking the tubes of the GSS respecting the integrity of materials and ensuring the harmlessness of cleaning procedures. The procedure used was to completely remove magnetite deposits in order to recover a passage diameter and a surface finish equivalent to the origin, thus avoiding the replacement of the GSS and obtaining a considerable reduction of costs. The achieve these objectives we have developed a procedure that is basically a mechanical pre-cleaning of all tubes of the GSS in order to unblock tem, followed by a chemical cleaning where magnetite is dissolved and crawled out of the tube bundle. The main results were: -Corrosion less than 10 microns. 100-110 Kg of magnetite removed by heat exchanger. -Final pressure drop similar to that of new equipment. -Waste water: 70 m{sup 3} per exchanger, which were managed by an authorized waste management company. This procedure has been applied successfully in 14 GSS type heat exchangers in Fessenheim and Bugey nuclear power plants in France between 2009 and 2011. This project demonstrates that the long experience of LAINSA in the Spanish nuclear industry along with the knowledge and experience in chemical cleaning of SOLARCA, have served to successfully work demanding and mature markets such as the French nuclear market, solving the problem of deposits of magnetite with an effective and safe method for the treated

  18. ¹H and (15)N NMR Analyses on Heparin, Heparan Sulfates and Related Monosaccharides Concerning the Chemical Exchange Regime of the N-Sulfo-Glucosamine Sulfamate Proton. (United States)

    Pomin, Vitor H


    Heparin and heparan sulfate are structurally related glycosaminoglycans (GAGs). Both GAGs present, although in different concentrations, N-sulfo-glucosamine (GlcNS) as one of their various composing units. The conditional fast exchange property of the GlcNS sulfamate proton in these GAGs has been pointed as the main barrier to its signal detection via NMR experiments, especially ¹H-(15)N HSQC. Here, a series of NMR spectra is collected on heparin, heparan sulfate and related monosaccharides. The N-acetyl glucosamine-linked uronic acid types of these GAGs were properly assigned in the ¹H-(15)N HSQC spectra. Dynamic nuclear polarization (DNP) was employed in order to facilitate 1D spectral acquisition of the sulfamate (15)N signal of free GlcNS. Analyses on the multiplet pattern of scalar couplings of GlcNS (15)N has helped to understand the chemical properties of the sulfamate proton in solution. The singlet peak observed for GlcNS happens due to fast chemical exchange of the GlcNS sulfamate proton in solution. Analyses on kinetics of alpha-beta anomeric mutarotation via ¹H NMR spectra have been performed in GlcNS as well as other glucose-based monosaccharides. 1D ¹H and 2D ¹H-(15)N HSQC spectra recorded at low temperature for free GlcNS dissolved in a proton-rich solution showed signals from all exchangeable protons, including those belonging to the sulfamate group. This work suits well to the current grand celebration of one-century-anniversary of the discovery of heparin.

  19. A lanthanide complex with dual biosensing properties: CEST (chemical exchange saturation transfer) and BIRDS (biosensor imaging of redundant deviation in shifts) with europium DOTA-tetraglycinate. (United States)

    Coman, Daniel; Kiefer, Garry E; Rothman, Douglas L; Sherry, A Dean; Hyder, Fahmeed


    Responsive contrast agents (RCAs) composed of lanthanide(III) ion (Ln3R) complexes with a variety of1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA4S) derivatives have shown great potential as molecular imaging agents for MR. A variety of LnDOTA–tetraamide complexes have been demonstrated as RCAs for molecular imaging using chemical exchange saturation transfer (CEST). The CEST method detects proton exchange between bulk water and any exchangeable sites on the ligand itself or an inner sphere of bound water that is shifted by a paramagnetic Ln3R ion bound in the core of the macrocycle. It has also been shown that molecular imaging is possible when the RCA itself is observed (i.e. not its effect on bulk water) using a method called biosensor imaging of redundant deviation in shifts (BIRDS). The BIRDS method utilizes redundant information stored in the nonexchangeable proton resonances emanating from the paramagnetic RCA for ambient factors such as temperature and/or pH.Thus, CEST and BIRDS rely on exchangeable and nonexchangeable protons, respectively, for biosensing. We posited that it would be feasible to combine these two biosensing features into the same RCA (i.e. dual CEST and BIRDS properties). A complex between europium(III) ion (Eu3R) and DOTA–tetraglycinate [DOTA–(gly)S4] was used to demonstrate that its CEST characteristics are preserved, while its BIRDS properties are also detectable. The in vitro temperature sensitivity of EuDOTA–(gly)S4 was used to show that qualitative MR contrast with CEST can be calibrated using quantitative MR mapping with BIRDS, thereby enabling quantitative molecular imaging at high spatial resolution.

  20. Characterization of mu s-ms dynamics of proteins using a combined analysis of N-15 NMR relaxation and chemical shift: Conformational exchange in plastocyanin induced by histidine protonations

    DEFF Research Database (Denmark)

    Hass, M. A. S.; Thuesen, Marianne Hallberg; Christensen, Hans Erik Mølager


    An approach is presented that allows a detailed, quantitative characterization of conformational exchange processes in proteins on the mus-ms time scale. The approach relies on a combined analysis of NMR relaxation rates and chemical shift changes and requires that the chemical shift...... variabilis (A.v. PCu) (Ma, L.; Hass, M. A. S.; Vierick, N.; Kristensen, S. M.; Ulstrup, J.; Led, J. J. Biochemistry 2003, 42, 320-330). The R-1 and R-2 relaxation rates of the backbone N-15 nuclei were measured at a series of pH and temperatures on an 15N labeled sample of A.v. PCu, and the 15 N chemical...... quantitatively by the correlation between the R-ex terms and the corresponding chemical shift differences of the exchanging species. By this approach, the R-ex terms of N-15 nuclei belonging to contiguous regions in the protein could be assigned to the same exchange process. Furthermore, the analysis...


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  2. Intracellular water exchange for measuring the dry mass, water mass and changes in chemical composition of living cells.

    Directory of Open Access Journals (Sweden)

    Francisco Feijó Delgado

    Full Text Available We present a method for direct non-optical quantification of dry mass, dry density and water mass of single living cells in suspension. Dry mass and dry density are obtained simultaneously by measuring a cell's buoyant mass sequentially in an H2O-based fluid and a D2O-based fluid. Rapid exchange of intracellular H2O for D2O renders the cell's water content neutrally buoyant in both measurements, and thus the paired measurements yield the mass and density of the cell's dry material alone. Utilizing this same property of rapid water exchange, we also demonstrate the quantification of intracellular water mass. In a population of E. coli, we paired these measurements to estimate the percent dry weight by mass and volume. We then focused on cellular dry density - the average density of all cellular biomolecules, weighted by their relative abundances. Given that densities vary across biomolecule types (RNA, DNA, protein, we investigated whether we could detect changes in biomolecular composition in bacteria, fungi, and mammalian cells. In E. coli, and S. cerevisiae, dry density increases from stationary to exponential phase, consistent with previously known increases in the RNA/protein ratio from up-regulated ribosome production. For mammalian cells, changes in growth conditions cause substantial shifts in dry density, suggesting concurrent changes in the protein, nucleic acid and lipid content of the cell.

  3. Experimental results of acetone hydrogenation on a heat exchanger type reactor for solar chemical heat pump; Solar chemical heat pump ni okeru acetone suisoka hanno netsu kaishu jikken

    Energy Technology Data Exchange (ETDEWEB)

    Takashima, T.; Doi, T.; Tanaka, T.; Ando, Y. [Electrotechnical Laboratory, Tsukuba (Japan); Miyahara, R.; Kamoshida, J. [Shibaura Institute of Technology, Tokyo (Japan)


    With the purpose of converting solar heat energy to industrial heat energy, an experiment of acetone hydrogenation was carried out using a heat exchanger type reactor that recovers heat generated by acetone hydrogenation, an exothermic reaction, and supplies it to an outside load. In the experiment, a pellet-like activated carbon-supported ruthenium catalyst was used for the acetone hydrogenation with hydrogen and acetone supplied to the catalyst layer at a space velocity of 400-1,200 or so. In the external pipe of the double-pipe type reactor, a heating medium oil was circulated in parallel with the flow of the reactant, with the heat of reaction recovered that was generated from the acetone hydrogenation. In this experiment, an 1wt%Ru/C catalyst and a 5wt%Ru/C catalyst were used so as to examine the effects of variation in the space velocity. As a result, from the viewpoint of recovering the heat of reaction, it was found desirable to increase the reaction speed by raising catalytic density and also to supply the reactant downstream inside the reaction pipe by increasing the space velocity. 1 ref., 6 figs., 1 tab.

  4. Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T. (United States)

    Longo, Dario Livio; Dastrù, Walter; Digilio, Giuseppe; Keupp, Jochen; Langereis, Sander; Lanzardo, Stefania; Prestigio, Simone; Steinbach, Oliver; Terreno, Enzo; Uggeri, Fulvio; Aime, Silvio


    Iopamidol (Isovue®-Bracco Diagnostic Inc.) is a clinically approved X-Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH-dependent. Thus, a ratiometric method for pH assessment has been set-up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5-7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH-changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition.

  5. Chemical and radiation stability of a proprietary cesium ion exchange material manufactured from WWL membrane and SuperLig{reg_sign} 644

    Energy Technology Data Exchange (ETDEWEB)

    Brown, G.N.; Carson, K.J.; DesChane, J.R.; Elovich, R.J.; Berry, P.K.


    Pretreatment of nuclear process wastes for ion exchange removal of Cs and other radionuclides is one way to minimize amount of high-level radioactive waste at Hanford. This study evaluated Cs-selective SuperLig{reg_sign}644 (IBC Advanced Technologies, American Fork UT) entrapped in a proprietary WWL web membrane (3M) for chemical/radiation stability in simulated caustic neutralized current acid waste (NCAW), 0.5M HNO{sub 3}, water, and air. After exposure up to 2.0E+09 rad, the material was evaluated for Cs uptake in 5M sodium NCAW simulants with varying Cs contents. Radiolytic stability appears to be sufficient for ion exchange pretreatment of radioactive Cs: essentially no decrease in Cs selectivity or loading (Kd) was observed during {sup 60}Cs gamma irradiation in water or 0.5M HNO{sub 3} up to 1.0E+09 rad. Cs Kd decreased by a factor of 2 after 2.0E+09 rad exposure. Cs Kd did not change during irradiation in 5M NCAW or ambient air up to 1.0E+08 rad, but decreased by more than an order of magnitude between 1.0E+08 and 2.0E+09 rad (not typical of process conditions). Chemical stability under caustic conditions is lower than in air or under neutral/acidic conditions. Results indicate that this material is less stable in caustic solution irrespective of radiation exposure. Samples of the membrane retained their physical form throughout the entire experiment and were only slightly brittle after exposure to 2.0E+09 rad. (The material evaluated was a finely ground (400 mesh) particulate engineered to form a polymeric fiber (WWL), not the macroscopic form of SuperLig{reg_sign} 644 resin (20 to 50 mesh).)

  6. Modelling of the interaction between chemical and mechanical behaviour of ion exchange resins incorporated into a cement-based matrix

    Directory of Open Access Journals (Sweden)

    Le Bescop P.


    Full Text Available In this paper, we present a predictive model, based on experimental data, to determine the macroscopic mechanical behavior of a material made up of ion exchange resins solidified into a CEM III cement paste. Some observations have shown that in some cases, a significant macroscopic expansion of this composite material may be expected, due to internal pressures generated in the resin. To build the model, we made the choice to break down the problem in two scale’s studies. The first deals with the mechanical behavior of the different heterogeneities of the composite, i.e. the resin and the cement paste. The second upscales the information from the heterogeneities to the Representative Elementary Volume (REV of the composite. The heterogeneities effects are taken into account in the REV by applying a homogenization method derived from the Eshelby theory combined with an interaction coefficient drawn from the poroelasticity theory. At the first scale, from the second thermodynamic law, a formulation is developed to estimate the resin microscopic swelling. The model response is illustrated on a simple example showing the impact of the calculated internal pressure, on the macroscopic strain.

  7. Physico-chemical study of the degradation of membrane-electrode assemblies in a proton exchange membrane fuel cell stack (United States)

    Ferreira-Aparicio, P.; Gallardo-López, B.; Chaparro, A. M.; Daza, L.

    A proton exchange membrane fuel cell stack integrated by 8-elements has been evaluated in an accelerated stress test. The application of techniques such as TEM analyses of ultramicrotome-sliced sections of some samples and XRD, XPS and TGA of spent electrodes reveal the effects of several degradation processes contributing to reduce the cells performance. The reduction of the Pt surface area at the cathode is favored by the oxidation of carbon black agglomerates in the catalytic layer, the agglomeration of Pt particles and by the partial dissolution of Pt, which migrates towards the anode and precipitates within the membrane. In the light of the TEM, EDAX and XPS results, two combined effects are probably responsible of the increase of the internal resistance of the stack cells: (i) a lower proton conductivity of the membranes due to the high affinity of the sulfonic acid groups for ions originated from Pt crystallites and other peripherical elements such as the silicone elastomeric gaskets and (ii) the increment of electrically isolated islands in the cathode gas diffusion electrodes resulting from carbon corrosion and the degradation of the perfluorinated polymers. Water accumulation and inhomogeneous gas distribution throughout the stack cells originate different degradation rates in them.

  8. A theoretical analysis of the extraction of heterocyclic organic compounds from an organic phase using chemically mediated electrochemically modulated complexation in ion exchange polymer beads

    Energy Technology Data Exchange (ETDEWEB)

    Ozekin, K.; Noble, R.D.; Koval, C.A.


    A cyclical electrochemical process for the removal of heterocyclic organic compounds (pollutants) from an organic solvent using an ion-exchange polymer is analyzed. In this analysis, there are three main steps: In the first step, the polymer beads containing the active form of the complexing agent are contacted with the contaminated (feed) hydrocarbon phase. The pollutant diffuses into the beads and binds with the complexing agent which is in the reduced state. It is a fast reversible reaction. For the second step, the beads which contain a pollutant are contacted with a waste (receiving) phase and a chemical mediator is then used to oxidize the complexing agent and to reduce its affinity towards the pollutant so that it can be released. The oxidation of the complexing agent is an irreversible reaction. This is a moving boundary problem with countercurrent diffusion. For each mole of mediator that goes into the bead, one mole of pollutant exits since each complexing agent binds one pollutant. In the third step, the waste hydrocarbon phase is removed and a second chemical mediator is then used to reduce the complexing agent. The reduction of the complexing agent is also an irreversible reaction. Partial differential equations are used to analyze this process. 26 refs., 9 figs.

  9. Mixed ion-exchanger chemically modified carbon paste ion-selective electrodes for determination of triprolidine hydrochloride

    Directory of Open Access Journals (Sweden)

    Yousry M. Issa


    Full Text Available Triprolidine hydrochloride (TpCl ion-selective carbon paste electrodes were constructed using Tp-TPB/Tp-CoN and Tp-TPB/Tp-PTA as ion-exchangers. The two electrodes revealed Nernstian responses with slopes of 58.4 and 58.1 mV decade−1 at 25 °C in the ranges 6 × 10−6–1 × 10−2 and 2 × 10−5–1 × 10−2 M for Tp-TPB/Tp-CoN and Tp-TPB/Tp-PTA, respectively. The potentials of these electrodes were independent of pH in the ranges of 2.5–7.0 and 4.5–7.0, and detection limits were 6 × 10−6 and 1 × 10−5 M for Tp-TPB/Tp-CoN and Tp-TPB/Tp-PTA, respectively. The electrodes showed a very good selectivity for TpCl with respect to a large number of inorganic cations and compounds. The standard addition, potentiometric titration methods and FIA were applied to the determination of TpCl in pure solutions and pharmaceutical preparations. The results obtained were in close agreement with those found by the official method. The mean recovery values were 100.91% and 97.92% with low coefficient of variation values of 0.94%, and 0.56% in pure solutions, 99.82% and 98.53% with coefficient of variation values of 2.20%, and 0.73% for Actifed tablet and Actifed syrup, respectively, using the Tp-TPB/Tp-CoN electrode, and 98.85%, and 99.18% with coefficient of variation values of 0.48% and 0.85% for Actifed tablet and Actifed syrup, respectively, using the Tp-TPB/Tp-PTA electrode.

  10. Targeting of chemical mutagens to differentiating B-lymphocytes in vivo: detection by direct DNA labeling and sister chromatid exchange induction

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, S.E.; Nanna, U.C.; Dietert, R.R.


    In vivo systems for analyzing mutagen interactions with a specific differentiating cell population are rare. Taking advantage of the unique anatomical features of the bursa of Fabricius in the chicken, the authors explored the possibility of targeting chemical mutagens to a defined differentiating cell population in the animal, namely, the B-lymphocytes series. Such cells are known to be the targets for the oncogene-activating avian leukosis virus. Targeting of chemicals to cells of the bursa was demonstrated by application of the DNA-specific fluorochrome 4'-6-diamidino-2-phenylindole (DAPI) to the anal lips of neonatal chicks. Bright nuclear fluorescence of cells in the bursa demonstrated to occur within minutes after the application of of DAPI. DAPI labeling of nuclei was detected up to several days after a single application. No nuclear labeling was exhibited in cells of neighboring tissues. Methyl methanesulfonate (MMS)( was applied to the anal lips of day-old chicks to study dose-response kinetics for mutagen targeting to DNA of dividing B-lymphocytes in the bursa. Since the mitotic index was found to be quite high (25-30%) in the bursa, chromosome analysis was used to assay for genome damage. Sister chromatid exchange frequencies of 3.9, 7.3, and 9.0 (baseline 2.5) per cell were obtained at MMS dosages per animal of 50,, and, respectively. These results indicate the rapid and quantitative localization of DNA-binding chemicals to cells of the bursa, particularly the resident B-lymphocytes. The bursa should be a useful system for studying mutagen-DNA interactions in the differentiating B-lymphocyte and subsequent influences on the development of immunity and lymphoproliferative disease.

  11. Investigation into the Cause of Spontaneous Emulsification of a Free Steel Droplet; Validation of the Chemical Exchange Pathway (United States)

    Spooner, Stephen; Assis, Andre N.; Warnett, Jason; Fruehan, Richard; Williams, Mark A.; Sridhar, Seetharaman


    Small Fe-based droplets have been heated to a molten phase suspended within a slag medium to replicate a partial environment within the basic oxygen furnace (BOF). The confocal scanning laser microscope (CSLM) has been used as a heating platform to interrogate the effect of impurities and their transfer across the metal/slag interface, on the emulsification of the droplet into the slag medium. The samples were then examined through X-ray computer tomography (XCT) giving the mapping of emulsion dispersion in 3D space, calculating the changing of interfacial area between the two materials, and changes of material volume due to material transfer between metal and slag. Null experiments to rule out thermal gradients being the cause of emulsification have been conducted as well as replication of the previously reported study by Assis et al.[1] which has given insights into the mechanism of emulsification. Finally chemical analysis was conducted to discover the transfer of oxygen to be the cause of emulsification, leading to a new study of a system with undergoing oxygen equilibration.

  12. Theoretical investigation of the magnetic exchange interactions in copper(II) oxides under chemical and physical pressures. (United States)

    Rocquefelte, Xavier; Schwarz, Karlheinz; Blaha, Peter


    It remains a challenge to understand the unconventional mechanisms that cause high-T(C) superconductivity in cuprate superconductors, high-T(C) multiferroicity in CuO, or low-dimensional magnetism in the spin-Peierls transition compounds such as CuGeO(3). A common feature of all these copper oxide compounds (containing Cu(2+) ions) is the presence of large magnetic superexchange interactions J. It is a general strategy to apply chemical and/or physical pressure in order to tune these exotic properties. Here we show theoretically, for the first time, the impact of physical pressure on J on CuO, for which we predict a strong enhancement of the low-dimensionality of the magnetic interactions and the spin-frustration at high-pressures. Such modifications are expected to strongly influence the multiferroic properties of CuO. We finally demonstrate that PBE0 hybrid DFT calculations provide reliable J values for a wide range of copper(II) oxides compounds, i.e. CuGeO(3), BaCu(2)Si(2)O(7), BaCu(2)Ge(2)O(7), and La(2)CuO(4).

  13. Predicting binding poses and affinities for protein - ligand complexes in the 2015 D3R Grand Challenge using a physical model with a statistical parameter estimation (United States)

    Grudinin, Sergei; Kadukova, Maria; Eisenbarth, Andreas; Marillet, Simon; Cazals, Frédéric


    The 2015 D3R Grand Challenge provided an opportunity to test our new model for the binding free energy of small molecules, as well as to assess our protocol to predict binding poses for protein-ligand complexes. Our pose predictions were ranked 3-9 for the HSP90 dataset, depending on the assessment metric. For the MAP4K dataset the ranks are very dispersed and equal to 2-35, depending on the assessment metric, which does not provide any insight into the accuracy of the method. The main success of our pose prediction protocol was the re-scoring stage using the recently developed Convex-PL potential. We make a thorough analysis of our docking predictions made with AutoDock Vina and discuss the effect of the choice of rigid receptor templates, the number of flexible residues in the binding pocket, the binding pocket size, and the benefits of re-scoring. However, the main challenge was to predict experimentally determined binding affinities for two blind test sets. Our affinity prediction model consisted of two terms, a pairwise-additive enthalpy, and a non pairwise-additive entropy. We trained the free parameters of the model with a regularized regression using affinity and structural data from the PDBBind database. Our model performed very well on the training set, however, failed on the two test sets. We explain the drawback and pitfalls of our model, in particular in terms of relative coverage of the test set by the training set and missed dynamical properties from crystal structures, and discuss different routes to improve it.

  14. Kinetic identification of protein ligands in a 51,200 small-molecule library using microarrays and a label-free ellipsometric scanner (United States)

    Landry, James P.; Proudian, Andrew P.; Malovichko, Galina; Zhu, Xiangdong


    Drug discovery begins by identifying protein-small molecule binding pairs. Afterwards, binding kinetics and biofunctional assays are performed, to reduce candidates for further development. High-throughput screening, typically employing fluorescence, is widely used to find protein ligands in small-molecule libraries, but is rarely used for binding kinetics measurement because: (1) attaching fluorophores to proteins can alter kinetics and (2) most label-free technologies for kinetics measurement are inherently low-throughput and consume expensive sensing surfaces. We addressed this need with polarization-modulated ellipsometric scanning microscopes, called oblique-incidence reflectivity difference (OI-RD). Label-free ligand screening and kinetics measurement are performed simultaneously on small-molecule microarrays printed on relatively inexpensive isocyanate-functionalized glass slides. As a microarray is reacted, an OI-RD microscope tracks the change in surface-bound macromolecule density in real-time at every spot. We report progress applying OI-RD to screen purified proteins and virus particles against a 51,200-compound library from the National Cancer Institute. Four microarrays, each containing 12,800 library compounds, are installed in four flow cells in an automated OI-RD microscope. The slides are reacted serially, each giving 12,800 binding curves with ~30 sec time resolution. The entire library is kinetically screened against a single probe in ~14 hours and multiple probes can be reacted sequentially under automation. Real-time binding detection identifies both high-affinity and low-affinity (transient binding) interactions; fluorescence endpoint images miss the latter. OI-RD and microarrays together is a powerful high-throughput tool for early stage drug discovery and development. The platform also has great potential for downstream steps such as in vitro inhibition assays.

  15. Vertical exchange and chemical conversion of trace elements over topographically complex terrain; Vertikaler Austausch und chemische Umwandlung von Spurenstoffen ueber topographisch gegliedertem Gelaende

    Energy Technology Data Exchange (ETDEWEB)

    Kuntze, K.


    The influence of topography on the vertical exchange of trace elements was investigated with the aid of a numeric simulation model. It is a couopled 3D model consisting of the mesoscale model KAMM and the dispersion model DRAIS, extended by the gaseous phase mechanism of the RADM model. This way, both meteorological and chemical processes can be analyzed in a preselected time and spatial resolution. The simulations were validated by a comparison with measurements made during the TRACT campaign. Satisfactory agreement between the two was established. [German] In der vorliegenden Arbeit wurde der Einfluss der Topographie auf den vertikalen Austausch von Spurenstoffen mit Hilfe eines numerischen Simulationsmodells untersucht. Bei dem Simulationsmodell handelt es sich um ein dreidimensionales gekoppeltes Modell, welches aus dem mesoskaligen Modell KAMM und dem um den Gasphasenmechanismus des RADM-Modells erweiterten Ausbreitungsmodell DRAIS besteht. Mit diesem Modellsystem war es moeglich, sowohl meterologische als auch chemische Prozesse in einer vorher gewaehlten zeitlichen und raeumlichen Aufloesung zu betrachten. Um die Qualitaet der Simulation und damit deren Verwendbarkeit fuer die Untersuchungen festzustellen, wurde ein Vergleich mit Messungen durchgefuehrt. Dazu wurden berechnete meterologische und chemische Groessen mit den waehrend der Feldmesskampagne TRACT gemessenen Groessen verglichen. Der Vergleich der simulierten Groessen sowohl mit Radiosondenaufstiegen als auch mit Zeitreihen und Flugzeugmessungen lieferte eine gute Uebereinstimmung. (orig.)

  16. Long repetition time experiments for measurement of concentrations in systems with chemical exchange and undergoing temporal variation-comparison of methods with and without correction for saturation (United States)

    Galbán, Craig J.; Spencer, Richard G. S.


    The purpose of this paper is to compare two methods for quantifying metabolite concentrations using the one-pulse experiment for a sample undergoing chemical exchange and subject to an intervention or other temporal variation. The methods, LATR-C (Long Acquisition TR (interpulse delay); Corrected for partial saturation) and LATR-NC (Long Acquisition TR; Not Corrected), are compared in terms of signal-to-noise ratio, SNR, per unit time and quantitation errors. Parameters relevant to the isolated perfused rat heart are used as a specific application, although the results are general. We assume throughout that spin-lattice relaxation times, T1, do not change. For a given flip angle, θ, TR's are calculated which result in maximal SNR per unit time under 10%, 5%, and 1% constraints on quantitation errors. Additional simulations were performed to demonstrate explicitly the dependence of the quantitation errors on TR for a fixed θ. We find (i) if the allowed error is large, and when both metabolite concentrations and rate constants vary, LATR-C permits use of shorter TR, and hence yields greater SNR per unit time, than LATR-NC; (ii) for small allowed error, the two methods give similar TR's and SNR per unit time, so that the simpler LATR-NC experiment may be preferred; (iii) large values of θ result in similar constrained TR's and hence SNR per unit time for the two methods; (iv) the ratio of concentrations of metabolites with similar T1 exhibit similar errors for the two methods.

  17. Wet chemical preparation and isotope exchange process of H/D-terminated Si(111) and Si(110) studied by adsorbate vibrational analysis (United States)

    Kawamoto, Erina; Kang, Jungmin; Matsuda, Takuya; Yamada, Taro; Suto, Shozo


    A convenient procedure for preparing D-terminated Si(111)-(1×1) and Si(110)-(1×1) by wet chemical etching was developed and applied to the vibrational analysis of these surfaces by high-resolution electron-energy loss spectroscopy (HREELS). Fully H-terminated Si(111)/(110) was first prepared in regular 40% NH4F/H2O solution, followed by immersion in saturated KF/D2O solution. HREELS revealed partially D-terminated H:Si(111)/(110) with the amount of deuterium termination depending on the immersion time. A series of various immersion times revealed the H/D exchange reaction kinetics, which are associated with the Si substrate etching processes on Si(111) (step-flow etching) and Si(110) (zipper reaction). The H-Si and D-Si stretching vibration frequencies as functions of the surface D fraction did not appear to change on Si(111), but on Si(110) the H-Si signal red shifted at a high D fraction. This is due to the adsorbate-adsorbate interaction, which is more intense on Si(110) because of the short nearest-neighbor distance of the adsorbates.

  18. Microfluidic chemical reaction circuits (United States)

    Lee, Chung-cheng; Sui, Guodong; Elizarov, Arkadij; Kolb, Hartmuth C.; Huang, Jiang; Heath, James R.; Phelps, Michael E.; Quake, Stephen R.; Tseng, Hsian-rong; Wyatt, Paul; Daridon, Antoine


    New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents.

  19. Chemical exchange saturation transfer MR imaging of articular cartilage glycosaminoglycans at 3 T: Accuracy of B0 Field Inhomogeneity corrections with gradient echo method. (United States)

    Wei, Wenbo; Jia, Guang; Flanigan, David; Zhou, Jinyuan; Knopp, Michael V


    Glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) is an important molecular MRI methodology developed to assess changes in cartilage GAG concentrations. The correction for B0 field inhomogeneity is technically crucial in gagCEST imaging. This study evaluates the accuracy of the B0 estimation determined by the dual gradient echo method and the effect on gagCEST measurements. The results were compared with those from the commonly used z-spectrum method. Eleven knee patients and three healthy volunteers were scanned. Dual gradient echo B0 maps with different ∆TE values (1, 2, 4, 8, and 10 ms) were acquired. The asymmetry of the magnetization transfer ratio at 1 ppm offset referred to the bulk water frequency, MTRasym(1 ppm), was used to quantify cartilage GAG levels. The B0 shifts for all knee patients using the z-spectrum and dual gradient echo methods are strongly correlated for all ∆TE values used (r = 0.997 to 0.786, corresponding to ∆TE = 10 to 1 ms). The corrected MTRasym(1 ppm) values using the z-spectrum method (1.34% ± 0.74%) highly agree only with those using the dual gradient echo methods with ∆TE = 10 ms (1.72% ± 0.80%; r = 0.924) and 8 ms (1.50% ± 0.82%; r = 0.712). The dual gradient echo method with longer ∆TE values (more than 8 ms) has an excellent correlation with the z-spectrum method for gagCEST imaging at 3T.

  20. Chemical Exchange Saturation Transfer MR Imaging Is Superior to Diffusion Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: a Study on Substantia Nigra and Striatum

    Directory of Open Access Journals (Sweden)

    Chunmei eLi


    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date the diagnosis of PD is still based primarily on the clinical manifestations which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical-exchange-saturation-transfer (CEST imaging and diffusion-tensor imaging (DTI in PD at 3 Tesla by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3 Tesla MR system, using an 8-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym(3.5ppm, and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen and caudate. The MTRasym(3.5ppm value, the total CEST signal intensity and fractional anisotropy (FA value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004 and P < 0.001, respectively. The MTRasym(3.5ppm values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively. There were no significant differences for the mean diffusivity (MD in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

  1. Characterization of protein/ligand interactions by {sup 1}H/{sup 3}H exchange: application to the hAsf{sup 1}/ histone H{sup 3} complex; Caracterisation des interactions proteine / ligand par echange {sup 1}H/{sup 3}H: application au complexe entre la proteine hAsf{sup 1} et l'histone H{sup 3}

    Energy Technology Data Exchange (ETDEWEB)

    Mousseau, G


    In the first chapter will be exposed the main current methods of identification to high debit of the interactions protein-protein. Then the methods allowing to characterize the surfaces of interaction or to determine the structures of the complexes will be listed by discussing the main advantages and the inconveniences. Our approach of characterization of the zones of interaction protein-protein is a method of 'foot-printing' 1, based on the identification and radicals' quantification formed on the residues of proteins accessible to the water. The second chapter will so discuss the development of this method of radical identification using the atom of tritium as radioactive label. Our approach will finally be validated in the third chapter by applying it to the characterization of amino acids involved in the interaction enter the human protein anti silencing factor 1 (hAsf11-156) and a fragment of the histone H{sup 3}. (N.C.)

  2. Screening protein-ligand interactions using {sup 1}H NMR techniques for detecting the ligand; Mapeamento das interacoes proteina-ligante atraves de tecnicas de RMN de {sup 1}H utilizando deteccao do ligante

    Energy Technology Data Exchange (ETDEWEB)

    Figueiredo, Isis Martins; Marsaioli, Anita Jocelyne [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica. Dept. de Quimica Organica]. E-mail:


    NMR is a valuable screening tool for the binding of ligands to proteins providing structural information on both protein and ligands and is thus largely applied to drug-discovery. Among the recent NMR techniques to probe weak binding protein-ligand complexes we have critically evaluated the advantages and disadvantages of STD (Saturation Transfer Difference), WaterLOGSY (Water Ligand Observation with Gradient Spectroscopy), NOE pumping and DOSY-NOESY (Diffusion-Ordered NOESY) using a mixture of BSA (bovine serum albumin) plus salicylic acid, caffeine, citric acid, adipic acid and D-glucose. (author)

  3. Chemical-exchange-saturation-transfer magnetic resonance imaging to map gamma-aminobutyric acid, glutamate, myoinositol, glycine, and asparagine: Phantom experiments (United States)

    Oh, Jang-Hoon; Kim, Hyug-Gi; Woo, Dong-Cheol; Jeong, Ha-Kyu; Lee, Soo Yeol; Jahng, Geon-Ho


    The physical and technical development of chemical-exchange-saturation-transfer (CEST) magnetic resonance imaging (MRI) using clinical 3 T MRI was explored with the goal of mapping asparagine (Asn), gamma-aminobutyric acid (GABA), glutamate (Glu), glycine (Gly), and myoinositol (MI), which exist in the brain. Phantoms with nine different conditions at concentrations of 10, 30, and 50 mM and pH values of 5.6, 6.2, and 7.4 were prepared for the five target molecules to evaluate the dependence of the CEST effect in the concentration, the pH, and the amplitude of the applied radiofrequency field B1. CEST images in the offset frequency range of ±6 parts per million (ppm) were acquired using a pulsed radio-frequency saturation scheme with a clinical 3 T MRI system. A voxel-based main magnetic field B0 inhomogeneity correction, where B0 is the center frequency offset at zero ppm, was performed by using the spline interpolation method to fit the full Z-spectrum to estimate the center frequency. A voxel-based CEST asymmetry map was calculated to evaluate amide (-NH), amine (-NH2), and hydroxyl (-OH) groups for the five target molecules. The CEST effect for Glu, GABA, and Gly clearly increased with increasing concentrations. The CEST effect for MI was minimal, with no noticeable differences at different concentrations. The CEST effect for Glu and Gly increased with increasing acidity. The highest CEST asymmetry for GABA was observed at pH 6.2. The CEST effect for Glu, GABA, and Gly increased with increasing B1 amplitude. For all target molecules, the CEST effect for the human 3 T MRI system increased with increasing concentration and B1 amplitude, but varied with pH, depending on the characteristics of the molecules. The CEST effect for MI may be not suitable with clinical MRI systems. These results show that CEST imaging in the brain with the amine protons by using 3 T MRI is possible for several neuronal diseases.

  4. Lanthanide ion (III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate for dual biosensing of pH with chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS). (United States)

    Huang, Yuegao; Coman, Daniel; Ali, Meser M; Hyder, Fahmeed


    Relaxivity-based magnetic resonance of phosphonated ligands chelated with gadolinium (Gd(3+)) shows promise for pH imaging. However instead of monitoring the paramagnetic effect of lanthanide complexes on the relaxivity of water protons, biosensor (or molecular) imaging with magnetic resonance is also possible by detecting either the nonexchangeable or the exchangeable protons on the lanthanide complexes themselves. The nonexchangeable protons (e.g. -CHx, where 3 ≥ x ≥ 1) are detected using a three-dimensional chemical shift imaging method called biosensor imaging of redundant deviation in shifts (BIRDS), whereas the exchangeable protons (e.g. -OH or -NHy , where 2 ≥ y ≥ 1) are measured with chemical exchange saturation transfer (CEST) contrast. Here we tested the feasibility of BIRDS and CEST for pH imaging of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate (DOTA-4AmP(8-)) chelated with thulium (Tm(3+) ) and ytterbium (Yb(3+)). BIRDS and CEST experiments show that both complexes are responsive to pH and temperature changes. Higher pH and temperature sensitivities are obtained with BIRDS for either complex when using the chemical shift difference between two proton resonances vs using the chemical shift of a single proton resonance, thereby eliminating the need to use water resonance as reference. While CEST contrast for both agents is linearly dependent on pH within a relatively large range (i.e. 6.3-7.9), much stronger CEST contrast is obtained with YbDOTA-4AmP(5-) than with TmDOTA-4AmP(5-). In addition, we demonstrate the prospect of using BIRDS to calibrate CEST as new platform for quantitative pH imaging.

  5. Active microchannel heat exchanger (United States)

    Tonkovich, Anna Lee Y [Pasco, WA; Roberts, Gary L [West Richland, WA; Call, Charles J [Pasco, WA; Wegeng, Robert S [Richland, WA; Wang, Yong [Richland, WA


    The present invention is an active microchannel heat exchanger with an active heat source and with microchannel architecture. The microchannel heat exchanger has (a) an exothermic reaction chamber; (b) an exhaust chamber; and (c) a heat exchanger chamber in thermal contact with the exhaust chamber, wherein (d) heat from the exothermic reaction chamber is convected by an exothermic reaction exhaust through the exhaust chamber and by conduction through a containment wall to the working fluid in the heat exchanger chamber thereby raising a temperature of the working fluid. The invention is particularly useful as a liquid fuel vaporizer and/or a steam generator for fuel cell power systems, and as a heat source for sustaining endothermic chemical reactions and initiating exothermic reactions.

  6. Single domain SmCo5@Co exchange-coupled magnets prepared from core/shell Sm[Co(CN)6]·4H2O@GO particles: a novel chemical approach. (United States)

    Yang, Ce; Jia, Lihui; Wang, Shouguo; Gao, Chen; Shi, Dawei; Hou, Yanglong; Gao, Song


    SmCo5 based magnets with smaller size and larger maximum energy product have been long desired in various fields such as renewable energy technology, electronic industry and aerospace science. However, conventional relatively rough synthetic strategies will lead to either diminished magnetic properties or irregular morphology, which hindered their wide applications. In this article, we present a facile chemical approach to prepare 200 nm single domain SmCo5@Co core/shell magnets with coercivity of 20.7 kOe and saturation magnetization of 82 emu/g. We found that the incorporation of GO sheets is responsible for the generation of the unique structure. The single domain SmCo5 core contributes to the large coercivity of the magnets and the exchange-coupled Co shell enhances the magnetization. This method can be further utilized in the synthesis other Sm-Co based exchange-coupled magnets.

  7. Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion. (United States)

    Song, Xiaolei; Walczak, Piotr; He, Xiaowei; Yang, Xing; Pearl, Monica; Bulte, Jeff Wm; Pomper, Martin G; McMahon, Michael T; Janowski, Mirosław


    The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Predicted, focal opening of the BBB through intra-arterial infusion of hyperosmolar mannitol is feasible, but there is a need to facilitate imaging techniques (e.g. MRI) to guide interventional procedures and assess the outcomes. Here, we show that salicylic acid analogues (SAA) can depict the brain territory supplied by the catheter and detect the BBB opening, through chemical exchange saturation transfer (CEST) MRI. Hyperosmolar SAA solutions themselves are also capable of opening the BBB, and, when multiple SAA agents were co-injected, their locoregional perfusion could be differentiated.

  8. 基于技术系统进化理论的换热器化学除垢方法的研究%Research on Chemical Anti- fouling Methods of Heat Exchanger Based on Technical System Evolution Theory

    Institute of Scientific and Technical Information of China (English)

    李耀中; 李英利; 胡建超


    基于技术系统进化理论预测换热器化学除垢方法的研究方向,寻找一种能够代替或改善现有的除垢方法,从而解决现有化学法存在的污染环境、损伤设备、成本较高等缺点。%Based on technical system evolution theory to predict future research direction for chemical anti - fouling methods of heat exchanger and finding a method to replace or improve the present anti - fouling one. Furthmore, could overcome the shortcoming of the present chemical method such as polluting the environment, damaging equipment,and higher cost etc.

  9. Pharmaceutical Applications of Ion-Exchange Resins (United States)

    Elder, David


    The historical uses of ion-exchanged resins and a summary of the basic chemical principles involved in the ion-exchanged process are discussed. Specific applications of ion-exchange are provided that include drug stabilization, pharmaceutical excipients, taste-masking agents, oral sustained-release products, topical products for local application…

  10. Heat exchanger

    Energy Technology Data Exchange (ETDEWEB)

    Craig, L.B.; Farma, A.J.


    This invention concerns a heat exchanger as used in a space heater, of the type in which hot exhaust gases transfer heat to water or the like flowing through a helical heat exchange coil. A significant improvement to the efficiency of the heat exchange occurring between the air and water is achieved by using a conduit for the water having external helical fluting such that the hot gases circulate along two paths, rather than only one. A preferred embodiment of such a heat exchanger includes a porous combustion element for producing radiant heat from a combustible gas, surrounded by a helical coil for effectively transferring the heat in the exhaust gas, flowing radially from the combustion element, to the water flowing through the coil. 4 figs.

  11. The SQM/COSMO filter: reliable native pose identification based on the quantum-mechanical description of protein-ligand interactions and implicit COSMO solvation. (United States)

    Pecina, Adam; Meier, René; Fanfrlík, Jindřich; Lepšík, Martin; Řezáč, Jan; Hobza, Pavel; Baldauf, Carsten


    Current virtual screening tools are fast, but reliable scoring is elusive. Here, we present the 'SQM/COSMO filter', a novel scoring function featuring a quantitative semiempirical quantum mechanical (SQM) description of all types of noncovalent interactions coupled with implicit COSMO solvation. We show unequivocally that it outperforms eight widely used scoring functions. The accuracy and chemical generality of the SQM/COSMO filter make it a perfect tool for late stages of virtual screening.

  12. Next Generation Microchannel Heat Exchangers

    CERN Document Server

    Ohadi, Michael; Dessiatoun, Serguei; Cetegen, Edvin


    In Next Generation Microchannel Heat Exchangers, the authors’ focus on the new generation highly efficient heat exchangers and presentation of novel data and technical expertise not available in the open literature.  Next generation micro channels offer record high heat transfer coefficients with pressure drops much less than conventional micro channel heat exchangers. These inherent features promise fast penetration into many mew markets, including high heat flux cooling of electronics, waste heat recovery and energy efficiency enhancement applications, alternative energy systems, as well as applications in mass exchangers and chemical reactor systems. The combination of up to the minute research findings and technical know-how make this book very timely as the search for high performance heat and mass exchangers that can cut costs in materials consumption intensifies.

  13. International Exchanges

    Institute of Scientific and Technical Information of China (English)


    <正>On April 1st,2014,CPAPD Deputy Secretary General Ms.Chen Huaifan met with Mr.Djudjuk Juyoto Suntani,President of the World Peace Committee,Indonesia,who headed the delegation,in the CPAPD office.The two sides exchanged views on issues of common concern including cooperation between the two organizations and the inheritance of Chinese culture.

  14. Exchange Options

    NARCIS (Netherlands)

    Jamshidian, Farshid


    The contract is described and market examples given. Essential theoretical developments are introduced and cited chronologically. The principles and techniques of hedging and unique pricing are illustrated for the two simplest nontrivial examples: the classical Black-Scholes/Merton/Margrabe exchange

  15. Evidence from sup 18 O exchange measurements for steps involving a weak acid and a slow chemical transformation in the mechanism of phosphorylation of the gastric H sup + ,K sup + -ATPase by inorganic phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Faller, L.D.; Diaz, R.A. (Univ. of California School of Medicine and Veterans Administration Hospital Center, Los Angeles (USA))


    Phosphorylation of the gastric H,K-ATPase by P{sub i} has been studied by measuring the P{sup 18}O{sub j}{sup 16}O{sub 4-j} distribution as a function of time at different H{sup +}, K{sup +}, and ({sup 18}O)P{sub i} concentrations. The advantage of isotope exchange measurements is that the P{sup 18}O{sub j}{sup 16}O{sub 4-j} distribution depends on the relative rates of HOH loss to form the phosphoenzyme intermediate and P{sub i} dissociation from the enzyme. Therefore, {sup 18}O exchange is a sensitive probe of mechanism. K{sup +} increases the exchange rate ({nu}{sub ex}) but does not affect the partition coefficient (P{sub c}) that determines the P{sup 18}O{sub j}{sup 16}O{sub 4-j} distribution. Conversely, H{sup +} inhibits exchange. A single P{sub c} describes the data at every pH, but the value increases from 0.04 to pH 8 to 0.64 at pH 5.5. {nu}{sub ex} depends hyperbolically on (P{sub i}){sub 0}. K{sub m} for P{sub i} does not depend on pH, and P{sub c} does not depend on (P{sub i}){sub 0}. Individual rate constants in the phosphorylation mechanism are estimated. Formation of the E{center dot}P{sub i} complex that looses HOH is 1-2 orders of magnitude slower at pH 5.5 than at pH 8 and is not diffusion controlled. The observed change in P{sub c} with pH is compatible with catalysis occurring by a different mechanism when a group with pK{sub a} = 7.2 is protonated. Slower than diffusion-controlled formation of the E{center dot}P{sub i} complex that splits out HOH is evidence for a relatively slow, unimolecular chemical transformation involving an additional intermediate in the phosphorylation mechanism, such as a protein conformational change.

  16. Impact of the electrochemical porosity and chemical composition on the lithium ion exchange behavior of polypyrroles (ClO4-, TOS-, TFSI-) prepared electrochemically in propylene carbonate. comparative EQCM, EIS and CV studies. (United States)

    Dziewoński, Paweł Marek; Grzeszczuk, Maria


    Conditions of electrodeposition, i.e. a potential window of the process, addition of water, the current density, and morphology of substrate electrodes (Pt, Pt/TiO(2), Au), were shown to influence strongly ion-exchange properties of polypyrrole (PPy) synthesized in propylene carbonate (PC), doped with ClO(4)(-) or p-toluenesulfonate (TOS(-)). "Electrochemical porosity" and redox activity of PPy films were compared to the characteristics of poly(3,4-ethylenedioxythiophene) (PEDOT). A molecular indicator of the PPy film structure packing was bis(trifluoromethylsulfonyl)imide anion (TFSI(-)). Ion-exchange properties of PPy were found to be almost independent of chemical composition of the polymer, described in the literature as PPy(I), PPy(II), PPy(III). Instead, micro- and nanoscopic morphology of the polymer film and a molecular level packing of the polymer chains as well as the counterion nature are of the foremost importance. The polymer film structure/properties are shown to change upon prolonged redox/ionic stimulations. Lithium exchange between PPy films and contacting phases (PC electrolyte, TiO(2)) proceeds in addition to the anion exchange, the latter being a dominant process under conditions of the reversible electrochemical p-doping of PPy, although diffusion coefficients of PC solvated lithium ions in PPy are higher than diffusion coefficients of perchlorate, p-toluenesulfonate or bis(trifluoromethylsulfonyl)imide anions. The highest flux of Li(+) ions into/out of the PPy phase takes place about -1.0 V vs Ag/Ag(+) which is clearly evidenced by the cathodic/anodic CV peaks. Cation transport phenomena can be analyzed independently from anion transport when observed at a longer time scale (low values of potential scan rate) as each prevails at different redox states of the polymer. However, in a shorter time scale (v > or = 10 mV s(-1)), the opposite fluxes of cations and anions were observed to interfere. Furthermore, a net uptake of propylene carbonate by

  17. Solution structures of the prototypical 18 kDa translocator protein ligand, PK 11195, elucidated with 1H/13C NMR spectroscopy and quantum chemistry. (United States)

    Lee, Yong-Sok; Siméon, Fabrice G; Briard, Emmanuelle; Pike, Victor W


    Eighteen kilodalton translocator protein (TSPO) is an important target for drug discovery and for clinical molecular imaging of brain and peripheral inflammatory processes. PK 11195 [1a; 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide] is the major prototypical high-affinity ligand for TSPO. Elucidation of the solution structure of 1a is of interest for understanding small-molecule ligand interactions with the lipophilic binding site of TSPO. Dynamic (1)H/(13)C NMR spectroscopy of 1a revealed four quite stable but interconverting rotamers, due to amide bond and 2-chlorophenyl group rotation. These rotamers have been neglected in previous descriptions of the structure of 1a and of the binding of 1a to TSPO. Here, we used quantum chemistry at the level of B3LYP/6-311+G(2d,p) to calculate (13)C and (1)H chemical shifts for the rotamers of 1a and for the very weak TSPO ligand, N-desmethyl-PK 11195 (1b). These data, plus experimental NMR data, were then used to characterize the structures of rotamers of 1a and 1b in organic solution. Energy barriers for both the amide bond and 2'-chlorophenyl group rotation of 1a were determined from dynamic (1)H NMR to be similar (ca.17 to 18 kcal/mol), and they compared well with those calculated at the level of B3LYP/6-31G*. Furthermore, the computed barrier for Z to E rotation is considerably lower in 1a(18.7 kcal/mol) than in 1b (25.4 kcal/mol). NMR (NOE) unequivocally demonstrated that the E rotamer of 1a is the more stable in solution by about 0.4 kcal/mol. These detailed structural findings will aid future TSPO ligand design and support the notion that TSPO prefers to bind ligands as amide E-rotamers.

  18. Ion exchange equilibrium constants

    CERN Document Server

    Marcus, Y


    Ion Exchange Equilibrium Constants focuses on the test-compilation of equilibrium constants for ion exchange reactions. The book first underscores the scope of the compilation, equilibrium constants, symbols used, and arrangement of the table. The manuscript then presents the table of equilibrium constants, including polystyrene sulfonate cation exchanger, polyacrylate cation exchanger, polymethacrylate cation exchanger, polysterene phosphate cation exchanger, and zirconium phosphate cation exchanger. The text highlights zirconium oxide anion exchanger, zeolite type 13Y cation exchanger, and

  19. Online size-exclusion high-performance liquid chromatography light scattering and differential refractometry methods to determine degree of polymer conjugation to proteins and protein-protein or protein-ligand association states. (United States)

    Kendrick, B S; Kerwin, B A; Chang, B S; Philo, J S


    Characterizing the solution structure of protein-polymer conjugates and protein-ligand interactions is important in fields such as biotechnology and biochemistry. Size-exclusion high-performance liquid chromatography with online classical light scattering (LS), refractive index (RI), and UV detection offers a powerful tool in such characterization. Novel methods are presented utilizing LS, RI, and UV signals to rapidly determine the degree of conjugation and the molecular mass of the protein conjugate. Baseline resolution of the chromatographic peaks is not required; peaks need only be sufficiently separated to represent relatively pure fractions. An improved technique for determining the polypeptide-only mass of protein conjugates is also described. These techniques are applied to determining the degree of erythropoietin glycosylation, the degree of polyethylene glycol conjugation to RNase A and brain-derived neurotrophic factor, and the solution association states of these molecules. Calibration methods for the RI, UV, and LS detectors will also be addressed, as well as online methods to determine protein extinction coefficients and dn/dc values both unconjugated and conjugated protein molecules.

  20. Violation of homeostasis of the main types of exchange and immune resistance status in children with subclinical hypovitaminosis in conditions of exposure to chemical environmental factors

    Directory of Open Access Journals (Sweden)

    A.M. Yambulatov


    Full Text Available The study of the chemical substances’ content of anthropogenic origin in children with subclinical polyhypovitaminosis was conducted. It was found that a deficiency of vitamins A, C, E, B6 and B12 increases the risk of developing of elevated concentrations of organic substances of technogenic origin in blood in 1.4–6.9 times. In children with subclinical polyhypovitaminosis and high blood phenol, formaldehyde, aromatic hydrocarbons, and organ chlorine compounds increases the tension of erythropoiesis, decreases the activity of proliferating processes of lympfomonocytic germ cell factors of nonspecific resistance. Even subclinical forms of polyhypovitaminosis on the background of high content of organic compounds in the blood of children are accompanied by a slowdown of protein and carbohydrate metabolism, depletion of antioxidant defense system of reserves and shortage of energy metabolism. Developing disorders of fat metabolism in children with subclinical polyhypovitaminosis occur against a background of strained reactions of hormonal regulation that, in case of the progressive course may pose a threat to the early development of cardiovascular disease in older age groups.

  1. Development of carbon nanotubes based gas diffusion layers by in situ chemical vapor deposition process for proton exchange membrane fuel cells (United States)

    Kannan, A. M.; Kanagala, P.; Veedu, V.

    A proprietary in situ chemical vapor deposition (CVD) process was developed for gas diffusion layer (GDL) by growing a micro-porous layer on the macro-porous, non-woven fibrous carbon paper. The characteristics of the GDL samples such as, surface morphology, wetting characteristics, and cross-section were characterized using electron microscopes, goniometer and focused ion beam, respectively. Fuel cell performance of the GDLs was evaluated using single cell with hydrogen/oxygen as well as hydrogen/air at ambient pressure, at elevated temperature and various RH conditions using Nafion-212 as an electrolyte. The GDLs with in situ growth of micro-porous layers containing carbon nanotubes (CNTs) without any hydrophobic agent showed significant improvement in mechanical robustness as well as fuel cell performance at elevated temperature at lower RH conditions. The micro-porous layer of the GDLs as seen under scanning electron microscope showed excellent surface morphology with surface homogeneity through reinforcement by the multi-walled CNTs.

  2. Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR (United States)

    Witte, C.; Kunth, M.; Rossella, F.; Schröder, L.


    Xenon is well known to undergo host-guest interactions with proteins and synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical pumping, allowing the investigation of highly dilute systems, it makes an ideal nuclear magnetic resonance probe for such host molecules. The utility of xenon as a probe can be further improved using Chemical Exchange Saturation Transfer using hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires a polarizer and xenon infusion system optimized for such measurements. We present the design of a hyperpolarizer and xenon infusion system specifically designed to meet the requirements of Hyper-CEST measurements. One key element of this design is preventing rubidium runaway, a chain reaction induced by laser heating that prevents efficient utilization of high photon densities. Using thermocouples positioned along the pumping cell we identify the sources of heating and conditions for rubidium runaway to occur. We then demonstrate the effectiveness of actively cooling the optical cell to prevent rubidium runaway in a compact setup. This results in a 2-3-fold higher polarization than without cooling, allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min of 129Xe. The simplicity of this design also allows it to be retrofitted to many existing polarizers. Combined with a direction infusion system that reduces shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in unprecedented detail, allowing us to completely resolve peaks separated by just 1.62 ppm. Due to its high polarization and excellent stability, our design allows the comparison of underlying theories of host-guest systems with experiment at low concentrations, something extremely difficult with previous polarizers.

  3. Fault-Tolerant Heat Exchanger (United States)

    Izenson, Michael G.; Crowley, Christopher J.


    A compact, lightweight heat exchanger has been designed to be fault-tolerant in the sense that a single-point leak would not cause mixing of heat-transfer fluids. This particular heat exchanger is intended to be part of the temperature-regulation system for habitable modules of the International Space Station and to function with water and ammonia as the heat-transfer fluids. The basic fault-tolerant design is adaptable to other heat-transfer fluids and heat exchangers for applications in which mixing of heat-transfer fluids would pose toxic, explosive, or other hazards: Examples could include fuel/air heat exchangers for thermal management on aircraft, process heat exchangers in the cryogenic industry, and heat exchangers used in chemical processing. The reason this heat exchanger can tolerate a single-point leak is that the heat-transfer fluids are everywhere separated by a vented volume and at least two seals. The combination of fault tolerance, compactness, and light weight is implemented in a unique heat-exchanger core configuration: Each fluid passage is entirely surrounded by a vented region bridged by solid structures through which heat is conducted between the fluids. Precise, proprietary fabrication techniques make it possible to manufacture the vented regions and heat-conducting structures with very small dimensions to obtain a very large coefficient of heat transfer between the two fluids. A large heat-transfer coefficient favors compact design by making it possible to use a relatively small core for a given heat-transfer rate. Calculations and experiments have shown that in most respects, the fault-tolerant heat exchanger can be expected to equal or exceed the performance of the non-fault-tolerant heat exchanger that it is intended to supplant (see table). The only significant disadvantages are a slight weight penalty and a small decrease in the mass-specific heat transfer.

  4. Amide cis-trans isomerization in aqueous solutions of methyl N-formyl-D-glucosaminides and methyl N-acetyl-D-glucosaminides: chemical equilibria and exchange kinetics. (United States)

    Hu, Xiaosong; Zhang, Wenhui; Carmichael, Ian; Serianni, Anthony S


    Amide cis-trans isomerization (CTI) in methyl 2-deoxy-2-acylamido-d-glucopyranosides was investigated by (1)H and (13)C NMR spectroscopy. Singly (13)C-labeled methyl 2-deoxy-2-formamido-d-glucopyranoside (MeGlcNFm) anomers provided standard (1)H and (13)C chemical shifts and (1)H-(1)H and (13)C-(13)C spin-coupling constants for cis and trans amides that are detected readily in aqueous solution. Equipped with this information, doubly (13)C-labeled methyl 2-deoxy-2-acetamido-d-glucopyranoside (MeGlcNAc) anomers were investigated, leading to the detection and quantification of cis and trans amides in this biologically important aminosugar. In comparison to MeGlcNFm anomers, the percentage of cis amide in aqueous solutions of MeGlcNAc anomers is small ( approximately 23% for MeGlcNFm versus approximately 1.8% for MeGlcNAc at 42 degrees C) but nevertheless observable with assistance from (13)C-labeling. Temperature studies gave thermodynamic parameters DeltaG degrees , DeltaH degrees , and DeltaS degrees for cis-trans interconversion in MeGlcNFm and MeGlcNAc anomers. Cis/trans equilibria depended on anomeric configuration, with solutions of alpha-anomers containing less cis amide than those of beta-anomers. Confirmation of the presence of cis amide in MeGlcNAc solutions derived from quantitative (13)C saturation transfer measurements of CTI rate constants as a function of solution temperature, yielding activation parameters E(act), DeltaG degrees (), DeltaH degrees (), and DeltaS degrees () for saccharide CTI. Rate constants for the conversion of trans to cis amide in MeGlcNFm and MeGlcNAc anomers ranged from 0.02 to 3.59 s(-1) over 31-85 degrees C, compared to 0.24-80 s(-1) for the conversion of cis to trans amide over the same temperature range. Energies of activation ranged from 16-19 and 19-20 kcal/mol for the cis --> trans and trans --> cis processes, respectively. Complementary DFT calculations on MeGlcNFm and MeGlcNAc model structures were conducted to evaluate

  5. The system applying and analyzing of Z spectrum in chemical exchange saturation transfer%化学交换饱和转移的Z谱分析展示系统

    Institute of Scientific and Technical Information of China (English)

    白帅; 侯榆青; 贺小伟; 薛心雨


    Objective:To create a simple and friendly software toolkit to display and analyze Z spectrum of Chemical Exchange Saturation Transfer (CEST), which is convenient for clinicians and researchers to apply and research. Materials and Methods: The data is collected by conventional CEST imaging method, and the system is made by MATLAB GUI. Fitting the Z spectrum of different region of interest (ROI) which are selected by taking the mouse, and also carrying on its analysis and comparison. Results:The different positions and different pixel values of image’s ROI, the Z spectrum are different, which reflect different biological information. Conclusion:Z spectrum directly determines the final CEST signal analysis and relates biomedical information extraction. The functions of this system mainly include CEST image denoising, the formation of asymmetric magnetization transfer rate (MTRasym) mapping, selecting ROI and fitting the Z spectrum. To fit the Z spectra of ROI which are selected by taking the mouse.%目的:建立一个简单友好,显示和分析化学交换饱和转移(chemical exchange saturation transfer, CEST)Z谱的软件工具包,方便临床医生和研究者进行应用研究。材料与方法使用传统CEST成像方法采集数据,通过MATLAB GUI制作系统,并通过两种方法实现定制选取以鼠标指定点为中心的任意大小的多个感兴趣区域(region of interest, ROI),展示其Z谱,并对其进行分析比较。结果图像不同位置ROI、不同像素大小ROI得到的Z谱不同,反映出不同的生物学信息。结论 Z谱决定最终CEST信号分析与相关生物医学信息提取。系统主要功能包括CEST图像归一化去噪,不对称磁化传递速率(magnetization transfer ratio, MTRasym)映射的形成,ROI选取及Z谱拟合。

  6. International Exchanges

    Institute of Scientific and Technical Information of China (English)


    On October 12,2015,Mr.Zhu Rui,CPAPD Secretary General,chaired informal discussions with U.S.young experts and scholars on arms control and non-proliferation.The two sides exchanged views on international arms control,disarmament,non-proliferation and nuclear security,etc.During October 12 to 16,2015,at the invitation of the CPAPD,a four-member delegation from the Vietnam Peace Committee headed by its Vice-President Ms.Nguyen Thi Hoang Van

  7. Scraped surface heat exchangers. (United States)

    Rao, Chetan S; Hartel, Richard W


    Scraped surface heat exchangers (SSHEs) are commonly used in the food, chemical, and pharmaceutical industries for heat transfer, crystallization, and other continuous processes. They are ideally suited for products that are viscous, sticky, that contain particulate matter, or that need some degree of crystallization. Since these characteristics describe a vast majority of processed foods, SSHEs are especially suited for pumpable food products. During operation, the product is brought in contact with a heat transfer surface that is rapidly and continuously scraped, thereby exposing the surface to the passage of untreated product. In addition to maintaining high and uniform heat exchange, the scraper blades also provide simultaneous mixing and agitation. Heat exchange for sticky and viscous foods such as heavy salad dressings, margarine, chocolate, peanut butter, fondant, ice cream, and shortenings is possible only by using SSHEs. High heat transfer coefficients are achieved because the boundary layer is continuously replaced by fresh material. Moreover, the product is in contact with the heating surface for only a few seconds and high temperature gradients can be used without the danger of causing undesirable reactions. SSHEs are versatile in the use of heat transfer medium and the various unit operations that can be carried out simultaneously. This article critically reviews the current understanding of the operations and applications of SSHEs.

  8. The Foundations of Protein-Ligand Interaction (United States)

    Klebe, Gerhard

    For the specific design of a drug we must first answer the question: How does a drug achieve its activity? An active ingredient must, in order to develop its action, bind to a particular target molecule in the body. Usually this is a protein, but also nucleic acids in the form of RNA and DNA can be target structures for active agents. The most important condition for binding is at first that the active agent exhibits the correct size and shape in order to optimally fit into a cavity exposed to the surface of the protein, the "bindingpocket". It is further necessary for the surface properties of the ligand and protein to be mutually compatible to form specific interactions. In 1894 Emil Fischer compared the exact fit of a substrate for the catalytic centre of an enzyme with the picture of a "lock-and-key". Paul Ehrlich coined in 1913 "Corpora non agunt nisi fixata", literally "bodies do not work when they are not bound". He wanted to imply that active agents that are meant to kill bacteria or parasites must be "fixed" by them, i.e. linked to their structures. Both concepts form the starting point for any rational concept in the development of active pharmaceutical ingredients. In many respects they still apply today. A drug must, after being administered, reach its target and interact with a biological macromolecule. Specific agents have a large affinity and sufficient selectivity to bind to the macromolecule's active site. This is the only way they can develop the desired biological activity without side-effects.

  9. Segmented heat exchanger (United States)

    Baldwin, Darryl Dean; Willi, Martin Leo; Fiveland, Scott Byron; Timmons, Kristine Ann


    A segmented heat exchanger system for transferring heat energy from an exhaust fluid to a working fluid. The heat exchanger system may include a first heat exchanger for receiving incoming working fluid and the exhaust fluid. The working fluid and exhaust fluid may travel through at least a portion of the first heat exchanger in a parallel flow configuration. In addition, the heat exchanger system may include a second heat exchanger for receiving working fluid from the first heat exchanger and exhaust fluid from a third heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the second heat exchanger in a counter flow configuration. Furthermore, the heat exchanger system may include a third heat exchanger for receiving working fluid from the second heat exchanger and exhaust fluid from the first heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the third heat exchanger in a parallel flow configuration.

  10. Chemical Exchange Saturation Transfer MR Imaging is Superior to Diffusion-Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: A Study on Substantia Nigra and Striatum. (United States)

    Li, Chunmei; Wang, Rui; Chen, Haibo; Su, Wen; Li, Shuhua; Zhao, Xuna; Zhou, Jinyuan; Qiao, Jian; Lou, Baohui; Song, Guodong; Chen, Min


    Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date, the diagnosis of PD is still based primarily on the clinical manifestations, which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical exchange saturation transfer (CEST) imaging and diffusion-tensor imaging (DTI) in PD at 3 T by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3-T MR system, using an eight-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization transfer ratio asymmetry at 3.5 ppm, MTRasym(3.5 ppm), and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen, and caudate. The MTRasym(3.5 ppm) value, the total CEST signal intensity, and fractional anisotropy value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004, and P diffusivity in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

  11. Totalization Data Exchange (TDEX) (United States)

    Social Security Administration — The Totalization Data Exchange (TDEX) process is an exchange between SSA and its foreign country partners to identify deaths of beneficiaries residing abroad. The...

  12. Exchange frequency in replica exchange molecular dynamics (United States)

    Sindhikara, Daniel; Meng, Yilin; Roitberg, Adrian E.


    The effect of the exchange-attempt frequency on sampling efficiency is studied in replica exchange molecular dynamics (REMD). We show that sampling efficiency increases with increasing exchange-attempt frequency. This conclusion is contrary to a commonly expressed view in REMD. Five peptides (1-21 residues long) are studied with a spectrum of exchange-attempt rates. Convergence rates are gauged by comparing ensemble properties between fixed length test REMD simulations and longer reference simulations. To show the fundamental correlation between exchange frequency and convergence time, a simple model is designed and studied, displaying the same basic behavior of much more complex systems.

  13. 煤化工大型缠绕管式换热器的设计与制造%Design and Manufacturing of Large-scale Spiral Wound Heat Exchanger in Coal-chemical Industry

    Institute of Scientific and Technical Information of China (English)

    陈永东; 张贤安


    Due to its excellent heat transfer property,the adaptability to variable loads of unit and the op-eration reliability,large-scale spiral wound heat exchanger (SWHE)has a bright application prospect in such fields as the coal deep processing,refinery and natural gas of China.With respect to the multi-stream SWHE for large-scale coal-chemical plant,the design and manufacturing technology difficulties are ana-lyzed for large-scale SWHE.As to the multi-stream SWHE,such contents as the different structure styles of tube-sheet,particularity of tube-sheet design calculation,compatibility of each tube side in the same shell and the large-scale combined raw gas cooler are discussed.Additionally,the outlet structure between tube bundle and tube -sheet is also discussed .Combined with the analysis results of strain aging for austenitic stainless steel,the normal deformation rate range is obtained for the heat exchanger tube during wrapping. Radiographic testing (RT)is carried out for the weldment between tubes and tube-sheet of large-scale SWHE,and the RT operation rule is presented for reference.In China,the large-scale SWHE with area larger than 10000 m2 can be produced now,and abundant experience has been accumulated in the design and manufacturing technology.However,there is still a certain gap between our country and the advanced countries in Europe and America in such aspects as the material variety of SWHE,the process design of large-scale main cryogenic heat exchanger,the application of numerical simulation technology in design and the quantified technology of quality inspection for the weldment between heat exchanger tube and tube-sheet etc.%大型缠绕管式换热器不仅具有较好的传热性能,还同时具有对装置变负荷的适应性和运行可靠的操作特性,在我国煤炭深加工、炼油、天然气等领域的应用呈现出良好的发展前景。从煤化工大型多股流缠绕管式换热器出发,对缠绕管式换热器设计和制

  14. Mapeamento das interações proteína-ligante através de técnicas de RMN de ¹H utilizando detecção do ligante Screening protein-ligand interactions using ¹H NMR techniques for detecting the ligand

    Directory of Open Access Journals (Sweden)

    Isis Martins Figueiredo


    Full Text Available NMR is a valuable screening tool for the binding of ligands to proteins providing structural information on both protein and ligands and is thus largely applied to drug-discovery. Among the recent NMR techniques to probe weak binding protein-ligand complexes we have critically evaluated the advantages and disadvantages of STD (Saturation Transfer Difference, WaterLOGSY (Water Ligand Observation with Gradient Spectroscopy, NOE pumping and DOSY-NOESY (Diffusion-Ordered NOESY using a mixture of BSA (bovine serum albumin plus salicylic acid, caffeine, citric acid, adipic acid and D-glucose.

  15. Indiana Health Information Exchange (United States)

    The Indiana Health Information Exchange is comprised of various Indiana health care institutions, established to help improve patient safety and is recognized as a best practice for health information exchange.

  16. Synthesis, characterization and ion exchange properties of zirconium(IV) tungstoiodophosphate, a new cation exchanger

    Indian Academy of Sciences (India)

    Weqar Ahmad Siddiqui; Shakeel Ahmad Khan


    Zirconium(IV) tungstoiodophosphate has been synthesized under a variety of conditions. The most chemically and thermally stable sample is prepared by adding a mixture of aqueous solutions of 0.5 mol L-1 sodium tungstate, potassium iodate and 1 mol L-1 orthophosphoric acid to aqueous solution of 0.1 mol L-1 zirconium(IV) oxychloride. Its ion exchange capacity for Na+ and K+ was found to be 2.20 and 2.35 meq g-1 dry exchanger, respectively. The material has been characterized on the basis of chemical composition, pH titration, Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis. The effect on the exchange capacity of drying the exchanger at different temperatures has been studied. The analytical importance of the material has been established by quantitative separation of Pb2+ from other metal ions.

  17. Modeling of Crystalline Silicotitanate Ion Exchange Columns

    Energy Technology Data Exchange (ETDEWEB)

    Walker, D.D.


    Non-elutable ion exchange is being considered as a potential replacement for the In-Tank Precipitation process for removing cesium from Savannah River Site (SRS) radioactive waste. Crystalline silicotitanate (CST) particles are the reference ion exchange medium for the process. A major factor in the construction cost of this process is the size of the ion exchange column required to meet product specifications for decontaminated waste. To validate SRS column sizing calculations, SRS subcontracted two reknowned experts in this field to perform similar calculations: Professor R. G. Anthony, Department of Chemical Engineering, Texas A&038;M University, and Professor S. W. Wang, Department of Chemical Engineering, Purdue University. The appendices of this document contain reports from the two subcontractors. Definition of the design problem came through several meetings and conference calls between the participants and SRS personnel over the past few months. This document summarizes the problem definition and results from the two reports.

  18. Modern Chemical Technology, Volume 9. (United States)

    Pecsok, Robert L.; Chapman, Kenneth

    This volume is one of the series for the Chemical Technician Curriculum Project (ChemTeC) of the American Chemical Society funded by the National Science Foundation. It consists of discussions, exercises, and experiments on the following topics: ion exchange, electrphoresis, dialysis, electrochemistry, corrosion, electrolytic cells, coulometry,…

  19. Adaptively Compressed Exchange Operator

    CERN Document Server

    Lin, Lin


    The Fock exchange operator plays a central role in modern quantum chemistry. The large computational cost associated with the Fock exchange operator hinders Hartree-Fock calculations and Kohn-Sham density functional theory calculations with hybrid exchange-correlation functionals, even for systems consisting of hundreds of atoms. We develop the adaptively compressed exchange operator (ACE) formulation, which greatly reduces the computational cost associated with the Fock exchange operator without loss of accuracy. The ACE formulation does not depend on the size of the band gap, and thus can be applied to insulating, semiconducting as well as metallic systems. In an iterative framework for solving Hartree-Fock-like systems, the ACE formulation only requires moderate modification of the code, and can be potentially beneficial for all electronic structure software packages involving exchange calculations. Numerical results indicate that the ACE formulation can become advantageous even for small systems with tens...

  20. Microsoft Exchange 2013 cookbook

    CERN Document Server

    Van Horenbeeck, Michael


    This book is a practical, hands-on guide that provides the reader with a number of clear, step-by-step exercises.""Microsoft Exchange 2013 Cookbook"" is targeted at network administrators who deal with the Exchange server in their day-to-day jobs. It assumes you have some practical experience with previous versions of Exchange (although this is not a requirement), without being a subject matter expert.

  1. Exchange rate regime choice

    Directory of Open Access Journals (Sweden)

    Beker Emilija


    Full Text Available The choice of an adequate exchange rate regime proves to be a highly sensitive field within which the economic authorities present and confirm themselves. The advantages and disadvantages of fixed and flexible exchange rate regimes, which have been quite relativized from the conventional point of view, together with simultaneous, but not synchronized effects of structural and external factors, remain permanently questioned throughout a complex process of exchange rate regime decision making. The paper reflects the attempt of critical identification of the key exchange rate performances with emphasis on continuous non-uniformity and (uncertainty of shelf life of a relevant choice.

  2. Usable optimistic fair exchange


    Küpçü, Alptekin; Lysyanskaya, A.


    Fairly exchanging digital content is an everyday problem. It has been shown that fair exchange cannot be achieved without a trusted third party (called the Arbiter). Yet, even with a trusted party, it is still non-trivial to come up with an efficient solution, especially one that can be used in a p2p file sharing system with a high volume of data exchanged. We provide an efficient optimistic fair exchange mechanism for bartering digital files, where receiving a payment in return for a file (b...

  3. Anion exchange polymer electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Seung; Kim, Dae Sik; Lee, Kwan-Soo


    Solid anion exchange polymer electrolytes and compositions comprising chemical compounds comprising a polymeric core, a spacer A, and a guanidine base, wherein said chemical compound is uniformly dispersed in a suitable solvent and has the structure: ##STR00001## wherein: i) A is a spacer having the structure O, S, SO.sub.2, --NH--, --N(CH.sub.2).sub.n, wherein n=1-10, --(CH.sub.2).sub.n--CH.sub.3--, wherein n=1-10, SO.sub.2-Ph, CO-Ph, ##STR00002## wherein R.sub.5, R.sub.6, R.sub.7 and R.sub.8 each are independently --H, --NH.sub.2, F, Cl, Br, CN, or a C.sub.1-C.sub.6 alkyl group, or any combination of thereof; ii) R.sub.9, R.sub.10, R.sub.11, R.sub.12, or R.sub.13 each independently are --H, --CH.sub.3, --NH.sub.2, --NO, --CH.sub.nCH.sub.3 where n=1-6, HC.dbd.O--, NH.sub.2C.dbd.O--, --CH.sub.nCOOH where n=1-6, --(CH.sub.2).sub.n--C(NH.sub.2)--COOH where n=1-6, --CH--(COOH)--CH.sub.2--COOH, --CH.sub.2--CH(O--CH.sub.2CH.sub.3).sub.2, --(C.dbd.S)--NH.sub.2, --(C.dbd.NH)--N--(CH.sub.2).sub.nCH.sub.3, where n=0-6, --NH--(C.dbd.S)--SH, --CH.sub.2--(C.dbd.O)--O--C(CH.sub.3).sub.3, --O--(CH.sub.2).sub.n--CH--(NH.sub.2)--COOH, where n=1-6, --(CH.sub.2).sub.n--CH.dbd.CH wherein n=1-6, --(CH.sub.2).sub.n--CH--CN wherein n=1-6, an aromatic group such as a phenyl, benzyl, phenoxy, methylbenzyl, nitrogen-substituted benzyl or phenyl groups, a halide, or halide-substituted methyl groups; and iii) wherein the composition is suitable for use in a membrane electrode assembly.

  4. Building Relationships through Exchange (United States)

    Primavera, Angi; Hall, Ellen


    From the moment of birth, children form and develop relationships with others in their world based on exchange. Children recognize that engaging in such encounters offers them the opportunity to enter into a relationship with another individual and to nurture that relationship through the exchange of messages and gifts, items and ideas. At Boulder…

  5. Optimization of Heat Exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Ivan Catton


    The objective of this research is to develop tools to design and optimize heat exchangers (HE) and compact heat exchangers (CHE) for intermediate loop heat transport systems found in the very high temperature reator (VHTR) and other Generation IV designs by addressing heat transfer surface augmentation and conjugate modeling. To optimize heat exchanger, a fast running model must be created that will allow for multiple designs to be compared quickly. To model a heat exchanger, volume averaging theory, VAT, is used. VAT allows for the conservation of mass, momentum and energy to be solved for point by point in a 3 dimensional computer model of a heat exchanger. The end product of this project is a computer code that can predict an optimal configuration for a heat exchanger given only a few constraints (input fluids, size, cost, etc.). As VAT computer code can be used to model characteristics )pumping power, temperatures, and cost) of heat exchangers more quickly than traditional CFD or experiment, optimization of every geometric parameter simultaneously can be made. Using design of experiment, DOE and genetric algorithms, GE, to optimize the results of the computer code will improve heat exchanger disign.

  6. Shell-and-double concentric-tube heat exchangers (United States)

    Bougriou, Chérif; Baadache, Khireddine


    This study concerns a new type of heat exchangers, which is that of shell-and-double concentric-tube heat exchangers. These heat exchangers can be used in many specific applications such as air conditioning, waste heat recovery, chemical processing, pharmaceutical industries, power production, transport, distillation, food processing, cryogenics, etc. The case studies include both design calculations and performance calculations. It is demonstrated that the relative diameter sizes of the two tubes with respect to each other are the most important parameters that influence the heat exchanger size.

  7. Aberration Corrected Emittance Exchange

    CERN Document Server

    Nanni, Emilio A


    Full exploitation of emittance exchange (EEX) requires aberration-free performance of a complex imaging system including active radio-frequency (RF) elements which can add temporal distortions. We investigate the performance of an EEX line where the exchange occurs between two dimensions with normalized emittances which differ by orders of magnitude. The transverse emittance is exchanged into the longitudinal dimension using a double dog-leg emittance exchange setup with a 5 cell RF deflector cavity. Aberration correction is performed on the four most dominant aberrations. These include temporal aberrations that are corrected with higher order magnetic optical elements located where longitudinal and transverse emittance are coupled. We demonstrate aberration-free performance of emittances differing by 4 orders of magnitude, i.e. an initial transverse emittance of $\\epsilon_x=1$ pm-rad is exchanged with a longitudinal emittance of $\\epsilon_z=10$ nm-rad.

  8. Ion exchange tempering of glass ophthalmic lenses. (United States)

    Keeney, A H; Duerson, H L


    We performed low velocity drop-ball tests using 5/8-, 7/8-, and 1-inch diameter steel balls on ophthalmic crown glass lenses chemically tempered by the ion exchange process. Four representative dioptric strengths (+ 2.50 spherical, - 2.50 spherical, -2.50 cylindrical, and plano) were studied with the isolated lenses mounted, convex side up, on the American National Standards Institute Z80 test block. New ion exchange lenses exhibited a 100 to 350% greater capacity for attenuation of energy from low velocity, large size missiles than matched lenses of similar strength prepared by the conventional heat-treating and air-quenching process.

  9. Chemical Emergencies (United States)

    When a hazardous chemical has been released, it may harm people's health. Chemical releases can be unintentional, as in the case of an ... the case of a terrorist attack with a chemical weapon. Some hazardous chemicals have been developed by ...

  10. A Laboratory Exercise Using a Physical Model for Demonstrating Countercurrent Heat Exchange (United States)

    Loudon, Catherine; Davis-Berg, Elizabeth C.; Botz, Jason T.


    A physical model was used in a laboratory exercise to teach students about countercurrent exchange mechanisms. Countercurrent exchange is the transport of heat or chemicals between fluids moving in opposite directions separated by a permeable barrier (such as blood within adjacent blood vessels flowing in opposite directions). Greater exchange of…

  11. Roles of Na+/H+ exchange in regulation of p38 mitogen-activated protein kinase activity and cell death after chemical anoxia in NIH3T3 fibroblasts

    DEFF Research Database (Denmark)

    Rentsch, Maria L; Ossum, Carlo G; Hoffmann, Else K;


    , p38 mitogen-activated protein kinase (MAPK), ERK1/2, p53, and Akt activity, and cell death, after chemical anoxia in NIH3T3 fibroblasts. The NHE1 inhibitor 5'-(N-ethyl-N-isopropyl) amiloride (EIPA) (5 muM), as well as removal of extracellular Na(+) [replaced by N-methyl-D: -glucamine (NMDG......) and extracellular signal-regulated kinase (ERK) (PD98059). In contrast, chemical anoxia activated p38 MAPK in an NHE-dependent manner, while ERK1/2 activity was unaffected. Anoxia-induced cell death was caspase-3-independent, mildly attenuated by EIPA, potently exacerbated by SB203580, and unaffected by PD98059...

  12. Anion exchange membrane (United States)

    Verkade, John G; Wadhwa, Kuldeep; Kong, Xueqian; Schmidt-Rohr, Klaus


    An anion exchange membrane and fuel cell incorporating the anion exchange membrane are detailed in which proazaphosphatrane and azaphosphatrane cations are covalently bonded to a sulfonated fluoropolymer support along with anionic counterions. A positive charge is dispersed in the aforementioned cations which are buried in the support to reduce the cation-anion interactions and increase the mobility of hydroxide ions, for example, across the membrane. The anion exchange membrane has the ability to operate at high temperatures and in highly alkaline environments with high conductivity and low resistance.

  13. Heat exchanger design handbook

    CERN Document Server

    Thulukkanam, Kuppan


    Completely revised and updated to reflect current advances in heat exchanger technology, Heat Exchanger Design Handbook, Second Edition includes enhanced figures and thermal effectiveness charts, tables, new chapter, and additional topics--all while keeping the qualities that made the first edition a centerpiece of information for practicing engineers, research, engineers, academicians, designers, and manufacturers involved in heat exchange between two or more fluids.See What's New in the Second Edition: Updated information on pressure vessel codes, manufacturer's association standards A new c

  14. Exchange Rate in Focus

    Institute of Scientific and Technical Information of China (English)


    China announced the reform of its decade-old RMB exchange rate regime last July, linking the RMB to a basket of currencies rather than the U.S. dollar alone, and allowing the RMB to appreciate 2 percent against the U.S. currency. Since then, different viewpoints on the new regime have been voiced. The People's Bank of China, the central bank, said in a statement in late March that it would further improve the system, broadening the foreign exchange market, increasing the flexibility of the RMB exchange r...

  15. Data Exchange Inventory System (DEXI) (United States)

    Social Security Administration — Enterprise tool used to identify data exchanges occurring between SSA and our trading partners. DEXI contains information on both incoming and outgoing exchanges and...

  16. Emittance exchange results

    Energy Technology Data Exchange (ETDEWEB)

    Fliller, R.P., III; /Brookhaven; Koeth, T.; /Rutgers U., Piscataway


    The promise of next-generation light sources depends on the availability of ultra-low emittance electron sources. One method of producing low transverse emittance beams is to generate a low longitudinal emittance beam and exchange it with a large transverse emittance. Experiments are underway at Fermilab's A0 Photoinjector and ANL's Argonne Wakefield Accelerator using the exchange scheme of Kim and Sessler. The experiment at the A0 Photoinjector exchanges a large longitudinal emittance with a small transverse emittance. AWA expects to exchange a large transverse emittance with a small longitudinal emittance. In this paper we discuss recent results at A0 and AWA and future plans for these experiments.

  17. Emittance Exchange Results

    Energy Technology Data Exchange (ETDEWEB)

    Fliller III,R.; Koeth, T.


    The promise of next-generation light sources depends on the availability of ultra-low emittance electron sources. One method of producing low transverse emittance beams is to generate a low longitudinal emittance beam and exchange it with a large transverse emittance. Experiments are underway at Fermilab's A0 Photoinjector and ANL's Argonne Wakefield Accelerator using the exchange scheme of Kim and Sessler. The experiment at the A0 Photoinjector exchanges a large longitudinal emittance with a small transverse emittance. AWA expects to exchange a large transverse emittance with a small longitudinal emittance. In this paper we discuss recent results at A0 and AWA and future plans for these experiments.

  18. Exchange Risk Management Policy

    CERN Document Server


    At the Finance Committee of March 2005, following a comment by the CERN Audit Committee, the Chairman invited the Management to prepare a document on exchange risk management policy. The Finance Committee is invited to take note of this document.

  19. NASA Earth Exchange (NEX) (United States)

    National Aeronautics and Space Administration — The NASA Earth Exchange (NEX) represents a new platform for the Earth science community that provides a mechanism for scientific collaboration and knowledge sharing....

  20. HUD Exchange Grantee Database (United States)

    Department of Housing and Urban Development — The About Grantees section of the HUD Exchange brings up contact information, reports, award, jurisdiction, and location data for organizations that receive HUD...

  1. Microplate Heat Exchanger Project (United States)

    National Aeronautics and Space Administration — We propose a microplate heat exchanger for cryogenic cooling systems used for continuous flow distributed cooling systems, large focal plane arrays, multiple cooling...

  2. Surface exchange kinetics and chemical diffusivities of BaZr{sub 0.2}Ce{sub 0.65}Y{sub 0.15}O{sub 3−δ} by electrical conductivity relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Dae-Kwang; Jeon, Sang-Yun; Singh, Bhupendra [Ionics Lab, School of Materials Science and Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwang-Ju 500-757 (Korea, Republic of); Park, Jun-Young [Department of Advanced Materials Engineering, Sejong University, Seoul 143-747 (Korea, Republic of); Song, Sun-Ju, E-mail: [Ionics Lab, School of Materials Science and Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwang-Ju 500-757 (Korea, Republic of)


    Highlights: • Electrical conductivity relaxation in BaCe{sub 0.65}Zr{sub 0.2}Y{sub 0.15}O{sub 3−δ} was monitored. • Monotonic relaxation behavior was observed during oxidation/reduction. • Nonmonotonic twofold relaxation behavior was observed during hydration/dehydration. • Surface exchange coefficients and diffusivities of O and H were calculated. - Abstract: Perovskite-type oxide BaCe{sub 0.65}Zr{sub 0.2}Y{sub 0.15}O{sub 3−δ} (BCZY2015) was synthesized by a solid state reaction method. BCZY2015 samples were characterized by powder X-ray diffraction (XRD) and scanning electron microscopy (SEM). The time dependent variation in electrical conductivity of BCZY2015 was monitored during the oxidation/reduction in oxygen partial pressure (pO{sub 2}) range of −2.28 ⩽ log (pO{sub 2}/atm) ⩽ −0.68 at a fixed water vapor pressure (pH{sub 2}O), and during the hydration/dehydration in −3.15 ⩽ log (pH{sub 2}O/atm) ⩽ −2.35 range in air. The electrical conductivity showed a monotonic relaxation behavior by the ambipolar diffusion of V{sub o}{sup ··} and OH{sub o}{sup ·} during the oxidation/reduction and the relaxation process was governed by the diffusivity of oxygen (D-tilde{sub vO}). On the other hand, during the hydration/dehydration process, a non-monotonic twofold relaxation behavior was observed due to the decoupled diffusion of H and O components with the mediation of holes, and the conductivity relaxation process was governed by the diffusivities of both H (D-tilde{sub iH}) and O (D-tlde{sub vH}). The values of surface exchange coefficients and diffusivities of oxygen and hydrogen were calculated from Fick’s second law by the nonlinear least squares fitting of the conductivity data, as proposed by Yoo et al. (2008)

  3. Compact, super heat exchanger (United States)

    Fortini, A.; Kazaroff, J. M.


    Heat exchanger uses porous media to enhance heat transfer through walls of cooling channels, thereby lowering wall temperature. Porous media within cooling channel increases internal surface area from which heat can be transferred to coolant. Comparison data shows wall has lower temperature and coolant has higher temperature when porous medium is used within heat exchanger. Media can be sintered powedered metal, metal fibers, woven wire layers, or any porous metal having desired permeability and porosity.

  4. Exact exchange with non-orthogonal generalized Wannier functions (United States)

    Mountjoy, Jeff; Todd, Michelle; Mosey, Nicholas J.


    The evaluation of exact exchange (EXX) is an important component of quantum chemical calculations performed with ab initio and hybrid density functional methods. While evaluating exact exchange is routine in molecular quantum chemical calculations performed with localized basis sets, the non-local nature of the exchange operator presents a major impediment to the efficient use of exact exchange in calculations that employ planewave basis sets. Non-orthogonal generalized Wannier functions (NGWFs) corresponding to planewave expansions of localized basis functions are an alternative form of basis set that can be used in quantum chemical calculations. The periodic nature of these functions renders them suitable for calculations of periodic systems, while the contraction of sets of planewaves into individual basis functions reduces the number of variational parameters, permitting the construction and direct diagonalization of the Fock matrix. The present study examines how NGWFs corresponding to Fourier series representations of conventional atom-centered basis sets can be used to evaluate exact exchange in periodic systems. Specifically, an approach for constructing the exchange operator with NGWFs is presented and used to perform Hartree-Fock calculations with a series of molecules in periodically repeated simulation cells. The results demonstrate that the NGWF approach is significantly faster than the EXX method, which is a standard approach for evaluating exact exchange in periodic systems.

  5. Modeling of dual gradient elution in ion exchange and mixed-mode chromatography. (United States)

    Lee, Yi Feng; Schmidt, Michael; Graalfs, Heiner; Hafner, Mathias; Frech, Christian


    Protein retention using dual gradient elution in ion exchange- and mixed-mode chromatography can be modeled using the combination of a modified Yamamoto's LGE model and a conversion term to correlate the elution salt concentration and pH at any given gradient slope. Incorporation of the pH dependence of the binding charges into the model also provides some insights on the dual effects of salt and pH in protein-ligand interaction. The fitted thermodynamic parameters (ΔGP(0)/RT, ΔGS(0)/RT, number of charged amino acids involved in binding) of the dual gradient elution data using lysozyme and mAbs on SP Sepharose(®) FF, Eshmuno(®) HCX, and Capto(®) MMC ImpRes were consistent to the results of mono gradient data. This gives rise to an approach to perform thermodynamic modeling of protein retention in ion exchange- and mixed-mode chromatography by combining both salt and pH gradient into a single run of dual gradient elution which will increase time and cost efficiency. The dual gradients used in this study encompassed a wide range of pH (4-8) and NaCl concentrations (0-1M). Curve fits showed that ΔGP(0)/RT is protein type and ligand dependent. ΔGS(0)/RT is strongly dependent on the stationary phase but not the protein. For mAb04 on mixed-mode resin Capto(®) MMC, ΔGS(0)/RT is 5-6 times higher than the result reported for the same protein on cation exchanger Fractogel(®) EMD SO3(-) (S).

  6. Radiochemical separation of gold by amalgam exchange (United States)

    Ruch, R.R.


    A rapid and simple method for the radiochemical separation of gold after neutron activation. The technique is based on treatment with a dilute indium-gold amalgam, both chemical reduction and isotopic exchange being involved. The counting efficiency for 198Au in small volumes of the amalgam is good. Few interferences occur and the method is applicable to clays, rocks, salts and metals. The possibility of determining silver, platinum and palladium by a similar method is mentioned. ?? 1970.

  7. 换热器对化学吸附式制冷系统的影响%Study of the Effects of Heat Exchanger on the Chemical Adsorption Refrigeration System

    Institute of Scientific and Technical Information of China (English)

    彭庆龙; 齐朝晖


    The dynamic characteristics of the CaCl2-NH3 chemical adsorption refrigeration system driven by engine exhausted gas was studied. A thermal dynamic model is established to simulate the performanceofevaporation temperature, condensation temperature, evaporator and condenser outlet temperature in the running system and the article summarizes the varieties of system performance parameters in the different evaporation temperature and condensation temperature.Sothis result can provide a reference for the further research on the matching and optimization inthe chemical adsorption refrigeration system.%研究了内燃机尾气驱动的氯化钙-氨化学吸附式制冷系统的动态运行状况。通过建立热力学动态模型,仿真得到蒸发温度、冷凝温度、蒸发器与冷凝器出口温度在系统运行时的变化,并总结了在变蒸发温度或冷凝温度下系统性能参数的变化规律。结论可以为今后有关化学吸附式制冷系统各部件的匹配性和优化系统性能的进一步研究提供参考。

  8. Exchanging Description Logic Knowledge Bases

    NARCIS (Netherlands)

    Arenas, M.; Botoeva, E.; Calvanese, D.; Ryzhikov, V.; Sherkhonov, E.


    In this paper, we study the problem of exchanging knowledge between a source and a target knowledge base (KB), connected through mappings. Differently from the traditional database exchange setting, which considers only the exchange of data, we are interested in exchanging implicit knowledge. As rep

  9. Heat exchanger restart evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, J.M.; Hirst, C.W.; Lentz, T.F.


    On December 24, 1991, the K-Reactor was in the shutdown mode with full AC process water flow and full cooling water flow. Safety rod testing was being performed as part of the power ascension testing program. The results of cooling water samples indicated tritium concentrations higher than allowable. Further sampling and testing confirmed a Process Water System to Cooling Water System leak in heat exchanger 4A (HX 4A). The heat exchanger was isolated and the plant shutdown. Heat exchanger 4kA was removed from the plant and moved to C-Area prior to performing examinations and diagnostic testing. This included locating and identifying the leaking tube or tubes, eddy current examination of the leaking tube and a number of adjacent tubes, visually inspecting the leaking tube from both the inside as well as the area surrounding the failure mechanism. In addition ten other tubes that either exhibited eddy current indications or would represent a baseline condition were removed from heat exchanger 4A for metallurgical examination. Additional analysis and review of heat exchanger leakage history was performed to determine if there are any patterns which can be used for predictive purposes. Compensatory actions have been taken to improve the sensitivity and response time to any future events of this type. The results of these actions are summarized herein.

  10. Binding Energy Distribution Analysis Method: Hamiltonian Replica Exchange with Torsional Flattening for Binding Mode Prediction and Binding Free Energy Estimation. (United States)

    Mentes, Ahmet; Deng, Nan-Jie; Vijayan, R S K; Xia, Junchao; Gallicchio, Emilio; Levy, Ronald M


    Molecular dynamics modeling of complex biological systems is limited by finite simulation time. The simulations are often trapped close to local energy minima separated by high energy barriers. Here, we introduce Hamiltonian replica exchange (H-REMD) with torsional flattening in the Binding Energy Distribution Analysis Method (BEDAM), to reduce energy barriers along torsional degrees of freedom and accelerate sampling of intramolecular degrees of freedom relevant to protein-ligand binding. The method is tested on a standard benchmark (T4 Lysozyme/L99A/p-xylene complex) and on a library of HIV-1 integrase complexes derived from the SAMPL4 blind challenge. We applied the torsional flattening strategy to 26 of the 53 known binders to the HIV Integrase LEDGF site found to have a binding energy landscape funneled toward the crystal structure. We show that our approach samples the conformational space more efficiently than the original method without flattening when starting from a poorly docked pose with incorrect ligand dihedral angle conformations. In these unfavorable cases convergence to a binding pose within 2-3 Å from the crystallographic pose is obtained within a few nanoseconds of the Hamiltonian replica exchange simulation. We found that torsional flattening is insufficient in cases where trapping is due to factors other than torsional energy, such as the formation of incorrect intramolecular hydrogen bonds and stacking. Work is in progress to generalize the approach to handle these cases and thereby make it more widely applicable.


    Institute of Scientific and Technical Information of China (English)

    WU Chinyung; YANG Chaoshiung; YANG Chong


    The present article deals with the exchange process of bivalent metal ions, such as Zn2 +, Cd2 + and Hg2+, etc., taken up by non-crosslinked carboxylated polypropylene (CPP) resin. The control factor of the exchange rate deduced from the kinetic data is governed basically by the chemical reaction rather than the mass transfer effect particle diffusion and/or liquid film diffusion. In solution, all the graft chains in the outer shell ofa CPP resin could form a "quasi-macromolecular solution" domain. This opinion further demonstrates the structural pattern of CPP resin proposed in earlier paper[1].

  12. Ion exchange phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Bourg, I.C.; Sposito, G.


    Ion exchange phenomena involve the population of readily exchangeable ions, the subset of adsorbed solutes that balance the intrinsic surface charge and can be readily replaced by major background electrolyte ions (Sposito, 2008). These phenomena have occupied a central place in soil chemistry research since Way (1850) first showed that potassium uptake by soils resulted in the release of an equal quantity of moles of charge of calcium and magnesium. Ion exchange phenomena are now routinely modeled in studies of soil formation (White et al., 2005), soil reclamation (Kopittke et al., 2006), soil fertilitization (Agbenin and Yakubu, 2006), colloidal dispersion/flocculation (Charlet and Tournassat, 2005), the mechanics of argillaceous media (Gajo and Loret, 2007), aquitard pore water chemistry (Tournassat et al., 2008), and groundwater (Timms and Hendry, 2007; McNab et al., 2009) and contaminant hydrology (Chatterjee et al., 2008; van Oploo et al., 2008; Serrano et al., 2009).

  13. Microgravity condensing heat exchanger (United States)

    Thomas, Christopher M. (Inventor); Ma, Yonghui (Inventor); North, Andrew (Inventor); Weislogel, Mark M. (Inventor)


    A heat exchanger having a plurality of heat exchanging aluminum fins with hydrophilic condensing surfaces which are stacked and clamped between two cold plates. The cold plates are aligned radially along a plane extending through the axis of a cylindrical duct and hold the stacked and clamped portions of the heat exchanging fins along the axis of the cylindrical duct. The fins extend outwardly from the clamped portions along approximately radial planes. The spacing between fins is symmetric about the cold plates, and are somewhat more closely spaced as the angle they make with the cold plates approaches Passageways extend through the fins between vertex spaces which provide capillary storage and communicate with passageways formed in the stacked and clamped portions of the fins, which communicate with water drains connected to a pump externally to the duct. Water with no entrained air is drawn from the capillary spaces.

  14. Tuning Exchange Anisotropy of Exchange-Biased System

    Institute of Scientific and Technical Information of China (English)

    XU Yan; HU Jing-Guo; R.L.Stamps


    Exchange anisotropy in FM/AFM bilayers has given a lot of static magnetization properties such as enhanced coercivity and magnetization loop shifts.These phenomena are primarily from the effective anisotropies intro-duced into a ferromagnet by exchange coupling with a strongly anisotropic antiferromagnet.These effective anisotropies can also be used to explain the dynamic consequences of exchange-biased bilayers.In this article,the dynamic con-sequences such as exchange-induced susceptibility,exchange-induced permeability,and the corresponding domain wall characteristics in the exchange-biased structures of ferromagnet/antiferromagnetl/antiferromagnet2 are studied.The results show that the second antiferromagnetic layer can largely affect the dynamic consequences of exchange-biased bilayers.Especially in the ease of critical temperature,the effects become more obvious.Practically,the exchange anisotropy of biased bilayer system can be tuned by exchange coupling with the second antiferromagnetic layer.

  15. 15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH



    NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10% 15N-polarization (Theis, T.; et al. J. Am. Chem. Soc. 2015, 137, 1404). Hyperpolarization on 15N (an...

  16. Global evaluation of ammonia bi-directional exchange


    Zhu, L; D. Henze; J. Bash; G.-R. Jeong; Cady-Pereira, K.; Shephard, M; Luo, M; F. Paulot; Capps, S.


    Bi-directional air–surface exchange of ammonia (NH3) has been neglected in many air quality models. In this study, we implement the bi-directional exchange of NH3 in the GEOS-Chem global chemical transport model. We also introduce an updated diurnal variability scheme for NH3 livestock emissions and evaluate the recently developed MASAGE_NH3 bottom up inventory. While updated diurnal variability improves comparison of modeled-to-hourly in situ measurements i...

  17. Thermal performance modeling of cross-flow heat exchangers

    CERN Document Server

    Cabezas-Gómez, Luben; Saíz-Jabardo, José Maria


    This monograph introduces a numerical computational methodology for thermal performance modeling of cross-flow heat exchangers, with applications in chemical, refrigeration and automobile industries. This methodology allows obtaining effectiveness-number of transfer units (e-NTU) data and has been used for simulating several standard and complex flow arrangements configurations of cross-flow heat exchangers. Simulated results have been validated through comparisons with results from available exact and approximate analytical solutions. Very accurate results have been obtained over wide ranges

  18. Advanced ion exchange resins for PWR condensate polishing

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, B. [Rohm and Haas Co. (United States); Tsuzuki, S. [Rohm and Haas Co. (Japan)


    The severe chemical and mechanical requirements of a pressurized water reactor (PWR) condensate polishing plant (CPP) present a major challenge to the design of ion exchange resins. This paper describes the development and initial operating experience of improved cation and anion exchange resins that were specifically designed to meet PWR CPP needs. Although this paper focuses specifically on the ion exchange resins and their role in plant performance, it is also recognized and acknowledged that excellent mechanical design and operation of the CPP system are equally essential to obtaining good results. (authors)

  19. Gas exchange measurements in natural systems

    Energy Technology Data Exchange (ETDEWEB)

    Broecker, W.S.; Peng, T.H.


    Direct knowledge of the rates of gas exchange in lakes and the ocean is based almost entirely on measurements of the isotopes /sup 14/C, /sup 222/Rn and /sup 3/He. The distribution of natural radiocarbon has yielded the average rate of CO/sub 2/ exchange for the ocean and for several closed basin lakes. That of bomb produced radiocarbon has been used in the same systems. The /sup 222/Rn to /sup 226/Ra ratio in open ocean surface water has been used to give local short term gas exchange rates. The radon method generally cannot be used in lakes, rivers, estuaries or shelf areas because of the input of radon from sediments. A few attempts have been made to use the excess /sup 3/He produced by decay of bomb produced tritium in lakes to give gas transfer rates. The uncertainty in the molecular diffusivity of helium and in the diffusivity dependence of the rate of gas transfer holds back the application of this method. A few attempts have been made to enrich the surface waters of small lakes with /sup 226/Ra and /sup 3/H in order to allow the use of the /sup 222/Rn and /sup 3/He methods. While these studies give broadly concordant results, many questions remain unanswered. The wind velocity dependence of gas exchange rate has yet to be established in field studies. The dependence of gas exchange rate on molecular diffusivity also remains in limbo. Finally, the degree of enhancement of CO/sub 2/ exchange through chemical reactions has been only partially explored. 49 references, 2 figures, 2 tables.

  20. Baltic Exchange toodi Tallinna

    Index Scriptorium Estoniae


    Viimane osa merekonteineritesse kokkupakitud Londoni laevandus- ja merebörsi Baltic Exchange'i endise peakorteri detailidest jõudis 2007. a. juunis Tallinna. Hoone detailid ostnud ärimehed Heiti Hääl ja Eerik-Niiles Kross plaanivad leida hoonele koha Tallinna kesklinnas. E.-N. Krossi kommentaar

  1. Telephone Exchange Maintenance

    CERN Multimedia


    Urgent maintenance work on CERN telephone exchanges will be performed on 24 March from 6 a.m. to 8 a.m. Telephone services may be disrupted or even interrupted during this time. For more details, please contact us by email at

  2. Nature's Heat Exchangers. (United States)

    Barnes, George


    Discusses the heat-transfer systems of different animals. Systems include heat conduction into the ground, heat transferred by convection, heat exchange in lizards, fish and polar animals, the carotid rete system, electromagnetic radiation from animals and people, and plant and animal fiber optics. (MDH)

  3. Exchangeable lower previsions

    CERN Document Server

    de Cooman, Gert; Miranda, Enrique; 10.3150/09-BEJ182


    We extend de Finetti's [Ann. Inst. H. Poincar\\'{e} 7 (1937) 1--68] notion of exchangeability to finite and countable sequences of variables, when a subject's beliefs about them are modelled using coherent lower previsions rather than (linear) previsions. We derive representation theorems in both the finite and countable cases, in terms of sampling without and with replacement, respectively.

  4. Microtube strip heat exchanger (United States)

    Doty, F. D.


    During the last quarter, Doty Scientific, Inc. (DSI) continued to make progress on the microtube strip (MTS) heat exchangers. The team has begun a heat exchanger stress analysis; however, they have been concentrating the bulk of their analytical energies on a computational fluid dynmaics (CFD) model to determine the location and magnitude of shell-side flow maldistribution which decreases heat exchanger effectiveness. DSI received 120 fineblanked tubestrips from Southern Fineblanking (SFB) for manufacturing process development. Both SFB and NIST provided inspection reports of the tubestrips. DSI completed the tooling required to encapsulate a tube array and press tubestrips on the array. Pressing the tubestrips on tube arrays showed design deficiencies both in the tubestrip design and the tooling design. DSI has a number of revisions in process to correct these deficiencies. The research effort has identified a more economical fusible alloy for encapsulating the tube array, and determined the parameters required to successfully encapsulate the tube array with the new alloy. A more compact MTS heat exchanger bank was designed.

  5. Currency Exchange Rates. (United States)

    Siler, Carl R.

    This curriculum unit of the Muncie (Indiana) Southside High School is to simulate the dynamics of foreign currency exchange rates from the perspectives of: (1) a major U.S. corporation, ABB Power T & D Company, Inc., of Muncie, Indiana, a manufacturer of large power transformers for the domestic and foreign markets; and (2) individual…

  6. Counterflow Regolith Heat Exchanger (United States)

    Zubrin, Robert; Jonscher, Peter


    A problem exists in reducing the total heating power required to extract oxygen from lunar regolith. All such processes require heating a great deal of soil, and the heat energy is wasted if it cannot be recycled from processed material back into new material. The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat exchanger with internal and external augers attached to the inner rotating tube to move the regolith. Hot regolith in the outer tube is moved in one direction by a right-hand - ed auger, and the cool regolith in the inner tube is moved in the opposite direction by a left-handed auger attached to the inside of the rotating tube. In this counterflow arrangement, a large fraction of the heat from the expended regolith is transferred to the new regolith. The spent regolith leaves the heat exchanger close to the temperature of the cold new regolith, and the new regolith is pre-heated close to the initial temperature of the spent regolith. Using the CoRHE can reduce the heating requirement of a lunar ISRU system by 80%, reducing the total power consumption by a factor of two. The unique feature of this system is that it allows for counterflow heat exchange to occur between solids, instead of liquids or gases, as is commonly done. In addition, in variants of this concept, the hydrogen reduction can be made to occur within the counterflow heat exchanger itself, enabling a simplified lunar ISRU (in situ resource utilization) system with excellent energy economy and continuous nonbatch mode operation.

  7. Preparation of a Cation Exchanger from Cork Waste: Thermodynamic Study of the Ion Exchange Processes

    Institute of Scientific and Technical Information of China (English)


    An ion exchanger was prepared by sulfonation of cork-waste chars. The exchange properties of the resultant materialwere characterized using Na+, Ca2+ or Fe3+ aqueous solutions, The content of metal ions in the solutions weredetermined by atomic absorption spectrometry. On the basis of the results obtained, the chemical equilibrium andits thermodynamic aspects related to the ion exchange process were studied. It was found that equilibrium constantK varies by the order: Na+<Ca2+<Fe3+, its value increasing with increasing temperature, and that △H°>0 and△S°>0, with -△G° following the sequence: Ca2+>Na+>Fe3+,

  8. Analytical applications of ion exchangers

    CERN Document Server

    Inczédy, J


    Analytical Applications of Ion Exchangers presents the laboratory use of ion-exchange resins. This book discusses the development in the analytical application of ion exchangers. Organized into 10 chapters, this book begins with an overview of the history and significance of ion exchangers for technical purposes. This text then describes the properties of ion exchangers, which are large molecular water-insoluble polyelectrolytes having a cross-linked structure that contains ionic groups. Other chapters consider the theories concerning the operation of ion-exchange resins and investigate th

  9. Interdependence of coenzyme-induced conformational work and binding potential in yeast alcohol and porcine heart lactate dehydrogenases: a hydrogen-deuterium exchange study

    Energy Technology Data Exchange (ETDEWEB)

    De Weck, Z.; Pande, J.; Kaegi, J.H.R.


    Binding of NAD coenzymes to yeast alcohol dehydrogenase (YADH) and porcine heart lactate dehydrogenase (PHLDH) was studied by hydrogen-deuterium exchange with the infrared technique. Conformational changes in the enzymes specific to the coenzymes and their fragments were observed, and the pH dependence of the exchange reaction shows that it conforms to the EX-2 scheme. In both YADH and PHLDH the magnitude of the conformational change as measured by exchange retardation is considerably larger for the NAD/sup +/ than for NADH. Studies with coenzyme fragments like ADP-ribose, ADP, and AMP also highlight the lack of rigorous correlation between structural features such as charge and size and their influence on exchange behavior. Ternary complexes such as YADH-NAD/sup +/-pyrazole, PHLDH-NAD/sup +/-oxalate, and PHLDH-NADH-oxamate, which mimic the transition state, have a significantly more pronounced effect on exchange rates than the corresponding binary complexes. The outstanding feature of this study is the demonstration that in the binary enzyme-coenzyme complexes the more loosely bound NAD/sup +/ is more effective in retarding exchange than the more firmly bound NADH. These differences are attributed to the unequal structural constraints exerted by the two coenzymes upon the enzymes, which translate to unequal expenditure of transconformational work in the formation of the two complexes. The opposing variation in the free energy of binding and the transconformational work expended can be viewed as an unequal partitioning of the net free energy gain resulting from the protein-ligand interaction into a binding term and that required for conformational change.

  10. Interdependence of coenzyme-induced conformational work and binding potential in yeast alcohol and porcine heart lactate dehydrogenases: a hydrogen-deuterium exchange study. (United States)

    De Weck, Z; Pande, J; Kägi, J H


    Binding of NAD coenzymes to yeast alcohol dehydrogenase (YADH) and porcine heart lactate dehydrogenase (PHLDH) was studied by hydrogen-deuterium exchange with the infrared technique. Conformational changes in the enzymes specific to the coenzymes and their fragments were observed, and the pH dependence of the exchange reaction shows that it conforms to the EX-2 scheme. In both YADH and PHLDH the magnitude of the conformational change of measured by exchange retardation is considerably larger for NAD+ than for NADH. Studies with coenzyme fragments like ADP-ribose, ADP, and AMP also highlight the lack of rigorous correlation between structural features such as charge and size and their influence on exchange behavior. Ternary complexes such as YADH-NAD+-pyrazole, PHLDH-NAD+-oxalate, and PHLDH-NADH-oxamate, which mimic the transition state, have a significantly more pronounced effect on exchange rates than the corresponding binary complexes. The outstanding feature of this study is the demonstration that in the binary enzyme-coenzyme complexes the more loosely bound NAD+ is more effective in retarding exchange than the more firmly bound NADH. These differences are attributed to the unequal structural constraints exerted by the two coenzymes upon the enzymes, which translate to unequal expenditure of transconformational work in the formation of the two complexes. The opposing variation in the free energy of binding and the transconformational work expended can be viewed as an unequal partitioning of the net free energy gain resulting from the protein-ligand interaction into a binding term and that required for conformational change.

  11. Determination of Equine Cytochrome c Backbone Amide Hydrogen/Deuterium Exchange Rates by Mass Spectrometry Using a Wider Time Window and Isotope Envelope (United States)

    Hamuro, Yoshitomo


    A new strategy to analyze amide hydrogen/deuterium exchange mass spectrometry (HDX-MS) data is proposed, utilizing a wider time window and isotope envelope analysis of each peptide. While most current scientific reports present HDX-MS data as a set of time-dependent deuteration levels of peptides, the ideal HDX-MS data presentation is a complete set of backbone amide hydrogen exchange rates. The ideal data set can provide single amide resolution, coverage of all exchange events, and the open/close ratio of each amide hydrogen in EX2 mechanism. Toward this goal, a typical HDX-MS protocol was modified in two aspects: measurement of a wider time window in HDX-MS experiments and deconvolution of isotope envelope of each peptide. Measurement of a wider time window enabled the observation of deuterium incorporation of most backbone amide hydrogens. Analysis of the isotope envelope instead of centroid value provides the deuterium distribution instead of the sum of deuteration levels in each peptide. A one-step, global-fitting algorithm optimized exchange rate and deuterium retention during the analysis of each amide hydrogen by fitting the deuterated isotope envelopes at all time points of all peptides in a region. Application of this strategy to cytochrome c yielded 97 out of 100 amide hydrogen exchange rates. A set of exchange rates determined by this approach is more appropriate for a patent or regulatory filing of a biopharmaceutical than a set of peptide deuteration levels obtained by a typical protocol. A wider time window of this method also eliminates false negatives in protein-ligand binding site identification.

  12. Radiation effects on ion exchange materials

    Energy Technology Data Exchange (ETDEWEB)

    Gangwer, T.E.; Goldstein, M.; Pillay, K.K.S.


    An extensive literature review and data compilation has been completed on the radiation-damage of ion exchange resins. The primary goal of the study has been to review the available literature on ion exchange materials used in, as well as those with potential for use in, the nuclear fuel and waste reprocessing areas. The physical and chemical properties of ion exchangers are reviewed. Experimental parameters useful in characterizing the effects of radiation on synthetic ion exchange resins are identified or defined. In compiling the diverse types of data, an effort was made to present the experimental data or experimentally based parameters in a format that would be useful for inter-comparing radiation effects on resins. When subject to radiation there are various general trends or qualitative effects displayed by the different types of resins. These radiation-trends and effects have been formulated into qualitative statements. The present day level of understanding of the behavior of resins under ionizing radiation is too limited to justify quantitative predictive modeling. The limitations and deficiencies of the literature are discussed and the experimentation needed to achieve quantitative modeling are outlined. 14 figs., 108 references.

  13. The Deuterator: software for the determination of backbone amide deuterium levels from H/D exchange MS data

    Directory of Open Access Journals (Sweden)

    Tsinoremas NF


    Full Text Available Abstract Background The combination of mass spectrometry and solution phase amide hydrogen/deuterium exchange (H/D exchange experiments is an effective method for characterizing protein dynamics, and protein-protein or protein-ligand interactions. Despite methodological advancements and improvements in instrumentation and automation, data analysis and display remains a tedious process. The factors that contribute to this bottleneck are the large number of data points produced in a typical experiment, each requiring manual curation and validation, and then calculation of the level of backbone amide exchange. Tools have become available that address some of these issues, but lack sufficient integration, functionality, and accessibility required to address the needs of the H/D exchange community. To date there is no software for the analysis of H/D exchange data that comprehensively addresses these issues. Results We have developed an integrated software system for the automated analysis and representation of H/D exchange data that has been titled "The Deuterator". Novel approaches have been implemented that enable high throughput analysis, automated determination of deuterium incorporation, and deconvolution of overlapping peptides. This has been achieved by using methods involving iterative theoretical envelope fitting, and consideration of peak data within expected m/z ranges. Existing common file formats have been leveraged to allow compatibility with the output from the myriad of MS instrument platforms and peptide sequence database search engines. A web-based interface is used to integrate the components of The Deuterator that are able to analyze and present mass spectral data from instruments with varying resolving powers. The results, if necessary, can then be confirmed, adjusted, re-calculated and saved. Additional tools synchronize the curated calculation parameters with replicate time points, increasing throughput. Saved results can then


    Directory of Open Access Journals (Sweden)

    Novak Lučić


    Full Text Available Exchange rate of one currency is the price of the currency expressed in units of other currency. It is formed by the interaction of supply and demand in the foreign exchange market. Given that the exchange rate has a direct impact on the competitiveness of a country in terms of features of its exports and imports, in its balance of payments, and indirectly the overall economic and social development, in addition to acting in market principles - supply and demand in the formation of the equilibrium exchange rate, exchange rate is subject to different, stronger or weaker, more or less, forms of intervention. In the search for the optimal exchange rate policy of the national currency, the monetary authorities are positioned between the two extremes - the complete abandonment of the exchange rate to the market laws of supply and demand, or fixing the exchange rate for any of the selected anchor currency.

  15. Data Exchange Inventory (DEXI) System (United States)

    Social Security Administration — DEXI is an intranet application used by SSA users to track all incoming and outgoing data exchanges between SSA and our data exchange partners. Information such as...

  16. The Exchange Rate Forecasting Puzzle


    Francis Vitek


    We survey and update the empirical literature concerning the predictability of nominal exchange rates using structural macroeconomic models over the recent floating exchange rate period. In particular, we consider both flexible and sticky price versions of the monetary model of nominal exchange rate determination. In agreement with the existing empirical literature, we find that nominal exchange rate movements are difficult to forecast, with a random walk generally dominating the monetary mod...

  17. Lipid exchange by ultracentrifugation

    DEFF Research Database (Denmark)

    Drachmann, Nikolaj Düring; Olesen, Claus


    Lipids play an important role in maintaining P-type ATPase structure and function, and often they are crucial for ATPase activity. When the P-type ATPases are in the membrane, they are surrounded by a mix of different lipids species with varying aliphatic chain lengths and saturation......, and the complex interplay between the lipids and the P-type ATPases are still not well understood. We here describe a robust method to exchange the majority of the lipids surrounding the ATPase after solubilisation and/or purification with a target lipid of interest. The method is based on an ultracentrifugation...... step, where the protein sample is spun through a dense buffer containing large excess of the target lipid, which results in an approximately 80-85 % lipid exchange. The method is a very gently technique that maintains protein folding during the process, hence allowing further characterization...

  18. Geology Exchange Program (United States)

    Because geology professors cannot bring ore deposits from around the globe into their classrooms, the next best thing is to take their students to the deposits, according to David Norman, an associate professor of geochemistry at New Mexico Tech and Angus Moore of the Royal School of Mines. They organized a new exchange program between the New Mexico Institute of Mining and Technology in Socorro, N.M., and the Royal School of Mines in London, England. In May, 14 students from England toured deposits in New Mexico, Arizona, Utah, and Colorado; in the photograph, Norman (on the right) describes a rock from a New Mexico ore deposit to some of the visitors from England. In early June a contingency from New Mexico Tech began studying deposits in England, Spain, and Portugal. Norman and Moore say that the exchange program may be expanded next year.

  19. Exchange rate rebounds after foreign exchange market interventions (United States)

    Hoshikawa, Takeshi


    This study examined the rebounds in the exchange rate after foreign exchange intervention. When intervention is strongly effective, the exchange rate rebounds at next day. The effect of intervention is reduced slightly by the rebound after the intervention. The exchange rate might have been 67.12-77.47 yen to a US dollar without yen-selling/dollar-purchasing intervention of 74,691,100 million yen implemented by the Japanese government since 1991, in comparison to the actual exchange rate was 103.19 yen to the US dollar at the end of March 2014.

  20. Chemical use (United States)

    US Fish and Wildlife Service, Department of the Interior — This is a summary of research and activities related to chemical use on Neal Smith National Wildlife Refuge between 1992 and 2009. The chemicals used on the Refuge...

  1. Chemical Reactors. (United States)

    Kenney, C. N.


    Describes a course, including content, reading list, and presentation on chemical reactors at Cambridge University, England. A brief comparison of chemical engineering education between the United States and England is also given. (JN)

  2. Hydrogen Exchange Mass Spectrometry. (United States)

    Mayne, Leland


    Hydrogen exchange (HX) methods can reveal much about the structure, energetics, and dynamics of proteins. The addition of mass spectrometry (MS) to an earlier fragmentation-separation HX analysis now extends HX studies to larger proteins at high structural resolution and can provide information not available before. This chapter discusses experimental aspects of HX labeling, especially with respect to the use of MS and the analysis of MS data.

  3. Thermoelectric heat exchange element (United States)

    Callas, James J.; Taher, Mahmoud A.


    A thermoelectric heat exchange module includes a first substrate including a heat receptive side and a heat donative side and a series of undulatory pleats. The module may also include a thermoelectric material layer having a ZT value of 1.0 or more disposed on at least one of the heat receptive side and the heat donative side, and an electrical contact may be in electrical communication with the thermoelectric material layer.

  4. Exchange Rate Predictions


    Yablonskyy, Karen


    The aim of this thesis is to analyze the foreign exchange currency forecasting techniques. Moreover the central idea behind the topic is to develop the strategy of forecasting by choosing indicators and techniques to make own forecast on currency pair EUR/USD. This thesis work is a mixture of theory and practice analyses. The goal during the work on this project was to study different types of forecasting techniques and make own forecast, practice forecasting and trading on Forex platform, ba...

  5. Heat exchange apparatus (United States)

    Degtiarenko, Pavel V.


    A heat exchange apparatus comprising a coolant conduit or heat sink having attached to its surface a first radial array of spaced-apart parallel plate fins or needles and a second radial array of spaced-apart parallel plate fins or needles thermally coupled to a body to be cooled and meshed with, but not contacting the first radial array of spaced-apart parallel plate fins or needles.

  6. Integrated foreign exchange risk management

    DEFF Research Database (Denmark)

    Aabo, Tom; Høg, Esben; Kuhn, Jochen


    Empirical research has focused on export as a proxy for exchange rate exposure and the use of foreign exchange derivatives as an instrument to deal with this exposure. This empirical study applies an integrated foreign exchange risk management approach with a particular focus on the role of impor...

  7. On Exchange QB∞-Rings

    Institute of Scientific and Technical Information of China (English)

    Huanyin Chen


    In this paper, we introduce a new class of rings, the QB∞-rings. We investigate necessary and sufficient conditions under which an exchange ring is a QB∞-ring. The modules over an exchange QB∞-ring are studied. Also, we prove that every regular square matrix over an exchange QB∞-ring admits a diagonal reduction by pseudo-invertible matrices.

  8. The stability of exchange networks

    NARCIS (Netherlands)

    Doğan, G.; Assen, M. van; Rijt, A. van de; Buskens, V.W.


    Economic and sociological exchange theories predict divisions of exchange benefits given an assumed fixed network of exchange relations. Since network structure has been found to have a large impact on actors’ payoffs, actors have strong incentives for network change.Weanswer the question what happe

  9. The exchangeability of shape

    Directory of Open Access Journals (Sweden)

    Kaba Dramane


    Full Text Available Abstract Background Landmark based geometric morphometrics (GM allows the quantitative comparison of organismal shapes. When applied to systematics, it is able to score shape changes which often are undetectable by traditional morphological studies and even by classical morphometric approaches. It has thus become a fast and low cost candidate to identify cryptic species. Due to inherent mathematical properties, shape variables derived from one set of coordinates cannot be compared with shape variables derived from another set. Raw coordinates which produce these shape variables could be used for data exchange, however they contain measurement error. The latter may represent a significant obstacle when the objective is to distinguish very similar species. Results We show here that a single user derived dataset produces much less classification error than a multiple one. The question then becomes how to circumvent the lack of exchangeability of shape variables while preserving a single user dataset. A solution to this question could lead to the creation of a relatively fast and inexpensive systematic tool adapted for the recognition of cryptic species. Conclusions To preserve both exchangeability of shape and a single user derived dataset, our suggestion is to create a free access bank of reference images from which one can produce raw coordinates and use them for comparison with external specimens. Thus, we propose an alternative geometric descriptive system that separates 2-D data gathering and analyzes.

  10. Timing Foreign Exchange Markets

    Directory of Open Access Journals (Sweden)

    Samuel W. Malone


    Full Text Available To improve short-horizon exchange rate forecasts, we employ foreign exchange market risk factors as fundamentals, and Bayesian treed Gaussian process (BTGP models to handle non-linear, time-varying relationships between these fundamentals and exchange rates. Forecasts from the BTGP model conditional on the carry and dollar factors dominate random walk forecasts on accuracy and economic criteria in the Meese-Rogoff setting. Superior market timing ability for large moves, more than directional accuracy, drives the BTGP’s success. We explain how, through a model averaging Monte Carlo scheme, the BTGP is able to simultaneously exploit smoothness and rough breaks in between-variable dynamics. Either feature in isolation is unable to consistently outperform benchmarks throughout the full span of time in our forecasting exercises. Trading strategies based on ex ante BTGP forecasts deliver the highest out-of-sample risk-adjusted returns for the median currency, as well as for both predictable, traded risk factors.

  11. Experimental study on heat exchange of several types of exchangers

    Institute of Scientific and Technical Information of China (English)

    周志华; 赵振华; 于洋


    Aiming at the ground-coupled source heat pump that possesses the shortcomings of occupying larger land,this article studies the heat exchanged of heat exchanger in piling,and compares it with common heat exchangers buried directly. The result indicates that the heat exchanger makes the best use of structure of building,saves land,reduces the construction cost,and the heat exchanged is obviously more than exchangers buried directly. In winter condition,when W-shape pipe heat exchanger in pile foundation is 50 m deep and diameter is 800 mm,it transfers 1.2-1.3 times as large as the one of single U-shape buried directly at the flow rate of 0.6 m/s,whose borehole diameter is 300 mm. And in summer condition it does about 2.0-2.3 times as that of U-shape one.

  12. Computational studies of protein-ligand molecular recognition

    NARCIS (Netherlands)

    Gillies, M.B.


    Structure-based drug design is made possible by our understanding of molecular recognition. The utility of this approach was apparent in the development of the clinically e V ective HIV-1 PR inhibitors, where crystal structures of complexes of HIV-1 protease and inhibitors gave pivotal information.

  13. Topological Analyses of Protein-Ligand Binding: a Network Approach. (United States)

    Costanzi, Stefano


    Proteins can be conveniently represented as networks of interacting residues, thus allowing the study of several network parameters that can shed light onto several of their structural and functional aspects. With respect to the binding of ligands, which are central for the function of many proteins, network analysis may constitute a possible route to assist the identification of binding sites. As the bulk of this review illustrates, this has generally been easier for enzymes than for non-enzyme proteins, perhaps due to the different topological nature of the binding sites of the former over those of the latter. The article also illustrates how network representations of binding sites can be used to search PDB structures in order to identify proteins that bind similar molecules and, lastly, how codifying proteins as networks can assist the analysis of the conformational changes consequent to ligand binding.

  14. Protein-ligand binding sites. Identification, characterization and interrelations


    Schmidtke, Peter


    El trabajo presentado en esta tesis cubre varios campos de investigación relacionados con el desarrollo de moléculas bioactivas. Se compone de cinco partes distintas que se resumen aquí. Predicción de la utilidad farmacológica de dianas terapéuticas. El desarrollo de fármacos está generalmente dirigido a inhibir la función de una proteína específica. Pero para validar esta proteína como diana terapéutica, al principio de un proyecto de descubrimiento de fármacos se tiene que saber si ...

  15. NMR-based screening of membrane protein ligands

    NARCIS (Netherlands)

    Yanamala, Naveena; Dutta, Arpana; Beck, Barbara; Van Fleet, Bart; Hay, Kelly; Yazbak, Ahmad; Ishima, Rieko; Doemling, Alexander; Klein-Seetharaman, Judith


    Membrane proteins pose problems for the application of NMR-based ligand-screening methods because of the need to maintain the proteins in a membrane mimetic environment such as detergent micelles: they add to the molecular weight of the protein, increase the viscosity of the solution, interact with

  16. Integrated Foreign Exchange Risk Management

    DEFF Research Database (Denmark)

    Aabo, Tom; Høg, Esben; Kuhn, Jochen

    Empirical research has focused on export as a proxy for the exchange rate exposure and the use of foreign exchange derivatives as the instrument to deal with this exposure. This empirical study applies an integrated foreign exchange risk management approach with a particular focus on the role...... of import in medium-sized, manufacturing firms in Denmark (a small, open economy). We find a strong, negative relation between import and foreign exchange derivatives usage on the aggregate level. Our findings are consistent with the notion that firms use import to match the foreign exchange exposure...

  17. Mastering Microsoft Exchange Server 2010

    CERN Document Server

    McBee, Jim


    A top-selling guide to Exchange Server-now fully updated for Exchange Server 2010. Keep your Microsoft messaging system up to date and protected with the very newest version, Exchange Server 2010, and this comprehensive guide. Whether you're upgrading from Exchange Server 2007 SP1 or earlier, installing for the first time, or migrating from another system, this step-by-step guide provides the hands-on instruction, practical application, and real-world advice you need.: Explains Microsoft Exchange Server 2010, the latest release of Microsoft's messaging system that protects against spam and vir

  18. Real Exchange Rate Targets, Nominal Exchange Rate Policies, and Inflation Real Exchange Rate Targets, Nominal Exchange Rate Policies, and Inflation

    Directory of Open Access Journals (Sweden)

    J. Saúl Lizondo


    Full Text Available Real Exchange Rate Targets, Nominal Exchange Rate Policies, and Inflation Thh paper examines the implications of some nominal exchange rate policies aimed or attaining a given real exchange rate target. A policy rule that sets the rate of nominal depreciation as a function of the departures of the real exchange rate from its target level is unable to achieve the target. In contrast, a policv rule that sets the change in the rate of depreciation as a function of those departures may lead the economy to the target, under certain conditions. However, this policy could also lead the economy to a process of accelerating inflation.

  19. Preparation of anion exchange membrane using polyvinyl chloride (PVC) for alkaline water electrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Gab-Jin; Bong, Soo-Yeon; Ryu, Cheol-Hwi [Hoseo University, Asan (Korea, Republic of); Lim, Soo-Gon [Energy and Machinery Korea Co., Ltd., Changwon (Korea, Republic of); Choi, Ho-Sang [Kyungil University, Gyeongsan (Korea, Republic of)


    An anion exchange membrane was prepared by the chloromethylation and the amination of polyvinyl chloride (PVC), as the base polymer. The membrane properties of the prepared anion exchange membrane, including ionic conductivity, ion exchange capacity, and water content were measured. The ionic conductivity of the prepared anion exchange membrane was in the range of 0.098x10{sup -2} -7.0x10{sup -2}S cm{sup -1}. The ranges of ion exchange capacity and water content were 1.9-3.7meq./g-dry-membrane and 35.1-63.1%, respectively. The chemical stability of the prepared anion exchange membrane was tested by soaking in 30 wt% KOH solution to determine its availability as a separator in the alkaline water electrolysis. The ionic conductivity during the chemical stability test largely did not change.

  20. AIScore chemically diverse empirical scoring function employing quantum chemical binding energies of hydrogen-bonded complexes. (United States)

    Raub, Stephan; Steffen, Andreas; Kämper, Andreas; Marian, Christel M


    In this work we report on a novel scoring function that is based on the LUDI model and focuses on the prediction of binding affinities. AIScore extends the original FlexX scoring function using a chemically diverse set of hydrogen-bonded interactions derived from extensive quantum chemical ab initio calculations. Furthermore, we introduce an algorithmic extension for the treatment of multifurcated hydrogen bonds (XFurcate). Charged and resonance-assisted hydrogen bond energies and hydrophobic interactions as well as a scaling factor for implicit solvation were fitted to experimental data. To this end, we assembled a set of 101 protein-ligand complexes with known experimental binding affinities. Tightly bound water molecules in the active site were considered to be an integral part of the binding pocket. Compared to the original FlexX scoring function, AIScore significantly improves the prediction of the binding free energies of the complexes in their native crystal structures. In combination with XFurcate, AIScore yields a Pearson correlation coefficient of R P = 0.87 on the training set. In a validation run on the PDBbind test set we achieved an R P value of 0.46 for 799 attractively scored complexes, compared to a value of R P = 0.17 and 739 bound complexes obtained with the FlexX original scoring function. The redocking capability of AIScore, on the other hand, does not fully reach the good performance of the original FlexX scoring function. This finding suggests that AIScore should rather be used for postscoring in combination with the standard FlexX incremental ligand construction scheme.

  1. State Health Facts - State Decisions on Exchanges (United States)

    U.S. Department of Health & Human Services — State Decisions For Creating Health Insurance Exchanges, including Exchange Decision, Federal Approval Status, Structure of Exchange, and Type of Exchange.

  2. Multichannel Exchange-Scattering Spin Polarimetry. (United States)

    Ji, Fuhao; Shi, Tan; Ye, Mao; Wan, Weishi; Liu, Zhen; Wang, Jiajia; Xu, Tao; Qiao, Shan


    Electron spin plays important roles in determining the physical and chemical properties of matter. However, measurements of electron spin are of poor quality, impeding the development of material sciences, because the spin polarimeter has a low efficiency. Here, we show an imaging-type exchange-scattering spin polarimeter with 6786 channels and an 8.5×10^{-3} single channel efficiency. As a demonstration, the fine spin structure of the electronic states in bismuth (111) is investigated, for which strong Rashba-type spin splitting behavior is seen in both the bulk and surface states. This improvement paves the way to study novel spin related phenomena with unprecedented accuracy.

  3. Proton exchange membrane fuel cells modeling

    CERN Document Server

    Gao, Fengge; Miraoui, Abdellatif


    The fuel cell is a potential candidate for energy storage and conversion in our future energy mix. It is able to directly convert the chemical energy stored in fuel (e.g. hydrogen) into electricity, without undergoing different intermediary conversion steps. In the field of mobile and stationary applications, it is considered to be one of the future energy solutions.Among the different fuel cell types, the proton exchange membrane (PEM) fuel cell has shown great potential in mobile applications, due to its low operating temperature, solid-state electrolyte and compactness.This book pre

  4. Small particle heat exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, A.J.


    A dispersion of small absorbing particles forms an ideal system to collect radiant energy, transform it to heat, and efficiently transfer the heat to a surrounding fluid. If the heated fluid is a pressurized gas, it can be passed through an expansion turbine to create useful mechanical energy. The most obvious application of this technique is its use in a solar collection system. In this case, the incoming sunlight is used to heat a compressed gas in an engine utilizing a Brayton cycle. The solar collection system may utilize high concentration as provided by a central receiver or parabolic dish, medium concentration from a linear collector, or possibly no concentration using a flat plate collector, if precautions were taken to reduce the heat losses. The same concept may be applied generally to non-solar heat exchangers. These may be of the type used to heat a gas from a combustion source, or in general as a gas to gas heat exchanger. The latter application may be limited to rather high temperature. Each of the above applications is discussed. First, a description of the concept is applied to a solar central-tower system. The general principles are described, including the optical and physical characteristics of the particles, the confinement of the gas-particle mixture, and the system considerations; the latter include the amount and type of particles, the receiver efficiency and the generation of the particles. The same considerations are reviewed for applications to linear trough and flat plate receivers. Finally, the use of small particles in non-solar heat exchangers is considered.

  5. Cryogenic regenerative heat exchangers

    CERN Document Server

    Ackermann, Robert A


    An in-depth survey of regenerative heat exchangers, this book chronicles the development and recent commercialization of regenerative devices for cryogenic applications. Chapters cover historical background, concepts, practical applications, design data, and numerical solutions, providing the latest information for engineers to develop advanced cryogenic machines. The discussions include insights into the operation of a regenerator; descriptions of the cyclic and fluid temperature distributions in a regenerator; data for various matrix geometries and materials, including coarse and fine bronze, stainless steel-woven wire mesh screens, and lead spheres; and unique operating features of cryocoolers that produce deviations from ideal regenerator theory.

  6. Study on actinoid isolation by antimonide ion exchanger

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Masamichi [Tokyo Inst. of Tech. (Japan). Faculty of Science; Kubota, Masumitsu; Yamagishi, Isao


    To establish a containment of long-life nuclides and an effective reduction of waste volume is important to reduce the loadings on the natural environment. Chemical isolation of radioactive nuclides from wastes was attempted by using inorganic ion exchanger with high specificity and thermal stability. In this study, titanium antimonide was used as an ion exchanger to investigate the adsorption of trivalent metallic ions according to Kielland plot curves. When the ionic equivalent fraction (X-bar{sub M}) was around 0.005, Kielland plot curve of either of 3-valent metallic ions was bent, suggesting the exchanger had two different adsorption sites. The slope of the curve became smaller as an elevation of temperature. These results show that the ion radius was decreased resulting from partial elimination of the hydrated water of ion and thus, the steric conditions around the exchange site might be improved. (M.N.)

  7. Preparation of sulfonated cation exchangers from petroleum asphaltites

    Energy Technology Data Exchange (ETDEWEB)

    Pokonova, Yu.V.; Pol' kin, G.B.; Proskuryakov, V.A.


    It was established that the reaction of petroleum asphaltite sulfonation is determined in the first step by the chemical reaction rate, and in the last --- by diffusion factors. The kinetic constants were found for each reaction step. Sulfonated cation exchangers were obtained having the characteristics: specific volume of the swollen cation exchanger 3.30 mL/g, bulk density of the air-dry product 0.58 g/mL., moisture content 23.4%, swelling in water 41.6%, mechanical strength 80.0%, static exchange capacity with respect to 0.1N NaOH solution 2.76 mg equiv/g, dynamic exchange capacity with respect to 0.0035N CaC1/sub 2/ solution for a specific load of 10 L/L.h 465 mg equiv/L.

  8. A Review on Heat Transfer Improvent of Plate Heat Exchanger

    Directory of Open Access Journals (Sweden)

    Abhishek Nandan


    Full Text Available Plate heat exchanger has found a wide range of application in various industries like food industries, chemical industries, power plants etc. It reduces the wastage of energy and improves the overall efficiency of the system. Hence, it must be designed to obtain the maximum heat transfer possible. This paper is presented in order to study the various theories and results given over the improvement of heat transfer performance in a plate heat exchanger. However, there is still a lack in data and generalized equations for the calculation of different parameters in the heat exchanger. It requires more attention to find out various possible correlations and generalized solutions for the performance improvement of plate heat exchanger.

  9. Phosphorus-contained polycondensation type ion-exchange resins

    Directory of Open Access Journals (Sweden)

    Tulkun Tursunov


    Full Text Available This work describes synthesis and research of new polycondensation type phosphorus-contained ion-exchange polymers by phosphorylation of polymers received through the interaction of furfural (accessible and cheap product of hydrolytic and cotton scraping industry of Uzbekistan with benzyl bromide (chloride. Furfural and its derivatives possess high reactionary ability thanks to presence of carbonyl groups, and presence of a heterocyclic cycle gives to the received polymers high thermal and chemical stability. Polycondensation reaction kinetics of furfural and benzyl bromide, and phosphorylation reaction of the received benzyl bromide-furfural polymer were studied. Sorption, kinetic and thermo-chemical properties of received ion-exchange resins were studied using physico-chemical and chemical analyses to find out specific objects of practical application. Particularly, sorption and selective properties of received ion-exchange resins to ions of such metals as copper, nickel, calcium, magnesium, and uranyl ion were studied. Received results support the application of the investigated ion-exchange resins in processes of clearing of industrial and waste waters of hydrometallurgical manufactures.

  10. Physical explosion analysis in heat exchanger network design (United States)

    Pasha, M.; Zaini, D.; Shariff, A. M.


    The failure of shell and tube heat exchangers is being extensively experienced by the chemical process industries. This failure can create a loss of production for long time duration. Moreover, loss of containment through heat exchanger could potentially lead to a credible event such as fire, explosion and toxic release. There is a need to analyse the possible worst case effect originated from the loss of containment of the heat exchanger at the early design stage. Physical explosion analysis during the heat exchanger network design is presented in this work. Baker and Prugh explosion models are deployed for assessing the explosion effect. Microsoft Excel integrated with process design simulator through object linking and embedded (OLE) automation for this analysis. Aspen HYSYS V (8.0) used as a simulation platform in this work. A typical heat exchanger network of steam reforming and shift conversion process was presented as a case study. It is investigated from this analysis that overpressure generated from the physical explosion of each heat exchanger can be estimated in a more precise manner by using Prugh model. The present work could potentially assist the design engineer to identify the critical heat exchanger in the network at the preliminary design stage.

  11. Synthesis of Heat Exchanger Network Considering Multipass Exchangers

    Institute of Scientific and Technical Information of China (English)

    李绍军; 姚平经


    Many methods have been proposed for synthesis of heat exchanger networks in recent years, most of which consider single pass exchangers. In this study some evolutionary rules have been proposed for synthesis of multipass exchanger networks. The method is based on the heuristic that optimal networks should feature maximum energy recovery and have the minimum number of shells. The effectiveness of the developed evolutionary rules is demonstrated through some literature examples.

  12. Real exchange rate fluctuations, endogenous tradability and exchange rate regime


    Kanda Naknoi


    This paper, empirically and theoretically, studies variance decomposition of real exchange rate. We find that deviations from the law of one price for traded goods drive most real exchange rates. However, the relative price of nontraded goods is also important for some countries maintaining stable exchange rate. We propose an explanation based on dynamics of comparative advantage. Our model predicts that comovement of terms of trade and productivity differentials of the nontraded and the expo...

  13. Capital Flows, Exchange Rate Flexibility, and the Real Exchange Rate


    Jean-Louis Combes; Patrick Plane; Tidiane Kinda


    This paper analyzes the impact of capital inflows and exchange rate flexibility on the real exchange rate in developing countries based on panel cointegration techniques. The results show that public and private flows are associated with a real exchange rate appreciation. Among private flows, portfolio investment has the highest appreciation effect-almost seven times that of foreign direct investment or bank loans-and private transfers have the lowest effect. Using a de facto measure of excha...

  14. Global evaluation of ammonia bidirectional exchange and livestock diurnal variation schemes (United States)

    Bidirectional air–surface exchange of ammonia (NH3) has been neglected in many air quality models. In this study, we implement the bidirectional exchange of NH3 in the GEOS-Chem global chemical transport model. We also introduce an updated diurnal variability scheme for NH3...

  15. Er3+/Yb3+ Codoped Phosphate Glass for Ion-Exchanged Planar Waveguide Amplifiers

    Institute of Scientific and Technical Information of China (English)

    Shilong Zhao; Baoyu Chen; Zhuping Liu; Lili Hu


    A novel Er3+/Yb3+ codoped phosphate glass was developed, which exhibited good chemical durability in molten salts and excellent spectroscopic properties. Preliminary results of ion exchange at different time and temperature, and with varying melt concentrations indicated that WM4 glass was suitable for ion-exchange experiments and there was no deterioration of surface quality.

  16. Er~(3+)/Yb~(3+) Codoped Phosphate Glass for Ion-Exchanged Planar Waveguide Amplifiers

    Institute of Scientific and Technical Information of China (English)


    A novel Er3+/Yb3+ codoped phosphate glass was developed, which exhibited good chemical durability in molten salts and excellent spectroscopic properties. Preliminary results of ion exchange at different time and temperature, and with varying melt concentrations indicated that WM4 glass was suitable for ion-exchange experiments and there was no deterioration of surface quality.

  17. Interfacing heat exchanger network synthesis and detailed heat exchanger design

    Energy Technology Data Exchange (ETDEWEB)

    Polley, G.T.; Panjeh Shahi, M.H. (Manchester Univ. (United Kingdom). Inst. of Science and Technology)


    Current heat exchanger network synthesis targeting and design procedures involve the use of assumed stream heat transfer coefficients. However, during detailed heat exchanger design, allowable pressure drops are often the most critical factors. The result can be big differences between the exchanger sizes and costs anticipated by the network designer and those realised by the exchanger designer. This in turn prejudices any optimisation attempted at the network design stage. In this paper it is shown how allowable pressure drop can be used as a basis of network design and consistency between expectation and realisation achieved. (author).

  18. Mechanism of Polysulfone-Based Anion Exchange Membranes Degradation in Vanadium Flow Battery. (United States)

    Yuan, Zhizhang; Li, Xianfeng; Zhao, Yuyue; Zhang, Huamin


    The stability of hydrocarbon ion exchange membranes is one of the critical issues for a flow battery. However, the degradation mechanism of ion exchange membranes has been rarely investigated especially for anion exchange membranes. Here, the degradation mechanism of polysulfone based anion exchange membranes, carrying pyridine ion exchange groups, under vanadium flow battery (VFB) medium was investigated in detail. We find that sp(2) hybrid orbital interactions between pyridinic-nitrogen in 4,4'-bipyridine and benzylic carbon disrupt the charge state balance of pristine chloromethylated polysulfone. This difference in electronegativity inversely induces an electrophilic carbon center in the benzene ring, which can be attacked by the lone pair electron on the vanadium(V) oxygen species, further leading to the degradation of polymer backbone, while leaving the 4,4'-bipyridine ion exchange groups stable. This work represents a step toward design and construction of alternative type of chemically stable hydrocarbon ion exchange membranes for VFB.


    Institute of Scientific and Technical Information of China (English)

    YuXintian; SunZhaoxiang


    In this paper,a new complex inorganic ion exchanger Titanium Phosphate-Ammonium Tungstophosphate(abbreviated as Tip-AWP) was synthesized,whose exchange character and chemical structure were studied.This compound exhibits high exchange capacity and selectivity for Cs+,its exchange capacity accains 0.95 mmol/g in the medium of 0.1mol/L HNO3,and which almost doesn′t change in the 1AW imitated waste solution.There are no change in exchange capacity and structute after several times of exchanging,eluting,regenerating,which is of great importance to the separation and uptaking of radio-nuclides.Further more,this exchanger has good thermal and redioactive stability.

  20. Fixed Exchange Rates and Trade


    Michael W. Klein; Jay C. Shambaugh


    A classic argument for a fixed exchange rate is its promotion of trade. Empirical support for this, however, is mixed. While one branch of research consistently shows a small negative effect of exchange rate volatility on trade, another, more recent, branch presents evidence of a large positive impact of currency unions on trade. This paper helps resolve this disconnect. Our results, which use a new data-based classification of fixed exchange rate regimes, show a large, significant effect of ...

  1. Exchange Rates, Innovations and Forecasting


    Wolff, Christian C


    In this paper an ex-post forecasting experiment is performed on the basis of a version of the "news" model of exchange rate determination. A general finding is that the "news" formulation of monetary exchange rate models leads to relatively accurate ex post exchange rate forecasts. Often the results compare favourably with those obtained from the naive random walk forecasting rule. Thus, the evidence presented in this paper supports the argument that the 1983 finding by Meese and Rogoff (that...

  2. Chemical sensors (United States)

    Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.


    Sensors responsive to small changes in the concentration of chemical species are disclosed. The sensors comprise a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment. They are operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical response. 9 figures.

  3. Data Exchange in Grid Workflow

    Institute of Scientific and Technical Information of China (English)

    ZENG Hongwei; MIAO Huaikou


    In existing web services-based workflow, data exchanging across the web services is centralized, the workflow engine intermediates at each step of the application sequence.However, many grid applications, especially data intensive scientific applications, require exchanging large amount of data across the grid services.Having a central workfiow engine relay the data between the services would results in a bottleneck in these cases.This paper proposes a data exchange model for individual grid workflow and multiworkflows composition respectively.The model enables direct communication for large amounts of data between two grid services.To enable data to exchange among multiple workflows, the bridge data service is used.

  4. Mastering Microsoft Exchange Server 2013

    CERN Document Server

    Elfassy, David


    The bestselling guide to Exchange Server, fully updated for the newest version Microsoft Exchange Server 2013 is touted as a solution for lowering the total cost of ownership, whether deployed on-premises or in the cloud. Like the earlier editions, this comprehensive guide covers every aspect of installing, configuring, and managing this multifaceted collaboration system. It offers Windows systems administrators and consultants a complete tutorial and reference, ideal for anyone installing Exchange Server for the first time or those migrating from an earlier Exchange Server version.Microsoft

  5. Theoretical investigation of exchange bias

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhi-Jie; Wang Huai-Yu; Ding Ze-Jun


    The exchange bias of bilayer magnetic films consisting of ferromagnetic (FM) and antiferromagnetic (AFM) layers in an uncompensated case is studied by use of the many-body Green's function method of quantum statistical theory.The effects of the layer thickness and temperature and the interfacial coupling strength on the exchange bias HE are investigated. The dependence of the exchange bias HE on the FM layer thickness and temperature is qualitatively in agreement with experimental results. When temperature varies, both the coercivity HC and HE decrease with the temperature increasing. For each FM thickness, there exists a least AFM thickness in which the exchange bias occurs,which is called pinning thickness.

  6. The Radioecology Exchange

    Energy Technology Data Exchange (ETDEWEB)

    Barnett, Catherine L.; Beresford, Nicholas A.; Patel, Sabera; Wells, Claire; Howard, Brenda J. [NERC Centre for Ecology and Hydrology, CEH Lancaster, Lancaster Environment Centre, Library Av., Bailrigg, Lancaster, LA1 4AP (United Kingdom); Mora, Juan Carlos; Real, Almudena [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Avenida complutense 22, Madrid, 28040 (Spain); Beaugelin-Seiller, Karine; Gilbin, Rodolphe; Hinton, Thomas [IRSN-Institut de Radioprotection et de Surete Nucleaire, 31, Avenue de la Division Leclerc, 92260 Fontenay-Aux-Roses (France); Vesterbacka, Pia; Muikku, Maarit; Outola, Iisa [Radiation and Nuclear Safety Authority, P.O. Box 14, FI-00881 Helsinki (Finland); Skuterud, Lavrans; AlbumYtre-Eide, Martin [Norwegian Radiation Protection Authority, Grini Naeringspark 13, Oesteraas, 1332 (Norway); Bradshaw, Clare; Stark, Karolina; Jaeschke, Ben [Stockholms Universitet, Universitetsvaegen 10, Stockholm, 10691 (Sweden); Oughton, Deborah; Skipperud, Lindis [NMBU Norwegian University of Life Science P.O. Box 5003N-1432 Aas, Oslo (Norway); Vandenhove, Hildegarde; Vanhoudt, Nathalie [SCK.CEN, Studiecentrum voor Kernenergie/Centre d' Etude de l' Energie Nucleaire, Avenue Herrmann-Debroux 40, BE-1160 Brussels (Belgium); Willrodt, Christine; Steiner, Martin [Bundesamt fuer Strahlenschutz, Willy-Brandt-Strasse 5, 38226 Salzgitter (Germany)


    The Radioecology Exchange ( was created in 2011 under the EU FP7 STAR (Strategy for Allied Radioecology) network of excellence. The project aims to integrate the research efforts on radioecology of nine European organisations into a sustainable network. The web site (together with associated Twitter feeds and Facebook page) currently provides the gateway to project outputs and other on-line radiation protection and radioecological resources. In 2013, the EU FP7 COMET (Coordination and implementation of a pan-European instrument for radioecology) project commenced; it aims to strengthen research on the impact of radiation on man and the environment. COMET includes the STAR partners with the addition of one Japanese and two Ukrainian research institutes. As STAR and COMET interact closely together and with the European Radioecology Alliance (, the Radioecology Exchange will be modified to become an international 'hub' for information related to radioecology. Project specific information will be hosted on separate web sites and This paper will present an overview of the resources hosted on the Radioecology Exchange inviting other scientists to contribute. Highlighted aspects of the site include: Social media (News blog, Twitter, Facebook) - Items announcing project outputs, training courses, jobs, studentships etc. Virtual laboratory - Information which encourages integration through joint research and integrated use of data and sample materials. These pages will focus on three categories: (1) Methodological: descriptions and video clips of commonly used analytical methods and protocols and the procedures used in STAR and COMET; (2) Informative: databases made available by STAR/COMET partners together with details of sample archives held. Fact-sheets on radio-ecologically important radionuclides and 'topical descriptions' which show absorbed

  7. Hybrid Heat Exchangers (United States)

    Tu, Jianping Gene; Shih, Wei


    A hybrid light-weight heat exchanger concept has been developed that uses high-conductivity carbon-carbon (C-C) composites as the heat-transfer fins and uses conventional high-temperature metals, such as Inconel, nickel, and titanium as the parting sheets to meet leakage and structural requirements. In order to maximize thermal conductivity, the majority of carbon fiber is aligned in the fin direction resulting in 300 W/m.K or higher conductivity in the fin directions. As a result of this fiber orientation, the coefficient of thermal expansion (CTE) of the C-C composite in both non-fiber directions matches well with the CTE of various high-temperature metal alloys. This allows the joining of fins and parting sheets by using high-temperature braze alloys.

  8. Asymmetric exchange in flocks

    CERN Document Server

    Dadhichi, Lokrshi Prawar; Maitra, Ananyo; Ramaswamy, Sriram


    As the constituents of a flock are polar, one expects a fore-aft asymmetry in their interactions. We show here that the resulting antisymmetric part of the "exchange coupling" between a bird and its neighbours, if large enough, destabilizes the flock through spontaneous turning of the birds. The same asymmetry also yields a natural mechanism for a difference between the speed of advection of information along the flock and the speed of the flock itself. We show that the absence of detailed balance, and not merely the breaking of Galilean invariance, is responsible for this difference. We delineate the conditions on parameters and wavenumber for the existence of the turning instability. Lastly we present an alternative perspective based on flow-alignment effects in an active liquid crystal with turning inertia in contact with a momentum sink.

  9. Binary stars: Mass transfer and chemical composition (United States)

    Lambert, D. L.


    It is noted that mass exchange (and mass loss) within a binary system should produce observable changes in the surface chemical composition of both the mass losing and mass gaining stars as a stellar interior exposed to nucleosyntheses is uncovered. Three topics relating mass exchange and/or mass loss to nucleosynthesis are sketched: the chemical composition of Algol systems; the accretion disk of a cataclysmic variable fed by mass from a dwarf secondary star; and the hypothesis that classical Ba II giants result from mass transfer from a more evolved companion now present as a white dwarf.

  10. Ion exchange materials, method of forming ion exchange materials, and methods of treating liquids (United States)

    Wertsching, Alan K.; Peterson, Eric S.; Wey, John E.


    The invention includes an ion affinity material having an organic component which is sulfonated and which is chemically bonded to an inorganic substrate component. The invention includes a method of forming a metal binding material. A solid support material comprising surface oxide groups is provided and an organic component having at least one alkyl halide is covalently linked to at least some of the surface oxide groups to form a modified support material. The at least one alkyl halide is subsequently converted into an alkyl sulfonate. The invention further includes a method and system for extracting ions from a liquid. An ion exchange material having a sulfonated alkyl silane component covalently bonded to a metal oxide support material is provided and a liquid is exposed to the ion exchange material.

  11. Chemical intolerance

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz; Andersson, Linus; Nordin, Steven;


    Chemical intolerance (CI) is a term used to describe a condition in which the sufferer experiences a complex array of recurrent unspecific symptoms attributed to low-level chemical exposure that most people regard as unproblematic. Severe CI constitutes the distinguishing feature of multiple...... chemical sensitivity (MCS). The symptoms reported by CI subjects are manifold, involving symptoms from multiple organs systems. In severe cases of CI, the condition can cause considerable life-style limitations with severe social, occupational and economic consequences. As no diagnostic tools for CI...

  12. Hazardous Chemicals

    Centers for Disease Control (CDC) Podcasts


    Chemicals are a part of our daily lives, providing many products and modern conveniences. With more than three decades of experience, The Centers for Disease Control and Prevention (CDC) has been in the forefront of efforts to protect and assess people's exposure to environmental and hazardous chemicals. This report provides information about hazardous chemicals and useful tips on how to protect you and your family from harmful exposure.  Created: 4/10/2007 by CDC National Center for Environmental Health.   Date Released: 4/13/2007.

  13. Macroreticular chelating ion-exchangers. (United States)

    Hirsch, R F; E Gancher, R; Russo, F R


    Two macroreticular chelating ion-exchangers have been prepared and characterized. One contains the iminodiacetate group and the second contains the arsonate group as the ion-exchanging site. The macroreticular resins show selectivities among metal ions similar to those of the commercially available naicroreticular chelating resins. Chromatographie separations on the new resins are rapid and sharp.

  14. Exchange Rates and Old People. (United States)

    Dowd, James J.


    Extends earlier work on aging as a process of exchange by focusing on the issue of exchange rates and how they are negotiated. Access to power resources declines with age, placing the old person in the position of negotiating from weakness. (Author)

  15. Transendothelial lipoprotein exchange and microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, Jan Skov; Feldt-Rasmussen, Bo; Jensen, Kurt Svarre


    . METHODS: Using an in vivo isotope technique, transendothelial exchange of low density lipoprotein (LDL) was measured in 77 non-diabetic individuals. Autologous 131-iodinated LDL was reinjected intravenously, and the 1-h fractional escape rate was calculated as index of transendothelial exchange. RESULTS...... transformed) plasma insulin: beta=0.6 (95% CI: 0.1-1.1); R=0.22; P

  16. Liquid/liquid heat exchanger (United States)

    Miller, C. G.


    Conceptual design for heat exchanger, utilizing two immiscible liquids with dissimilar specific gravities in direct contact, is more efficient mechanism of heat transfer than conventional heat exchangers with walls or membranes. Concept could be adapted for collection of heat from solar or geothermal sources.

  17. Educators Exchange: A Program Evaluation. (United States)

    Armstrong, William B.

    The Educators Exchange Program (EEP) was established under a training and educational exchange agreement reached by California's San Diego Community College District (SDCCD) and the republic of Mexico. In the program, the District provided a 4-week technological training program to faculty at Centros de Capacitacion Tecnologica Industrial…

  18. Value Appropriation in Business Exchange

    DEFF Research Database (Denmark)

    Ellegaard, Chris; Medlin, Christopher J.; Geersbro, Jens


    Purpose – Value appropriation is a central, yet neglected aspect in business exchange research. The purpose of the paper is to generate an overview of research on active value appropriation in business exchange and provide the foundation for further research into value appropriation, as well as s...

  19. EXCHANGE. Volume 9-92

    Energy Technology Data Exchange (ETDEWEB)

    Boltz, J.C. [ed.


    EXCHANGE is published monthly by the Idaho National Engineering Laboratory (INEL), a multidisciplinary facility operated for the US Department of Energy (DOE). The purpose of EXCHANGE is to inform computer users about about recent changes and innovations in both the mainframe and personal computer environments and how these changes can affect work being performed at DOE facilities.

  20. Performance of Helical Coil Heat Recovery Exchanger using Nanofluid as Coolant

    Directory of Open Access Journals (Sweden)

    Navid Bozorgan


    Full Text Available Nanofluids are expected to be a promising coolant condidate in chemical processes for heat transfer system size reduction. This paper focuses on reducing the number of turns in a helical coil heat recovery exchanger with a given heat exchange capacity in a biomass heating plant using γ-Al2O3/n-decane nanofluid as coolant. The nanofluid flows through the tubes and the hot n-hexane flows through the shell. The numerical results show that using nanofluid as coolant in a helical coil heat exchanger can reduce the manufacturing cost of the heat exchanger and pumping power by reducing the number of turns of the coil.

  1. Heat exchanger leakage problem location

    Directory of Open Access Journals (Sweden)

    Jícha Miroslav


    Full Text Available Recent compact heat exchangers are very often assembled from numerous parts joined together to separate heat transfer fluids and to form the required heat exchanger arrangement. Therefore, the leak tightness is very important property of the compact heat exchangers. Although, the compact heat exchangers have been produced for many years, there are still technological problems associated with manufacturing of the ideal connection between the individual parts, mainly encountered with special purpose heat exchangers, e.g. gas turbine recuperators. This paper describes a procedure used to identify the leakage location inside the prime surface gas turbine recuperator. For this purpose, an analytical model of the leaky gas turbine recuperator was created to assess its performance. The results obtained are compared with the experimental data which were acquired during the recuperator thermal performance analysis. The differences between these two data sets are used to indicate possible leakage areas.

  2. High Temperature Heat Exchanger Project

    Energy Technology Data Exchange (ETDEWEB)

    Anthony E. Hechanova, Ph.D.


    The UNLV Research Foundation assembled a research consortium for high temperature heat exchanger design and materials compatibility and performance comprised of university and private industry partners under the auspices of the US DOE-NE Nuclear Hydrogen Initiative in October 2003. The objectives of the consortium were to conduct investigations of candidate materials for high temperature heat exchanger componets in hydrogen production processes and design and perform prototypical testing of heat exchangers. The initial research of the consortium focused on the intermediate heat exchanger (located between the nuclear reactor and hydrogen production plan) and the components for the hydrogen iodine decomposition process and sulfuric acid decomposition process. These heat exchanger components were deemed the most challenging from a materials performance and compatibility perspective

  3. Heat exchanger leakage problem location (United States)

    Hejčík, Jiří; Jícha, Miroslav


    Recent compact heat exchangers are very often assembled from numerous parts joined together to separate heat transfer fluids and to form the required heat exchanger arrangement. Therefore, the leak tightness is very important property of the compact heat exchangers. Although, the compact heat exchangers have been produced for many years, there are still technological problems associated with manufacturing of the ideal connection between the individual parts, mainly encountered with special purpose heat exchangers, e.g. gas turbine recuperators. This paper describes a procedure used to identify the leakage location inside the prime surface gas turbine recuperator. For this purpose, an analytical model of the leaky gas turbine recuperator was created to assess its performance. The results obtained are compared with the experimental data which were acquired during the recuperator thermal performance analysis. The differences between these two data sets are used to indicate possible leakage areas.



    Karthikeyan. D


    In present day shell and tube heat exchanger is the most common type heat exchanger widely use in oil refinery and other large chemical process, because it suits high pressure application. The process in solving simulation consists of modeling and meshing the basic geometry of...

  5. Asynchronous Replica Exchange Software for Grid and Heterogeneous Computing (United States)

    Gallicchio, Emilio; Xia, Junchao; Flynn, William F.; Zhang, Baofeng; Samlalsingh, Sade; Mentes, Ahmet; Levy, Ronald M.


    Parallel replica exchange sampling is an extended ensemble technique often used to accelerate the exploration of the conformational ensemble of atomistic molecular simulations of chemical systems. Inter-process communication and coordination requirements have historically discouraged the deployment of replica exchange on distributed and heterogeneous resources. Here we describe the architecture of a software (named ASyncRE) for performing asynchronous replica exchange molecular simulations on volunteered computing grids and heterogeneous high performance clusters. The asynchronous replica exchange algorithm on which the software is based avoids centralized synchronization steps and the need for direct communication between remote processes. It allows molecular dynamics threads to progress at different rates and enables parameter exchanges among arbitrary sets of replicas independently from other replicas. ASyncRE is written in Python following a modular design conducive to extensions to various replica exchange schemes and molecular dynamics engines. Applications of the software for the modeling of association equilibria of supramolecular and macromolecular complexes on BOINC campus computational grids and on the CPU/MIC heterogeneous hardware of the XSEDE Stampede supercomputer are illustrated. They show the ability of ASyncRE to utilize large grids of desktop computers running the Windows, MacOS, and/or Linux operating systems as well as collections of high performance heterogeneous hardware devices. PMID:27103749

  6. Asynchronous replica exchange software for grid and heterogeneous computing (United States)

    Gallicchio, Emilio; Xia, Junchao; Flynn, William F.; Zhang, Baofeng; Samlalsingh, Sade; Mentes, Ahmet; Levy, Ronald M.


    Parallel replica exchange sampling is an extended ensemble technique often used to accelerate the exploration of the conformational ensemble of atomistic molecular simulations of chemical systems. Inter-process communication and coordination requirements have historically discouraged the deployment of replica exchange on distributed and heterogeneous resources. Here we describe the architecture of a software (named ASyncRE) for performing asynchronous replica exchange molecular simulations on volunteered computing grids and heterogeneous high performance clusters. The asynchronous replica exchange algorithm on which the software is based avoids centralized synchronization steps and the need for direct communication between remote processes. It allows molecular dynamics threads to progress at different rates and enables parameter exchanges among arbitrary sets of replicas independently from other replicas. ASyncRE is written in Python following a modular design conducive to extensions to various replica exchange schemes and molecular dynamics engines. Applications of the software for the modeling of association equilibria of supramolecular and macromolecular complexes on BOINC campus computational grids and on the CPU/MIC heterogeneous hardware of the XSEDE Stampede supercomputer are illustrated. They show the ability of ASyncRE to utilize large grids of desktop computers running the Windows, MacOS, and/or Linux operating systems as well as collections of high performance heterogeneous hardware devices.


    Energy Technology Data Exchange (ETDEWEB)

    Nash, C.; Hang, T.; Aleman, S.


    Ion exchange modeling was conducted at the Savannah River National Laboratory to compare the performance of two organic resins in support of Small Column Ion Exchange (SCIX). In-tank ion exchange (IX) columns are being considered for cesium removal at Hanford and the Savannah River Site (SRS). The spherical forms of resorcinol formaldehyde ion exchange resin (sRF) as well as a hypothetical spherical SuperLig{reg_sign} 644 (SL644) are evaluated for decontamination of dissolved saltcake wastes (supernates). Both SuperLig{reg_sign} and resorcinol formaldehyde resin beds can exhibit hydraulic problems in their granular (nonspherical) forms. SRS waste is generally lower in potassium and organic components than Hanford waste. Using VERSE-LC Version 7.8 along with the cesium Freundlich/Langmuir isotherms to simulate the waste decontamination in ion exchange columns, spherical SL644 was found to reduce column cycling by 50% for high-potassium supernates, but sRF performed equally well for the lowest-potassium feeds. Reduced cycling results in reduction of nitric acid (resin elution) and sodium addition (resin regeneration), therefore, significantly reducing life-cycle operational costs. These findings motivate the development of a spherical form of SL644. This work demonstrates the versatility of the ion exchange modeling to study the effects of resin characteristics on processing cycles, rates, and cold chemical consumption. The value of a resin with increased selectivity for cesium over potassium can be assessed for further development.

  8. Building Structural Complexity in Semiconductor Nanocrystals through Chemical Transformations


    Sadtler, Bryce F


    Methods are presented for synthesizing nanocrystal heterostructures comprised of two semiconductor materials epitaxially attached within individual nanostructures. The chemical transformation of cation exchange, where the cations within the lattice of an ionic nanocrystal are replaced with a different metal ion species, is used to alter the chemical composition at specific regions of a nanocrystal. Partial cation exchange was performed in cadmium sulfide (CdS) nanorods of well-defined size an...

  9. Fixed Points for Stochastic Open Chemical Systems

    CERN Document Server

    Malyshev, V A


    In the first part of this paper we give a short review of the hierarchy of stochastic models, related to physical chemistry. In the basement of this hierarchy there are two models --- stochastic chemical kinetics and the Kac model for Boltzman equation. Classical chemical kinetics and chemical thermodynamics are obtained as some scaling limits in the models, introduced below. In the second part of this paper we specify some simple class of open chemical reaction systems, where one can still prove the existence of attracting fixed points. For example, Michaelis\\tire Menten kinetics belongs to this class. At the end we present a simplest possible model of the biological network. It is a network of networks (of closed chemical reaction systems, called compartments), so that the only source of nonreversibility is the matter exchange (transport) with the environment and between the compartments. Keywords: chemical kinetics, chemical thermodynamics, Kac model, mathematical biology

  10. Electrically switched ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M.A. [Pacific Northwest National Lab., Richland, WA (United States); Schwartz, D.T.; Genders, D.


    A variety of waste types containing radioactive {sup 137}Cs are found throughout the DOE complex. These waste types include water in reactor cooling basins, radioactive high-level waste (HLW) in underground storage tanks, and groundwater. Safety and regulatory requirements and economics require the removal of radiocesium before these wastes can be permanently disposed of. Electrically Switched Ion Exchange (ESIX) is an approach for radioactive cesium separation that combines IX and electrochemistry to provide a selective, reversible, and economic separation method that also produces little or no secondary waste. In the ESIX process, an electroactive IX film is deposited electrochemically onto a high-surface area electrode, and ion uptake and elution are controlled directly by modulating the potential of the film. For cesium, the electroactive films under investigation are ferrocyanides, which are well known to have high selectivities for cesium in concentrated sodium solutions. When a cathode potential is applied to the film, Fe{sup +3} is reduced to the Fe{sup +2} state, and a cation must be intercalated into the film to maintain charge neutrality (i.e., Cs{sup +} is loaded). Conversely, if an anodic potential is applied, a cation must be released from the film (i.e., Cs{sup +} is unloaded). Therefore, to load the film with cesium, the film is simply reduced; to unload cesium, the film is oxidized.

  11. Energy-Exchange Project

    Energy Technology Data Exchange (ETDEWEB)


    The purpose of the study was to determine what energy savings can be achieved by coordinating the resources and requirements of two facilities, the 26th Ward Water Pollution Control Plant (WPCP) and a housing development named Starrett City with its own total energy system. It was determined that three energy exchange options were economically and technically feasible. These include: the transfer of digester gas produced at the 26th Ward to the boilers at the Starrett City's total energy plant (TEP); the transfer of hot water heated at the TEP to the 26th Ward for space and process heating; and the transfer of coal effluent waste water from the 26th Ward to the condenser cooling systems at the TEP. Technical information is presented to support the findings. The report addresses those tasks of the statement of work dedicated to data acquisition, analysis, and energy conservation strategies internal to the Starrett City TEP and the community it supplies as well as to the 26th Ward WPCP. (MCW)

  12. Ion-exchange chromatographic protein refolding. (United States)

    Freydell, Esteban J; van der Wielen, Luuk; Eppink, Michel; Ottens, Marcel


    The application of ion-exchange (IEX) chromatography to protein refolding (IExR) has been successfully proven, as supported by various studies using different model proteins, ion-exchange media and flow configurations. Ion-exchange refolding offers a relatively high degree of process intensification, represented by the possibility of performing protein refolding, product purification and product concentration, in one unit operation. Besides its high degree of process intensification, IExR offers an additional set of key advantages including: spatial isolation of the bound protein molecules and the controllable change in chemical composition using gradients. Despite of the acknowledgement of the former advantages, the lack of mechanistic understanding on how they influence the process performance of the ion-exchange refolding reactor, limits the ability to exploit them in order to optimize the performance of the unit. This paper presents a quantitative analysis that assesses the effect that the spatial isolation and the urea gradient, have on the IExR performance, judged on the basis of the refolding yield (Y(N)) and the fractional mass recovery (f(Prot,Rec)). Additionally, this work discusses the effect of the protein load, the protein loading state (i.e., native, denatured, denatured and reduced (D&R)) and the adsorbent type on f(Prot,Rec). The presented work shows: (1) that the protein load has a direct effect on f(Prot,Rec), and the magnitude of this effect depends on the loading state of the protein solution and the adsorbent type; (2) that irrespectively of the type of adsorbent used, the saturation capacity of a denatured protein is less than the native protein and that this difference can be linked to differences in accessible binding surface area; (3) that there is a clear correlation between fractional surface coverage (θ) and f(Prot,Rec), indicating that the former could serve as a good descriptor to assess spatial isolation, and (4) that the urea

  13. Custom, contract, and kidney exchange. (United States)

    Healy, Kieran; Krawiec, Kimberly D


    In this Essay, we examine a case in which the organizational and logistical demands of a novel form of organ exchange (the nonsimultaneous, extended, altruistic donor (NEAD) chain) do not map cleanly onto standard cultural schemas for either market or gift exchange, resulting in sociological ambiguity and legal uncertainty. In some ways, a NEAD chain resembles a form of generalized exchange, an ancient and widespread instance of the norm of reciprocity that can be thought of simply as the obligation to “pay it forward” rather than the obligation to reciprocate directly with the original giver. At the same time, a NEAD chain resembles a string of promises and commitments to deliver something in exchange for some valuable consideration--that is, a series of contracts. Neither of these salient "social imaginaries" of exchange--gift giving or formal contract--perfectly meets the practical demands of the NEAD system. As a result, neither contract nor generalized exchange drives the practice of NEAD chains. Rather, the majority of actual exchanges still resemble a simpler form of exchange: direct, simultaneous exchange between parties with no time delay or opportunity to back out. If NEAD chains are to reach their full promise for large-scale, nonsimultaneous organ transfer, legal uncertainties and sociological ambiguities must be finessed, both in the practices of the coordinating agencies and in the minds of NEAD-chain participants. This might happen either through the further elaboration of gift-like language and practices, or through a creative use of the cultural form and motivational vocabulary, but not necessarily the legal and institutional machinery, of contract.

  14. Effect of polyamine reagents on exchange capacity in ion exchangers (United States)

    Petrova, T. I.; Dyachenko, F. V.; Bogatyreva, Yu. V.; Borodastov, A. K.; Ershova, I. S.


    Effect of compounds involved in complex reagents is described using Helamin 906H reagent as an example. The working exchange capacity of KU-2-8chs cation exchanger in hydrogen form and Amberlite IRA 900Cl anion exchanger in OH form remained almost unchanged when they were used repeatedly to purify water that contained Helamin 906H reagent; in addition, this capacity was the same upon filtration of water that did not contain this reagent. Leakage of total organic carbon was observed earlier than that of calcium ions upon filtration of the solution through the cation exchanger layer. The test results obtained in industrial conditions indicated that using H-OH filters to purify turbine condensate enables the decrease of the concentration of organic and other impurities therein.

  15. Heat exchanger using graphite foam (United States)

    Campagna, Michael Joseph; Callas, James John


    A heat exchanger is disclosed. The heat exchanger may have an inlet configured to receive a first fluid and an outlet configured to discharge the first fluid. The heat exchanger may further have at least one passageway configured to conduct the first fluid from the inlet to the outlet. The at least one passageway may be composed of a graphite foam and a layer of graphite material on the exterior of the graphite foam. The layer of graphite material may form at least a partial barrier between the first fluid and a second fluid external to the at least one passageway.


    Energy Technology Data Exchange (ETDEWEB)

    Alsobrook, A. N.; Hobbs, D. T.


    This report presents a summary of testing the affinity of titanosilicates (TSP), germanium-substituted titanosilicates (Ge-TSP) and multiwall carbon nanotubes (MWCNT) for lanthanide ions in dilute nitric acid solution. The K-TSP ion exchanger exhibited the highest affinity for lanthanides in dilute nitric acid solutions. The Ge-TSP ion exchanger shows promise as a material with high affinity, but additional tests are needed to confirm the preliminary results. The MWCNT exhibited much lower affinities than the K-TSP in dilute nitric acid solutions. However, the MWCNT are much more chemically stable to concentrated nitric acid solutions and, therefore, may candidates for ion exchange in more concentrated nitric acid solutions. This technical report serves as the deliverable documenting completion of the FY13 research milestone, M4FT-13SR0303061 – measure actinide and lanthanide distribution values in nitric acid solutions with sodium and potassium titanosilicate materials.

  17. Gradient ascent pulse engineering for rapid exchange saturation transfer (United States)

    Rancan, G.; Nguyen, T. T.; Glaser, S. J.


    Efforts in the clinical translation of the paraCEST contrast agent Yb-HPDO3A have prompted an investigation into saturation pulse optimality under energy constraints. The GRAPE algorithm has been adapted and implemented for saturation pulse optimization with chemical exchange. The flexibility of the methodology, both in extracting the microscopical parameter ensemble for the algorithm as well as in determining the characteristics of this new class of rising amplitude waveforms allows rapid testing and implementation. Optimal pulses achieve higher saturation efficiencies than the continuous wave gold standard for rapid and especially for variable exchange rates, as brought about by pH-catalysis. Gains of at least 5-15% without any tradeoff have been confirmed both on a spectrometer and on a clinical imager. Pool specific solutions, with pulses optimized for a specific exchange rate value, additionally increase the flexibility of the CEST ratiometric analysis. A simple experimental approach to determine close to optimal triangular pulses is presented.

  18. Anion selective membrane. [ion exchange resins and ion exchange membrane electrolytes for electrolytic cells (United States)

    Alexander, S. S.; Geoffroy, R. R.; Hodgdon, R. B.


    Experimental anion permselective membranes were prepared and tested for their suitability as cell separators in a chemical redox power storage system being developed at NASA-Lewis Research Center. The goals of long-term (1000 hr) oxidative and thermal stability at 80 C in FeCl3 and CrCl3 electrolytes were met by most of the weak base and strong base amino exchange groups considered in the program. Good stability is exhibited by several of the membrane substrate resins. These are 'styrene' divinylbenzene copolymer and PVC film. At least four membrane systems produce strong flexible films with electrochemical properties (resistivity, cation transfer) superior to those of the 103QZL, the most promising commercial membrane. The physical and chemical properties of the resins are listed.

  19. Tacrolimus alleviates acute liver graft rejection by inhibiting glucocorticoid-induced tumor necrosis factor-related protein ligand in rats%他克莫司通过抑制GITRL减轻大鼠肝移植排斥反应的研究

    Institute of Scientific and Technical Information of China (English)

    魏思东; 龚建平; 李金政; 黄中荣


    目的 探讨他克莫司(FK506)抑制大鼠肝移植排除反应中的作用机制。方法建立大鼠原位肝移植模型,分为3组。耐受组为Brown Norway (BN)到Lewis肝移植;排斥组为Lewis到BN肝移植;他克莫司(FK506)组在建立排斥模型基础上于术后注射FK506。术后7d检测肝组织病理改变及糖皮质激素诱导的肿瘤坏死因子相关蛋白配体(GITRL)的表达、Kupffer细胞GITRL的表达及细胞因子的改变。结果与耐受组比较,排斥组肝脏及kupffer细胞中GITRL表达升高,采用FK506后,降低了GITRL表达(P<0.05)。与耐受组比较,排斥组血清及kupffer细胞中IFN-γ表达升高,IL-10降低(P<0.05),而在FK506组,与排斥组比较,血清及kupffer细胞中IFN-γ表达降低,IL-10表达升高(P<0.05)。结论FK506能减轻大鼠肝移植后的急性排斥反应,其机制与降低GITRL的表达有关。%Objective To investigate the mechanism underlying the inhibitory effect of tacrolimus (FK506) against acute liver graft rejection. Methods Rat models of orthotopic liver transplantation were divided into 3 groups, namely the tolerance group with Brown Norway (BN) rats as the donors and Lewis rats as the recipients, rejection group with Lewis rats as donors and BN rats as recipients, and FK506 group with the same donor-recipient pair as in the rejection group and FK506 treatment. The recipients were sacrificed 7 days after the transplantation, and the hepatic histology, cytokine levels, and glucocorticoid-induced tumor necrosis factor-related protein ligand (GITRL) expression in the liver and Kupffer cells were observed and detected. Results Compared with the tolerance group, the rejection group showed increased GITRL expressions in the liver and Kupffer cells (PO.05), which was significantly lowered by FK506 treatment (PO.05). Acute liver graft rejection caused significantly elevated interferon-y (IFN-y) levels and decreased interieukin-10 (IL-10) levels in the plasma

  20. VLER Health Exchange by Area (United States)

    Department of Veterans Affairs — “Connect Your Docs” through the Virtual Lifetime Electronic Record (VLER) Health Exchange program. This program gives VA and community health care providers secure...

  1. Identifiability, exchangeability and confounding revisited


    Greenland, Sander; Robins, James Matthew


    In 1986 the International Journal of Epidemiology published "Identifiability, Exchangeability and Epidemiological Confounding". We review the article from the perspective of a quarter century after it was first drafted and relate it to subsequent developments on confounding, ignorability, and collapsibility.

  2. Exchange couplings in magnetic films

    Institute of Scientific and Technical Information of China (English)

    Liu Wei; Liu Xiong-Hua; Cui Wei-Bin; Gong Wen-Jie; Zhang Zhi-Dong


    Recent advances in the study of exchange couplings in magnetic films are introduced.To provide a comprehensive understanding of exchange coupling,we have designed different bilayers,trilayers and multilayers,such as anisotropic hard/soft-magnetic multilayer films,ferromagnetic/antiferromagnetic/ferromagnetic trilayers,[Pt/Co]/NiFe/NiO heterostructures,Co/NiO and Co/NiO/Fe trilayers on an anodic aluminum oxide (AAO) template.The exchange-coupling interaction between soft-and hard-magnetic phases,interlayer and interfacial exchange couplings and magnetic and magnetotransport properties in these magnetic films have been investigated in detail by adjusting the magnetic anisotropy of ferromagnetic layers and by changing the thickness of the spacer layer,ferromagnetic layer,and antiferromagnetic layer.Some particular physical phenomena have been observed and explained.

  3. Pu Anion Exchange Process Intensification

    Energy Technology Data Exchange (ETDEWEB)

    Taylor-Pashow, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)


    This project seeks to improve the efficiency of the plutonium anion-exchange process for purifying Pu through the development of alternate ion-exchange media. The objective of the project in FY15 was to develop and test a porous foam monolith material that could serve as a replacement for the current anion-exchange resin, Reillex® HPQ, used at the Savannah River Site (SRS) for purifying Pu. The new material provides advantages in efficiency over the current resin by the elimination of diffusive mass transport through large granular resin beads. By replacing the large resin beads with a porous foam there is much more efficient contact between the Pu solution and the anion-exchange sites present on the material. Several samples of a polystyrene based foam grafted with poly(4-vinylpyridine) were prepared and the Pu sorption was tested in batch contact tests.

  4. Quantum Exchangeable Sequences of Algebras

    CERN Document Server

    Curran, Stephen


    We extend the notion of quantum exchangeability, introduced by K\\"ostler and Speicher in arXiv:0807.0677, to sequences (\\rho_1,\\rho_2,...c) of homomorphisms from an algebra C into a noncommutative probability space (A,\\phi), and prove a free de Finetti theorem: an infinite quantum exchangeable sequence (\\rho_1,\\rho_2,...c) is freely independent and identically distributed with respect to a conditional expectation. As a corollary we obtain a free analogue of the Hewitt Savage zero-one law. As in the classical case, the theorem fails for finite sequences. We give a characterization of finite quantum exchangeable sequences, which can be viewed as a noncommutative analogue of sampling without replacement. We then give an approximation to how far a finite quantum exchangeable sequence is from being freely independent with amalgamation.

  5. Yuan Exchange Rate 'Properly Adjusted'

    Institute of Scientific and Technical Information of China (English)


      The currency exchange rate was "properly adjusted" this year and takes into account effects on the country's neighbors and the world, Premier Wen Jiabao said at a regional meeting in Malaysia.……

  6. Counterflow Regolith Heat Exchanger Project (United States)

    National Aeronautics and Space Administration — The counterflow regolith heat exchanger (CoRHE) is a device that transfers heat from hot regolith to cold regolith. The CoRHE is essentially a tube-in-tube heat...

  7. Estimating Foreign Exchange Reserve Adequacy

    Directory of Open Access Journals (Sweden)

    Abdul Hakim


    Full Text Available Accumulating foreign exchange reserves, despite their cost and their impacts on other macroeconomics variables, provides some benefits. This paper models such foreign exchange reserves. To measure the adequacy of foreign exchange reserves for import, it uses total reserves-to-import ratio (TRM. The chosen independent variables are gross domestic product growth, exchange rates, opportunity cost, and a dummy variable separating the pre and post 1997 Asian financial crisis. To estimate the risky TRM value, this paper uses conditional Value-at-Risk (VaR, with the help of Glosten-Jagannathan-Runkle (GJR model to estimate the conditional volatility. The results suggest that all independent variables significantly influence TRM. They also suggest that the short and long run volatilities are evident, with the additional evidence of asymmetric effects of negative and positive past shocks. The VaR, which are calculated assuming both normal and t distributions, provide similar results, namely violations in 2005 and 2008.

  8. Investigation of the Ion-Exchange Behavior of Zeolite Y in the Presence of Resin

    Institute of Scientific and Technical Information of China (English)

    Zhang Yi; Zheng Jinyu; Liu Zhongqing; Gao Xiuzhi; Luo Yibin; Zong Baoning


    Ion-exchange process of zeolite Y using ammonium-type resin as an exchange reagent was successfully carried out. The effect of temperature, space velocity and ion concentration on the breakthrough curves was carefully investigated. At the ifrst exchange section, the maximum proportion of qualiifed zeolites (QR) was obtained at a temperature of 70℃, a weight hourly space velocity of 0.61 h-1, and an ion concentration of 197 mg/L. The minimum length of mass-transfer zone (MTZ) of the resin bed was achieved at a temperature of 70℃, a space velocity of 0.61 h-1, and an ion concentration of 423 mg/L. At the second exchange section, the length of MTZ of the resin bed was signiifcantly increased, and the exchange of Na+ions contained in zeolite Y was more dififcult than that achieved at the ifrst exchange section. In both the ifrst and the second exchange sections, the zeolite Y subjected to ion exchange with the resin maintained the similar physical and chemi-cal properties as compared to those exchanged by the conventional approaches, but the zeolite Y, which was obtained after ion exchange, contained a signiifcantly lower content of Na2O.

  9. Universality in the stock exchange

    CERN Document Server

    Gonçalves, Rui


    We analyze the constituents stocks of the Dow Jones Industrial Average and the Standard & Poor's 100 index of the NYSE stock exchange market. Surprisingly, we discovered that the distribution of the fluctuations of the cubic root of the squared daily return are close to the universal non-parametric Bramwell-Holdsworth-Pinton (BHP) distribution. Since the BHP probability density function appears in several other dissimilar phenomena, our result reveals an universal feature of the stock exchange market.

  10. Shared Year Exchange in Nursing

    DEFF Research Database (Denmark)

    Vedsegaard, Helle Wendner; Wederkinck, Elisabeth


    Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien.......Beskrivelse af Shared Year Exchange in Nursing, et udviklingsporjekt omhandlende udvikling, beskrivelse og implementering af et fælles studieår for sygeplejerskestuderende ved Metropol og La Trobe University Australien....

  11. Chemical Mahjong (United States)

    Cossairt, Travis J.; Grubbs, W. Tandy


    An open-access, Web-based mnemonic game is described whereby introductory chemistry knowledge is tested using mahjong solitaire game play. Several tile sets and board layouts are included that are themed upon different chemical topics. Introductory tile sets can be selected that prompt the player to match element names to symbols and metric…

  12. Chemical dispersants

    NARCIS (Netherlands)

    Rahsepar, Shokouhalsadat; Smit, Martijn P.J.; Murk, Albertinka J.; Rijnaarts, Huub H.M.; Langenhoff, Alette A.M.


    Chemical dispersants were used in response to the Deepwater Horizon oil spill in the Gulf of Mexico, both at the sea surface and the wellhead. Their effect on oil biodegradation is unclear, as studies showed both inhibition and enhancement. This study addresses the effect of Corexit on oil biodeg

  13. Microbial treatment of ion exchange resins

    Energy Technology Data Exchange (ETDEWEB)

    Kouznetsov, A.; Kniazev, O. [D. Mendeleyev University of Chemical Technology of Russia, Dept. Biotechnology, Mocow (Russian Federation)


    A bioavailability of ion exchange resins to a microbial destruction as one of the alternative methods of compacting used ionites from the nuclear fuel manufacturing cycle enterprises has been investigated. The bio-destruction was studied after a preliminary chemical treatment or without it. A sensitivity of the ion exchange resins (including highly acidic cationite KU-2-8) to the microbial destruction by heterotrophic and chemo-litho-trophic microorganisms under aerobic conditions was shown in principle. The biodegradation of the original polymer is possible in the presence of the water soluble fraction of the resin obtained after its treatment by Fenton reagent and accelerated in the presence of Mn-ions in optimal concentration 1-2 g of Mn per liter of medium. Thus, the process of bio-destruction of ionite polymer by heterotrophic microorganisms can be compared with the bio-destruction of lignin or humic substances. The optimum parameters of bio-destruction and microorganisms used must be different for resins with different functional groups. (authors)

  14. Negative Joule Heating in Ion-Exchange Membranes


    Biesheuvel, P. M.; D. Brogioli; Hamelers, H. V. M.


    In ion-exchange membrane processes, ions and water flow under the influence of gradients in hydrostatic pressure, ion chemical potential, and electrical potential (voltage), leading to solvent flow, ionic fluxes and ionic current. At the outer surfaces of the membranes, electrical double layers (EDLs) are formed (Donnan layers). When a current flows through the membrane, we argue that besides the positive Joule heating in the bulk of the membrane and in the electrolyte outside the membrane, t...

  15. Ion exchange performance of commercial crystalline silicotitanates for cesium removal

    Energy Technology Data Exchange (ETDEWEB)

    Braun, R.; Dangieri, T.J.; Fennelly, D.J. [and others


    A new class of inorganic ion exchangers called crystalline silicotitanates (CST), invented by researchers at Sandia National Laboratories and Texas A&M University, has been commercialized in a joint Sandia-UOP effort. The original developmental materials exhibited high selectivity for the ion exchange of cesium, strontium, and several other radionuclides from highly alkaline solutions containing molar concentrations of Na{sup +}. The materials also showed excellent chemical and radiation stability. Together, the high selectivity and stability of the CSTs made them excellent candidates for treatment of solutions such as the Hanford tank supernates and other DOE radwastes. Sandia National Laboratories and UOP have teamed under a Cooperative Research and Development Agreement (CRADA) to develop CSTs in the powdered form and in an engineered form suitable for column ion exchange use. A continuous-flow, column ion exchange process is expected to be used to remove Cs and other radionuclides from the Hanford supernatant. The powder material invented by the Sandia and Texas A&M team consists of submicron-size particles. It is not designed for column ion exchange but may be used in other applications.

  16. Global evaluation of ammonia bi-directional exchange

    Directory of Open Access Journals (Sweden)

    L. Zhu


    Full Text Available Bi-directional air–surface exchange of ammonia (NH3 has been neglected in many air quality models. In this study, we implement the bi-directional exchange of NH3 in the GEOS-Chem global chemical transport model. We also introduce an updated diurnal variability scheme for NH3 livestock emissions and evaluate the recently developed MASAGE_NH3 bottom up inventory. While updated diurnal variability improves comparison of modeled-to-hourly in situ measurements in the Southeastern US, NH3 concentrations decrease throughout the globe, up to 17 ppb in India and Southeastern China, with corresponding decreases in aerosol nitrate by up to 7 μg m−3. The ammonium (NH4+ soil pool in the bi-directional exchange model largely extends the NH3 lifetime in the atmosphere. Including bi-directional exchange generally increases NH3 gross emissions (7.1% and surface concentrations (up to 3.9 ppb throughout the globe in July, except in India and Southeastern China. In April and October, it decreases NH3 gross emissions in the Northern Hemisphere (e.g., 43.6% in April in China and increases NH3 gross emissions in the Southern Hemisphere. Bi-directional exchange does not largely impact NH4+ wet deposition overall. While bi-directional exchange is fundamentally a better representation of NH3 emissions from fertilizers, emissions from primary sources are still underestimated and thus significant model biases remain when compared to in situ measurements in the US. The adjoint of bi-directional exchange has also been developed for the GEOS-Chem model and is used to investigate the sensitivity of NH3 concentrations with respect to soil pH and fertilizer application rate. This study thus lays the groundwork for future inverse modeling studies to more directly constrain these physical processes rather than tuning bulk uni-directional NH3 emissions.

  17. Global evaluation of ammonia bi-directional exchange (United States)

    Zhu, L.; Henze, D.; Bash, J.; Jeong, G.-R.; Cady-Pereira, K.; Shephard, M.; Luo, M.; Paulot, F.; Capps, S.


    Bi-directional air-surface exchange of ammonia (NH3) has been neglected in many air quality models. In this study, we implement the bi-directional exchange of NH3 in the GEOS-Chem global chemical transport model. We also introduce an updated diurnal variability scheme for NH3 livestock emissions and evaluate the recently developed MASAGE_NH3 bottom up inventory. While updated diurnal variability improves comparison of modeled-to-hourly in situ measurements in the Southeastern US, NH3 concentrations decrease throughout the globe, up to 17 ppb in India and Southeastern China, with corresponding decreases in aerosol nitrate by up to 7 μg m-3. The ammonium (NH4+) soil pool in the bi-directional exchange model largely extends the NH3 lifetime in the atmosphere. Including bi-directional exchange generally increases NH3 gross emissions (7.1%) and surface concentrations (up to 3.9 ppb) throughout the globe in July, except in India and Southeastern China. In April and October, it decreases NH3 gross emissions in the Northern Hemisphere (e.g., 43.6% in April in China) and increases NH3 gross emissions in the Southern Hemisphere. Bi-directional exchange does not largely impact NH4+ wet deposition overall. While bi-directional exchange is fundamentally a better representation of NH3 emissions from fertilizers, emissions from primary sources are still underestimated and thus significant model biases remain when compared to in situ measurements in the US. The adjoint of bi-directional exchange has also been developed for the GEOS-Chem model and is used to investigate the sensitivity of NH3 concentrations with respect to soil pH and fertilizer application rate. This study thus lays the groundwork for future inverse modeling studies to more directly constrain these physical processes rather than tuning bulk uni-directional NH3 emissions.

  18. Flows and chemical reactions in heterogeneous mixtures

    CERN Document Server

    Prud'homme, Roger


    This book - a sequel of previous publications 'Flows and Chemical Reactions' and 'Chemical Reactions in Flows and Homogeneous Mixtures' - is devoted to flows with chemical reactions in heterogeneous environments.  Heterogeneous media in this volume include interfaces and lines. They may be the site of radiation. Each type of flow is the subject of a chapter in this volume. We consider first, in Chapter 1, the question of the generation of environments biphasic individuals: dusty gas, mist, bubble flow.  Chapter 2 is devoted to the study at the mesoscopic scale: particle-fluid exchange of mom

  19. Rhizosphere chemical dialogues: plant-microbe interactions

    Energy Technology Data Exchange (ETDEWEB)

    Badri, D.V.; van der Lelie, D.; Weir, T. L.; Vivanco, J. M.


    Every organism on earth relies on associations with its neighbors to sustain life. For example, plants form associations with neighboring plants, microflora, and microfauna, while humans maintain symbiotic associations with intestinal microbial flora, which is indispensable for nutrient assimilation and development of the innate immune system. Most of these associations are facilitated by chemical cues exchanged between the host and the symbionts. In the rhizosphere, which includes plant roots and the surrounding area of soil influenced by the roots, plants exude chemicals to effectively communicate with their neighboring soil organisms. Here we review the current literature pertaining to the chemical communication that exists between plants and microorganisms and the biological processes they sustain.

  20. Nominal exchange rate flexibility and real exchange rate adjustment : evidence from dual exchange rates in developing countries


    Cheung, Yin-Wong; Lai, Kon-Sun


    This study investigates whether exchange rate flexibility aids real exchange rate adjustment based on intra-period data on dual exchange rates from developing countries. Specifically, it analyzes whether the flexible parallel market rate produces faster or slower real exchange rate adjustment than the much less flexible official rate does. Half-life estimates of adjustment speeds are obtained using fractional time series analysis. We find no systematic evidence that greater exchange rate flex...

  1. Degradation mechanism of sulfonated poly(ether ether ketone) (SPEEK) ion exchange membranes under vanadium flow battery medium. (United States)

    Yuan, Zhizhang; Li, Xianfeng; Hu, Jinbo; Xu, Wanxing; Cao, Jingyu; Zhang, Huamin


    The degradation mechanism of hydrocarbon ion exchange membranes under vanadium flow battery (VFB) medium was investigated and clarified for the first time. This work will be highly beneficial for improving the chemical stability of hydrocarbon ion exchange membranes, which is one of the most challenging issues for VFB application.

  2. Fair Exchange in Strand Spaces

    Directory of Open Access Journals (Sweden)

    Joshua D. Guttman


    Full Text Available Many cryptographic protocols are intended to coordinate state changes among principals. Exchange protocols coordinate delivery of new values to the participants, e.g. additions to the set of values they possess. An exchange protocol is fair if it ensures that delivery of new values is balanced: If one participant obtains a new possession via the protocol, then all other participants will, too. Fair exchange requires progress assumptions, unlike some other protocol properties. The strand space model is a framework for design and verification of cryptographic protocols. A strand is a local behavior of a single principal in a single session of a protocol. A bundle is a partially ordered global execution built from protocol strands and adversary activities. The strand space model needs two additions for fair exchange protocols. First, we regard the state as a multiset of facts, and we allow strands to cause changes in this state via multiset rewriting. Second, progress assumptions stipulate that some channels are resilient-and guaranteed to deliver messages-and some principals are assumed not to stop at certain critical steps. This method leads to proofs of correctness that cleanly separate protocol properties, such as authentication and confidentiality, from invariants governing state evolution. G. Wang's recent fair exchange protocol illustrates the approach.

  3. Hartree potential dependent exchange functional

    CERN Document Server

    Constantin, L A; Della Sala, F


    We introduce a novel non-local ingredient for the construction of exchange density functionals: the reduced Hartree parameter, which is invariant under the uniform scaling of the density and represents the exact exchange enhancement factor for one- and two-electron systems. The reduced Hartree parameter is used together with the conventional meta-generalized gradient approximation (meta-GGA) semilocal ingredients (i.e. the electron density, its gradient and the kinetic energy density) to construct a new generation exchange functional, termed u-meta-GGA. This u-meta-GGA functional is exact for {the exchange of} any one- and two-electron systems, is size-consistent and non-empirical, satisfies the uniform density scaling relation, and recovers the modified gradient expansion derived from the semiclassical atom theory. For atoms, ions, jellium spheres, and molecules, it shows a good accuracy, being often better than meta-GGA exchange functionals. Our construction validates the use of the reduced Hartree ingredie...

  4. Influence of nonlinear chemical reactions on the transport coefficients in oscillatory Couette flow (United States)

    Barik, Swarup; Dalal, D. C.


    A multiple-scale method of averaging is applied to the study of transport of a chemical species in oscillatory Couette flow where the species may undergoes a reversible phase exchange with the boundary wall and nonlinear chemical reactions both within the fluid and at the boundary wall. Analytical expressions are obtained for transport coefficients. The results shows how the transport coefficients are influenced by the reversible phase exchange reaction kinetics and the rate and degree of the nonlinear decay chemical reaction.

  5. Inflationary trispectrum from graviton exchange

    DEFF Research Database (Denmark)

    Seery, David; Sloth, Martin Snoager; Vernizzi, Filippo


    We compute the connected four-point correlation function of the primordial curvature perturbation generated during inflation with standard kinetic terms, where the correlation is established via exchange of a graviton between two pairs of scalar fluctuations. Any such correlation yields a contrib......We compute the connected four-point correlation function of the primordial curvature perturbation generated during inflation with standard kinetic terms, where the correlation is established via exchange of a graviton between two pairs of scalar fluctuations. Any such correlation yields...... where the momentum of the graviton which is exchanged becomes much smaller than the external momenta. We conclude that the total non-linearity parameter generated by single-field models of slow-roll inflation is at maximum tauNL ~ r....

  6. Density Functionals of Chemical Bonding

    Directory of Open Access Journals (Sweden)

    Mihai V. Putz


    Full Text Available The behavior of electrons in general many-electronic systems throughout the density functionals of energy is reviewed. The basic physico-chemical concepts of density functional theory are employed to highlight the energy role in chemical structure while its extended influence in electronic localization function helps in chemical bonding understanding. In this context the energy functionals accompanied by electronic localization functions may provide a comprehensive description of the global-local levels electronic structures in general and of chemical bonds in special. Becke-Edgecombe and author’s Markovian electronic localization functions are discussed at atomic, molecular and solid state levels. Then, the analytical survey of the main workable kinetic, exchange, and correlation density functionals within local and gradient density approximations is undertaken. The hierarchy of various energy functionals is formulated by employing both the parabolic and statistical correlation degree of them with the electronegativity and chemical hardness indices by means of quantitative structure-property relationship (QSPR analysis for basic atomic and molecular systems.

  7. Chemical carcinogenesis

    Directory of Open Access Journals (Sweden)

    Paula A. Oliveira


    Full Text Available The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair - i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.A sociedade obtém numerosos benefícios da utilização de compostos químicos. A aplicação dos pesticidas, por exemplo, permitiu obter alimento em quantidade suficiente para satisfazer as necessidades alimentares de milhões de pessoas, condição relacionada com o aumento da esperança de vida. Os benefícios estão, por


    Directory of Open Access Journals (Sweden)



    Full Text Available The experience of recentyears showsthat it hasa fundamentalroleformation mechanismof the exchange rateinmacroeconomic stabilization. Global economiccrises, oil shockshave shownthe difficultyoffloatingsustainabilitybyparticipants in the system. EuropeanMonetary System, focused onconcertedfloatingcurrenciestoECU, was formedunder the conditionsin which somecountries have adoptedregional monetaryarrangements(EU countries, with suchbasescurrencyregimeshybridthat combinesspecific mechanismsto those offixedratefree floating. This paperaims to demonstratethe important role thatithasthe choice ofexchange rateregimeas abasic elementin thefoundationofmacroeconomic stabilizationinstruments. Consideredan expression of thestateof the domestic economyandinternationalcompetitiveness, the exchange rate is determined bya complex set ofexternal factorsorinternalstabilityisa prerequisite forthe crisis.

  9. Evaluating China's Exchange Rate Regime

    Institute of Scientific and Technical Information of China (English)

    Charlie Xiao Feng


    @@ In 1994 China established a de facto currency peg.1 The dollar-RMB exchange rate was fixed at 8.28.The People's Bank of China(PBC) allowed the rate a narrow band of around .01 to .02 percent in which it could shift daily.The exchange rate program did not become newsworthy until U.S.Treasury Secretary John Snow's visit in 2003.In fact as a study by Frankel and Wei (2007)showed, the RMB's forward was actually selling at a discount against the dollar prior to Secretary Snow's visit to China and his subsequent report, signaling that investors were anticipating RMB depreciation.

  10. Common Knowledge in Email Exchanges

    CERN Document Server

    Sietsma, Floor


    We consider a framework in which a group of agents communicates by means of emails, with the possibility of replies, forwards and blind carbon copies (BCC). We study the epistemic consequences of such email exchanges by introducing an appropriate epistemic language and semantics. This allows us to determine when a group of agents acquires common knowledge of the formula expressing that an email was sent. We also show that in our framework from the epistemic point of view the BCC feature of emails cannot be simulated using messages without BCC recipients. Finally, we clarify the notion of a causal relationship between emails using the concept of properly terminating email exchanges.

  11. Proton exchange membrane fuel cells

    CERN Document Server

    Qi, Zhigang


    Preface Proton Exchange Membrane Fuel CellsFuel CellsTypes of Fuel CellsAdvantages of Fuel CellsProton Exchange Membrane Fuel CellsMembraneCatalystCatalyst LayerGas Diffusion MediumMicroporous LayerMembrane Electrode AssemblyPlateSingle CellStackSystemCell Voltage Monitoring Module (CVM)Fuel Supply Module (FSM)Air Supply Module (ASM)Exhaust Management Module (EMM)Heat Management Module (HMM)Water Management Module (WMM)Internal Power Supply Module (IPM)Power Conditioning Module (PCM)Communications Module (COM)Controls Module (CM)SummaryThermodynamics and KineticsTheoretical EfficiencyVoltagePo

  12. Chemical cosmology

    CERN Document Server

    Boeyens, Jan CA


    The composition of the most remote objects brought into view by the Hubble telescope can no longer be reconciled with the nucleogenesis of standard cosmology and the alternative explanation, in terms of the LAMBDA-Cold-Dark-Matter model, has no recognizable chemical basis. A more rational scheme, based on the chemistry and periodicity of atomic matter, opens up an exciting new interpretation of the cosmos in terms of projective geometry and general relativity. The response of atomic structure to environmental pressure predicts non-Doppler cosmical redshifts and equilibrium nucleogenesis by alp


    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, D.; Visser, A.; Bridges, N.


    This project seeks to determine if (1) inorganic-based ion exchange materials or (2) electrochemical methods in ionic liquids can be exploited to provide effective Am and Cm separations. Specifically, we seek to understand the fundamental structural and chemical factors responsible for the selectivity of inorganic-based ion-exchange materials for actinide and lanthanide ions. Furthermore, we seek to determine whether ionic liquids can serve as the electrolyte that would enable formation of higher oxidation states of Am and other actinides. Experiments indicated that pH, presence of complexants and Am oxidation state exhibit significant influence on the uptake of actinides and lanthanides by layered sodium titanate and hybrid zirconium and tin phosphonate ion exchangers. The affinity of the ion exchangers increased with increasing pH. Greater selectivity among Ln(III) ions with sodium titanate materials occurs at a pH close to the isoelectric potential of the ion exchanger. The addition of DTPA decreased uptake of Am and Ln, whereas the addition of TPEN generally increases uptake of Am and Ln ions by sodium titanate. Testing confirmed two different methods for producing Am(IV) by oxidation of Am(III) in ionic liquids (ILs). Experimental results suggest that the unique coordination environment of ionic liquids inhibits the direct electrochemical oxidation of Am(III). The non-coordinating environment increases the oxidation potential to a higher value, while making it difficult to remove the inner coordination of water. Both confirmed cases of Am(IV) were from the in-situ formation of strong chemical oxidizers.

  14. Intensification of heat and mass transfer by ultrasound: application to heat exchangers and membrane separation processes. (United States)

    Gondrexon, N; Cheze, L; Jin, Y; Legay, M; Tissot, Q; Hengl, N; Baup, S; Boldo, P; Pignon, F; Talansier, E


    This paper aims to illustrate the interest of ultrasound technology as an efficient technique for both heat and mass transfer intensification. It is demonstrated that the use of ultrasound results in an increase of heat exchanger performances and in a possible fouling monitoring in heat exchangers. Mass transfer intensification was observed in the case of cross-flow ultrafiltration. It is shown that the enhancement of the membrane separation process strongly depends on the physico-chemical properties of the filtered suspensions.

  15. The Portfolio Selection by Using Quadratic Programming Approach Case Study of Malaysia Stock Exchange

    Directory of Open Access Journals (Sweden)



    Full Text Available This paper uses the quadratic approach to select the optimum portfolio of the Malaysian stovk exchange. This framework deals with ten biggest firms posted on the stock exchange during 2014. The result shows that the optimum portfolio includes 22 % of Axiata Group shares, 11% of Genting shares, 30 % of Petronas Chemicals shares, 1% of Sime Darbi shares and 36 % of Tenaga Nasional shares.

  16. Study by XPS of different conditioning processes to improve the cation exchange in clinoptilolite (United States)

    Ruiz-Serrano, D.; Flores-Acosta, M.; Conde-Barajas, E.; Ramírez-Rosales, D.; Yáñez-Limón, J. M.; Ramírez-Bon, R.


    We report the X-ray photoelectron spectroscopy (XPS) analysis of natural clinoptilolite from a mine in Sonora, México. From these measurements we determined the chemical state and binding energy of the elements in the zeolite framework and of those in the extra framework sites. The analysis was done on natural clinoptilolite and on cation-exchanged clinoptilolites with Na + and NH4+ ions. Complementary analysis by several experimental techniques was performed to determine the structural, chemical composition and chemical state modifications experimented by clinoptilolite samples processed by the two types of cation exchange. The clinoptilolite samples were studied by X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) to determine their structural composition, Energy Dispersive Spectroscopy (EDS) to measure the chemical composition and electronic paramagnetic resonance (EPR) spectroscopy to determine the chemical state of iron inside the natural zeolites.

  17. Elongating axial conduction path design to enhance performance of cryogeinc compact pche (printed circuit heat exchanger) (United States)

    Baek, Seungwhan; Kim, Jinhyuck; Hwang, Gyuwan; Jeong, Sangkwon


    PCHE (Printed Circuit Heat Exchanger) is one of the promising cryogenic compact heat exchangers due to its compactness, high NTU and robustness. The essential procedure for fabricating PCHE is chemical etching and diffusion bonding. These technologies can create sufficiently large heat transfer area for a heat exchanger with numerous micro channels (Dhheat exchanger when it is operated with a large temperature difference. Elongating the heat conduction path is implemented to reduce axial conduction in PCHE in this study. Two PCHEs with identical channel configuration are fabricated, for comparison, one of which is modified to have longer heat conduction path. Both heat exchangers are tested in cryogenic environment (300~70 K), and the modified PCHE shows better performance with significantly reduced axial conduction. The experimental results indicate that the modification of the heat conduction path is effective to increase the performance of PCHE. This paper discusses and analyses the thermal characteristics of the modified PCHE obtained experimentally.

  18. 'Carbon-Money Exchange' to contain global warming and deforestation

    Energy Technology Data Exchange (ETDEWEB)

    Nagase, Kozo E-mail:


    This paper builds a basic theory of 'Carbon-Money Exchange' in which carbon as currency in nature's household (ecosystems) and money as currency in humankind's household (economy) are exchanged just like in a foreign exchange. The simple chemical equation below makes it possible (CO{sub 2}{yields}C+O{sub 2}=C+O{sub 2}{yields}CO{sub 2}). The left-hand side represents the work of plants to remove atmospheric CO{sub 2}. The right-hand side represents the work of humans as fossil fuel consumers to produce it. The exchange of the two currencies is possible by copying the fossil fuel market. The paper concludes that this new exchange can automatically contain global warming and deforestation, replacing onerous emissions trading. Moreover, it could revolutionize the conventional economy, creating counter-capitalism, or 'carbonism'.

  19. Selective catalytic reduction of nitric oxide by ammonia over Cu-exchanged Cuban natural zeolites

    Energy Technology Data Exchange (ETDEWEB)

    Moreno-Tost, Ramon; Santamaria-Gonzalez, Jose; Rodriguez-Castellon, Enrique; Jimenez-Lopez, Antonio [Departamento de Quimica Inorganica, Cristalografia y Mineralogia, Facultad de Ciencias, Unidad Asociada del Instituto de Catalisis y Petroleoquimica, CSIC, Universidad de Malaga, Campus de Teatinos, 29071 Malaga (Spain); Autie, Miguel A.; Glacial, Marisol Carreras [Centro Nacional de Investigaciones Cientificas, Ciudad de la Habana, La Habana (Cuba); Gonzalez, Edel [Instituto Superior Pedagogico ' Enrique Jose Varona' , La Habana (Cuba); Pozas, Carlos De las [Centro de Gerencia de Programas y Proyectos Priorizados, La Habana (Cuba)


    The catalytic selective reduction of NO over Cu-exchanged natural zeolites (mordenite (MP) and clinoptilolite (HC)) from Cuba using NH{sub 3} as reducing agent and in the presence of excess oxygen was studied. Cu(II)-exchanged zeolites are very active catalysts, with conversions of NO of 95%, a high selectivity to N{sub 2} at low temperatures, and exhibiting good water tolerance. The chemical state of the Cu(II) in exchanged zeolites was characterized by H{sub 2}-TPR and XPS. Cu(II)-exchanged clinoptilolite underwent a severe deactivation in the presence of SO{sub 2}. However, Cu(II)-exchanged mordenite not only maintained its catalytic activity, but even showed a slight improvement after 20h of reaction in the presence of 100ppm of SO{sub 2}.

  20. A mesoscale chemical transport model (MEDIUM) nested in a global chemical transport model (MEDIANTE)

    Energy Technology Data Exchange (ETDEWEB)

    Claveau, J.; Ramaroson, R. [Office National d`Etudes et de Recherches Aerospatiales (ONERA), 92 - Chatillon (France)


    The lower stratosphere and upper troposphere (UT-LS) are frequently subject to mesoscale or local scale exchange of air masses occurring along discontinuities. This exchange (e.g. downward) can constitute one of the most important source of ozone from the stratosphere down to the middle troposphere where strong mixing dilutes the air mass and competing the non-linear chemistry. The distribution of the chemical species in the troposphere and the lower stratosphere depends upon various source emissions, e.g. from polluted boundary layer or from aircraft emissions. Global models, as well as chemical transport models describe the climatological state of the atmosphere and are not able to describe correctly the stratosphere and troposphere exchange. Mesoscale models go further in the description of smaller scales and can reasonably include a rather detailed chemistry. They can be used to assess the budget of NO{sub x} from aircraft emissions in a mesoscale domain. (author) 4 refs.

  1. Endocrine disrupting chemicals in indoor and outdoor air


    Rudel, Ruthann A; Perovich, Laura J.


    The past 50 years have seen rapid development of new building materials, furnishings, and consumer products and a corresponding explosion in new chemicals in the built environment. While exposure levels are largely undocumented, they are likely to have increased as a wider variety of chemicals came into use, people began spending more time indoors, and air exchange rates decreased to improve energy efficiency. As a result of weak regulatory requirements for chemical safety testing, only limit...

  2. Nonadiabatic exchange dynamics during adiabatic frequency sweeps. (United States)

    Barbara, Thomas M


    A Bloch equation analysis that includes relaxation and exchange effects during an adiabatic frequency swept pulse is presented. For a large class of sweeps, relaxation can be incorporated using simple first order perturbation theory. For anisochronous exchange, new expressions are derived for exchange augmented rotating frame relaxation. For isochronous exchange between sites with distinct relaxation rate constants outside the extreme narrowing limit, simple criteria for adiabatic exchange are derived and demonstrate that frequency sweeps commonly in use may not be adiabatic with regard to exchange unless the exchange rates are much larger than the relaxation rates. Otherwise, accurate assessment of the sensitivity to exchange dynamics will require numerical integration of the rate equations. Examples of this situation are given for experimentally relevant parameters believed to hold for in-vivo tissue. These results are of significance in the study of exchange induced contrast in magnetic resonance imaging.

  3. Baltic Exchange teper v Tallinne

    Index Scriptorium Estoniae


    Viimane osa merekonteineritesse kokkupakitud Londoni laevandus- ja merebörsi Baltic Exchange'i endise peakorteri detailidest jõudis 2007. a. juunis Tallinna. Hoone detailid ostnud ärimehed Heiti Hääl ja Eerik-Niiles Kross plaanivad leida hoonele koha Tallinna kesklinnas. E.-N. Krossi kommentaar

  4. Fragmentary model of exchange interactions

    CERN Document Server

    Kotov, V M


    This article makes attempt to refusal from using neutrino for explanation continuous distribution of beta particle energy by conversion to characteristic exchange interaction particles in nucleolus. It is taking formulation for nuclear position with many different fragments. It is computing half-value period of spontaneous fission of heavy nucleolus. (author)

  5. Milk fouling in heat exchangers.

    NARCIS (Netherlands)

    Jeurnink, Th.J.M.


    The mechanisms of fouling of heat exchangers by milk were studied. Two major fouling mechanisms were indentified during the heat treatment of milk: (i) the formation and the subsequent deposition of activated serum protein molecules as a result of the heat denaturation; (ii) the precipitation of cal

  6. "Bottle-Brush" Heat Exchanger (United States)

    Tward, E.; Gatewood, J. R.


    Heat exchanger consists of a metal tube with wires extending inward from wall. Conduction of heat along wires improves heat transfer to gas or other filling. Fluid is heated throughout the cross section of tube. Suggested applications are refrigerators, heat engines, thermal instrumentation, and heat switches.

  7. Calculations of Shipboard Heat Exchangers, (United States)


    Constrained moticn is created by the external exciting forces - pumps, compresors , fars, agitators. During the heat exchange distinguish the phenomena...cast tcttozs. (5). fcr fla*/plane covers/caps. FOOTNOTE 1. Is taken stall value. !NDFOCINOIE. Additional requirements fox the dished bcttcss. -w j DOC

  8. The Commodity and its Exchange

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset


    This chapter examines fishing quota as a commodity in both a conceptual perspective and through ethnographic examples. Inspired by Marx’s ideas of the commodity, use-value, exchange-value, and ground rent, the chapter combines a theoretical approach with ethnographic material. The different aspec...

  9. Knowledge Exchange with Sistema Scotland (United States)

    Allan, Julie; Moran, Nikki; Duffy, Celia; Loening, Gica


    This paper reports on a knowledge exchange project, funded by the Scottish Funding Council and undertaken by a group of researchers from three higher education institutions in Scotland and the project partner, Sistema Scotland. This newly established charity is attempting to implement a major programme of social change, developed in Venezuela,…

  10. The Commodity and its Exchange

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset


    and the value of the quota are examined through the concrete exchange of fishing rights, and it is explained why quota trade can give rise to speculation and monopolies. In the final part of the chapter, it is argued that the value of transferable fishing quotas rely on a social relation between owners...... and nonowners of quota, as a form of monopoly rent....

  11. Study of Sorption Properties of Anion Exchangers with Long-Chained Cross-Linking Agents for Tungsten Hydrometallurgy

    Institute of Scientific and Technical Information of China (English)

    O.N.Kononova; S.V.Kachin; O.P.Kalyakina; G.L.Pashkov; A.G.Kholmogorov


    The macroporous anion exchangers with long-chained cross-linking agents were investigated for the tungsten recovery from salt solutions. The physical-chemical characteristics of these sorbents were studied by means of sorption-desorption experiment aswell as electron and IR-spectroscopy. The anion exchangers on the basis of macroporous copolymers of methylacrylate and divinyl-ester of diethyleneglycol or tetravinyl-ester of pentaerythritol possess the exchange capacity to tungsten 2--5 times greater than the porous anion exchangers on the basis of styrene and divinylbenzene, therefore they can be used for selective tungsten recovery from comulex salt solutions.

  12. Foreign Exchange Reserves: Bangladesh Perspective

    Directory of Open Access Journals (Sweden)

    Md Zahangir Alam


    Full Text Available This study is about foreign exchangereserves of Bangladesh. The mainpurpose of this study is to the influence of exchange rates on foreign exchangereserves to the Bangladesh context.  Both the primary and secondary data has been used inthis study. The primary data has been collected through a structuredquestionnaire from 50 respondents. The secondary data, namely Bangladeshforeign exchange reserves (FER, Bangladesh current account balance (CAB,Bangladesh capital andfinancial account balance (CFAB, and BDT/USD exchange rates (ER.  This study covers yearly data from July 01,1996 to June 30, 2005 and quarterly data from July 01, 2005 to June 30, 2012. Findingsof this study shows that out of the selected 16 factors affecting foreignexchange reserves, exchange rates occupy the first position, weighted averagescore (WAS being 4.56. Foreign exchange reserves (FER and current accountbalance (CAB have increased by 502.9087% and 1451.218%,whereas capital and financial account (CFAB has decreased by -649.024% on June30, 2012 compared to June 30, 1997. The influence of other factors heldconstant, as ER changes by 285.6894 units due to one unit change in FER, onaverage in the same direction which represents that ER has positive effect on theFER and this relationship is statistically significant.  62.1526 percentof the variation in FER is explained by ER. The outcomes of Breusch-Godfrey test (LM test, ARCHtest, and the Normality test are that there is a serial correlation among residuals, the variance of residuals is notconstant, and the residuals are not normally distributed.

  13. Chemical Analyses (United States)

    Bulluck, J. W.; Rushing, R. A.


    As a preliminary study on the effects of chemical aging of polymer materials MERL and TRI have examined two polymeric materials that are typically used for offshore umbilical applications. These two materials were Tefzel, a copolymer of ethylene and tetrafluoroethylene, and Coflon, polyvinylidene fluoride. The Coflon specimens were cut from pipe sections and exposed to H2S at various temperatures and pressures. One of these specimens was tested for methane permeation, and another for H2S permeation. The Tefzel specimens were cut from .05 mm sheet stock material and were exposed to methanol at elevated temperature and pressure. One of these specimens was exposed to methanol permeation for 2 days at 100 C and 2500 psi. An additional specimen was exposed to liquid methanol for 3 days at 150 C and 15 Bar. Virgin specimens of each material were similarly prepared and tested.

  14. Thermal Propulsion Capture System Heat Exchanger Design (United States)

    Richard, Evan M.


    One of the biggest challenges of manned spaceflight beyond low earth orbit and the moon is harmful radiation that astronauts would be exposed to on their long journey to Mars and further destinations. Using nuclear energy has the potential to be a more effective means of propulsion compared to traditional chemical engines (higher specific impulse). An upper stage nuclear engine would allow astronauts to reach their destination faster and more fuel efficiently. Testing these engines poses engineering challenges due to the need to totally capture the engine exhaust. The Thermal Propulsion Capture System is a concept for cost effectively and safely testing Nuclear Thermal Engines. Nominally, hydrogen exhausted from the engine is not radioactive, but is treated as such in case of fuel element failure. The Thermal Propulsion Capture System involves injecting liquid oxygen to convert the hydrogen exhaust into steam. The steam is then cooled and condensed into liquid water to allow for storage. The Thermal Propulsion Capture System concept for ground testing of a nuclear powered engine involves capturing the engine exhaust to be cooled and condensed before being stored. The hydrogen exhaust is injected with liquid oxygen and burned to form steam. That steam must be cooled to saturation temperatures before being condensed into liquid water. A crossflow heat exchanger using water as a working fluid will be designed to accomplish this goal. Design a cross flow heat exchanger for the Thermal Propulsion Capture System testing which: Eliminates the need for water injection cooling, Cools steam from 5800 F to saturation temperature, and Is efficient and minimizes water requirement.

  15. Superconductivity from perturbative one-gluon exchange in high density quark matter

    CERN Document Server

    Schäfer, T; Schaefer, Thomas; Wilczek, Frank


    We study color superconductivity in QCD at asymptotically large chemical potential. In this limit, pairing is dominated by perturbative one-gluon exchange. We derive the Eliashberg equation for the pairing gap and solve this equation numerically. Taking into account both magnetic and electric gluon exchanges, we find $\\Delta\\sim g^{-5}\\exp(-c/g)$ with $c=3\\pi^2/\\sqrt{2}$, verifying a recent result by Son. For chemical potentials that are of physical interest, $\\mu< 1$ GeV, the calculation ceases to be reliable quantitatively, but our results suggest that the gap can be as large as 100 MeV.

  16. Constant Power Control of a Proton Exchange Membrane Fuel Cell through Adaptive Fuzzy Sliding Mode

    Directory of Open Access Journals (Sweden)

    Minxiu Yan


    Full Text Available Fuel cell is a device that converts the chemical energy from a fuel into electricity through a chemical reaction with oxygen or another oxidizing agent. The paper describes a mathematical model of proton exchange membrane fuel cells by analyzing the working mechanism of the proton exchange membrane fuel cell. Furthermore, an adaptive fuzzy sliding mode controller is designed for the constant power output of PEMFC system. Simulation results prove that adaptive fuzzy sliding mode control has better control effect than conventional fuzzy sliding mode control.

  17. RMB Exchange Market Pressure and Central Bank Exchange Market Intervention

    Institute of Scientific and Technical Information of China (English)

    Xiaohui Liu; Jing Zhang


    The present paper uses the model-dependent and the model-independent approach to measure the RMB exchange market pressure (EMP) and the central bank's intervention using monthly data from January 1999 to June 2008. It is determined that the RMB has been under great appreciation pressure over the past decade. However, the pressure has been weakening since 2005. The two approaches provide significantly different results in terms of the estimated RMB EMP indices and the estimated central bank's interventions. The differences may lead to different predictions of potential currency crises. According to the estimation of the RMB EMP, and based on the model-independent approach, the paper shows that China has been under threat of an appreciation currency crisis since 2008. Therefore, China should adopt a more flexible exchange rate regime to prevent a potential crisis.

  18. Computer simulation of methanol exchange dynamics around cations and anions

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Santanu; Dang, Liem X.


    In this paper, we present the first computer simulation of methanol exchange dynamics between the first and second solvation shells around different cations and anions. After water, methanol is the most frequently used solvent for ions. Methanol has different structural and dynamical properties than water, so its ion solvation process is different. To this end, we performed molecular dynamics simulations using polarizable potential models to describe methanol-methanol and ion-methanol interactions. In particular, we computed methanol exchange rates by employing the transition state theory, the Impey-Madden-McDonald method, the reactive flux approach, and the Grote-Hynes theory. We observed that methanol exchange occurs at a nanosecond time scale for Na+ and at a picosecond time scale for other ions. We also observed a trend in which, for like charges, the exchange rate is slower for smaller ions because they are more strongly bound to methanol. This work was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. The calculations were carried out using computer resources provided by the Office of Basic Energy Sciences.

  19. Waste separation and pretreatment using crystalline silicotitanate ion exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Tadros, M.E.; Miller, J.E. [Sandia National Lab., Albuquerque, NM (United States); Anthony, R.G. [Texas A& M Univ., College Station, TX (United States)


    A new class of inorganic ion exchangers called crystalline silicotitanates (CSTs) has been developed jointly by Sandia National Laboratories and Texas A&M University to selectively remove Cs and other radionuclides from a wide spectrum of radioactive defense wastes. The CST exhibits high selectivity and affinity for Cs and Sr under a wide range of conditions. Tests show it can remove part-per-million concentrations of Cs{sup +} from highly alkaline, high-sodium simulated radioactive waste solutions modeled after those at Hanford, Oak Ridge, and Savannah River. The materials exhibit ion exchange properties based on ionic size selectivity. Specifically, crystalline lattice spacing is controlled to be highly selective for Cs ions even in waste streams containing very high (5 to 10 M) concentrations of sodium. The CST technology is being demonstrated with actual waste at several DOE facilities. The use of inorganic ion exchangers. The inorganics are more resistant to chemical, thermal, and radiation degradation. Their high selectivities result in more efficient operations offering the possibility of a simple single-pass operation. In contrast, regenerable organic ion exchangers require additional processing equipment to handle the regeneration liquids and the eluant with the dissolved Cs.

  20. Lung Structure and the Intrinsic Challenges of Gas Exchange. (United States)

    Hsia, Connie C W; Hyde, Dallas M; Weibel, Ewald R


    Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints.

  1. Physico-chemical study of the thermal degradation of ions exchange resins of nuclear origin: research of conditions to limit the pollution transfer, application to electric cables; Etude physico-chimique de la degradation thermique des resines echangeuses d'ions d'origine nucleaire: recherche des conditions limitant le transfert de pollution, application aux cables electriques

    Energy Technology Data Exchange (ETDEWEB)

    Antonetti, P


    The ions exchange resins are one solid form of radioactive wastes. They are found mainly during the demineralization operations of the water from reactors cooling systems. This study aims to determine the conditions of a thermal processing leading to the production of a smaller residue, containing the whole activity. A protocol is proposed and validated on resins allowing a decrease of the volume of 63% for 99,93% of the activity. (A.L.B.)

  2. A core alternative[Heat exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, R.H. [Chart Heat Exchangers, Wisconsin (United States)


    The development of the efficient Core-in-kettle heat exchangers by Chart Heat Exchangers as an alternative to shell and tube exchangers is reported, and its use as condensers and reboilers in ethylene plants and refrigerant condensers and chillers in natural gas processing and liquid natural gas (LNG) plants are discussed. The novel technology is described with details given of the replacement of the tube bundle with a Chart brazed aluminium plate-fin heat exchanger core, the operation of the exchanger, the savings achieved by installing these heat exchangers in new or existing plants, and Core-in-Kettle retrofits of existing shell and tube heat exchangers. The limitations of the use of Core-in-Kettle heat exchangers to clean fluids typical of hydrocarbon processing, and temperature and pressure limitations are noted.

  3. A simple nonlocal model for exchange. (United States)

    Janesko, Benjamin G


    This work presents a new nonlocal model for the exchange energy density. The model is obtained from the product of the Kohn-Sham one-particle density matrix used to construct exact [Hartree-Fock-like (HF)] exchange, and an approximate density matrix used to construct local spin-density approximation (LSDA) exchange. The proposed exchange energy density has useful formal properties, including correct spin and coordinate scaling and the correct uniform limit. It can readily be evaluated in finite basis sets, with a computational scaling intermediate between HF exchange and semilocal quantities such as the noninteracting kinetic energy density. Applications to representative systems indicate that its properties are typically intermediate between HF and LSDA exchange, and often similar to global hybrids of HF and LSDA exchange. The model is proposed as a novel "Rung 3.5" ingredient for constructing approximate exchange-correlation functionals.

  4. Flexible Exchange of Farming Device Data

    DEFF Research Database (Denmark)

    Iftikhar, Nadeem; Pedersen, Torben Bach


    A new trend in the farming business is to replace conventional farming devices with computerized farming devices. Accordingly, numerous computer-based farming devices for logging, processing and exchanging data have recently been installed on moving farm machinery such as tractors. The exchange...... of data generally takes place between the devices and farming systems, mostly installed at the premises of farmers, contractors, advisory services etc. In most cases, data exchange is based on farming data exchange standards and is bi-directional. Bi-directional data exchange allows different devices...... and systems to exchange data based on a predefined set of rules. In consequence, many hand-coded data exchange solutions have been developed in the farming business. Although efforts regarding incorporating data exchange standards have been made, their actual usage so far has been limited, due to the fact...

  5. Micrometeorological Measurements of Air-Surface Exchange Rates of PBTs in the Great Lakes Region (United States)

    Tobias, D. E.; Perlinger, J. A.; Morrow, P.


    The fate of persistent bioaccumulative toxic chemicals (PBTs) in the environment is controlled by their exchange with various aquatic and terrestrial surfaces. Many of the PBTs are semivolatile and present in the atmosphere almost entirely in the vapor phase. The rate of exchange of these vapor phase chemicals can be predicted from physicochemical properties of the chemical and the surface and the meteorological conditions during the exchange. However, field studies of the uptake of the PBTs are extremely limited or nonexistent making it difficult to evaluate the modeled transfer velocities. This presentation describes a novel method to directly measure air-surface exchange rates of PBTs above aquatic and terrestrial surfaces by the micrometeorological technique known as the modified Bowen ratio approach. Simultaneous measurements of the air temperature, water vapor content, windspeed, and the chemical species concentration at two heights above the surface are required to derive the transfer velocity of the chemical. Advanced techniques that minimize the number of sample preparation steps are required to make the two concentration measurements with adequate relative accuracy. To accomplish this task, ambient air is sampled with a multicapillary column and the analytes are directly desorbed into a high-resolution gas chromatograph for quantitation. This presentation will summarize preliminary measurements made in the near-shore region of Upper Michigan's Keweenaw Peninsula on Lake Superior during the summer of 2001 and 2002.


    Energy Technology Data Exchange (ETDEWEB)

    Calvin, Melvin


    How did life come to be on the surface of the earth? Darwin himself recognized that his basic idea of evolution by variation and natural selection must be a continuous process extending backward in time through that period in which the first living things arose and into the period of 'Chemical Evolution' which preceded it. We are approaching the examination of these events by two routes. One is to seek for evidence in the ancient rocks of the earth which were laid down prior to that time in which organisms capable of leaving their skeletons in the rocks to be fossilized were in existence. This period is sometime prior to approximately 600 million years ago. The earth is believed to have taken its present form approximately 4700 million years ago. We have found in rocks whose age is about 1000 million years certain organic molecules which are closely related to the green pigment of plants, chlorophyll. This seems to establish that green plants were already fluorishing prior to that time. We have now found in rocks of still greater age, namely, 2500 million years, the same kinds of molecules mentioned above which can be attributed to the presence of living organisms. If these molecules are as old as the rocks, we have thus shortened the time available for the generation of the complex biosynthetic sequences which give rise to these specific hydrocarbons (polyisoprenoids) to less than 2000 million years.

  7. Exchange Rate Volatility in BRICS Countries



    This paper measures the impact of bilateral exchange rates, the world agricultural GDP and third-country exchange rate volatilities (Yen/USD and Euro/USD) on the BRICS agricultural exports using a vector autoregressive (VAR) model. Two measures of volatility are used: the standard deviation and the coefficient of variation of the rates of change of the real exchange rates. We found that most variables are integrated of order two except the third-country exchange rate volatilities which are st...

  8. The RMB Exchange Rate Keeps Increasing

    Institute of Scientific and Technical Information of China (English)


    @@ In July 2005, the People's Bank of China officially announced that it would adopt a manageable floating exchange rate, adjusted according to a basket of currencies based on market supply and demand. On that day, the exchange rate of the RMB to the U.S. Dollar increased by 21 percent, and since then the RMB exchange rate has gradually turned to a more flexible exchange rate convention, rather than focusing on the Dollar only.

  9. Wealth Distributions in Asset Exchange Models

    CERN Document Server

    Krapivsky, P L


    How do individuals accumulate wealth as they interact economically? We outline the consequences of a simple microscopic model in which repeated pairwise exchanges of assets between individuals build the wealth distribution of a population. This distribution is determined for generic exchange rules --- transactions that involve a fixed amount or a fixed fraction of individual wealth, as well as random or greedy exchanges. In greedy multiplicative exchange, a continuously evolving power law wealth distribution arises, a feature that qualitatively mimics empirical observations.

  10. Bistability in radiative heat exchange (United States)

    Rudakov, V. I.; Ovcharov, V. V.; Prigara, V. P.


    The possibility of a bistable regime in systems with radiative heat exchange is theoretically demonstrated for the first time. The transfer characteristics of a radiation-closed stationary system have been calculated, in which the radiator is a blackbody and the absorber is made of a material with the absorptivity sharply increasing in a certain temperature interval. The radiator and absorber are separated by a vacuum gap. The heat exchange between the system and the environment is controlled by varying the flow rate of a heat-transfer agent cooling the absorber. The output parameter of a bistable system is the absorber temperature, while the input parameter can be either the radiator temperature or the heat-transfer agent flow rate. Depending on the choice of the input parameter, the transfer characteristic of the system is either represented by a usual S-like curve or has an inverted shape.

  11. Inflationary trispectrum from graviton exchange

    CERN Document Server

    Seery, David; Vernizzi, Filippo


    We compute the connected four-point correlation function of the primordial curvature perturbation generated during inflation with standard kinetic terms, where the correlation is established via exchange of a graviton between two pairs of scalar fluctuations. Any such correlation yields a contribution to the scalar trispectrum of the order of the tensor to scalar ratio r. This contribution is numerically one order of magnitude larger than the one previously calculated on the basis of scalar perturbations interacting at a point and satisfies a simple relation in the limit where the momentum of the graviton which is exchanged becomes much smaller than the external momenta. We conclude that the total non-linearity parameter generated by single-field models of slow-roll inflation is at maximum tauNL ~ r.

  12. Inflationary trispectrum from graviton exchange

    Energy Technology Data Exchange (ETDEWEB)

    Seery, David [Department of Applied Mathematics and Theoretical Physics, Wilberforce Road, Cambridge, CB3 0WA (United Kingdom); Sloth, Martin S. [Department of Physics and Astronomy, University of Aarhus, Ny Munkegade, DK-8000 Aarhus C (Denmark); Vernizzi, Filippo, E-mail:, E-mail:, E-mail: [CEA, IPhT, 91191 Gif-sur-Yvette cedex, France CNRS, URA-2306, 91191 Gif-sur-Yvette cedex (France)


    We compute the connected four-point correlation function of the primordial curvature perturbation generated during inflation with standard kinetic terms, where the correlation is established via exchange of a graviton between two pairs of scalar fluctuations. Any such correlation yields a contribution to the scalar trispectrum of the order of the tensor to scalar ratio r. This contribution is numerically one order of magnitude larger than the one previously calculated on the basis of scalar perturbations interacting at a point and satisfies a simple relation in the limit where the momentum of the graviton which is exchanged becomes much smaller than the external momenta. We conclude that the total non-linearity parameter generated by single-field models of slow-roll inflation is at maximum |{tau}{sub NL}| {approx} r.

  13. Groundwater–Surface Water Exchange

    DEFF Research Database (Denmark)

    Karan, Sachin

    The exchange of groundwater-surface water has been invetigated in the western part of Denmark. Holtum AA provides the framework for all the performed investigations. Several methods are used, primarily eld based measurements ombined with numerical models to achieve insight to the governing...... processes of interaction between groundwater and surface water. By using heat as a tracer it has been possible to use temperature directly as calibrationtargets in a groundwater and heat transport model. Thus, it is possible to use heat investigate the change in groundwater discharge in dynamic conditions...... by using simple temperature devices along a stream to delineate the areas of interest in regard to GW{SW exchange. Thus, at several locations in a stream a temperature data logger was placed in the water column and right at the streambed-water interface. By looking at the correlation of streambed...

  14. Energy exchanges in reconnection outflows (United States)

    Lapenta, Giovanni; Goldman, Martin V.; Newman, David L.; Markidis, Stefano


    Reconnection outflows are highly energetic directed flows that interact with the ambient plasma or with flows from other reconnection regions. Under these conditions the flow becomes highly unstable and chaotic, as any flow jets interacting with a medium. We report here massively parallel simulations of the two cases of interaction between outflow jets and between a single outflow with an ambient plasma. We find in both case the development of a chaotic magnetic field, subject to secondary reconnection events that further complicate the topology of the field lines. The focus of the present analysis is on the energy balance. We compute each energy channel (electromagnetic, bulk, thermal, for each species) and find where the most energy is exchanged and in what form. The main finding is that the largest energy exchange is not at the reconnection site proper but in the regions where the outflowing jets are destabilized.

  15. Chemical information science coverage in Chemical Abstracts. (United States)

    Wiggins, G


    For many years Chemical Abstracts has included in its coverage publications on chemical documentation or chemical information science. Although the bulk of those publications can be found in section 20 of Chemical Abstracts, many relevant articles were found scattered among 39 other sections of CA in 1984-1985. In addition to the scattering of references in CA, the comprehensiveness of Chemical Abstracts as a secondary source for chemical information science is called into question. Data are provided on the journals that contributed the most references on chemical information science and on the languages of publication of relevant articles.

  16. On Multiple Gluon Exchange Webs

    CERN Document Server

    Harley, Mark


    I present an overview of the study of infrared singularities through the eikonal approximation and the concept of webs. Our work reveals the interesting structure of an infinite subclass of webs, Multiple Gluon Exchange Webs. We find that they can be expressed as sums of products of functions depending upon only a single cusp angle, spanned by a simple basis of functions, and conjecture that this structure will hold to all orders.

  17. Value-Added Exchange Rates


    Rudolfs Bems; Robert C. Johnson


    This paper updates the conceptual foundations for measuring real effective exchange rates (REERs) to allow for vertical specialization in trade. We derive a value-added REER describing how demand for the value added that a country produces changes as the price of its value added changes relative to competitors. We then compute this index for 42 countries from 1970-2009 using trade measured in value added terms and GDP deflators. There are substantial differences between value-added and conven...

  18. [Biofouling of heat exchange tubes]. (United States)

    Montero, F; Pintado, J L


    We compared the biofouling behavior of different materials (admiralty brass, stainless steel, and titanium) commonly used to construct heat exchangers in thermoelectric plants. The incidence of film formation on the loss of heat during transference was assessed, and analyzed in terms of plant efficiency and corrosion, both general and localized development. Our results showed that the resistance of titanium and stainless steel to corrosion was similar, and much better than that of admiralty brass. Biofouling, however, was higher in the first two materials.

  19. Electrically controlled cesium ion exchange

    Energy Technology Data Exchange (ETDEWEB)

    Lilga, M. [Pacific Northwest Lab., Richland, WA (United States)


    Several sites within the DOE complex (Savannah River, Idaho, Oak Ridge and Hanford) have underground storage tanks containing high-level waste resulting from nuclear engineering activities. To facilitate final disposal of the tank waste, it is advantageous to separate and concentrate the radionuclides for final immobilization in a vitrified glass matrix. This task proposes a new approach for radionuclide separation by combining ion exchange (IX) and electrochemistry to provide a selective and economic separation method.

  20. On forecasting Exchange Rate Volatility.


    Hafner, Christian


    In an efficient market, foreign exchange rates have to guarantee absence of triangular arbitrage. This note shows that the no-arbitrage condition can be exploited for forecasting the volatility of a single rate by using the information contained in the other rates. Linearly transforming the volatility forecasts of a bivariate model is shown to be more efficient than using a univariate model for the cross-rate.

  1. Washi Painting Exchanges Promote Friendship

    Institute of Scientific and Technical Information of China (English)

    Chuan; You


    <正>Invited by the Sichuan Provincial People’s Association for Friendship with Foreign Countries(SIFA),a washi painting exchange delegation headed by Umeko Iwai,President of Rainbow Society of Japan,a Hiroshima-based non-profit organization,visited Sichuan Province from November 3 to 5,2013.Rice paper was invented in China in ancient times.When the paper-making

  2. Acoustic streaming with heat exchange (United States)

    Gubaidullin, A. A.; Pyatkova, A. V.


    Acoustic streaming in a cylindrical cavity with heat exchange is numerically investigated. The cavity is filled with air. The boundaries of the cavity are maintained at constant temperature. The features of acoustic streaming manifesting with the decrease in the frequency of vibration in comparison with the resonant frequency are determined. The influence of the nonlinearity of process on acoustic streaming is shown. The nonlinearity is caused by the increase of the vibration amplitude.

  3. Neighbourhood Book Exchanges: Localising Information Practices (United States)

    Webster, Tenny; Gollner, Kathleen; Nathan, Lisa


    Introduction: Through this paper we report on an exploratory study into the design and use of neighbourhood book exchanges in North America. We identify dominant media framings of these book exchanges in North America, along with claims made concerning the influence of the exchanges. We compare the media claims with insights from interviews with…

  4. A Brisk Year in Chinese Cultural Exchange

    Institute of Scientific and Technical Information of China (English)


    CULTURAL Exchange has learned from the Bureaufor Cultural Relations with Foreign Countries ofthe Ministry of Culture that in 1992 China’scultural exchanges made great progress under the policyof reform and opening to the outside world.Some 1,200exchange projects were examined and approved by theMinistry of Culture(800 delegations sent abroad,more

  5. Cryogenic Heat Exchanger with Turbulent Flows (United States)

    Amrit, Jay; Douay, Christelle; Dubois, Francis; Defresne, Gerard


    An evaporator-type cryogenic heat exchanger is designed and built for introducing fluid-solid heat exchange phenomena to undergraduates in a practical and efficient way. The heat exchanger functions at liquid nitrogen temperature and enables cooling of N[subscript 2] and He gases from room temperatures. We present first the experimental results of…

  6. Ion-exchange chromatographic protein refolding

    NARCIS (Netherlands)

    Freydell, E.; Wielen, van der L.; Eppink, M.H.M.; Ottens, M.


    The application of ion-exchange (IEX) chromatography to protein refolding (IExR) has been successfully proven, as supported by various studies using different model proteins, ion-exchange media and flow configurations. Ion-exchange refolding offers a relatively high degree of process intensification

  7. The magic of knowledge exchange

    CERN Multimedia

    CERN Bulletin


    “If you have an apple and I have an apple and we exchange these apples then you and I will still each have one apple. But if you have an idea and I have an idea and we exchange these ideas, then each of us will have two ideas”. (George Bernard Shaw). The CERN Global Network is a new, ideal place for past and present members of the CERN community to share ideas and create new links.   On 29 April, CERN’s Knowledge and Technology Transfer (KTT) Group launched the CERN Global Network, a tool whose aim is to facilitate knowledge exchanges inside and outside CERN. "Among the greatest ambassadors of knowledge are people who have been trained and educated at CERN and also at other institutes: here is where the Global Network comes into play", says Rolf Heuer, CERN Director General. “During the first phase, the Network will be open to current and former members of the CERN personnel, that is, staff, fellows, apprentices, associates, students a...

  8. Nature's chemicals and synthetic chemicals: comparative toxicology.


    Ames, B N; Profet, M; Gold, L S


    The toxicology of synthetic chemicals is compared to that of natural chemicals, which represent the vast bulk of the chemicals to which humans are exposed. It is argued that animals have a broad array of inducible general defenses to combat the changing array of toxic chemicals in plant food (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in brocco...

  9. Chemical Oceanography and the Marine Carbon Cycle (United States)

    Emerson, Steven; Hedges, John

    The principles of chemical oceanography provide insight into the processes regulating the marine carbon cycle. The text offers a background in chemical oceanography and a description of how chemical elements in seawater and ocean sediments are used as tracers of physical, biological, chemical and geological processes in the ocean. The first seven chapters present basic topics of thermodynamics, isotope systematics and carbonate chemistry, and explain the influence of life on ocean chemistry and how it has evolved in the recent (glacial-interglacial) past. This is followed by topics essential to understanding the carbon cycle, including organic geochemistry, air-sea gas exchange, diffusion and reaction kinetics, the marine and atmosphere carbon cycle and diagenesis in marine sediments. Figures are available to download from Ideal as a textbook for upper-level undergraduates and graduates in oceanography, environmental chemistry, geochemistry and earth science and a valuable reference for researchers in oceanography.

  10. ASME code considerations for the compact heat exchanger

    Energy Technology Data Exchange (ETDEWEB)

    Nestell, James [MPR Associates Inc., Alexandria, VA (United States); Sham, Sam [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)


    The mission of the U.S. Department of Energy (DOE), Office of Nuclear Energy is to advance nuclear power in order to meet the nation's energy, environmental, and energy security needs. Advanced high temperature reactor systems such as sodium fast reactors and high and very high temperature gas-cooled reactors are being considered for the next generation of nuclear reactor plant designs. The coolants for these high temperature reactor systems include liquid sodium and helium gas. Supercritical carbon dioxide (sCO₂), a fluid at a temperature and pressure above the supercritical point of CO₂, is currently being investigated by DOE as a working fluid for a nuclear or fossil-heated recompression closed Brayton cycle energy conversion system that operates at 550°C (1022°F) at 200 bar (2900 psi). Higher operating temperatures are envisioned in future developments. All of these design concepts require a highly effective heat exchanger that transfers heat from the nuclear or chemical reactor to the chemical process fluid or the to the power cycle. In the nuclear designs described above, heat is transferred from the primary to the secondary loop via an intermediate heat exchanger (IHX) and then from the intermediate loop to either a working process or a power cycle via a secondary heat exchanger (SHX). The IHX is a component in the primary coolant loop which will be classified as "safety related." The intermediate loop will likely be classified as "not safety related but important to safety." These safety classifications have a direct bearing on heat exchanger design approaches for the IHX and SHX. The very high temperatures being considered for the VHTR will require the use of very high temperature alloys for the IHX and SHX. Material cost considerations alone will dictate that the IHX and SHX be highly effective; that is, provide high heat transfer area in a small volume. This feature must be accompanied by low pressure drop and mechanical reliability and


    Institute of Scientific and Technical Information of China (English)

    ZhengDong; ChenKefei


    As more ubsiness is conduced over the Internet,the fair exchange problem assumes increasing importance,However,the problem of multi-party fair exchange has not been studied as widely as the more fundamental problem of 2-party fair exchange,Recently,Franklin and Tsudik proposed two protocols for n-parth multi-item exchange on FC'98,SUCEX-1 and SUCES-2,This paper first gives an attack on the proposed protocol SUCEX-1,then presents two protocols for multi-item exchange,one is an improoved protocol of SUCEX-1,another is the extension of protocol SUCEX-2.

  12. Optimal counter-current exchange networks

    CERN Document Server

    Farr, Robert S


    We construct a general analysis for exchange devices linking their efficiency to the (potentially fractal) geometry of the exchange surface and supply network. For certain parameter ranges, we show that the optimal exchanger consists of densely packed pipes which span a thin sheet of large area, which may be crumpled into a fractal surface and supplied with a fractal network of pipes. We present the efficiencies of such fractal exchangers, showing factor gains compared to regular exchangers, using parameters relevant for systems such as pigeon lungs and salmon gills.

  13. Solid state exchange reactions and thermal decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Albarran, G.; Archundia, C.; Maddock, A.G.


    A further study of exchange of the cobalt atoms in solid Co(H/sub 2/O)/sub 6/(Co EDTA)/sub 2/ x 4H/sub 2/O has been made. The exchange is more easily measured when the compound has been ..gamma.. irradiated before heating. Without irradiation the exchange is complicated by substantial concurrent thermal decomposition. Vacuum dehydration to the tetrahydrate can be effected at 366 K without appreciable exchange. A relation between exchange, annealing of radiolytic decomposition and thermal decomposition in such compounds is suggested.


    Institute of Scientific and Technical Information of China (English)

    Zheng Dong; Chen Kefei


    As more business is conduced over the Internet, the fair exchange problem assumes increasing importance. However, the problem of multi-party fair exchange has not been studied as widely as the more fundamental problem of 2-party fair exchange. Recently, Franklin and Tsudik proposed two protocols for n-party multi-item exchange on FC'98, SUCEX-1 and SUCES-2. This paper first gives an attack on the proposed protocol SUCEX-1, then presents two protocols for multi-item exchange, one is an improved protocol of SUCEX-1, another is the extension of protocol SUCEX-2.

  15. SAFE gas turbine cycle primary heat exchangers (United States)

    Reid, Robert S.; Kapernick, Richard J.


    Los Alamos National Laboratory and Marshall Space Flight Center are jointly developing two modular heat pipe heat exchangers, collectively named FIGMENT (Fission Inert Gas Metal Exchanger for Non-nuclear Testing). The FIGMENT heat exchangers are designed to transfer power from the SAFE nuclear reactor cores to gas turbine energy converters. A stainless steel prototype heat exchanger will be built during 2002 in preparation for the construction of a larger refractory metal version. Two promising FIGMENT stainless steel heat exchanger concepts are reviewed here. .

  16. Finned Small Diameter Tube Heat Exchanger (United States)

    Dang, Chaobin; Daiguji, Hirofumi; Hihara, Eiji; Tokunaga, Masahide

    The performance of fined small tube heat exchangers was investigated both experimentally and theoretically. The Inner diameters of tubes were 1.0mm, 2.1mm and 4.0mm. Exchanged heat and pressure drop obtained from numerical simulation agreed well with the experimental ones. Calculation results show that the volume of a 2.0mm tube heat exchanger can be reduced to 33% of that of a 4mm tube heat exchanger with the same capacity. In addition the distribution of two-phase flow in a branching unit was investigated by measuring downstream temperature distribution. The flow distribution in a branching unit strongly affects the exchanged heat.

  17. NMR studies of proton exchange kinetics in aqueous formaldehyde solutions (United States)

    Rivlin, Michal; Eliav, Uzi; Navon, Gil


    Aqueous solutions of formaldehyde, formalin, are commonly used for tissue fixation and preservation. Treatment with formalin is known to shorten the tissue transverse relaxation time T2. Part of this shortening is due to the effect of formalin on the water T2. In the present work we show that the shortening of water T2 is a result of proton exchange between water and the major constituent of aqueous solutions of formaldehyde, methylene glycol. We report the observation of the signal of the hydroxyl protons of methylene glycol at 2 ppm to high frequency of the water signal that can be seen at low temperatures and at pH range of 6.0 ± 1.5 and, at conditions where it cannot be observed by the single pulse experiment, it can be detected indirectly through the water signal by the chemical exchange saturation transfer (CEST) experiment. The above finding made it possible to obtain the exchange rate between the hydroxyl protons of the methylene glycol and water in aqueous formaldehyde solutions, either using the dispersion of the spin-lattice relaxation rate in the rotating frame (1/T1ρ) or, at the slow exchange regime, from the line width hydroxyl protons of methylene glycol. The exchange rate was ∼104 s-1 at pH 7.4 and 37 °C, the activation energy, 50.2 kJ/mol and its pH dependence at 1.1 °C was fitted to: k (s-1) = 520 + 6.5 × 107[H+] + 3.0 × 109[OH-].

  18. The Kuroshio exchange with the South and East China Seas

    Directory of Open Access Journals (Sweden)

    T. Matsuno


    Full Text Available The Kuroshio flows along the edges of the marginal East Asian seas such as the South China Sea (SCS and East China Sea (ECS. Exchanges of materials and energy between the Kuroshio and the marginal seas partly control the environments of the marginal seas. In particular, saline water from the Kuroshio maintains certain salinity in the shelf water in the ECS. Nutrients from the subsurface of the Kuroshio may influence primary production on the shelf. We summarize how the Kuroshio comes into contact with the shelf water or marginal seas, describing phenomena related to the exchange between the Kuroshio and the ECS along with the SCS, using reports in the literature along with original data. The Kuroshio tends to intrude into the SCS through the Luzon Strait in various manners such as direct intrusion, associated with eddies and as a loop current. The Kuroshio intrusion into the shelf region of the ECS has distinct seasonal variation and the Taiwan Warm Current plays a significant role in the determination of water properties in the outer shelf associated with the Kuroshio intrusion. We then examine physical processes related to the interaction between the Kuroshio and shelf water. Interaction between the Kuroshio and the bottom topography is an important process in the control of the exchange around the shelf break. Vertical mixing and frontal eddies are also important factors that control the water exchange and formation of water masses in the outer shelf. Wind stress plays a significant role in the exchange with a rather event-like manner. To determine the source of the water masses, chemical tracers could be powerful tools and it is suggested that a significant part of the shelf water consists of Kuroshio intermediate water.

  19. HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Mark S Borja

    Full Text Available High density lipoprotein (HDL cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

  20. Does the Nominal Exchange Rate Regime Affect the Long Run Properties of Real Exchange Rates?


    Dreger, Christian; Girardin, Eric


    This paper examines whether the behaviour of the real exchange rate is associated with a particular regime for the nominal exchange rate, like fixed and flexible exchange rate arrangements. The analysis is based on 16 annual real exchange rates and covers a long time span, 1870-2006. Four subperiods are distinguished and linked to exchange rate regimes: the Gold Standard, the interwar float, the Bretton Woods system and the managed float thereafter. Panel integration techniques are applied to...

  1. The determinants of exchange rate in Croatia

    Directory of Open Access Journals (Sweden)

    Manuel BENAZIC


    Full Text Available The dilemma for every country with an independent monetary policy is which kind of exchange rate arrangement should be applied. Through the exchange rate policy, countries can influence their economies, i.e. price stability and export competiveness. Croatia is a new EU member state, it has its own monetary policy and currency but it is on the way to euro introduction. Regarding the experiences from the beginning of the 1990s when Croatia was faced with serious monetary instabilities and hyperinflation, the goal of Croatian National Bank (CNB is to ensure price stability and one way to do so is through exchange rate policy. Croatia, as a small and open economy, has applied a managed floating exchange rate regime. The exchange rate is determined primarily by the foreign exchange supply and demand on the foreign exchange market, with occasional market interventions by the CNB. Therefore, in order to maintain exchange rate stability, policymakers must be able to recognize how changes in these factors affect changes in the exchange rate. This research aims to find a relationship among the main sources of foreign currency inflow and outflow and the level of exchange rate in Croatia. The analysis is carried out by using the bounds testing (ARDL approach for co-integration. The results indicate the existence of a stable co-integration relationship between the observed variables, whereby an increase in the majority of variables leads to an exchange rate appreciation.

  2. Tear exchange and contact lenses: a review. (United States)

    Muntz, Alex; Subbaraman, Lakshman N; Sorbara, Luigina; Jones, Lyndon


    Tear exchange beneath a contact lens facilitates ongoing fluid replenishment between the ocular surface and the lens. This exchange is considerably lower during the wear of soft lenses compared with rigid lenses. As a result, the accumulation of tear film debris and metabolic by-products between the cornea and a soft contact lens increases, potentially leading to complications. Lens design innovations have been proposed, but no substantial improvement in soft lens tear exchange has been reported. Researchers have determined post-lens tear exchange using several methods, notably fluorophotometry. However, due to technological limitations, little remains known about tear hydrodynamics around the lens and, to-date, true tear exchange with contact lenses has not been shown. Further knowledge regarding tear exchange could be vital in aiding better contact lens design, with the prospect of alleviating certain adverse ocular responses. This article reviews the literature to-date on the significance, implications and measurement of tear exchange with contact lenses.

  3. EPR of exchange coupled systems

    CERN Document Server

    Bencini, Alessandro


    From chemistry to solid state physics to biology, the applications of Electron Paramagnetic Resonance (EPR) are relevant to many areas. This unified treatment is based on the spin Hamiltonian approach and makes extensive use of irreducible tensor techniques to analyze systems in which two or more spins are magnetically coupled. This edition contains a new Introduction by coauthor Dante Gatteschi, a pioneer and scholar of molecular magnetism.The first two chapters review the foundations of exchange interactions, followed by examinations of the spectra of pairs and clusters, relaxation in oligon

  4. International Scientific Exchanges in 2001

    Institute of Scientific and Technical Information of China (English)


    In 2001, China Institute of Atomic Energy (CIAE) signed 4 agreements 、 memorandums and 10 technical contracts with some institutes and companies of Russia, Cambodia, Korea and Belgium. CIAE sent 277 scientists, engineers and technical visitors jointed academic exchanges. Among of them, there were 91 person-times attended international conferences and symposiums, 28 person-times went abroad on the studied tour, 158 person-times worked or were trained through collaboration as well as contract implementations, etc.In 2001, CIAE held 5 international conferences and training courses in Beijing. CIAE received 497 foreign visitors from more than 30 counties and regions, they gave more than 400

  5. Kinetics of metal exchange in Cd(II) octa(4-bromophenyl)porphyrinate with d-metal salts in organic solvents (United States)

    Zvezdina, S. V.; Chizhova, N. V.; Mamardashvili, N. Zh.


    The reaction of metal exchange between Cd(II) octa(4-bromophenyl)porphyrinate with CuCl2 and ZnCl2 in DMFA and DMSO is studied by means of spectrophotometry. The kinetic parameters of the metal exchange reaction are calculated, a stoichiometric reaction mechanism is proposed. The effect the natures of the solvent, salt solvate, and the chemical modification of tetrapyrrole macrocycle have on the kinetic parameters of the metal exchange reaction are revealed.

  6. Velocity profiles between two baffles in a shell and tube heat exchanger (United States)

    Chang, Tae-Hyun; Lee, Chang-Hoan; Lee, Hae-Soo; Lee, Kwon-Soo


    Heat exchangers are extensively utilized for waste heat recovery, oil refining, chemical processing, and steam generation. In this study, velocity profiles are measured using a 3D particle image velocimetry (PIV) system betweentwo baffles in a shell and tube heat exchanger for parallel and counter flows. The PIV and computational fluid dynamics results show the occurrence of some strong vectors near the bottom. These vectors are assumed due to the clearance between the inner tubes and the front baffle. Therefore, the major parts of the vectors are moved out through the bottom opening of the rear baffle, and other vectors produce a large circle between the two baffles. Numerical simulations are conducted to investigate the effects of the baffle on the heat exchanger using the Fluent software. The k-ɛ turbulence model is employed to calculate the flows along the heat exchanger

  7. Gases Working Group: Why is it important to study Air-Sea Gas Exchange?

    NARCIS (Netherlands)

    Liss, P.; Grimalt, J.O.; Hov, O.; Johannessen, T.; Larsen, S.E.; Oost, W.A.; Leeuw, G. de


    Exchange of trace gases between the oceans and the atmosphere affects the atrnospheric content and cycling of a range of chemical trace species which are related to climate change, ozone layer depletion, acid deposition, eutrophication amospheric pafticle formation, photo-oxidants, heavy metals and

  8. Heat exchange performance of stainless steel and carbon foams modified with carbon nano fibers

    NARCIS (Netherlands)

    Tuzovskaya, I.; Pacheco Benito, S.; Chinthaginjala, J.K.; Reed, C.P.; Lefferts, L.; Meer, van der T.H.


    Carbon nanofibers (CNF), with fishbone and parallel wall structures, were grown by catalytic chemical vapor deposition on the surface of carbon foam and stainless steel foam, in order to improve their heat exchange performance. Enhancement in heat transfer efficiency between 30% and 75% was achieved

  9. Development of novel strategy for the synthesis of organometallic compounds usable as protein ligands: application to the human cyclophilin hCyp-18; Developpement de ligands de proteines par assemblage combinatoire autour d'un coeur de rhenium{sup V}: application a la cyclophiline hCyp-18

    Energy Technology Data Exchange (ETDEWEB)

    Clavaud, C


    This thesis describes a new strategy for the development of bioactive organometallic compounds, basing on the combinatorial assembly of sub-chemical libraries (A and B) independent but complementary and able to coordinate a metallic heart M to form A-M-B complex potential ligands of biomolecules. The coordination of metals, well adapted to the production of molecular variety is usually used in medicinal chemistry, in diagnostic and therapeutic nuclear medicine. Among the useful elements, the rhenium and the technetium are metals of choice for the development of the assembly strategy because of their chemical and radiochemical properties and of the structure analogy of their complexes. This strategy was validated in vitro. The protein chosen for this purpose was the cyclophilin hCyp-18. (N.C.)

  10. Inorganic ion exchangers for nuclear waste remediation

    Energy Technology Data Exchange (ETDEWEB)

    Clearfield, A.; Bortun, A.; Bortun, L.; Behrens, E. [Texas A& M Univ., College Station, TX (United States)


    The objective of this work is to provide a broad spectrum of inorganic ion exchangers that can be used for a range of applications and separations involving remediation of groundwater and tank wastes. The authors intend to scale-up the most promising exchangers, through partnership with AlliedSignal Inc., to provide samples for testing at various DOE sites. While much of the focus is on exchangers for removal of Cs{sup +} and Sr{sup 2+} from highly alkaline tank wastes, especially at Hanford, the authors have also synthesized exchangers for acid wastes, alkaline wastes, groundwater, and mercury, cobalt, and chromium removal. These exchangers are now available for use at DOE sites. Many of the ion exchangers described here are new, and others are improved versions of previously known exchangers. They are generally one of three types: (1) layered compounds, (2) framework or tunnel compounds, and (3) amorphous exchangers in which a gel exchanger is used to bind a fine powder into a bead for column use. Most of these exchangers can be regenerated and used again.

  11. Exchange of astronomy teaching experiences (United States)

    Ros, Rosa M.

    The Working Group of the European Association for Astronomy Education responsible for Teacher Training organises an annual Summer School for teachers under expert guidance. For a week the teachers participating can exchange experiences, increase their knowledge and discuss different ideas and perspectives. In general, the instructors are professional astronomers, professors and teachers from different countries. The papers presented offer very practical activities, paying special attention to didactic aspects, and take the form of general lectures to all 40 participants and workshops to reduced groups of 20 participants. There are also day and night observations, without expensive equipment or complicated procedures, that are easy to set up and based on topics that it is possible to use in the classroom. The Summer Schools promote a scientific astronomical education at all levels of astronomy teaching, reinforce the link between professional astronomers and teachers with experience of teaching astronomy, allow debates among the participants on their pedagogical activities already carried out in their own classroom and help them to organise activities outside it. Astronomy teachers need special training, access to specific research, to new educational materials and methods and the opportunity to exchange experiences. All these things are provided by the Summer School.

  12. VHTR engineering design study: intermediate heat exchanger program. Final report

    Energy Technology Data Exchange (ETDEWEB)



    The work reported is the result of a follow-on program to earlier Very High Temperature Reactor (VHTR) studies. The primary use of the VHTR is to provide heat for various industrial processes, such as hydrocarbon reforming and coal gasification. For many processes the use of an intermediate heat transfer barrier between the reactor coolant and the process is desirable; for some processes it is mandatory. Various intermediate heat exchanger (IHX) concepts for the VHTR were investigated with respect to safety, cost, and engineering design considerations. The reference processes chosen were steam-hydrocarbon reforming, with emphasis on the chemical heat pipe, and steam gasification of coal. The study investigates the critically important area of heat transfer between the reactor coolant, helium, and the various chemical processes.

  13. Comparison of a Conventional Heat Exchangers with a New Designed Heat Exchanger Experimentally

    Directory of Open Access Journals (Sweden)

    Tansel Koyun


    Full Text Available In this study, the air-water heat exchanger designed have been experimentally compared to conventional heat exchangers with and without fin. The same parameters for the three heat exchangers (pump flow, heating power, etc... have been used. In the experiments, speed-flow adjustment has been made to supply heat transfer at an optimum. As a result, during the circulation of water in pipe of the air-water heat exchanger, the corrosion fouling factor has not been formed. In addition, the efficiency of the new designed heat exchanger has been found between fin and finless heat exchanger efficiencies. The results have been shown in the diagrams.

  14. The Role of Chemistry in Atmosphere-Forest Exchange (Invited) (United States)

    Thornton, J. A.; Wolfe, G. M.; Bouvier-Brown, N. C.; Goldstein, A. H.; Park, J.; McKay, M.; Matross, D. M.; Mao, J.; Brune, W. H.; Lafranchi, B. W.; Browne, E. C.; Min, K.; Wooldridge, P. J.; Cohen, R. C.; Crounse, J.; Faloona, I. C.; Gilman, J. B.; Kuster, W. C.; de Gouw, J. A.; Huisman, A. J.; Keutsch, F. N.


    Forest-atmosphere exchange of hydrocarbons, ozone, oxidized nitrogen and other reactive species impacts both atmospheric composition and ecosystem productivity, with broad implications for air quality and climate. Recent interpretations of measured ozone and acyl peroxy nitrate fluxes have inferred that intra-canopy chemistry plays an important role in governing both the sign and magnitude of the atmosphere-forest flux of these compounds. I review these observational insights and present results from a recently constructed 1-D vertically-resolved chemical transport model (CAFE) developed for analysis and interpretation of observations made during the Biosphere Effects on Aerosols and Photochemistry Experiment (BEARPEX). The model incorporates a fully resolved forest canopy; emissions from which are parameterized, in many cases, to match leaf-level and top-of-canopy fluxes measured at the ponderosa pine plantation. Model chemistry is based on the Master Chemical Mechanism (MCM), with several additions to simulate the oxidation of monoterpenes and sesquiterpenes not in the current MCM. The base model underestimates measured noontime OH concentrations by a factor of six. As a result we invoke enhanced OH-recycling from first generation isoprene and 2-methyl-3-buten-2-ol peroxy radicals to reconcile model and observed HOx components. Noting a few other aspects of model performance, I will focus on the model predictions of chemistry-induced fluxes. The model qualitatively reproduces the inferred sensitivity to intra-canopy chemistry for both ozone and acyl peroxy nitrates. In both cases, however, the model underestimates the observed exchange velocity suggesting non-stomatal losses (depositional or chemical) remain underestimated in the canopy. As an example of the potential importance of intra-canopy chemistry, the meteorological and structural characteristics of the forest are varied within the model. An intriguing result is that acyl peroxy nitrate (e.g., PAN) fluxes

  15. Characterization of ion-exchange membrane materials: properties vs structure. (United States)

    Berezina, N P; Kononenko, N A; Dyomina, O A; Gnusin, N P


    This review focuses on the preparation, structure and applications of ion-exchange membranes formed from various materials and exhibiting various functions (electrodialytic, perfluorinated sulphocation-exchange and novel laboratory-tested membranes). A number of experimental techniques for measuring electrotransport properties as well as the general procedure for membrane testing are also described. The review emphasizes the relationships between membrane structures, physical and chemical properties and mechanisms of electrochemical processes that occur in charged membrane materials. The water content in membranes is considered to be a key factor in the ion and water transfer and in polarization processes in electromembrane systems. We suggest the theoretical approach, which makes it possible to model and characterize the electrochemical properties of heterogeneous membranes using several transport-structural parameters. These parameters are extracted from the experimental dependences of specific electroconductivity and diffusion permeability on concentration. The review covers the most significant experimental and theoretical research on ion-exchange membranes that have been carried out in the Membrane Materials Laboratory of the Kuban State University. These results have been discussed at the conferences "Membrane Electrochemistry", Krasnodar, Russia for many years and were published mainly in Russian scientific sources.

  16. Mathematical simulation of heat exchanger working conditions (United States)

    Gavlas, Stanislav; Ďurčanský, Peter; Lenhard, Richard; Jandačka, Jozef


    One of the When designing a new heat exchanger it is necessary to consider all the conditions imposed on the exchanger and its desired properties. Most often the investigation of heat transfer is to find heat surface. When applying exchanger for proposed hot air engine, it will be a counter-flow heat exchanger of gas - gas type. Gas, which transfers the heat will be exhaust gas from the combustion of biomass. An important step in the design and verification is to analyze exchanger designed using numerical methods, the verification of the correctness of design and verification of boundary conditions which include temperatures, flow rates and pressure drops. Due to the fact that the heat transfer in the heat exchanger is a three-dimensional plot and timeindependent, the system is described by partial differential equations that need to be solved by numerical methods.

  17. Listening to agent agendas in student exchanges

    DEFF Research Database (Denmark)

    Tarp, Gertrud


    The paper is based upon a research study of short-term student exchanges. The study took place from 1996-2000, and comprises seven classes of students from six Danish business schools. Short-term student exchanges in terms of EU funded exchanges and local school exchanges are means to develop...... the students’ understanding of their own cultural background and of foreign cultures. The research study is an attempt to look at internationalisation and student exchanges from a student perspective. Thus the structural aim and the structural framework are considered given elements. The study is based upon...... institutional scepticism and placed within the theoretical framework of symbolic interactionism. The methodology applied is qualitative, grounded theory, and the data originate from diaries, semi-structured interviews and semi-open questionnaires. The findings show that the students have their own exchange...

  18. Inorganic chemically active adsorbents (ICAAs)

    Energy Technology Data Exchange (ETDEWEB)

    Ally, M.R. [Oak Ridge National Lab., TN (United States); Tavlarides, L.


    Oak Ridge National Laboratory (ORNL) researchers are developing a technology that combines metal chelation extraction technology and synthesis chemistry. They begin with a ceramic substrate such as alumina, titanium oxide or silica gel because they provide high surface area, high mechanical strength, and radiolytic stability. One preparation method involves silylation to hydrophobize the surface, followed by chemisorption of a suitable chelation agent using vapor deposition. Another route attaches newly designed chelating agents through covalent bonding by the use of coupling agents. These approaches provide stable and selective, inorganic chemically active adsorbents (ICAAs) tailored for removal of metals. The technology has the following advantages over ion exchange: (1) higher mechanical strength, (2) higher resistance to radiation fields, (3) higher selectivity for the desired metal ion, (4) no cation exchange, (5) reduced or no interference from accompanying anions, (6) faster kinetics, and (7) easy and selective regeneration. Target waste streams include metal-containing groundwater/process wastewater at ORNL`s Y-12 Plant (multiple metals), Savannah River Site (SRS), Rocky Flats (multiple metals), and Hanford; aqueous mixed wastes at Idaho National Engineering Laboratory (INEL); and scrubber water generated at SRS and INEL. Focus Areas that will benefit from this research include Mixed Waste, and Subsurface Contaminants.

  19. Model Uncertainty and Exchange Rate Forecasting


    Kouwenberg, Roy; Markiewicz, Agnieszka; Verhoeks, Ralph; Zwinkels, Remco


    textabstractWe propose a theoretical framework of exchange rate behavior where investors focus on a subset of economic fundamentals. We find that any adjustment in the set of predictors used by investors leads to changes in the relation between the exchange rate and fundamentals. We test the validity of this framework via a backward elimination rule which captures the current set of fundamentals that best predicts the exchange rate. Out-of-sample forecasting tests show that the backward elimi...

  20. Market Sentiment and Exchange Rate Directional Forecasting


    Vasilios Plakandaras; Theophilos Papadimitriou; Periklis Gogas; Konstantinos Diamantaras


    The microstructural approach to the exchange rate market claims that order flows on a currency can accurately reflect the short-run dynamics its exchange rate. In this paper, instead of focusing on order flows analysis we employ an alternative microstructural approach: we focus on investors' sentiment on a given exchange rate as a possible predictor of its future evolution. As a proxy of investors' sentiment we use StockTwits posts, a message board dedicated to finance. Within StockTwits inve...

  1. Online Ad Assignment with an Ad Exchange


    Dvořák, Wolfgang; Henzinger, Monika


    Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whe...

  2. Chemical Security Analysis Center (United States)

    Federal Laboratory Consortium — In 2006, by Presidential Directive, DHS established the Chemical Security Analysis Center (CSAC) to identify and assess chemical threats and vulnerabilities in the...

  3. Foreign Exchange Risk in International Transactions

    Directory of Open Access Journals (Sweden)

    Florentina-Olivia Balu


    In this article we will focus on forward and futures contracts for managing foreign exchange risk. A forward is a contract to buy or sell currency at an agreed upon exchange rate at a specific date in the future. Futures are similar to forwards except that they’re traded on exchanges which specify settlement dates. Also we make some recommendations related to the foreign exchange risk-management practices that are useful for companies involved in international trade and for financial institutions interested in providing hedging products to these companies.

  4. Exchange effects in a cold plasma

    CERN Document Server

    Ekman, Robin; Brodin, Gert


    We have studied the exchange corrections to linear electrostatic wave propagation in a plasma using a quantum kinetic formalism. Specifically we have considered the zero temperature limit. In order to simplify the calculations we have focused on the long wavelength limit, i.e. wavelengths much longer than the de Broglie wavelength. For the case of ion-acoustic waves we have calculated the exchange correction both to the damping rate and the real part of the frequency. For Langmuir waves the frequency shift due to exchange effects is found. Our results are compared with the frequency shifts deduced from commonly used exchange potentials which are computed from density functional theory.

  5. Exchangeability and sets of desirable gambles

    CERN Document Server

    de Cooman, Gert


    Sets of desirable gambles constitute a quite general type of uncertainty model with an interesting geometrical interpretation. We give a general discussion of such models and their rationality criteria. We study exchangeability assessments for them, and prove counterparts of de Finetti's finite and infinite representation theorems. We show that the finite representation in terms of count vectors has a very nice geometrical interpretation, and that the representation in terms of frequency vectors is tied up with multivariate Bernstein (basis) polynomials. We also lay bare the relationships between the representations of updated exchangeable models, and discuss conservative inference (natural extension) under exchangeability and the extension of exchangeable sequences.

  6. Entropy exchange for infinite-dimensional systems (United States)

    Duan, Zhoubo; Hou, Jinchuan


    In this paper the entropy exchange for channels and states in infinite-dimensional systems are defined and studied. It is shown that, this entropy exchange depends only on the given channel and the state. An explicit expression of the entropy exchange in terms of the state and the channel is proposed. The generalized Klein’s inequality, the subadditivity and the triangle inequality about the entropy including infinite entropy for the infinite-dimensional systems are established, and then, applied to compare the entropy exchange with the entropy change. PMID:28164995

  7. Apparent exchange rate mapping with diffusion MRI. (United States)

    Lasič, Samo; Nilsson, Markus; Lätt, Jimmy; Ståhlberg, Freddy; Topgaard, Daniel


    Water exchange through the cell membranes is an important feature of cells and tissues. The rate of exchange is determined by factors such as membrane lipid composition and organization, as well as the type and activity of aquaporins. A method for noninvasively estimating the rate of water exchange would be useful for characterizing pathological conditions, e.g., tumors, multiple sclerosis, and ischemic stroke, expected to be associated with a change of the membrane barrier properties. This study describes the filter exchange imaging method for determining the rate of water exchange between sites having different apparent diffusion coefficients. The method is based on the filter-exchange pulsed gradient spin-echo NMR spectroscopy experiment, which is here modified to be compatible with the constraints of clinical MR scanners. The data is analyzed using a model-free approach yielding maps of the apparent exchange rate, here being introduced in analogy with the concept of the apparent diffusion coefficient. Proof-of-principle experiments are performed on microimaging and whole-body clinical scanners using yeast suspension phantoms. The limitations and appropriate experimental conditions are examined. The results demonstrate that filter exchange imaging is a fast and reliable method for characterizing exchange, and that it has the potential to become a powerful diagnostic tool.

  8. Ion Exchange and Liquid Column Chromatography. (United States)

    Walton, Harold F.


    Emphasizes recent advances in principles and methodology in ion exchange and chromatography. Two tables list representative examples for inorganic ions and organic compounds. Cites 544 references. (CS)

  9. Adaptive Strategies in the Iterated Exchange Problem (United States)

    Baraov, Arthur


    We argue for clear separation of the exchange problem from the exchange paradox to avoid confusion about the subject matter of these two distinct problems. The exchange problem in its current format belongs to the domain of optimal decision making—it doesn't make any sense as a game of competition. But it takes just a tiny modification in the statement of the problem to breathe new life into it and make it a practicable and meaningful game of competition. In this paper, we offer an explanation for paradoxical priors and discuss adaptive strategies for both the house and the player in the restated exchange problem.

  10. Micro tube heat exchangers for Space Project (United States)

    National Aeronautics and Space Administration — Mezzo fabricates micro tube heat exchangers for a variety of applications, including aerospace, automotive racing, Department of Defense ground vehicles, economizers...

  11. Data Exchange Management Information System (DEMIS) (United States)

    Social Security Administration — DEMIS combines a database (Operational Data Store - ODS) of data exchange-related Management Information (MI) with the agency's querying and reporting utility, the...

  12. Evaluating benchmarks for Norwegian exchange rate forecasting


    Adrik, Samir


    In this thesis, we compare the out-of-sample forecasting abilities of three fundamental exchange rate models (EqCM) against the random walk (without drift), RW. The objective of the thesis is to see how well the RW model preforms against fundamental exchange rate models that in the literature have proven to be better at forecasting the Norwegian exchange rate. These models were tested on an out-of-sample period (2009:1-2015:4) that include two characteristic exchange rate regimes. The models ...

  13. Quantum Statistical Calculation of Exchange Bias

    Institute of Scientific and Technical Information of China (English)

    WANG Huai-Yu; DAI Zhen-Hong


    The phenomenon of exchange bias of ferromagnetic (FM) films, which are coupled with an antiferromagnetic (AFM) film, is studied by Heisenberg model by use of the many-body Green's function method of quantum statistical theory for the uncompensated case. Exchange bias HE and coercivity Hc are calculated as functions of the FM film thickness L, temperature, the strength of the exchange interaction across the interface between FM and AFM and the anisotropy of the FM. Hc decreases with increasing L when the FM film is beyond some thickness. The dependence of the exchange bias HE on the FM film thickness and on temperature is also qualitatively in agreement with experiments.

  14. Creation of an antiferromagnetic exchange spring

    Energy Technology Data Exchange (ETDEWEB)

    Scholl, A.; Liberati, M.; Arenholz, E.; Ohldag, H.; Stohr, J.


    We present evidence for the creation of an exchange spring in an antiferromagnet due to exchange coupling to a ferromagnet. X-ray magnetic linear dichroism spectroscopy on single crystal Co/NiO(001) shows that a partial domain wall is wound up at the surface of the antiferromagnet when the adjacent ferromagnet is rotated by a magnetic field. We determine the interface exchange stiffness and the antiferromagnetic domain wall energy from the field dependence of the direction of the antiferromagnetic axis, the antiferromagnetic pendant to a ferromagnetic hysteresis loop. The existence of a planar antiferromagnetic domain wall, proven by our measurement, is a key assumption of most exchange bias models.

  15. Exchange Rate Policy and Endogenous Price Flexibility


    Devereux, Michael B.


    A fixed exchange rate limits the ability of the real exchange rate to adjust to shocks, and tends to raise the volatility of real GDP. But adjustment may be enhanced if internal prices are more flexible under a fixed exchange rate. This Paper develops a model in which price setters incur a cost to retain the option of ex-post price flexibility. The benefit of flexibility is increasing in the variance of demand facing price-setters. We ask whether fixing the exchange rate is likely to increase...

  16. Alloyed copper chalcogenide nanoplatelets via partial cation exchange reactions. (United States)

    Lesnyak, Vladimir; George, Chandramohan; Genovese, Alessandro; Prato, Mirko; Casu, Alberto; Ayyappan, S; Scarpellini, Alice; Manna, Liberato


    We report the synthesis of alloyed quaternary and quinary nanocrystals based on copper chalcogenides, namely, copper zinc selenide-sulfide (CZSeS), copper tin selenide-sulfide (CTSeS), and copper zinc tin selenide-sulfide (CZTSeS) nanoplatelets (NPLs) (∼20 nm wide) with tunable chemical composition. Our synthesis scheme consisted of two facile steps: i.e., the preparation of copper selenide-sulfide (Cu2-xSeyS1-y) platelet shaped nanocrystals via the colloidal route, followed by an in situ cation exchange reaction. During the latter step, the cation exchange proceeded through a partial replacement of copper ions by zinc or/and tin cations, yielding homogeneously alloyed nanocrystals with platelet shape. Overall, the chemical composition of the alloyed nanocrystals can easily be controlled by the amount of precursors that contain cations of interest (e.g., Zn, Sn) to be incorporated/alloyed. We have also optimized the reaction conditions that allow a complete preservation of the size, morphology, and crystal structure as that of the starting Cu2-xSeyS1-y NPLs. The alloyed NPLs were characterized by optical spectroscopy (UV-vis-NIR) and cyclic voltammetry (CV), which demonstrated tunability of their light absorption characteristics as well as their electrochemical band gaps.

  17. Educational Exchanges Across the Equator (United States)

    Norman, D. J.; Walker, C. E.; Smith, M.; Pompea, S. M.; Orellana, D.


    What is color? What is light? How can we use a spectrometer to help students understand the answers to these questions? Even half a world apart and between people of different languages and cultures, how to teach these ideas to students can be a lively subject for discussion. And it is! Aided by Internet 2-based videoconferencing, NOAO North and South have sponsored three teacher professional development videoconference workshops, dubbed ASTRO-Chile, linking teachers in Tucson, AZ, and La Serena, Chile. The teachers exchange methods and ideas about how to explain and demonstrate physical concepts, important to the study of astronomy, to students of various ages. The workshops are conducted in Spanish with four bilingual science teachers from the Tucson area discussing pedagogical approaches with their teaching counterparts in Chile. Demonstrations and project presentations, from both sites, are included as part of each workshop. This work is supported, in part, through funding from the NSF Astronomy and Astrophysics Postdoctoral Fellowship.

  18. Energetics and control of ultracold isotope-exchange reactions between heteronuclear dimers in external fields

    CERN Document Server

    Tomza, Michał


    We show that isotope-exchange reactions between ground-state alkali-metal, alkaline-earth-metal, and lanthanide heteronuclear dimers consisting of two isotopes of the same atom are exothermic with an energy change in the range of 1-8000$\\,$MHz thus resulting in cold or ultracold products. For these chemical reactions there are only one rovibrational and at most several hyperfine possible product states. The number and energetics of open and closed reactive channels can be controlled by the laser and magnetic fields. The exothermic isotope-exchange reactions can be tuned to become endothermic by employing a laser-induced state-selective Stark shift control thus providing a ground for testing models of the chemical reactivity. The present proposal opens the way for studying the state-to-state dynamics of ultracold chemical reactions beyond the universal limit with a meaningful control over quantum states of both reactants and products.

  19. Energetics and Control of Ultracold Isotope-Exchange Reactions between Heteronuclear Dimers in External Fields (United States)

    Tomza, Michał


    We show that isotope-exchange reactions between ground-state alkali-metal, alkaline-earth-metal, and lanthanide heteronuclear dimers consisting of two isotopes of the same atom are exothermic with an energy change in the range of 1-8000 MHz, thus resulting in cold or ultracold products. For these chemical reactions, there are only one rovibrational and at most several hyperfine possible product states. The number and energetics of open and closed reactive channels can be controlled by the laser and magnetic fields. We suggest a laser-induced isotope- and state-selective Stark shift control to tune the exothermic isotope-exchange reactions to become endothermic, thus providing the ground for testing models of the chemical reactivity. The present proposal opens the way for studying the state-to-state dynamics of ultracold chemical reactions beyond the universal limit with a meaningful control over the quantum states of both reactants and products.

  20. Multiscale Investigation of Chemical Interference in Proteins

    CERN Document Server

    Samiotakis, Antonios; Cheung, Margaret S


    We developed a multiscale approach (MultiSCAAL) that integrates the potential of mean force (PMF) obtained from all-atomistic molecular dynamics simulations with a knowledge-based energy function for coarse-grained molecular simulations in better exploring the energy landscape of a small protein under chemical interference such as chemical denaturation. An excessive amount of water molecules in all-atomistic molecular dynamics simulations often negatively impacts the sampling efficiency of some advanced sampling techniques such as the replica exchange method and it makes the investigation of chemical interferences on protein dynamics difficult. Thus, there is a need to develop an effective strategy that focuses on sampling structural changes in protein conformations rather than solvent molecule fluctuations. In this work, we address this issue by devising a multiscale simulation scheme (MultiSCAAL) that bridges the gap between all-atomistic molecular dynamics simulation and coarse-grained molecular simulation...