WorldWideScience

Sample records for single protein-ligand complexes

  1. AMMOS2: a web server for protein-ligand-water complexes refinement via molecular mechanics.

    Science.gov (United States)

    Labbé, Céline M; Pencheva, Tania; Jereva, Dessislava; Desvillechabrol, Dimitri; Becot, Jérôme; Villoutreix, Bruno O; Pajeva, Ilza; Miteva, Maria A

    2017-07-03

    AMMOS2 is an interactive web server for efficient computational refinement of protein-small organic molecule complexes. The AMMOS2 protocol employs atomic-level energy minimization of a large number of experimental or modeled protein-ligand complexes. The web server is based on the previously developed standalone software AMMOS (Automatic Molecular Mechanics Optimization for in silico Screening). AMMOS utilizes the physics-based force field AMMP sp4 and performs optimization of protein-ligand interactions at five levels of flexibility of the protein receptor. The new version 2 of AMMOS implemented in the AMMOS2 web server allows the users to include explicit water molecules and individual metal ions in the protein-ligand complexes during minimization. The web server provides comprehensive analysis of computed energies and interactive visualization of refined protein-ligand complexes. The ligands are ranked by the minimized binding energies allowing the users to perform additional analysis for drug discovery or chemical biology projects. The web server has been extensively tested on 21 diverse protein-ligand complexes. AMMOS2 minimization shows consistent improvement over the initial complex structures in terms of minimized protein-ligand binding energies and water positions optimization. The AMMOS2 web server is freely available without any registration requirement at the URL: http://drugmod.rpbs.univ-paris-diderot.fr/ammosHome.php. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Force spectroscopy studies on protein-ligand interactions: a single protein mechanics perspective.

    Science.gov (United States)

    Hu, Xiaotang; Li, Hongbin

    2014-10-01

    Protein-ligand interactions are ubiquitous and play important roles in almost every biological process. The direct elucidation of the thermodynamic, structural and functional consequences of protein-ligand interactions is thus of critical importance to decipher the mechanism underlying these biological processes. A toolbox containing a variety of powerful techniques has been developed to quantitatively study protein-ligand interactions in vitro as well as in living systems. The development of atomic force microscopy-based single molecule force spectroscopy techniques has expanded this toolbox and made it possible to directly probe the mechanical consequence of ligand binding on proteins. Many recent experiments have revealed how ligand binding affects the mechanical stability and mechanical unfolding dynamics of proteins, and provided mechanistic understanding on these effects. The enhancement effect of mechanical stability by ligand binding has been used to help tune the mechanical stability of proteins in a rational manner and develop novel functional binding assays for protein-ligand interactions. Single molecule force spectroscopy studies have started to shed new lights on the structural and functional consequence of ligand binding on proteins that bear force under their biological settings. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  3. iview: an interactive WebGL visualizer for protein-ligand complex.

    Science.gov (United States)

    Li, Hongjian; Leung, Kwong-Sak; Nakane, Takanori; Wong, Man-Hon

    2014-02-25

    Visualization of protein-ligand complex plays an important role in elaborating protein-ligand interactions and aiding novel drug design. Most existing web visualizers either rely on slow software rendering, or lack virtual reality support. The vital feature of macromolecular surface construction is also unavailable. We have developed iview, an easy-to-use interactive WebGL visualizer of protein-ligand complex. It exploits hardware acceleration rather than software rendering. It features three special effects in virtual reality settings, namely anaglyph, parallax barrier and oculus rift, resulting in visually appealing identification of intermolecular interactions. It supports four surface representations including Van der Waals surface, solvent excluded surface, solvent accessible surface and molecular surface. Moreover, based on the feature-rich version of iview, we have also developed a neat and tailor-made version specifically for our istar web platform for protein-ligand docking purpose. This demonstrates the excellent portability of iview. Using innovative 3D techniques, we provide a user friendly visualizer that is not intended to compete with professional visualizers, but to enable easy accessibility and platform independence.

  4. Strength and Character of Halogen Bonds in Protein-Ligand Complexes

    Czech Academy of Sciences Publication Activity Database

    Riley, Kevin Eugene; Hobza, Pavel

    2011-01-01

    Roč. 11, č. 10 (2011), s. 4272-4278 ISSN 1528-7483 R&D Projects: GA MŠk LC512 Grant - others:Research and Development for Innovations of European Social Fund(XE) CZ.1.05/2.1.00/03.0058 Institutional research plan: CEZ:AV0Z40550506 Keywords : halogen bond * protein-ligand complexes * calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.720, year: 2011

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

    Directory of Open Access Journals (Sweden)

    Lippert Tobias

    2009-08-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Stierand Katrin

    2011-06-01

    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.

  7. @TOME-2: a new pipeline for comparative modeling of protein-ligand complexes.

    Science.gov (United States)

    Pons, Jean-Luc; Labesse, Gilles

    2009-07-01

    @TOME 2.0 is new web pipeline dedicated to protein structure modeling and small ligand docking based on comparative analyses. @TOME 2.0 allows fold recognition, template selection, structural alignment editing, structure comparisons, 3D-model building and evaluation. These tasks are routinely used in sequence analyses for structure prediction. In our pipeline the necessary software is efficiently interconnected in an original manner to accelerate all the processes. Furthermore, we have also connected comparative docking of small ligands that is performed using protein-protein superposition. The input is a simple protein sequence in one-letter code with no comment. The resulting 3D model, protein-ligand complexes and structural alignments can be visualized through dedicated Web interfaces or can be downloaded for further studies. These original features will aid in the functional annotation of proteins and the selection of templates for molecular modeling and virtual screening. Several examples are described to highlight some of the new functionalities provided by this pipeline. The server and its documentation are freely available at http://abcis.cbs.cnrs.fr/AT2/

  8. Acetylcholinesterase complexed with bivalent ligands related to huperzine a: experimental evidence for species-dependent protein-ligand complementarity.

    Science.gov (United States)

    Wong, Dawn M; Greenblatt, Harry M; Dvir, Hay; Carlier, Paul R; Han, Yi-Fan; Pang, Yuan-Ping; Silman, Israel; Sussman, Joel L

    2003-01-15

    active-site gorge explain the switch in inhibitory potency of (-)-2a and 2b and the larger dimer/(-)-HupA potency ratios observed for TcAChE relative to rat AChE. The results offer new insights into factors affecting protein-ligand complementarity within the gorge and should assist the further development of improved AChE inhibitors.

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

    Science.gov (United States)

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

    2015-01-22

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

    Science.gov (United States)

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

    2007-12-01

    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

  11. Do All X-ray Structures of Protein-Ligand Complexes Represent Functional States? EPOR, a Case Study.

    Science.gov (United States)

    Corbett, Michael S P; Mark, Alan E; Poger, David

    2017-02-28

    Based on differences between the x-ray crystal structures of ligand-bound and unbound forms, the activation of the erythropoietin receptor (EPOR) was initially proposed to involve a cross-action scissorlike motion. However, the validity of the motions involved in the scissorlike model has been recently challenged. Here, atomistic molecular dynamics simulations are used to examine the structure of the extracellular domain of the EPOR dimer in the presence and absence of erythropoietin and a series of agonistic or antagonistic mimetic peptides free in solution. The simulations suggest that in the absence of crystal packing effects, the EPOR chains in the different dimers adopt very similar conformations with no clear distinction between the agonist and antagonist-bound complexes. This questions whether the available x-ray crystal structures of EPOR truly represent active or inactive conformations. The study demonstrates the difficulty in using such structures to infer a mechanism of action, especially in the case of membrane receptors where just part of the structure has been considered in addition to potential confounding effects that arise from the comparison of structures in a crystal as opposed to a membrane environment. The work highlights the danger of assigning functional significance to small differences between structures of proteins bound to different ligands in a crystal environment without consideration of the effects of the crystal lattice and thermal motion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-09-01

    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.

  13. Models of protein-ligand crystal structures: trust, but verify.

    Science.gov (United States)

    Deller, Marc C; Rupp, Bernhard

    2015-09-01

    X-ray crystallography provides the most accurate models of protein-ligand structures. These models serve as the foundation of many computational methods including structure prediction, molecular modelling, and structure-based drug design. The success of these computational methods ultimately depends on the quality of the underlying protein-ligand models. X-ray crystallography offers the unparalleled advantage of a clear mathematical formalism relating the experimental data to the protein-ligand model. In the case of X-ray crystallography, the primary experimental evidence is the electron density of the molecules forming the crystal. The first step in the generation of an accurate and precise crystallographic model is the interpretation of the electron density of the crystal, typically carried out by construction of an atomic model. The atomic model must then be validated for fit to the experimental electron density and also for agreement with prior expectations of stereochemistry. Stringent validation of protein-ligand models has become possible as a result of the mandatory deposition of primary diffraction data, and many computational tools are now available to aid in the validation process. Validation of protein-ligand complexes has revealed some instances of overenthusiastic interpretation of ligand density. Fundamental concepts and metrics of protein-ligand quality validation are discussed and we highlight software tools to assist in this process. It is essential that end users select high quality protein-ligand models for their computational and biological studies, and we provide an overview of how this can be achieved.

  14. Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes.

    Science.gov (United States)

    Raschka, Sebastian; Wolf, Alex J; Bemister-Buffington, Joseph; Kuhn, Leslie A

    2018-04-01

    Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.

  15. Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes

    Science.gov (United States)

    Raschka, Sebastian; Wolf, Alex J.; Bemister-Buffington, Joseph; Kuhn, Leslie A.

    2018-02-01

    Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.

  16. Quantitative analysis of protein-ligand interactions by NMR.

    Science.gov (United States)

    Furukawa, Ayako; Konuma, Tsuyoshi; Yanaka, Saeko; Sugase, Kenji

    2016-08-01

    Protein-ligand interactions have been commonly studied through static structures of the protein-ligand complex. Recently, however, there has been increasing interest in investigating the dynamics of protein-ligand interactions both for fundamental understanding of the underlying mechanisms and for drug development. NMR is a versatile and powerful tool, especially because it provides site-specific quantitative information. NMR has widely been used to determine the dissociation constant (KD), in particular, for relatively weak interactions. The simplest NMR method is a chemical-shift titration experiment, in which the chemical-shift changes of a protein in response to ligand titration are measured. There are other quantitative NMR methods, but they mostly apply only to interactions in the fast-exchange regime. These methods derive the dissociation constant from population-averaged NMR quantities of the free and bound states of a protein or ligand. In contrast, the recent advent of new relaxation-based experiments, including R2 relaxation dispersion and ZZ-exchange, has enabled us to obtain kinetic information on protein-ligand interactions in the intermediate- and slow-exchange regimes. Based on R2 dispersion or ZZ-exchange, methods that can determine the association rate, kon, dissociation rate, koff, and KD have been developed. In these approaches, R2 dispersion or ZZ-exchange curves are measured for multiple samples with different protein and/or ligand concentration ratios, and the relaxation data are fitted to theoretical kinetic models. It is critical to choose an appropriate kinetic model, such as the two- or three-state exchange model, to derive the correct kinetic information. The R2 dispersion and ZZ-exchange methods are suitable for the analysis of protein-ligand interactions with a micromolar or sub-micromolar dissociation constant but not for very weak interactions, which are typical in very fast exchange. This contrasts with the NMR methods that are used

  17. A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach.

    Science.gov (United States)

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

    2012-07-01

    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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Characterization of protein/ligand interactions by 1H/3H exchange: application to the hAsf1/ histone H3 complex

    International Nuclear Information System (INIS)

    Mousseau, G.

    2007-05-01

    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 3 . (N.C.)

  19. 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

    2007-05-15

    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.)

  20. THERMODYNAMICS OF PROTEIN-LIGAND INTERACTIONS AND THEIR ANALYSIS

    Directory of Open Access Journals (Sweden)

    Rummi Devi Saini

    2017-11-01

    Full Text Available Physiological processes are controlled mainly by intermolecular recognition mechanisms which involve protein–protein and protein–ligand interactions with a high specificity and affinity to form a specific complex. Proteins being an important class of macromolecules in biological systems, it is important to understand their actions through binding to other molecules of proteins or ligands. In fact, the binding of low molecular weight ligands to proteins plays a significant role in regulating biological processes such as cellular metabolism and signal transmission. Therefore knowledge of the protein–ligand interactions and the knowledge of the mechanisms involved in the protein-ligand recognition and binding are key in understanding biology at molecular level which will facilitate the discovery, design, and development of drugs. In this review, the mechanisms involved in protein–ligand binding, the binding kinetics, thermodynamic concepts and binding driving forces are discussed. Thermodynamic mechanisms involved in a few important protein-ligand binding are described. Various spectroscopic, non-spectroscopic and computational method for analysis of protein–ligand binding are also discussed.

  1. Statistical Estimation of the Protein-Ligand Binding Free Energy Based On Direct Protein-Ligand Interaction Obtained by Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Haruki Nakamura

    2012-09-01

    Full Text Available We have developed a method for estimating protein-ligand binding free energy (DG based on the direct protein-ligand interaction obtained by a molecular dynamics simulation. Using this method, we estimated the DG value statistically by the average values of the van der Waals and electrostatic interactions between each amino acid of the target protein and the ligand molecule. In addition, we introduced fluctuations in the accessible surface area (ASA and dihedral angles of the protein-ligand complex system as the entropy terms of the DG estimation. The present method included the fluctuation term of structural change of the protein and the effective dielectric constant. We applied this method to 34 protein-ligand complex structures. As a result, the correlation coefficient between the experimental and calculated DG values was 0.81, and the average error of DG was 1.2 kcal/mol with the use of the fixed parameters. These results were obtained from a 2 nsec molecular dynamics simulation.

  2. Comparison of molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics-three-dimensional reference interaction site model (MM-3D-RISM) method to calculate the binding free energy of protein-ligand complexes: Effect of metal ion and advance statistical test

    Science.gov (United States)

    Pandey, Preeti; Srivastava, Rakesh; Bandyopadhyay, Pradipta

    2018-03-01

    The relative performance of MM-PBSA and MM-3D-RISM methods to estimate the binding free energy of protein-ligand complexes is investigated by applying these to three proteins (Dihydrofolate Reductase, Catechol-O-methyltransferase, and Stromelysin-1) differing in the number of metal ions they contain. None of the computational methods could distinguish all the ligands based on their calculated binding free energies (as compared to experimental values). The difference between the two comes from both polar and non-polar part of solvation. For charged ligand case, MM-PBSA and MM-3D-RISM give a qualitatively different result for the polar part of solvation.

  3. Descriptor Data Bank (DDB): A Cloud Platform for Multiperspective Modeling of Protein-Ligand Interactions.

    Science.gov (United States)

    Ashtawy, Hossam M; Mahapatra, Nihar R

    2018-01-22

    Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Currently, a large number of hypotheses and perspectives to model these interaction forces are scattered throughout the literature and largely forgotten. Instead, had they been assembled and utilized collectively, they would have substantially improved the accuracy of predicting binding affinity of protein-ligand complexes. In this work, we present Descriptor Data Bank (DDB), a data-driven platform on the cloud for facilitating multiperspective modeling of PL interactions. DDB is an open-access hub for depositing, hosting, executing, and sharing descriptor extraction tools and data for a large number of interaction modeling hypotheses. The platform also implements a machine-learning (ML) toolbox for automatic descriptor filtering and analysis and scoring function (SF) fitting and prediction. The descriptor filtering module is used to filter out irrelevant and/or noisy descriptors and to produce a compact subset from all available features. We seed DDB with 16 diverse descriptor extraction tools developed in-house and collected from the literature. The tools altogether generate over 2700 descriptors that characterize (i) proteins, (ii) ligands, and (iii) protein-ligand complexes. The in-house descriptors we extract are protein-specific which are based on pairwise primary and tertiary alignment of protein structures followed by clustering and trilateration. We built and used DDB's ML library to fit SFs to the in-house descriptors and those collected from the literature. We then evaluated them on several data sets that were constructed to reflect real-world drug screening scenarios. We found that multiperspective SFs that were constructed using a large number

  4. Calculation of protein-ligand binding affinities.

    Science.gov (United States)

    Gilson, Michael K; Zhou, Huan-Xiang

    2007-01-01

    Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

  5. [Supercomputer investigation of the protein-ligand system low-energy minima].

    Science.gov (United States)

    Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

    2015-01-01

    The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

  6. Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima.

    Science.gov (United States)

    Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Alexey V; Kutov, Danil C; Sobolev, Sergey I; Voevodin, Vladimir V; Sulimov, Vladimir B

    2015-01-01

    The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

  7. Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-Ligand Energy Minima

    Directory of Open Access Journals (Sweden)

    Igor V. Oferkin

    2015-01-01

    Full Text Available The adequate choice of the docking target function impacts the accuracy of the ligand positioning as well as the accuracy of the protein-ligand binding energy calculation. To evaluate a docking target function we compared positions of its minima with the experimentally known pose of the ligand in the protein active site. We evaluated five docking target functions based on either the MMFF94 force field or the PM7 quantum-chemical method with or without implicit solvent models: PCM, COSMO, and SGB. Each function was tested on the same set of 16 protein-ligand complexes. For exhaustive low-energy minima search the novel MPI parallelized docking program FLM and large supercomputer resources were used. Protein-ligand binding energies calculated using low-energy minima were compared with experimental values. It was demonstrated that the docking target function on the base of the MMFF94 force field in vacuo can be used for discovery of native or near native ligand positions by finding the low-energy local minima spectrum of the target function. The importance of solute-solvent interaction for the correct ligand positioning is demonstrated. It is shown that docking accuracy can be improved by replacement of the MMFF94 force field by the new semiempirical quantum-chemical PM7 method.

  8. PSOVina: The hybrid particle swarm optimization algorithm for protein-ligand docking.

    Science.gov (United States)

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

    2015-06-01

    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 http://cbbio.cis.umac.mo .

  9. Forging the Basis for Developing Protein-Ligand Interaction Scoring Functions.

    Science.gov (United States)

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

    2017-02-21

    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

  10. 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.

  11. Protein-Ligand Empirical Interaction Components for Virtual Screening.

    Science.gov (United States)

    Yan, Yuna; Wang, Weijun; Sun, Zhaoxi; Zhang, John Z H; Ji, Changge

    2017-08-28

    A major shortcoming of empirical scoring functions is that they often fail to predict binding affinity properly. Removing false positives of docking results is one of the most challenging works in structure-based virtual screening. Postdocking filters, making use of all kinds of experimental structure and activity information, may help in solving the issue. We describe a new method based on detailed protein-ligand interaction decomposition and machine learning. Protein-ligand empirical interaction components (PLEIC) are used as descriptors for support vector machine learning to develop a classification model (PLEIC-SVM) to discriminate false positives from true positives. Experimentally derived activity information is used for model training. An extensive benchmark study on 36 diverse data sets from the DUD-E database has been performed to evaluate the performance of the new method. The results show that the new method performs much better than standard empirical scoring functions in structure-based virtual screening. The trained PLEIC-SVM model is able to capture important interaction patterns between ligand and protein residues for one specific target, which is helpful in discarding false positives in postdocking filtering.

  12. Cloud computing for protein-ligand binding site comparison.

    Science.gov (United States)

    Hung, Che-Lun; Hua, Guan-Jie

    2013-01-01

    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.

  13. Recent Progress in Treating Protein-Ligand Interactions with Quantum-Mechanical Methods.

    Science.gov (United States)

    Yilmazer, Nusret Duygu; Korth, Martin

    2016-05-16

    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.

  14. Accuracy and precision of protein-ligand interaction kinetics determined from chemical shift titrations

    Energy Technology Data Exchange (ETDEWEB)

    Markin, Craig J.; Spyracopoulos, Leo, E-mail: leo.spyracopoulos@ualberta.ca [University of Alberta, Department of Biochemistry (Canada)

    2012-12-15

    NMR-monitored chemical shift titrations for the study of weak protein-ligand interactions represent a rich source of information regarding thermodynamic parameters such as dissociation constants (K{sub D}) in the micro- to millimolar range, populations for the free and ligand-bound states, and the kinetics of interconversion between states, which are typically within the fast exchange regime on the NMR timescale. We recently developed two chemical shift titration methods wherein co-variation of the total protein and ligand concentrations gives increased precision for the K{sub D} value of a 1:1 protein-ligand interaction (Markin and Spyracopoulos in J Biomol NMR 53: 125-138, 2012). In this study, we demonstrate that classical line shape analysis applied to a single set of {sup 1}H-{sup 15}N 2D HSQC NMR spectra acquired using precise protein-ligand chemical shift titration methods we developed, produces accurate and precise kinetic parameters such as the off-rate (k{sub off}). For experimentally determined kinetics in the fast exchange regime on the NMR timescale, k{sub off} {approx} 3,000 s{sup -1} in this work, the accuracy of classical line shape analysis was determined to be better than 5 % by conducting quantum mechanical NMR simulations of the chemical shift titration methods with the magnetic resonance toolkit GAMMA. Using Monte Carlo simulations, the experimental precision for k{sub off} from line shape analysis of NMR spectra was determined to be 13 %, in agreement with the theoretical precision of 12 % from line shape analysis of the GAMMA simulations in the presence of noise and protein concentration errors. In addition, GAMMA simulations were employed to demonstrate that line shape analysis has the potential to provide reasonably accurate and precise k{sub off} values over a wide range, from 100 to 15,000 s{sup -1}. The validity of line shape analysis for k{sub off} values approaching intermediate exchange ({approx}100 s{sup -1}), may be facilitated by

  15. Accuracy and precision of protein-ligand interaction kinetics determined from chemical shift titrations.

    Science.gov (United States)

    Markin, Craig J; Spyracopoulos, Leo

    2012-12-01

    NMR-monitored chemical shift titrations for the study of weak protein-ligand interactions represent a rich source of information regarding thermodynamic parameters such as dissociation constants (K ( D )) in the micro- to millimolar range, populations for the free and ligand-bound states, and the kinetics of interconversion between states, which are typically within the fast exchange regime on the NMR timescale. We recently developed two chemical shift titration methods wherein co-variation of the total protein and ligand concentrations gives increased precision for the K ( D ) value of a 1:1 protein-ligand interaction (Markin and Spyracopoulos in J Biomol NMR 53: 125-138, 2012). In this study, we demonstrate that classical line shape analysis applied to a single set of (1)H-(15)N 2D HSQC NMR spectra acquired using precise protein-ligand chemical shift titration methods we developed, produces accurate and precise kinetic parameters such as the off-rate (k ( off )). For experimentally determined kinetics in the fast exchange regime on the NMR timescale, k ( off ) ~ 3,000 s(-1) in this work, the accuracy of classical line shape analysis was determined to be better than 5 % by conducting quantum mechanical NMR simulations of the chemical shift titration methods with the magnetic resonance toolkit GAMMA. Using Monte Carlo simulations, the experimental precision for k ( off ) from line shape analysis of NMR spectra was determined to be 13 %, in agreement with the theoretical precision of 12 % from line shape analysis of the GAMMA simulations in the presence of noise and protein concentration errors. In addition, GAMMA simulations were employed to demonstrate that line shape analysis has the potential to provide reasonably accurate and precise k ( off ) values over a wide range, from 100 to 15,000 s(-1). The validity of line shape analysis for k ( off ) values approaching intermediate exchange (~100 s(-1)), may be facilitated by more accurate K ( D ) measurements

  16. Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

    Science.gov (United States)

    Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

    2014-09-01

    The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effect of urea on protein-ligand association.

    Science.gov (United States)

    Stepanian, Lora; Son, Ikbae; Chalikian, Tigran V

    2017-12-01

    We combine experimental and theoretical approaches to investigate the influence of a cosolvent on a ligand-protein association event. We apply fluorescence measurements to determining the affinity of the inhibitor tri-N-acetylglucosamine [(GlcNAc) 3 ] for lysozyme at urea concentrations ranging from 0 to 8M. Notwithstanding that, at room temperature and neutral pH, lysozyme retains its native conformation up to the solubility limit of urea, the affinity of (GlcNAc) 3 for the protein steadily decreases as the concentration of urea increases. We analyze the urea dependence of the binding free energy within the framework of a simplified statistical thermodynamics-based model that accounts for the excluded volume effect and direct solute-solvent interactions. The analysis reveals that the detrimental action of urea on the inhibitor-lysozyme binding originates from competition between the free energy contributions of the excluded volume effect and direct solute-solvent interactions. The free energy contribution of direct urea-solute interactions narrowly overcomes the excluded volume contribution thereby resulting in urea weakening the protein-ligand association. More broadly, the successful application of the simple model employed in this work points to the possibility of its use in quantifying the stabilizing/destabilizing action of individual cosolvents on biochemical folding and binding reactions. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition.

    Science.gov (United States)

    Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; De Biasi, Federico; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

    2017-07-13

    The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the monolayer itself and with the solvent. We further describe how the nature and plasticity of these interactions modulate nanoparticle-based chemosensing. Importantly, we found that self-organization of coating thiols can induce the formation of binding pockets in AuNPs. These transient cavities can accommodate small molecules, mimicking protein-ligand recognition, which could explain the selectivity and sensitivity observed for different organic analytes in NMR chemosensing experiments. Thus, our findings advocate for the rational design of tailored coating groups to form specific recognition binding sites on monolayer-protected AuNPs.

  19. Enhance the performance of current scoring functions with the aid of 3D protein-ligand interaction fingerprints.

    Science.gov (United States)

    Liu, Jie; Su, Minyi; Liu, Zhihai; Li, Jie; Li, Yan; Wang, Renxiao

    2017-07-18

    In structure-based drug design, binding affinity prediction remains as a challenging goal for current scoring functions. Development of target-biased scoring functions provides a new possibility for tackling this problem, but this approach is also associated with certain technical difficulties. We previously reported the Knowledge-Guided Scoring (KGS) method as an alternative approach (BMC Bioinformatics, 2010, 11, 193-208). The key idea is to compute the binding affinity of a given protein-ligand complex based on the known binding data of an appropriate reference complex, so the error in binding affinity prediction can be reduced effectively. In this study, we have developed an upgraded version, i.e. KGS2, by employing 3D protein-ligand interaction fingerprints in reference selection. KGS2 was evaluated in combination with four scoring functions (X-Score, ChemPLP, ASP, and GoldScore) on five drug targets (HIV-1 protease, carbonic anhydrase 2, beta-secretase 1, beta-trypsin, and checkpoint kinase 1). In the in situ scoring test, considerable improvements were observed in most cases after application of KGS2. Besides, the performance of KGS2 was always better than KGS in all cases. In the more challenging molecular docking test, application of KGS2 also led to improved structure-activity relationship in some cases. KGS2 can be applied as a convenient "add-on" to current scoring functions without the need to re-engineer them, and its application is not limited to certain target proteins as customized scoring functions. As an interpolation method, its accuracy in principle can be improved further with the increasing knowledge of protein-ligand complex structures and binding affinity data. We expect that KGS2 will become a practical tool for enhancing the performance of current scoring functions in binding affinity prediction. The KGS2 software is available upon contacting the authors.

  20. Empirical scoring functions for advanced protein-ligand docking with PLANTS.

    Science.gov (United States)

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

    2009-01-01

    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.

  1. Recent improvements to Binding MOAD: a resource for protein-ligand binding affinities and structures.

    Science.gov (United States)

    Ahmed, Aqeel; Smith, Richard D; Clark, Jordan J; Dunbar, James B; Carlson, Heather A

    2015-01-01

    For over 10 years, Binding MOAD (Mother of All Databases; http://www.BindingMOAD.org) has been one of the largest resources for high-quality protein-ligand complexes and associated binding affinity data. Binding MOAD has grown at the rate of 1994 complexes per year, on average. Currently, it contains 23,269 complexes and 8156 binding affinities. Our annual updates curate the data using a semi-automated literature search of the references cited within the PDB file, and we have recently upgraded our website and added new features and functionalities to better serve Binding MOAD users. In order to eliminate the legacy application server of the old platform and to accommodate new changes, the website has been completely rewritten in the LAMP (Linux, Apache, MySQL and PHP) environment. The improved user interface incorporates current third-party plugins for better visualization of protein and ligand molecules, and it provides features like sorting, filtering and filtered downloads. In addition to the field-based searching, Binding MOAD now can be searched by structural queries based on the ligand. In order to remove redundancy, Binding MOAD records are clustered in different families based on 90% sequence identity. The new Binding MOAD, with the upgraded platform, features and functionalities, is now equipped to better serve its users. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Identification of individual protein-ligand NOEs in the limit of intermediate exchange

    International Nuclear Information System (INIS)

    Reibarkh, Mikhail; Malia, Thomas J.; Hopkins, Brian T.; Wagner, Gerhard

    2006-01-01

    Interactions of proteins with small molecules or other macromolecules play key roles in many biological processes and in drug action, and NMR is an excellent tool for their structural characterization. Frequently, however, line broadening due to intermediate exchange completely eliminates the signals needed for measuring specific intermolecular NOEs. This limits the use of NMR for detailed structural studies in such kinetic situations. Here we show that an optimally chosen excess of ligand over protein can reduce the extent of line broadening for both the ligand and the protein. This makes observation of ligand resonances possible but reduces the size of the measurable NOEs due to the residual line broadening and the non-stoichiometric concentrations. Because the solubility of small molecule drug leads are often limited to high micromolar concentrations, protein concentrations are restricted to even lower values in the low micromolar range. At these non-stoichiometric concentrations and in the presence of significant residual line broadening, conventional NOESY experiments very often are not sensitive enough to observe intermolecular NOEs since the signals inverted by the NOESY preparation pulse sequence relax prior to significant NOE build up. Thus, we employ methods related to driven NOE spectroscopy to investigate protein-ligand interactions in the intermediate exchange regime. In this approach, individual protein resonances are selectively irradiated for up to five seconds to build up measurable NOEs at the ligand resonances. To enable saturation of individual protein resonances we prepare deuterated protein samples selectively protonated at a few sites so that the 1D 1 H spectrum of the protein is resolved well enough to permit irradiation of individual protein signals, which do not overlap with the ligand spectrum. This approach is suitable for measuring a sufficiently large number of protein-ligand NOEs that allow calculation of initial complex structures

  3. Simple knowledge-based descriptors to predict protein-ligand interactions. Methodology and validation

    Science.gov (United States)

    Nissink, J. Willem M.; Verdonk, Marcel L.; Klebe, Gerhard

    2000-11-01

    A new type of shape descriptor is proposed to describe the spatial orientation for non-covalent interactions. It is built from simple, anisotropic Gaussian contributions that are parameterised by 10 adjustable values. The descriptors have been used to fit propensity distributions derived from scatter data stored in the IsoStar database. This database holds composite pictures of possible interaction geometries between a common central group and various interacting moieties, as extracted from small-molecule crystal structures. These distributions can be related to probabilities for the occurrence of certain interaction geometries among different functional groups. A fitting procedure is described that generates the descriptors in a fully automated way. For this purpose, we apply a similarity index that is tailored to the problem, the Split Hodgkin Index. It accounts for the similarity in regions of either high or low propensity in a separate way. Although dependent on the division into these two subregions, the index is robust and performs better than the regular Hodgkin index. The reliability and coverage of the fitted descriptors was assessed using SuperStar. SuperStar usually operates on the raw IsoStar data to calculate propensity distributions, e.g., for a binding site in a protein. For our purpose we modified the code to have it operate on our descriptors instead. This resulted in a substantial reduction in calculation time (factor of five to eight) compared to the original implementation. A validation procedure was performed on a set of 130 protein-ligand complexes, using four representative interacting probes to map the properties of the various binding sites: ammonium nitrogen, alcohol oxygen, carbonyl oxygen, and methyl carbon. The predicted `hot spots' for the binding of these probes were compared to the actual arrangement of ligand atoms in experimentally determined protein-ligand complexes. Results indicate that the version of SuperStar that applies to

  4. istar: a web platform for large-scale protein-ligand docking.

    Directory of Open Access Journals (Sweden)

    Hongjian Li

    Full Text Available Protein-ligand docking is a key computational method in the design of starting points for the drug discovery process. We are motivated by the desire to automate large-scale docking using our popular docking engine idock and thus have developed a publicly-accessible web platform called istar. Without tedious software installation, users can submit jobs using our website. Our istar website supports 1 filtering ligands by desired molecular properties and previewing the number of ligands to dock, 2 monitoring job progress in real time, and 3 visualizing ligand conformations and outputting free energy and ligand efficiency predicted by idock, binding affinity predicted by RF-Score, putative hydrogen bonds, and supplier information for easy purchase, three useful features commonly lacked on other online docking platforms like DOCK Blaster or iScreen. We have collected 17,224,424 ligands from the All Clean subset of the ZINC database, and revamped our docking engine idock to version 2.0, further improving docking speed and accuracy, and integrating RF-Score as an alternative rescoring function. To compare idock 2.0 with the state-of-the-art AutoDock Vina 1.1.2, we have carried out a rescoring benchmark and a redocking benchmark on the 2,897 and 343 protein-ligand complexes of PDBbind v2012 refined set and CSAR NRC HiQ Set 24Sept2010 respectively, and an execution time benchmark on 12 diverse proteins and 3,000 ligands of different molecular weight. Results show that, under various scenarios, idock achieves comparable success rates while outperforming AutoDock Vina in terms of docking speed by at least 8.69 times and at most 37.51 times. When evaluated on the PDBbind v2012 core set, our istar platform combining with RF-Score manages to reproduce Pearson's correlation coefficient and Spearman's correlation coefficient of as high as 0.855 and 0.859 respectively between the experimental binding affinity and the predicted binding affinity of the docked

  5. istar: a web platform for large-scale protein-ligand docking.

    Science.gov (United States)

    Li, Hongjian; Leung, Kwong-Sak; Ballester, Pedro J; Wong, Man-Hon

    2014-01-01

    Protein-ligand docking is a key computational method in the design of starting points for the drug discovery process. We are motivated by the desire to automate large-scale docking using our popular docking engine idock and thus have developed a publicly-accessible web platform called istar. Without tedious software installation, users can submit jobs using our website. Our istar website supports 1) filtering ligands by desired molecular properties and previewing the number of ligands to dock, 2) monitoring job progress in real time, and 3) visualizing ligand conformations and outputting free energy and ligand efficiency predicted by idock, binding affinity predicted by RF-Score, putative hydrogen bonds, and supplier information for easy purchase, three useful features commonly lacked on other online docking platforms like DOCK Blaster or iScreen. We have collected 17,224,424 ligands from the All Clean subset of the ZINC database, and revamped our docking engine idock to version 2.0, further improving docking speed and accuracy, and integrating RF-Score as an alternative rescoring function. To compare idock 2.0 with the state-of-the-art AutoDock Vina 1.1.2, we have carried out a rescoring benchmark and a redocking benchmark on the 2,897 and 343 protein-ligand complexes of PDBbind v2012 refined set and CSAR NRC HiQ Set 24Sept2010 respectively, and an execution time benchmark on 12 diverse proteins and 3,000 ligands of different molecular weight. Results show that, under various scenarios, idock achieves comparable success rates while outperforming AutoDock Vina in terms of docking speed by at least 8.69 times and at most 37.51 times. When evaluated on the PDBbind v2012 core set, our istar platform combining with RF-Score manages to reproduce Pearson's correlation coefficient and Spearman's correlation coefficient of as high as 0.855 and 0.859 respectively between the experimental binding affinity and the predicted binding affinity of the docked conformation. istar

  6. LiGRO: a graphical user interface for protein-ligand molecular dynamics.

    Science.gov (United States)

    Kagami, Luciano Porto; das Neves, Gustavo Machado; da Silva, Alan Wilter Sousa; Caceres, Rafael Andrade; Kawano, Daniel Fábio; Eifler-Lima, Vera Lucia

    2017-10-04

    To speed up the drug-discovery process, molecular dynamics (MD) calculations performed in GROMACS can be coupled to docking simulations for the post-screening analyses of large compound libraries. This requires generating the topology of the ligands in different software, some basic knowledge of Linux command lines, and a certain familiarity in handling the output files. LiGRO-the python-based graphical interface introduced here-was designed to overcome these protein-ligand parameterization challenges by allowing the graphical (non command line-based) control of GROMACS (MD and analysis), ACPYPE (ligand topology builder) and PLIP (protein-binder interactions monitor)-programs that can be used together to fully perform and analyze the outputs of complex MD simulations (including energy minimization and NVT/NPT equilibration). By allowing the calculation of linear interaction energies in a simple and quick fashion, LiGRO can be used in the drug-discovery pipeline to select compounds with a better protein-binding interaction profile. The design of LiGRO allows researchers to freely download and modify the software, with the source code being available under the terms of a GPLv3 license from http://www.ufrgs.br/lasomfarmacia/ligro/ .

  7. PLASS: Protein-ligand affinity statistical score a knowledge-based force-field model of interaction derived from the PDB

    Science.gov (United States)

    Ozrin, V. D.; Subbotin, M. V.; Nikitin, S. M.

    2004-04-01

    We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken from the Protein Data Bank (PDB). Statistical distributions are converted into distance-dependent contributions to the Gibbs free interaction energy for 10 atomic types using the Boltzmann hypothesis, with only one adjustable parameter. For a representative set of 72 protein-ligand structures, PLASS scores correlate well with the experimentally measured dissociation constants: a correlation coefficient R of 0.82 and RMS error of 2.0 kcal/mol. Such high accuracy results from our novel treatment of the volume correction term, which takes into account the inhomogeneous properties of the protein-ligand complexes. PLASS is able to rank reliably the affinity of complexes which have as much diversity as in the PDB.

  8. Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.

    Science.gov (United States)

    Katkova, E V; Onufriev, A V; Aguilar, B; Sulimov, V B

    2017-03-01

    In this study several commonly used implicit solvent models are compared with respect to their accuracy of estimating solvation energies of small molecules and proteins, as well as desolvation penalty in protein-ligand binding. The test set consists of 19 small proteins, 104 small molecules, and 15 protein-ligand complexes. We compared predicted hydration energies of small molecules with their experimental values; the results of the solvation and desolvation energy calculations for small molecules, proteins and protein-ligand complexes in water were also compared with Thermodynamic Integration calculations based on TIP3P water model and Amber12 force field. The following implicit solvent (water) models considered here are: PCM (Polarized Continuum Model implemented in DISOLV and MCBHSOLV programs), GB (Generalized Born method implemented in DISOLV program, S-GB, and GBNSR6 stand-alone version), COSMO (COnductor-like Screening Model implemented in the DISOLV program and the MOPAC package) and the Poisson-Boltzmann model (implemented in the APBS program). Different parameterizations of the molecules were examined: we compared MMFF94 force field, Amber12 force field and the quantum-chemical semi-empirical PM7 method implemented in the MOPAC package. For small molecules, all of the implicit solvent models tested here yield high correlation coefficients (0.87-0.93) between the calculated solvation energies and the experimental values of hydration energies. For small molecules high correlation (0.82-0.97) with the explicit solvent energies is seen as well. On the other hand, estimated protein solvation energies and protein-ligand binding desolvation energies show substantial discrepancy (up to 10kcal/mol) with the explicit solvent reference. The correlation of polar protein solvation energies and protein-ligand desolvation energies with the corresponding explicit solvent results is 0.65-0.99 and 0.76-0.96 respectively, though this difference in correlations is caused

  9. Complex single gene disorders and epilepsy.

    LENUS (Irish Health Repository)

    Merwick, Aine

    2012-09-01

    Epilepsy is a heterogeneous group of disorders, often associated with significant comorbidity, such as intellectual disability and skin disorder. The genetic underpinnings of many epilepsies are still being elucidated, and we expect further advances over the coming 5 years, as genetic technology improves and prices fall for whole exome and whole genome sequencing. At present, there are several well-characterized complex epilepsies associated with single gene disorders; we review some of these here. They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene. These disorders are important in informing genetic testing to confirm a diagnosis and to permit better understanding of the variability in phenotype-genotype correlation.

  10. Quantitative chemogenomics: machine-learning models of protein-ligand interaction.

    Science.gov (United States)

    Andersson, Claes R; Gustafsson, Mats G; Strömbergsson, Helena

    2011-01-01

    Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed. © 2011 Bentham Science Publishers

  11. Structural analysis of protein-ligand interactions: the binding of endogenous compounds and of synthetic drugs.

    Science.gov (United States)

    Gallina, Anna M; Bork, Peer; Bordo, Domenico

    2014-02-01

    The large number of macromolecular structures deposited with the Protein Data Bank (PDB) describing complexes between proteins and either physiological compounds or synthetic drugs made it possible a systematic analysis of the interactions occurring between proteins and their ligands. In this work, the binding pockets of about 4000 PDB protein-ligand complexes were investigated and amino acid and interaction types were analyzed. The residues observed with lowest frequency in protein sequences, Trp, His, Met, Tyr, and Phe, turned out to be the most abundant in binding pockets. Significant differences between drug-like and physiological compounds were found. On average, physiological compounds establish with respect to drugs about twice as many hydrogen bonds with protein atoms, whereas drugs rely more on hydrophobic interactions to establish target selectivity. The large number of PDB structures describing homologous proteins in complex with the same ligand made it possible to analyze the conservation of binding pocket residues among homologous protein structures bound to the same ligand, showing that Gly, Glu, Arg, Asp, His, and Thr are more conserved than other amino acids. Also in the cases in which the same ligand is bound to unrelated proteins, the binding pockets showed significant conservation in the residue types. In this case, the probability of co-occurrence of the same amino acid type in the binding pockets could be up to thirteen times higher than that expected on a random basis. The trends identified in this study may provide an useful guideline in the process of drug design and lead optimization. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Exact and Effective Pair-Wise Potential for Protein-Ligand Interactions Obtained from a Semiempirical Energy Partition

    Directory of Open Access Journals (Sweden)

    André Melo

    2008-09-01

    Full Text Available In this work, the partition method introduced by Carvalho and Melo was used to study the complex between Cucurbita maxima trypsin inhibitor (CMTI-I and glycerol at the AM1 level. An effective potential, combining non-bonding and polarization plus charge transfer (PLCT terms, was introduced to evaluate the magnitude of the interaction between each amino acid and the ligand. In this case study, the nonbonding–PLCT noncompensation characterizes the stabilization energy of the association process in study. The main residues (Gly29, Cys3 and Arg5 with net attractive effects and Arg1 (with a net repulsive effect, responsible by the stability of protein-ligand complex, are associated with large nonbonding energies non-compensated by PLCT effects. The results obtained enable us to conclude that the present decomposition scheme can be used for understanding the cohesive phenomena in proteins.

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

    KAUST Repository

    Chen, Peng

    2015-12-03

    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

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

    KAUST Repository

    Chen, Peng; Hu, ShanShan; Zhang, Jun; Gao, Xin; Li, Jinyan; Xia, Junfeng; Wang, Bing

    2015-01-01

    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

  15. Discovering protein-ligand chalcogen bonding in the protein data bank using endocyclic sulfur-containing heterocycles as ligand search subsets.

    Science.gov (United States)

    Mitchell, Miguel O

    2017-09-24

    The chalcogen bond, the noncovalent, electrostatic attraction between covalently bonded atoms in group 16 and Lewis bases, is present in protein-ligand interactions based on X-ray structures deposited in the Protein Data Bank (PDB). Discovering protein-ligand chalcogen bonding in the PDB employed a strategy that focused on searching the database for protein complexes of five-membered, heterocyclic ligands containing endocyclic sulfur with endo electron-withdrawing groups (isothiazoles; thiazoles; 1,2,3-, 1,2.4-, 1,2,5-, 1,3,4-thiadiazoles) and thiophenes with exo electron-withdrawing groups, e.g., 2-chloro, 2-bromo, 2-amino, 2-alkylthio. Out of 930 ligands investigated, 33 or 3.5% have protein-ligand S---O interactions of which 31 are chalcogen bonds and two appear to be S---HO hydrogen bonds. The bond angles for some of the chalcogen bonds found in the PDB are less than 90°, and an electrostatic model is proposed to explain this phenomenon.

  16. 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.

  17. Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies.

    Science.gov (United States)

    Bryce, Richard A

    2011-04-01

    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.

  18. Computational multiscale modeling in protein--ligand docking.

    Science.gov (United States)

    Taufer, Michela; Armen, Roger; Chen, Jianhan; Teller, Patricia; Brooks, Charles

    2009-01-01

    In biological systems, the binding of small molecule ligands to proteins is a crucial process for almost every aspect of biochemistry and molecular biology. Enzymes are proteins that function by catalyzing specific biochemical reactions that convert reactants into products. Complex organisms are typically composed of cells in which thousands of enzymes participate in complex and interconnected biochemical pathways. Some enzymes serve as sequential steps in specific pathways (such as energy metabolism), while others function to regulate entire pathways and cellular functions [1]. Small molecule ligands can be designed to bind to a specific enzyme and inhibit the biochemical reaction. Inhibiting the activity of key enzymes may result in the entire biochemical pathways being turned on or off [2], [3]. Many small molecule drugs marketed today function in this generic way as enzyme inhibitors. If research identifies a specific enzyme as being crucial to the progress of disease, then this enzyme may be targeted with an inhibitor, which may slow down or reverse the progress of disease. In this way, enzymes are targeted from specific pathogens (e.g., virus, bacteria, fungi) for infectious diseases [4], [5], and human enzymes are targeted for noninfectious diseases such as cardiovascular disease, cancer, diabetes, and neurodegenerative diseases [6].

  19. Post hoc support vector machine learning for impedimetric biosensors based on weak protein-ligand interactions.

    Science.gov (United States)

    Rong, Y; Padron, A V; Hagerty, K J; Nelson, N; Chi, S; Keyhani, N O; Katz, J; Datta, S P A; Gomes, C; McLamore, E S

    2018-04-30

    Impedimetric biosensors for measuring small molecules based on weak/transient interactions between bioreceptors and target analytes are a challenge for detection electronics, particularly in field studies or in the analysis of complex matrices. Protein-ligand binding sensors have enormous potential for biosensing, but achieving accuracy in complex solutions is a major challenge. There is a need for simple post hoc analytical tools that are not computationally expensive, yet provide near real time feedback on data derived from impedance spectra. Here, we show the use of a simple, open source support vector machine learning algorithm for analyzing impedimetric data in lieu of using equivalent circuit analysis. We demonstrate two different protein-based biosensors to show that the tool can be used for various applications. We conclude with a mobile phone-based demonstration focused on the measurement of acetone, an important biomarker related to the onset of diabetic ketoacidosis. In all conditions tested, the open source classifier was capable of performing as well as, or better, than the equivalent circuit analysis for characterizing weak/transient interactions between a model ligand (acetone) and a small chemosensory protein derived from the tsetse fly. In addition, the tool has a low computational requirement, facilitating use for mobile acquisition systems such as mobile phones. The protocol is deployed through Jupyter notebook (an open source computing environment available for mobile phone, tablet or computer use) and the code was written in Python. For each of the applications, we provide step-by-step instructions in English, Spanish, Mandarin and Portuguese to facilitate widespread use. All codes were based on scikit-learn, an open source software machine learning library in the Python language, and were processed in Jupyter notebook, an open-source web application for Python. The tool can easily be integrated with the mobile biosensor equipment for rapid

  20. Computational Approaches to the Chemical Equilibrium Constant in Protein-ligand Binding.

    Science.gov (United States)

    Montalvo-Acosta, Joel José; Cecchini, Marco

    2016-12-01

    The physiological role played by protein-ligand recognition has motivated the development of several computational approaches to the ligand binding affinity. Some of them, termed rigorous, have a strong theoretical foundation but involve too much computation to be generally useful. Some others alleviate the computational burden by introducing strong approximations and/or empirical calibrations, which also limit their general use. Most importantly, there is no straightforward correlation between the predictive power and the level of approximation introduced. Here, we present a general framework for the quantitative interpretation of protein-ligand binding based on statistical mechanics. Within this framework, we re-derive self-consistently the fundamental equations of some popular approaches to the binding constant and pinpoint the inherent approximations. Our analysis represents a first step towards the development of variants with optimum accuracy/efficiency ratio for each stage of the drug discovery pipeline. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Automatic generation of bioinformatics tools for predicting protein-ligand binding sites.

    Science.gov (United States)

    Komiyama, Yusuke; Banno, Masaki; Ueki, Kokoro; Saad, Gul; Shimizu, Kentaro

    2016-03-15

    Predictive tools that model protein-ligand binding on demand are needed to promote ligand research in an innovative drug-design environment. However, it takes considerable time and effort to develop predictive tools that can be applied to individual ligands. An automated production pipeline that can rapidly and efficiently develop user-friendly protein-ligand binding predictive tools would be useful. We developed a system for automatically generating protein-ligand binding predictions. Implementation of this system in a pipeline of Semantic Web technique-based web tools will allow users to specify a ligand and receive the tool within 0.5-1 day. We demonstrated high prediction accuracy for three machine learning algorithms and eight ligands. The source code and web application are freely available for download at http://utprot.net They are implemented in Python and supported on Linux. shimizu@bi.a.u-tokyo.ac.jp Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  2. GalaxyDock BP2 score: a hybrid scoring function for accurate protein-ligand docking

    Science.gov (United States)

    Baek, Minkyung; Shin, Woong-Hee; Chung, Hwan Won; Seok, Chaok

    2017-07-01

    Protein-ligand docking is a useful tool for providing atomic-level understanding of protein functions in nature and design principles for artificial ligands or proteins with desired properties. The ability to identify the true binding pose of a ligand to a target protein among numerous possible candidate poses is an essential requirement for successful protein-ligand docking. Many previously developed docking scoring functions were trained to reproduce experimental binding affinities and were also used for scoring binding poses. However, in this study, we developed a new docking scoring function, called GalaxyDock BP2 Score, by directly training the scoring power of binding poses. This function is a hybrid of physics-based, empirical, and knowledge-based score terms that are balanced to strengthen the advantages of each component. The performance of the new scoring function exhibits significant improvement over existing scoring functions in decoy pose discrimination tests. In addition, when the score is used with the GalaxyDock2 protein-ligand docking program, it outperformed other state-of-the-art docking programs in docking tests on the Astex diverse set, the Cross2009 benchmark set, and the Astex non-native set. GalaxyDock BP2 Score and GalaxyDock2 with this score are freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.

  3. Interaction Entropy: A New Paradigm for Highly Efficient and Reliable Computation of Protein-Ligand Binding Free Energy.

    Science.gov (United States)

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

    2016-05-04

    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.

  4. Increased precision for analysis of protein-ligand dissociation constants determined from chemical shift titrations

    Energy Technology Data Exchange (ETDEWEB)

    Markin, Craig J.; Spyracopoulos, Leo, E-mail: leo.spyracopoulos@ualberta.ca [University of Alberta, Department of Biochemistry (Canada)

    2012-06-15

    NMR is ideally suited for the analysis of protein-protein and protein ligand interactions with dissociation constants ranging from {approx}2 {mu}M to {approx}1 mM, and with kinetics in the fast exchange regime on the NMR timescale. For the determination of dissociation constants (K{sub D}) of 1:1 protein-protein or protein-ligand interactions using NMR, the protein and ligand concentrations must necessarily be similar in magnitude to the K{sub D}, and nonlinear least squares analysis of chemical shift changes as a function of ligand concentration is employed to determine estimates for the parameters K{sub D} and the maximum chemical shift change ({Delta}{delta}{sub max}). During a typical NMR titration, the initial protein concentration, [P{sub 0}], is held nearly constant. For this condition, to determine the most accurate parameters for K{sub D} and {Delta}{delta}{sub max} from nonlinear least squares analyses requires initial protein concentrations that are {approx}0.5 Multiplication-Sign K{sub D}, and a maximum concentration for the ligand, or titrant, of {approx}10 Multiplication-Sign [P{sub 0}]. From a practical standpoint, these requirements are often difficult to achieve. Using Monte Carlo simulations, we demonstrate that co-variation of the ligand and protein concentrations during a titration leads to an increase in the precision of the fitted K{sub D} and {Delta}{delta}{sub max} values when [P{sub 0}] > K{sub D}. Importantly, judicious choice of protein and ligand concentrations for a given NMR titration, combined with nonlinear least squares analyses using two independent variables (ligand and protein concentrations) and two parameters (K{sub D} and {Delta}{delta}{sub max}) is a straightforward approach to increasing the accuracy of measured dissociation constants for 1:1 protein-ligand interactions.

  5. 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

    2012-07-01

    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.

  6. The XChemExplorer graphical workflow tool for routine or large-scale protein-ligand structure determination.

    Science.gov (United States)

    Krojer, Tobias; Talon, Romain; Pearce, Nicholas; Collins, Patrick; Douangamath, Alice; Brandao-Neto, Jose; Dias, Alexandre; Marsden, Brian; von Delft, Frank

    2017-03-01

    XChemExplorer (XCE) is a data-management and workflow tool to support large-scale simultaneous analysis of protein-ligand complexes during structure-based ligand discovery (SBLD). The user interfaces of established crystallographic software packages such as CCP4 [Winn et al. (2011), Acta Cryst. D67, 235-242] or PHENIX [Adams et al. (2010), Acta Cryst. D66, 213-221] have entrenched the paradigm that a `project' is concerned with solving one structure. This does not hold for SBLD, where many almost identical structures need to be solved and analysed quickly in one batch of work. Functionality to track progress and annotate structures is essential. XCE provides an intuitive graphical user interface which guides the user from data processing, initial map calculation, ligand identification and refinement up until data dissemination. It provides multiple entry points depending on the need of each project, enables batch processing of multiple data sets and records metadata, progress and annotations in an SQLite database. XCE is freely available and works on any Linux and Mac OS X system, and the only dependency is to have the latest version of CCP4 installed. The design and usage of this tool are described here, and its usefulness is demonstrated in the context of fragment-screening campaigns at the Diamond Light Source. It is routinely used to analyse projects comprising 1000 data sets or more, and therefore scales well to even very large ligand-design projects.

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

    Science.gov (United States)

    A Santos, Jose C; Nassif, Houssam; Page, David; Muggleton, Stephen H; E Sternberg, Michael J

    2012-07-11

    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. 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. 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.

  8. High Throughput, Label-free Screening Small Molecule Compound Libraries for Protein-Ligands using Combination of Small Molecule Microarrays and a Special Ellipsometry-based Optical Scanner.

    Science.gov (United States)

    Landry, James P; Fei, Yiyan; Zhu, X D

    2011-12-01

    Small-molecule compounds remain the major source of therapeutic and preventative drugs. Developing new drugs against a protein target often requires screening large collections of compounds with diverse structures for ligands or ligand fragments that exhibit sufficiently affinity and desirable inhibition effect on the target before further optimization and development. Since the number of small molecule compounds is large, high-throughput screening (HTS) methods are needed. Small-molecule microarrays (SMM) on a solid support in combination with a suitable binding assay form a viable HTS platform. We demonstrate that by combining an oblique-incidence reflectivity difference optical scanner with SMM we can screen 10,000 small-molecule compounds on a single glass slide for protein ligands without fluorescence labeling. Furthermore using such a label-free assay platform we can simultaneously acquire binding curves of a solution-phase protein to over 10,000 immobilized compounds, thus enabling full characterization of protein-ligand interactions over a wide range of affinity constants.

  9. Single molecule magnet behaviour in robust dysprosium-biradical complexes.

    Science.gov (United States)

    Bernot, Kevin; Pointillart, Fabrice; Rosa, Patrick; Etienne, Mael; Sessoli, Roberta; Gatteschi, Dante

    2010-09-21

    A Dy-biradical complex was synthesized and characterized down to very low temperature. ac magnetic measurements reveal single molecule magnet behaviour visible without any application of dc field. The transition to the quantum tunneling regime is evidenced. Photophysical and EPR measurements provide evidence of the excellent stability of these complexes in solution.

  10. Ligand Conformational and Solvation/Desolvation Free Energy in Protein-Ligand Complex Formation

    Czech Academy of Sciences Publication Activity Database

    Kolář, Michal; Fanfrlík, Jindřich; Hobza, Pavel

    2011-01-01

    Roč. 115, č. 16 (2011), s. 4718-4724 ISSN 1520-6106 R&D Projects: GA MŠk LC512; GA ČR GAP208/11/0295 Grant - others:Korea Science and Engineering Foundation(KR) R32-2008-000-10180-0; European Science Fund(XE) CZ.1.05/2.1.00/03.0058 Institutional research plan: CEZ:AV0Z40550506 Keywords : solvation free energy * SMD * HIV protease inhibitors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.696, year: 2011

  11. Generation of pharmacophores and classification of drugs using protein-ligand complexes

    Directory of Open Access Journals (Sweden)

    Eliana Velasquez

    2014-04-01

    Full Text Available Pharmacophore identification is a veryimportant step in de novo design, leadoptimization, chemogenomics, and virtualscreening of drugs. Unfortunately,the high cost of comercial software forpharmacophore detection is a commonlimiting factor for researchers with limitedfunding. This paper presents a set offreely available perl routines that weredesigned to help in the process of 3Dpharmacophore identification and QSARstudies. These routines also allowed theclassification of ligands based on theirtridimensional similarity and bindingmechanism. The family of phosphodiesterasesand their inhibitors were used astest model.

  12. Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations.

    Science.gov (United States)

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

    2013-10-28

    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

  13. A method for fast energy estimation and visualization of protein-ligand interaction

    Science.gov (United States)

    Tomioka, Nobuo; Itai, Akiko; Iitaka, Yoichi

    1987-10-01

    A new computational and graphical method for facilitating ligand-protein docking studies is developed on a three-dimensional computer graphics display. Various physical and chemical properties inside the ligand binding pocket of a receptor protein, whose structure is elucidated by X-ray crystal analysis, are calculated on three-dimensional grid points and are stored in advance. By utilizing those tabulated data, it is possible to estimate the non-bonded and electrostatic interaction energy and the number of possible hydrogen bonds between protein and ligand molecules in real time during an interactive docking operation. The method also provides a comprehensive visualization of the local environment inside the binding pocket. With this method, it becomes easier to find a roughly stable geometry of ligand molecules, and one can therefore make a rapid survey of the binding capability of many drug candidates. The method will be useful for drug design as well as for the examination of protein-ligand interactions.

  14. Protein-ligand interactions investigated by thermal shift assays (TSA) and dual polarization interferometry (DPI).

    Science.gov (United States)

    Grøftehauge, Morten K; Hajizadeh, Nelly R; Swann, Marcus J; Pohl, Ehmke

    2015-01-01

    Over the last decades, a wide range of biophysical techniques investigating protein-ligand interactions have become indispensable tools to complement high-resolution crystal structure determinations. Current approaches in solution range from high-throughput-capable methods such as thermal shift assays (TSA) to highly accurate techniques including microscale thermophoresis (MST) and isothermal titration calorimetry (ITC) that can provide a full thermodynamic description of binding events. Surface-based methods such as surface plasmon resonance (SPR) and dual polarization interferometry (DPI) allow real-time measurements and can provide kinetic parameters as well as binding constants. DPI provides additional spatial information about the binding event. Here, an account is presented of new developments and recent applications of TSA and DPI connected to crystallography.

  15. A web server for analysis, comparison and prediction of protein ligand binding sites.

    Science.gov (United States)

    Singh, Harinder; Srivastava, Hemant Kumar; Raghava, Gajendra P S

    2016-03-25

    One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands. In order to address this problem, we developed a web server named 'LPIcom' to facilitate users in understanding protein-ligand interaction. Analysis, comparison and prediction modules are available in the "LPIcom' server to predict protein-ligand interacting residues for 824 ligands. Each ligand must have at least 30 protein binding sites in PDB. Analysis module of the server can identify residues preferred in interaction and binding motif for a given ligand; for example residues glycine, lysine and arginine are preferred in ATP binding sites. Comparison module of the server allows comparing protein-binding sites of multiple ligands to understand the similarity between ligands based on their binding site. This module indicates that ATP, ADP and GTP ligands are in the same cluster and thus their binding sites or interacting residues exhibit a high level of similarity. Propensity-based prediction module has been developed for predicting ligand-interacting residues in a protein for more than 800 ligands. In addition, a number of web-based tools have been integrated to facilitate users in creating web logo and two-sample between ligand interacting and non-interacting residues. In summary, this manuscript presents a web-server for analysis of ligand interacting residue. This server is available for public use from URL http://crdd.osdd.net/raghava/lpicom .

  16. Fluorescence spectroscopy of conformational changes of single LH2 complexes

    NARCIS (Netherlands)

    Rutkauskas, D.; Novoderezhkin, V.; Cogdell, R.J.; van Grondelle, R.

    2005-01-01

    We have investigated the energy landscape of the bacterial photosynthetic peripheral light-harvesting complex LH2 of purple bacterium Rhodopseudomonas acidophila by monitoring sequences of fluorescence spectra of single LH2 assemblies, at room temperature, with different excitation intensities as

  17. White OLED with a single-component europium complex.

    Science.gov (United States)

    Law, Ga-Lai; Wong, Ka-Leung; Tam, Hoi-Lam; Cheah, Kok-Wai; Wong, Wing-Tak

    2009-11-16

    A new direction for white organic light-emitting devices is shown, fabricated from a novel europium complex; this single component contains a double emission center of bluish-green and red, combined to a give a pure white emission (CIE x = 0.34 and y = 0.35).

  18. Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins

    DEFF Research Database (Denmark)

    Rognan, D; Lauemoller, S L; Holm, A

    1999-01-01

    A simple and fast free energy scoring function (Fresno) has been developed to predict the binding free energy of peptides to class I major histocompatibility (MHC) proteins. It differs from existing scoring functions mainly by the explicit treatment of ligand desolvation and of unfavorable protein...... coordinates of the MHC-bound peptide have first been determined with an accuracy of about 1-1.5 A. Furthermore, it may be easily recalibrated for any protein-ligand complex.......) and of a series of 16 peptides to H-2K(k). Predictions were more accurate for HLA-A2-binding peptides as the training set had been built from experimentally determined structures. The average error in predicting the binding free energy of the test peptides was 3.1 kJ/mol. For the homology model-derived equation...

  19. Locating binding poses in protein-ligand systems using reconnaissance metadynamics

    Science.gov (United States)

    Söderhjelm, Pär; Tribello, Gareth A.; Parrinello, Michele

    2012-01-01

    A molecular dynamics-based protocol is proposed for finding and scoring protein-ligand binding poses. This protocol uses the recently developed reconnaissance metadynamics method, which employs a self-learning algorithm to construct a bias that pushes the system away from the kinetic traps where it would otherwise remain. The exploration of phase space with this algorithm is shown to be roughly six to eight times faster than unbiased molecular dynamics and is only limited by the time taken to diffuse about the surface of the protein. We apply this method to the well-studied trypsin–benzamidine system and show that we are able to refind all the poses obtained from a reference EADock blind docking calculation. These poses can be scored based on the length of time the system remains trapped in the pose. Alternatively, one can perform dimensionality reduction on the output trajectory and obtain a map of phase space that can be used in more expensive free-energy calculations. PMID:22440749

  20. Intuitive Density Functional Theory-Based Energy Decomposition Analysis for Protein-Ligand Interactions.

    Science.gov (United States)

    Phipps, M J S; Fox, T; Tautermann, C S; Skylaris, C-K

    2017-04-11

    First-principles quantum mechanical calculations with methods such as density functional theory (DFT) allow the accurate calculation of interaction energies between molecules. These interaction energies can be dissected into chemically relevant components such as electrostatics, polarization, and charge transfer using energy decomposition analysis (EDA) approaches. Typically EDA has been used to study interactions between small molecules; however, it has great potential to be applied to large biomolecular assemblies such as protein-protein and protein-ligand interactions. We present an application of EDA calculations to the study of ligands that bind to the thrombin protein, using the ONETEP program for linear-scaling DFT calculations. Our approach goes beyond simply providing the components of the interaction energy; we are also able to provide visual representations of the changes in density that happen as a result of polarization and charge transfer, thus pinpointing the functional groups between the ligand and protein that participate in each kind of interaction. We also demonstrate with this approach that we can focus on studying parts (fragments) of ligands. The method is relatively insensitive to the protocol that is used to prepare the structures, and the results obtained are therefore robust. This is an application to a real protein drug target of a whole new capability where accurate DFT calculations can produce both energetic and visual descriptors of interactions. These descriptors can be used to provide insights for tailoring interactions, as needed for example in drug design.

  1. Single Molecule Spectroscopy on Photosynthetic Pigment-Protein Complexes

    CERN Document Server

    Jelezko, F; Schuler, S; Thews, E; Tietz, C; Wechsler, A; Wrachtrup, J

    2001-01-01

    Single molecule spectroscopy was applied to unravel the energy transfer pathway in photosynthetic pigment-protein complexes. Detailed analysis of excitation and fluorescence emission spectra has been made for peripheral plant antenna LHC II and Photosystem I from cyanobacterium Synechococcus elongatus. Optical transitions of individual pigments were resolved under nonselective excitation of antenna chlorophylls. High-resolution fluorescence spectroscopy of individual plant antenna LHC II indicates that at low temperatures, the excitation energy is localized on the red-most Chl a pool absorbing at 680 nm. More than one pigment molecule is responsible for the fluorescence emission of the LHC II trimer. The spectral lines of single Chl a molecules absorbing at 675 nm are broadened because of the Foerster energy transfer towards the red-most pigments. Low-temperature spectroscopy on single PS I trimers indicates that two subgroups of pigments, which are present in the red antenna pool, differ by the strength of t...

  2. Single photon emission computed tomography in AIDS dementia complex

    International Nuclear Information System (INIS)

    Pohl, P.; Vogl, G.; Fill, H.; Roessler, H.Z.; Zangerle, R.; Gerstenbrand, F.

    1988-01-01

    Single photon emission computed tomography (SPECT) studies were performed in AIDS dementia complex using IMP in 12 patients (and HM-PAO in four of these same patients). In all patients, SPECT revealed either multiple or focal uptake defects, the latter corresponding with focal signs or symptoms in all but one case. Computerized tomography showed a diffuse cerebral atrophy in eight of 12 patients, magnetic resonance imaging exhibited changes like atrophy and/or leukoencephalopathy in two of five cases. Our data indicate that both disturbance of cerebral amine metabolism and alteration of local perfusion share in the pathogenesis of AIDS dementia complex. SPECT is an important aid in the diagnosis of AIDS dementia complex and contributes to the understanding of the pathophysiological mechanisms of this disorder

  3. PL-PatchSurfer: a novel molecular local surface-based method for exploring protein-ligand interactions.

    Science.gov (United States)

    Hu, Bingjie; Zhu, Xiaolei; Monroe, Lyman; Bures, Mark G; Kihara, Daisuke

    2014-08-27

    Structure-based computational methods have been widely used in exploring protein-ligand interactions, including predicting the binding ligands of a given protein based on their structural complementarity. Compared to other protein and ligand representations, the advantages of a surface representation include reduced sensitivity to subtle changes in the pocket and ligand conformation and fast search speed. Here we developed a novel method named PL-PatchSurfer (Protein-Ligand PatchSurfer). PL-PatchSurfer represents the protein binding pocket and the ligand molecular surface as a combination of segmented surface patches. Each patch is characterized by its geometrical shape and the electrostatic potential, which are represented using the 3D Zernike descriptor (3DZD). We first tested PL-PatchSurfer on binding ligand prediction and found it outperformed the pocket-similarity based ligand prediction program. We then optimized the search algorithm of PL-PatchSurfer using the PDBbind dataset. Finally, we explored the utility of applying PL-PatchSurfer to a larger and more diverse dataset and showed that PL-PatchSurfer was able to provide a high early enrichment for most of the targets. To the best of our knowledge, PL-PatchSurfer is the first surface patch-based method that treats ligand complementarity at protein binding sites. We believe that using a surface patch approach to better understand protein-ligand interactions has the potential to significantly enhance the design of new ligands for a wide array of drug-targets.

  4. Single stage reconstruction of complex anterior urethral strictures

    Directory of Open Access Journals (Sweden)

    Deepak Dubey

    2001-01-01

    Full Text Available Purpose: Single stage reconstruction of long, com-plex urethral strictures is technically demanding and may require the use of more than one tissue transfer technique. We describe our experience in the manage-ment of such strictures with a variety of urethroplasty techniques. Materials and Methods: Between 1989 and 1999, 25 men (mean age 38.5 years underwent single stage re-construction of panurethral, multiple segment or focally dense strictures [mean length 11.2 cm (range 8-17 cm]. 8 patients had combined substitution urethroplasty with a circumpenile fasciocutaneous flap and a free graft of bladder/buccal mucosa or tunica vaginalis . flap. In 10 patients a single tissue transfer technique was used. 3 patients underwent an augmented roof/floor strip ure-throplasty with a penile skin flap. 4 patients with multi-ple segment strictures (separate pendulous and bulbar underwent distal onlay flap and proximal anastomotic urethroplasty. Results: The median ,follow-up was 46.5 months (range 6-88 months. The mean postoperative flow rate improved to 22.5 ml/sec. 2 patients developed fistulae requiring repair. Recurrent stricture developed in 5 (20.8% patients, of which 2 were managed with visual internal urethrotomy, 2 with anastomotic urethroplasty and 1 with a two-stage procedure. Pseudodiverticulum and post-void dribbling were seen in 6 (25% patients. Conclusions: Successful outcome of single stage re-construction of long complex strictures can be achieved with a combination of various tissue transfer methods. The urologist who has a thorough knowledge of penile skin and urethral vascular anatomy and a wide array of substitution techniques in his armamentarium can un-dertake approach to such strictures.

  5. Large scale free energy calculations for blind predictions of protein-ligand binding: the D3R Grand Challenge 2015.

    Science.gov (United States)

    Deng, Nanjie; Flynn, William F; Xia, Junchao; Vijayan, R S K; Zhang, Baofeng; He, Peng; Mentes, Ahmet; Gallicchio, Emilio; Levy, Ronald M

    2016-09-01

    We describe binding free energy calculations in the D3R Grand Challenge 2015 for blind prediction of the binding affinities of 180 ligands to Hsp90. The present D3R challenge was built around experimental datasets involving Heat shock protein (Hsp) 90, an ATP-dependent molecular chaperone which is an important anticancer drug target. The Hsp90 ATP binding site is known to be a challenging target for accurate calculations of ligand binding affinities because of the ligand-dependent conformational changes in the binding site, the presence of ordered waters and the broad chemical diversity of ligands that can bind at this site. Our primary focus here is to distinguish binders from nonbinders. Large scale absolute binding free energy calculations that cover over 3000 protein-ligand complexes were performed using the BEDAM method starting from docked structures generated by Glide docking. Although the ligand dataset in this study resembles an intermediate to late stage lead optimization project while the BEDAM method is mainly developed for early stage virtual screening of hit molecules, the BEDAM binding free energy scoring has resulted in a moderate enrichment of ligand screening against this challenging drug target. Results show that, using a statistical mechanics based free energy method like BEDAM starting from docked poses offers better enrichment than classical docking scoring functions and rescoring methods like Prime MM-GBSA for the Hsp90 data set in this blind challenge. Importantly, among the three methods tested here, only the mean value of the BEDAM binding free energy scores is able to separate the large group of binders from the small group of nonbinders with a gap of 2.4 kcal/mol. None of the three methods that we have tested provided accurate ranking of the affinities of the 147 active compounds. We discuss the possible sources of errors in the binding free energy calculations. The study suggests that BEDAM can be used strategically to discriminate

  6. PL-PatchSurfer: A Novel Molecular Local Surface-Based Method for Exploring Protein-Ligand Interactions

    Directory of Open Access Journals (Sweden)

    Bingjie Hu

    2014-08-01

    Full Text Available Structure-based computational methods have been widely used in exploring protein-ligand interactions, including predicting the binding ligands of a given protein based on their structural complementarity. Compared to other protein and ligand representations, the advantages of a surface representation include reduced sensitivity to subtle changes in the pocket and ligand conformation and fast search speed. Here we developed a novel method named PL-PatchSurfer (Protein-Ligand PatchSurfer. PL-PatchSurfer represents the protein binding pocket and the ligand molecular surface as a combination of segmented surface patches. Each patch is characterized by its geometrical shape and the electrostatic potential, which are represented using the 3D Zernike descriptor (3DZD. We first tested PL-PatchSurfer on binding ligand prediction and found it outperformed the pocket-similarity based ligand prediction program. We then optimized the search algorithm of PL-PatchSurfer using the PDBbind dataset. Finally, we explored the utility of applying PL-PatchSurfer to a larger and more diverse dataset and showed that PL-PatchSurfer was able to provide a high early enrichment for most of the targets. To the best of our knowledge, PL-PatchSurfer is the first surface patch-based method that treats ligand complementarity at protein binding sites. We believe that using a surface patch approach to better understand protein-ligand interactions has the potential to significantly enhance the design of new ligands for a wide array of drug-targets.

  7. Alignment of SWNTs by protein-ligand interaction of functionalized magnetic particles under low magnetic fields.

    Science.gov (United States)

    Park, Tae Jung; Park, Jong Pil; Lee, Seok Jae; Jung, Dae-Hwan; Ko, Young Koan; Jung, Hee-Tae; Lee, Sang Yup

    2011-05-01

    Carbon nanotubes (CNTs) have attracted considerable attention for applications using their superior mechanical, thermal and electrical properties. A simple method to controllably align single-walled CNTs (SWNTs) by using magnetic particles embedded with superparamagnetic iron oxide as an accelerator under the magnetic field was developed. The functionalization of SWNTs using biotin, interacted with streptavidin-coupled magnetic particles (micro-to-nano in diameter), and layer-by-layer assembly were performed for the alignment of a particular direction onto the clean silicon and the gold substrate at very low magnetic forces (0.02-0.89 T) at room temperature. The successful alignment of the SWNTs with multi-layer film was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By changing the orientation and location of the substrates, crossed-networks of SWNTs-magnetic particle complex could easily be fabricated. We suggest that this approach, which consists of a combination of biological interaction among streptavidin-biotin and magnetite particles, should be useful for lateral orientation of individual SWNTs with controllable direction.

  8. Protein-Ligand Informatics Force Field (PLIff): Toward a Fully Knowledge Driven "Force Field" for Biomolecular Interactions.

    Science.gov (United States)

    Verdonk, Marcel L; Ludlow, R Frederick; Giangreco, Ilenia; Rathi, Prakash Chandra

    2016-07-28

    The Protein Data Bank (PDB) contains a wealth of data on nonbonded biomolecular interactions. If this information could be distilled down to nonbonded interaction potentials, these would have some key advantages over standard force fields. However, there are some important outstanding issues to address in order to do this successfully. This paper introduces the protein-ligand informatics "force field", PLIff, which begins to address these key challenges ( https://bitbucket.org/AstexUK/pli ). As a result of their knowledge-based nature, the next-generation nonbonded potentials that make up PLIff automatically capture a wide range of interaction types, including special interactions that are often poorly described by standard force fields. We illustrate how PLIff may be used in structure-based design applications, including interaction fields, fragment mapping, and protein-ligand docking. PLIff performs at least as well as state-of-the art scoring functions in terms of pose predictions and ranking compounds in a virtual screening context.

  9. Evaluation of several two-step scoring functions based on linear interaction energy, effective ligand size, and empirical pair potentials for prediction of protein-ligand binding geometry and free energy.

    Science.gov (United States)

    Rahaman, Obaidur; Estrada, Trilce P; Doren, Douglas J; Taufer, Michela; Brooks, Charles L; Armen, Roger S

    2011-09-26

    The performances of several two-step scoring approaches for molecular docking were assessed for their ability to predict binding geometries and free energies. Two new scoring functions designed for "step 2 discrimination" were proposed and compared to our CHARMM implementation of the linear interaction energy (LIE) approach using the Generalized-Born with Molecular Volume (GBMV) implicit solvation model. A scoring function S1 was proposed by considering only "interacting" ligand atoms as the "effective size" of the ligand and extended to an empirical regression-based pair potential S2. The S1 and S2 scoring schemes were trained and 5-fold cross-validated on a diverse set of 259 protein-ligand complexes from the Ligand Protein Database (LPDB). The regression-based parameters for S1 and S2 also demonstrated reasonable transferability in the CSARdock 2010 benchmark using a new data set (NRC HiQ) of diverse protein-ligand complexes. The ability of the scoring functions to accurately predict ligand geometry was evaluated by calculating the discriminative power (DP) of the scoring functions to identify native poses. The parameters for the LIE scoring function with the optimal discriminative power (DP) for geometry (step 1 discrimination) were found to be very similar to the best-fit parameters for binding free energy over a large number of protein-ligand complexes (step 2 discrimination). Reasonable performance of the scoring functions in enrichment of active compounds in four different protein target classes established that the parameters for S1 and S2 provided reasonable accuracy and transferability. Additional analysis was performed to definitively separate scoring function performance from molecular weight effects. This analysis included the prediction of ligand binding efficiencies for a subset of the CSARdock NRC HiQ data set where the number of ligand heavy atoms ranged from 17 to 35. This range of ligand heavy atoms is where improved accuracy of predicted ligand

  10. Screening small-molecule compound microarrays for protein ligands without fluorescence labeling with a high-throughput scanning microscope.

    Science.gov (United States)

    Fei, Yiyan; Landry, James P; Sun, Yungshin; Zhu, Xiangdong; Wang, Xiaobing; Luo, Juntao; Wu, Chun-Yi; Lam, Kit S

    2010-01-01

    We describe a high-throughput scanning optical microscope for detecting small-molecule compound microarrays on functionalized glass slides. It is based on measurements of oblique-incidence reflectivity difference and employs a combination of a y-scan galvometer mirror and an x-scan translation stage with an effective field of view of 2 cm x 4 cm. Such a field of view can accommodate a printed small-molecule compound microarray with as many as 10,000 to 20,000 targets. The scanning microscope is capable of measuring kinetics as well as endpoints of protein-ligand reactions simultaneously. We present the experimental results on solution-phase protein reactions with small-molecule compound microarrays synthesized from one-bead, one-compound combinatorial chemistry and immobilized on a streptavidin-functionalized glass slide.

  11. A Critical Review of Validation, Blind Testing, and Real- World Use of Alchemical Protein-Ligand Binding Free Energy Calculations.

    Science.gov (United States)

    Abel, Robert; Wang, Lingle; Mobley, David L; Friesner, Richard A

    2017-01-01

    Protein-ligand binding is among the most fundamental phenomena underlying all molecular biology, and a greater ability to more accurately and robustly predict the binding free energy of a small molecule ligand for its cognate protein is expected to have vast consequences for improving the efficiency of pharmaceutical drug discovery. We briefly reviewed a number of scientific and technical advances that have enabled alchemical free energy calculations to recently emerge as a preferred approach, and critically considered proper validation and effective use of these techniques. In particular, we characterized a selection bias effect which may be important in prospective free energy calculations, and introduced a strategy to improve the accuracy of the free energy predictions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. 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.

  13. Single-molecule magnetism in a single-ion triamidoamine uranium(V) terminal mono-oxo complex

    International Nuclear Information System (INIS)

    King, David M.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Liddle, Stephen T.; Tuna, Floriana; McInnes, Eric J.L.

    2013-01-01

    Straightforward oxidation of a triamidoamine uranium(III) complex with trimethyl-N-oxide affords a uranium(V) terminal mono-oxo complex which is the first clear-cut example of a uranium(V) single-molecule magnet (SMM). This monometallic complex unambiguously shows that a strongly axially ligated and thus anisotropic ligand field can be used to overcome the limited magnetic anisotropy of uranium(V). [de

  14. Singlet-triplet annihilation in single LHCII complexes

    NARCIS (Netherlands)

    Gruber, J.M.; Chmeliov, J.; Kruger, T.P.J.; Valkunas, L.; van Grondelle, R.

    2015-01-01

    In light harvesting complex II (LHCII) of higher plants and green algae, carotenoids (Cars) have an important function to quench chlorophyll (Chl) triplet states and therefore avoid the production of harmful singlet oxygen. The resulting Car triplet states lead to a non-linear self-quenching

  15. Single-stranded nucleic acids promote SAMHD1 complex formation.

    Science.gov (United States)

    Tüngler, Victoria; Staroske, Wolfgang; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; Schmidt, Franziska; Krug, Claudia; Lorenz, Mike; Chara, Osvaldo; Schwille, Petra; Lee-Kirsch, Min Ae

    2013-06-01

    SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.

  16. Measuring the complex field scattered by single submicron particles

    Energy Technology Data Exchange (ETDEWEB)

    Potenza, Marco A. C., E-mail: marco.potenza@unimi.it; Sanvito, Tiziano [Department of Physics, University of Milan, via Celoria, 16 – I-20133 Milan (Italy); CIMAINA, University of Milan, via Celoria, 16 – I-20133 Milan (Italy); EOS s.r.l., viale Ortles 22/4, I-20139 Milan (Italy); Pullia, Alberto [Department of Physics, University of Milan, via Celoria, 16 – I-20133 Milan (Italy)

    2015-11-15

    We describe a method for simultaneous measurements of the real and imaginary parts of the field scattered by single nanoparticles illuminated by a laser beam, exploiting a self-reference interferometric scheme relying on the fundamentals of the Optical Theorem. Results obtained with calibrated spheres of different materials are compared to the expected values obtained through a simplified analytical model without any free parameters, and the method is applied to a highly polydisperse water suspension of Poly(D,L-lactide-co-glycolide) nanoparticles. Advantages with respect to existing methods and possible applications are discussed.

  17. Antimony(3) ethylenediaminetetraacetate complexes with single- and doubly charged cations

    International Nuclear Information System (INIS)

    Davidovich, R.L.; Logvinova, V.B.; Kajdalova, T.A.

    1998-01-01

    The antimony(3) ethylenediaminetetraacetate complexes with alkaline and bivalent metals cations of the M + Sb(Edta) · H 2 O (M + = K, Rb, Cs, NH 4 ), M 2+ [Sb(Edta)] 2 · 8H 2 O (M 2+ = Mg, Ca, Sr, Co, Cd) composition are synthesized. Roentgenographic and IR-spectroscopic characteristics of the synthesized substances are determined. Two groups of the isostructural compounds: M + Sb(Edta) · H 2 O (M + = K, Rb, NH 4 ) and M 2+ [Sb(Edta)] 2 · 8H 2 O (M 2+ = Mg, Ca, Sr, Mn, Co, Cd) are established [ru

  18. High pressure as a tool for investigating protein-ligand interactions

    International Nuclear Information System (INIS)

    Marchal, S; Lange, R; Tortora, P; Balny, C

    2004-01-01

    In recent years, the application of pressure on biological systems has gained increasing interest. Pressure-induced destabilization of electrostatic and hydrophobic interactions is currently exploited to study conformational protein stability and macromolecular assemblies of proteins. Due to links between severe human pathologies and ordered protein oligomerization into aggregates, which have become apparent, a better knowledge of the molecular and structural determinants that ensure the packing efficiency and stability of such complexes has taken on special importance. Here, we report the effect of pressure on the property of human ataxin-3 of aggregation. The results indicate the importance of its polyglutamine chain length in the stability and the tendency of the protein to form spheroids. Partial unfolding of the protein leading to solvent exposure of hydrophobic domains appears to be a prerequisite in the aggregation process of ataxin-3

  19. Single-molecule magnetism in a single-ion triamidoamine uranium(V) terminal mono-oxo complex

    Energy Technology Data Exchange (ETDEWEB)

    King, David M.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Liddle, Stephen T. [School of Chemistry, University of Nottingham (United Kingdom); Tuna, Floriana; McInnes, Eric J.L. [School of Chemistry and Photon Science Institute, University of Manchester (United Kingdom)

    2013-04-26

    Straightforward oxidation of a triamidoamine uranium(III) complex with trimethyl-N-oxide affords a uranium(V) terminal mono-oxo complex which is the first clear-cut example of a uranium(V) single-molecule magnet (SMM). This monometallic complex unambiguously shows that a strongly axially ligated and thus anisotropic ligand field can be used to overcome the limited magnetic anisotropy of uranium(V). (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Single-molecule magnetism in a single-ion triamidoamine uranium(V) terminal mono-oxo complex

    International Nuclear Information System (INIS)

    King, David M.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Liddle, Stephen T.; Tuna, Floriana; McInnes, Eric J.L.

    2013-01-01

    Straightforward oxidation of a triamidoamine uranium(III) complex with trimethyl-N-oxide affords a uranium(V) terminal mono-oxo complex which is the first clear-cut example of a uranium(V) single-molecule magnet (SMM). This monometallic complex unambiguously shows that a strongly axially ligated and thus anisotropic ligand field can be used to overcome the limited magnetic anisotropy of uranium(V). (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Natural HLA-B*2705 Protein Ligands with Glutamine as Anchor Motif

    Science.gov (United States)

    Infantes, Susana; Lorente, Elena; Barnea, Eilon; Beer, Ilan; Barriga, Alejandro; Lasala, Fátima; Jiménez, Mercedes; Admon, Arie; López, Daniel

    2013-01-01

    The presentation of short viral peptide antigens by human leukocyte antigen (HLA) class I molecules on cell surfaces is a key step in the activation of cytotoxic T lymphocytes, which mediate the killing of pathogen-infected cells or initiate autoimmune tissue damage. HLA-B27 is a well known class I molecule that is used to study both facets of the cellular immune response. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HLA-B*2705+ cells, we identified 200 naturally processed HLA-B*2705 ligands. Our analyses revealed that a change in the position (P) 2 anchor motif was detected in the 3% of HLA-B*2705 ligands identified. B*2705 class I molecules were able to bind these six GlnP2 peptides, which showed significant homology to pathogenic bacterial sequences, with a broad range of affinities. One of these ligands was able to bind with distinct conformations to HLA-B27 subtypes differentially associated with ankylosing spondylitis. These conformational differences could be sufficient to initiate autoimmune damage in patients with ankylosing spondylitis-associated subtypes. Therefore, these kinds of peptides (short, with GlnP2, and similar low affinity to all HLA-B27 subtypes tested but with unlike conformations in differentially ankylosing spondylitis-associated subtypes) must not be excluded from future researches involving potential arthritogenic peptides. PMID:23430249

  2. Magnetic levitation as a platform for competitive protein-ligand binding assays.

    Science.gov (United States)

    Shapiro, Nathan D; Soh, Siowling; Mirica, Katherine A; Whitesides, George M

    2012-07-17

    This paper describes a method based on magnetic levitation (MagLev) that is capable of indirectly measuring the binding of unlabeled ligands to unlabeled protein. We demonstrate this method by measuring the affinity of unlabeled bovine carbonic anhydrase (BCA) for a variety of ligands (most of which are benzene sulfonamide derivatives). This method utilizes porous gel beads that are functionalized with a common aryl sulfonamide ligand. The beads are incubated with BCA and allowed to reach an equilibrium state in which the majority of the immobilized ligands are bound to BCA. Since the beads are less dense than the protein, protein binding to the bead increases the overall density of the bead. This change in density can be monitored using MagLev. Transferring the beads to a solution containing no protein creates a situation where net protein efflux from the bead is thermodynamically favorable. The rate at which protein leaves the bead for the solution can be calculated from the rate at which the levitation height of the bead changes. If another small molecule ligand of BCA is dissolved in the solution, the rate of protein efflux is accelerated significantly. This paper develops a reaction-diffusion (RD) model to explain both this observation, and the physical-organic chemistry that underlies it. Using this model, we calculate the dissociation constants of several unlabeled ligands from BCA, using plots of levitation height versus time. Notably, although this method requires no electricity, and only a single piece of inexpensive equipment, it can measure accurately the binding of unlabeled proteins to small molecules over a wide range of dissociation constants (K(d) values within the range from ~10 nM to 100 μM are measured easily). Assays performed using this method generally can be completed within a relatively short time period (20 min-2 h). A deficiency of this system is that it is not, in its present form, applicable to proteins with molecular weight greater

  3. Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes

    DEFF Research Database (Denmark)

    Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.

    2017-01-01

    to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton...... is mechanically manipulated. The implication is that force and conductance provide complementary information about the evolution of molecules in junctions that can be used to interrogate basic structure-transport relations at the single-molecule limit....

  4. Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography

    NARCIS (Netherlands)

    Dudkina, Natalya V.; Kudryashev, Mikhail; Stahlberg, Henning; Boekema, Egbert J.

    2011-01-01

    The respirasome is a multisubunit supercomplex of the respiratory chain in mitochondria. Here we report the 3D reconstruction of the bovine heart respirasome, composed of dimeric complex III and single copies of complex I and IV, at about 2.2-nm resolution, determined by cryoelectron tomography and

  5. Control of Anther Cell Differentiation by the Small Protein Ligand TPD1 and Its Receptor EMS1 in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Jian Huang

    2016-08-01

    Full Text Available A fundamental feature of sexual reproduction in plants and animals is the specification of reproductive cells that conduct meiosis to form gametes, and the associated somatic cells that provide nutrition and developmental cues to ensure successful gamete production. The anther, which is the male reproductive organ in seed plants, produces reproductive microsporocytes (pollen mother cells and surrounding somatic cells. The microsporocytes yield pollen via meiosis, and the somatic cells, particularly the tapetum, are required for the normal development of pollen. It is not known how the reproductive cells affect the differentiation of these somatic cells, and vice versa. Here, we use molecular genetics, cell biological, and biochemical approaches to demonstrate that TPD1 (TAPETUM DETERMINANT1 is a small secreted cysteine-rich protein ligand that interacts with the LRR (Leucine-Rich Repeat domain of the EMS1 (EXCESS MICROSPOROCYTES1 receptor kinase at two sites. Analyses of the expressions and localizations of TPD1 and EMS1, ectopic expression of TPD1, experimental missorting of TPD1, and ablation of microsporocytes yielded results suggesting that the precursors of microsporocyte/microsporocyte-derived TPD1 and pre-tapetal-cell-localized EMS1 initially promote the periclinal division of secondary parietal cells and then determine one of the two daughter cells as a functional tapetal cell. Our results also indicate that tapetal cells suppress microsporocyte proliferation. Collectively, our findings show that tapetal cell differentiation requires reproductive-cell-secreted TPD1, illuminating a novel mechanism whereby signals from reproductive cells determine somatic cell fate in plant sexual reproduction.

  6. Single-molecule magnetism in a single-ion triamidoamine uranium(V) terminal mono-oxo complex

    Energy Technology Data Exchange (ETDEWEB)

    King, David M.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Liddle, Stephen T. [Nottingham Univ. (United Kingdom). School of Chemistry; Tuna, Floriana; McInnes, Eric J.L. [Manchester Univ. (United Kingdom). School of Chemistry

    2013-04-26

    Straightforward oxidation of a triamidoamine uranium(III) complex with trimethyl-N-oxide affords a uranium(V) terminal mono-oxo complex which is the first clear-cut example of a uranium(V) single-molecule magnet (SMM). This monometallic complex unambiguously shows that a strongly axially ligated and thus anisotropic ligand field can be used to overcome the limited magnetic anisotropy of uranium(V). [German] Die direkte Oxidation eines Triamidoamin-Uran(III)-Komplexes mit Trimethyl-N-oxid liefert einen terminalen Uran(V)-Mono(oxo)komplex, der das erste gesicherte Beispiel eines Uran(V)-Einzelmolekuelmagnets ist. Dieser monometallische Komplex zeigt eindeutig, dass ein starkes axiales und somit anisotropes Ligandenfeld die begrenzte magnetische Anisotropie von Uran(V) beseitigen kann.

  7. Cleavage and formation of molecular dinitrogen in a single system assisted by molybdenum complexes bearing ferrocenyldiphosphine.

    Science.gov (United States)

    Miyazaki, Takamasa; Tanaka, Hiromasa; Tanabe, Yoshiaki; Yuki, Masahiro; Nakajima, Kazunari; Yoshizawa, Kazunari; Nishibayashi, Yoshiaki

    2014-10-20

    The N≡N bond of molecular dinitrogen bridging two molybdenum atoms in the pentamethylcyclopentadienyl molybdenum complexes that bear ferrocenyldiphosphine as an auxiliary ligand is homolytically cleaved under visible light irradiation at room temperature to afford two molar molybdenum nitride complexes. Conversely, the bridging molecular dinitrogen is reformed by the oxidation of the molybdenum nitride complex at room temperature. This result provides a successful example of the cleavage and formation of molecular dinitrogen induced by a pair of two different external stimuli using a single system assisted by molybdenum complexes bearing ferrocenyldiphosphine under ambient conditions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Determining Complex Structures using Docking Method with Single Particle Scattering Data

    Directory of Open Access Journals (Sweden)

    Haiguang Liu

    2017-04-01

    Full Text Available Protein complexes are critical for many molecular functions. Due to intrinsic flexibility and dynamics of complexes, their structures are more difficult to determine using conventional experimental methods, in contrast to individual subunits. One of the major challenges is the crystallization of protein complexes. Using X-ray free electron lasers (XFELs, it is possible to collect scattering signals from non-crystalline protein complexes, but data interpretation is more difficult because of unknown orientations. Here, we propose a hybrid approach to determine protein complex structures by combining XFEL single particle scattering data with computational docking methods. Using simulations data, we demonstrate that a small set of single particle scattering data collected at random orientations can be used to distinguish the native complex structure from the decoys generated using docking algorithms. The results also indicate that a small set of single particle scattering data is superior to spherically averaged intensity profile in distinguishing complex structures. Given the fact that XFEL experimental data are difficult to acquire and at low abundance, this hybrid approach should find wide applications in data interpretations.

  9. Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes

    Science.gov (United States)

    Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.; Franco, Ignacio

    2017-03-01

    The emerging ability to study physical properties at the single-molecule limit highlights the disparity between what is observable in an ensemble of molecules and the heterogeneous contributions of its constituent parts. A particularly convenient platform for single-molecule studies are molecular junctions where forces and voltages can be applied to individual molecules, giving access to a series of electromechanical observables that can form the basis of highly discriminating multidimensional single-molecule spectroscopies. Here, we computationally examine the ability of force and conductance to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton receptor that can form up to six simultaneous hydrogen bonds. The simulations combine classical molecular dynamics of the mechanical deformation of the junction with non-equilibrium Green's function computations of the electronic transport. As shown, in these complexes hydrogen bonds mediate transport either by directly participating as a possible transport pathway or by stabilizing molecular conformations with enhanced conductance properties. Further, we observe that force-conductance correlations can be very sensitive to small changes in the chemical structure of the complexes and provide detailed information about the behavior of single molecules that cannot be gleaned from either measurement alone. In fact, there are regions during the elongation that are only mechanically active, others that are only conductance active, and regions where both force and conductance changes as the complex is mechanically manipulated. The implication is that force and conductance provide complementary information about the evolution of molecules in junctions that can be used to

  10. Energy transfer from natural photosynthetic complexes to single-wall carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Wiwatowski, Kamil [Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun (Poland); Dużyńska, Anna; Świniarski, Michał [Faculty of Physics, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw (Poland); Szalkowski, Marcin [Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun (Poland); Zdrojek, Mariusz; Judek, Jarosław [Faculty of Physics, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw (Poland); Mackowski, Sebastian, E-mail: mackowski@fizyka.umk.pl [Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun (Poland); Wroclaw Research Center EIT+, Stablowicka 147, Wroclaw (Poland); Kaminska, Izabela [Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun (Poland)

    2016-02-15

    Combination of fluorescence imaging and spectroscopy results indicates that single-walled carbon nanotubes are extremely efficient quenchers of fluorescence emission associated with chlorophylls embedded in a natural photosynthetic complex, peridinin-chlorophyll-protein. When deposited on a network of the carbon nanotubes forming a thin film, the emission of the photosynthetic complexes diminishes almost completely. This strong reduction of fluorescence intensity is accompanied with dramatic shortening of the fluorescence lifetime. Concluding, such thin films of carbon nanotubes can be extremely efficient energy acceptors in structures involving biologically functional complexes. - Highlights: • Fluorescence imaging of carbon nanotube - based hybrid structure. • Observation of efficient energy transfer from chlorophylls to carbon nanotubes.

  11. Probing Single Pt Atoms in Complex Intermetallic Al13Fe4.

    Science.gov (United States)

    Yamada, Tsunetomo; Kojima, Takayuki; Abe, Eiji; Kameoka, Satoshi; Murakami, Yumi; Gille, Peter; Tsai, An Pang

    2018-03-21

    The atomic structure of a 0.2 atom % Pt-doped complex metallic alloy, monoclinic Al 13 Fe 4 , was investigated using a single crystal prepared by the Czochralski method. High-angle annular dark-field scanning transmission electron microscopy showed that the Pt atoms were dispersed as single atoms and substituted at Fe sites in Al 13 Fe 4 . Single-crystal X-ray structural analysis revealed that the Pt atoms preferentially substitute at Fe(1). Unlike those that have been reported, Pt single atoms in the surface layers showed lower activity and selectivity than those of Al 2 Pt and bulk Pt for propyne hydrogenation, indicating that the active state of a given single-atom Pt site is strongly dominated by the bonding to surrounding Al atoms.

  12. Fluorescence spectral fluctuations of single LH2 complexes from Rhodopseudomonas acidophila strain 10050

    NARCIS (Netherlands)

    Rutkauskas, D.; Novoderezkhin, V.; Cogdell, R.J.; van Grondelle, R.

    2004-01-01

    We have investigated the energy landscape of the bacterial photosynthetic peripheral light-harvesting complex LH2 of purple bacterium Rhodopseudomonas acidophila by monitoring sequences of fluorescence spectra of single LH2 assemblies, at room temperature, with different excitation intensities as

  13. Enumeration of Combinatorial Classes of Single Variable Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    A vector field in the space of degree d monic, centered single variable complex polynomial vector fields has a combinatorial structure which can be fully described by a combinatorial data set consisting of an equivalence relation and a marked subset on the integers mod 2d-2, satisfying certain...

  14. Single-molecule spectroscopy reveals photosynthetic LH2 complexes switch between emissive states.

    Science.gov (United States)

    Schlau-Cohen, Gabriela S; Wang, Quan; Southall, June; Cogdell, Richard J; Moerner, W E

    2013-07-02

    Photosynthetic organisms flourish under low light intensities by converting photoenergy to chemical energy with near unity quantum efficiency and under high light intensities by safely dissipating excess photoenergy and deleterious photoproducts. The molecular mechanisms balancing these two functions remain incompletely described. One critical barrier to characterizing the mechanisms responsible for these processes is that they occur within proteins whose excited-state properties vary drastically among individual proteins and even within a single protein over time. In ensemble measurements, these excited-state properties appear only as the average value. To overcome this averaging, we investigate the purple bacterial antenna protein light harvesting complex 2 (LH2) from Rhodopseudomonas acidophila at the single-protein level. We use a room-temperature, single-molecule technique, the anti-Brownian electrokinetic trap, to study LH2 in a solution-phase (nonperturbative) environment. By performing simultaneous measurements of fluorescence intensity, lifetime, and spectra of single LH2 complexes, we identify three distinct states and observe transitions occurring among them on a timescale of seconds. Our results reveal that LH2 complexes undergo photoactivated switching to a quenched state, likely by a conformational change, and thermally revert to the ground state. This is a previously unobserved, reversible quenching pathway, and is one mechanism through which photosynthetic organisms can adapt to changes in light intensities.

  15. Decay dynamics of neutral and charged excitonic complexes in single InAs/GaAs QDs

    International Nuclear Information System (INIS)

    Feucker, Max; Seguin, Robert; Rodt, Sven; Poetschke, Konstantin; Bimberg, Dieter

    2008-01-01

    Across the inhomogeneously broadened lineshape of a quantum dot (QD) ensemble the decay times are expected to vary since the wavefunctions and the oscillator strengths are sensitive to the actual geometry of the QD. We performed time-resolved cathodoluminescence spectroscopy of 26 different single InAs/GaAs QDs to investigate the decay dynamics of neutral and charged excitonic complexes. The largest decay rate was found for the XX + , followed by XX, X + and finally the X. We will show that the ratios of lifetimes of the different excitonic complexes are mainly governed by the number of involved recombination channels. There is excellent agreement between the measured and predicted values for the lifetime ratios of the neutral (X/XX) and the positively charged (X + /XX + ) complexes. Surprisingly the lifetime of the exciton (X) shows a much larger yet unexplained scatter than that of all the other complexes

  16. Enhanced photoluminescence from single nitrogen-vacancy defects in nanodiamonds coated with phenol-ionic complexes.

    Science.gov (United States)

    Bray, Kerem; Previdi, Rodolfo; Gibson, Brant C; Shimoni, Olga; Aharonovich, Igor

    2015-03-21

    Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing. We propose that the nanodiamond encapsulation reduces the non-radiative decay pathways of the NV color centers. Our results provide a versatile and assessable way to enhance photoluminescence from nanodiamond defects that can be used in a variety of sensing and imaging applications.

  17. Promising results after single-stage reconstruction of the nipple and areola complex

    DEFF Research Database (Denmark)

    Børsen-Koch, Mikkel; Bille, Camilla; Thomsen, Jørn B

    2013-01-01

    Introduction: Reconstruction of the nipple-areola complex (NAC) traditionally marks the end of breast reconstruction. Several different surgical techniques have been described, but most are staged procedures. This paper describes a simple single-stage approach. Material and Methods: We used...... reconstruction was 43 min. (30-50 min.). Conclusion: This simple single-stage NAC reconstruction seems beneficial for both patient and surgeon as it seems to be associated with faster reconstruction and reduced procedure-related time without compromising the aesthetic outcome or the morbidity associated...

  18. Single lipid vesicle assay for characterizing single-enzyme kinetics of phospholipid hydrolysis in a complex biological fluid.

    Science.gov (United States)

    Tabaei, Seyed R; Rabe, Michael; Zetterberg, Henrik; Zhdanov, Vladimir P; Höök, Fredrik

    2013-09-25

    Imaging of individual lipid vesicles is used to track single-enzyme kinetics of phospholipid hydrolysis. The method is employed to quantify the catalytic activity of phospholipase A2 (PLA2) in both pure and complex biological fluids. The measurements are demonstrated to offer a subpicomolar limit of detection (LOD) of human secretory PLA2 (sPLA2) in up to 1000-fold-diluted cerebrospinal fluid (CSF). An additional new feature provided by the single-enzyme sensitivity is that information about both relative concentration variations of active sPLA2 in CSF and the specific enzymatic activity can be simultaneously obtained. When CSF samples from healthy controls and individuals diagnosed with Alzheimer's disease (AD) are analyzed, the specific enzymatic activity is found to be preserved within 7% in the different CSF samples whereas the enzyme concentration differs by up to 56%. This suggests that the previously reported difference in PLA2 activity in CSF samples from healthy and AD individuals originates from differences in the PLA2 expression level rather than from the enzyme activity. Conventional ensemble averaging methods used to probe sPLA2 activity do not allow one to obtain such information. Together with an improvement in the LOD of at least 1 order of magnitude compared to that of conventional assays, this suggests that the method will become useful in furthering our understanding of the role of PLA2 in health and disease and in detecting the pharmacodynamic effects of PLA2-targeting drug candidates.

  19. Tetracoordinate Co(II) complexes containing bathocuproine and single molecule magnetism

    Czech Academy of Sciences Publication Activity Database

    Smolko, L.; Černák, J.; Dušek, Michal; Titiš, J.; Boča, R.

    2016-01-01

    Roč. 40, č. 8 (2016), s. 6593-6598 ISSN 1144-0546 R&D Projects: GA MŠk LO1603; GA ČR(CZ) GA15-12653S EU Projects: European Commission(XE) CZ.2.16/3.1.00/24510 Institutional support: RVO:68378271 Keywords : crystal structure * single molecule magnetism * Cu(II) complexes Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.269, year: 2016

  20. A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization.

    Science.gov (United States)

    Dickinson, Daniel J; Schwager, Francoise; Pintard, Lionel; Gotta, Monica; Goldstein, Bob

    2017-08-21

    Regulated protein-protein interactions are critical for cell signaling, differentiation, and development. For the study of dynamic regulation of protein interactions in vivo, there is a need for techniques that can yield time-resolved information and probe multiple protein binding partners simultaneously, using small amounts of starting material. Here we describe a single-cell protein interaction assay. Single-cell lysates are generated at defined time points and analyzed using single-molecule pull-down, yielding information about dynamic protein complex regulation in vivo. We established the utility of this approach by studying PAR polarity proteins, which mediate polarization of many animal cell types. We uncovered striking regulation of PAR complex composition and stoichiometry during Caenorhabditis elegans zygote polarization, which takes place in less than 20 min. PAR complex dynamics are linked to the cell cycle by Polo-like kinase 1 and govern the movement of PAR proteins to establish polarity. Our results demonstrate an approach to study dynamic biochemical events in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Enhanced photoluminescence from single nitrogen-vacancy defects in nanodiamonds coated with phenol-ionic complexes

    Science.gov (United States)

    Bray, Kerem; Previdi, Rodolfo; Gibson, Brant C.; Shimoni, Olga; Aharonovich, Igor

    2015-03-01

    Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing. We propose that the nanodiamond encapsulation reduces the non-radiative decay pathways of the NV color centers. Our results provide a versatile and assessable way to enhance photoluminescence from nanodiamond defects that can be used in a variety of sensing and imaging applications.Fluorescent nanodiamonds are attracting major attention in the field of bio-sensing and bio-labeling. In this work we demonstrate a robust approach to achieve an encapsulation of individual nanodiamonds with phenol-ionic complexes that enhance the photoluminescence from single nitrogen vacancy (NV) centers. We show that single NV centres in the coated nanodiamonds also exhibit shorter lifetimes, opening another channel for high resolution sensing. We propose that the nanodiamond encapsulation reduces the non-radiative decay pathways of the NV color centers. Our results provide a versatile and assessable way to enhance photoluminescence from nanodiamond defects that can be used in a variety of sensing and imaging applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07510b

  2. Processing of complex shapes with single-mode resonant frequency microwave applicators

    International Nuclear Information System (INIS)

    Fellows, L.A.; Delgado, R.; Hawley, M.C.

    1994-01-01

    Microwave processing is an alternative to conventional composite processing techniques. Single-mode microwave applicators efficiently couple microwave energy into the composite. The application of the microwave energy is greatly affected by the geometry of the composite. In the single mode microwave applicator, two types of modes are available. These modes are best suited to processing flat planar samples or cylindrical samples with geometries that align with the electric fields. Mode-switching is alternating between different electromagnetic modes with the intelligent selection of the modes to alleviate undesirable temperature profiles. This method has improved the microwave heating profiles of materials with complex shapes that do not align with either type of electric field. Parts with two different complex geometries were fabricated from a vinyl toluene/vinyl ester resin with a continuous glass fiber reinforcement by autoclaving and by microwave techniques. The flexural properties of the microwave processed samples were compared to the flexural properties of autoclaved samples. The trends of the mechanical properties for the complex shapes were consistent with the results of experiments with flat panels. This demonstrated that mode-switching techniques are as applicable for the complex shapes as they are for the simpler flat panel geometry

  3. Single-shot parallel full range complex Fourier-domain optical coherence tomography

    International Nuclear Information System (INIS)

    Huang Bingjie; Bu Peng; Nan Nan; Wang Xiangzhao

    2011-01-01

    We present a method of parallel full range complex Fourier-domain optical coherence tomography (FDOCT) that is capable of acquiring an artifacts-free two-dimensional (2-D) cross-sectional image, i.e. a full range B-scan tomogram, by a single shot of 2-D CCD camera. This method is based on a spatial carrier technique, in which the spatial carrier-frequency is instantaneously introduced into the 2-D spectral interferogram registered in parallel FDOCT by using a grating-generated reference beam. The spatial-carrier-contained 2-D spectral interferogram is processed through Fourier transformation to obtain a complex 2-D spectral interferogram. From the 2-D complex spectral interferomgram, a full range B-scan tomogram is reconstructed. The principle of our method is confirmed by imaging an onion sample.

  4. GraDeR: Membrane Protein Complex Preparation for Single-Particle Cryo-EM.

    Science.gov (United States)

    Hauer, Florian; Gerle, Christoph; Fischer, Niels; Oshima, Atsunori; Shinzawa-Itoh, Kyoko; Shimada, Satoru; Yokoyama, Ken; Fujiyoshi, Yoshinori; Stark, Holger

    2015-09-01

    We developed a method, named GraDeR, which substantially improves the preparation of membrane protein complexes for structure determination by single-particle cryo-electron microscopy (cryo-EM). In GraDeR, glycerol gradient centrifugation is used for the mild removal of free detergent monomers and micelles from lauryl maltose-neopentyl glycol detergent stabilized membrane complexes, resulting in monodisperse and stable complexes to which standard processes for water-soluble complexes can be applied. We demonstrate the applicability of the method on three different membrane complexes, including the mammalian FoF1 ATP synthase. For this highly dynamic and fragile rotary motor, we show that GraDeR allows visualizing the asymmetry of the F1 domain, which matches the ground state structure of the isolated domain. Therefore, the present cryo-EM structure of FoF1 ATP synthase provides direct structural evidence for Boyer's binding change mechanism in the context of the intact enzyme. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. From isolated light-harvesting complexes to the thylakoid membrane: a single-molecule perspective

    Science.gov (United States)

    Gruber, J. Michael; Malý, Pavel; Krüger, Tjaart P. J.; Grondelle, Rienk van

    2018-01-01

    The conversion of solar radiation to chemical energy in plants and green algae takes place in the thylakoid membrane. This amphiphilic environment hosts a complex arrangement of light-harvesting pigment-protein complexes that absorb light and transfer the excitation energy to photochemically active reaction centers. This efficient light-harvesting capacity is moreover tightly regulated by a photoprotective mechanism called non-photochemical quenching to avoid the stress-induced destruction of the catalytic reaction center. In this review we provide an overview of single-molecule fluorescence measurements on plant light-harvesting complexes (LHCs) of varying sizes with the aim of bridging the gap between the smallest isolated complexes, which have been well-characterized, and the native photosystem. The smallest complexes contain only a small number (10-20) of interacting chlorophylls, while the native photosystem contains dozens of protein subunits and many hundreds of connected pigments. We discuss the functional significance of conformational dynamics, the lipid environment, and the structural arrangement of this fascinating nano-machinery. The described experimental results can be utilized to build mathematical-physical models in a bottom-up approach, which can then be tested on larger in vivo systems. The results also clearly showcase the general property of biological systems to utilize the same system properties for different purposes. In this case it is the regulated conformational flexibility that allows LHCs to switch between efficient light-harvesting and a photoprotective function.

  6. Resolving dual binding conformations of cellulosome cohesin-dockerin complexes using single-molecule force spectroscopy.

    Science.gov (United States)

    Jobst, Markus A; Milles, Lukas F; Schoeler, Constantin; Ott, Wolfgang; Fried, Daniel B; Bayer, Edward A; Gaub, Hermann E; Nash, Michael A

    2015-10-31

    Receptor-ligand pairs are ordinarily thought to interact through a lock and key mechanism, where a unique molecular conformation is formed upon binding. Contrary to this paradigm, cellulosomal cohesin-dockerin (Coh-Doc) pairs are believed to interact through redundant dual binding modes consisting of two distinct conformations. Here, we combined site-directed mutagenesis and single-molecule force spectroscopy (SMFS) to study the unbinding of Coh:Doc complexes under force. We designed Doc mutations to knock out each binding mode, and compared their single-molecule unfolding patterns as they were dissociated from Coh using an atomic force microscope (AFM) cantilever. Although average bulk measurements were unable to resolve the differences in Doc binding modes due to the similarity of the interactions, with a single-molecule method we were able to discriminate the two modes based on distinct differences in their mechanical properties. We conclude that under native conditions wild-type Doc from Clostridium thermocellum exocellulase Cel48S populates both binding modes with similar probabilities. Given the vast number of Doc domains with predicted dual binding modes across multiple bacterial species, our approach opens up new possibilities for understanding assembly and catalytic properties of a broad range of multi-enzyme complexes.

  7. First Indian single center experience with pipeline embolization device for complex intracranial aneurysms.

    Science.gov (United States)

    Cherian, Mathew P; Yadav, Manish Kumar; Mehta, Pankaj; Vijayan, K; Arulselvan, V; Jayabalan, Suresh

    2014-01-01

    Flow diversion is a novel method of therapy wherein an endoluminal sleeve, the flow diverter stent is placed across the neck of complex aneurysms to curatively reconstruct abnormal vasculature. We present the first Indian single center experience with the pipeline embolization device (PED) and 6 months follow-up results of 5 patients. Five complex or recurrent intracranial aneurysms in five patients were treated with PED. The patients were followed-up with magnetic resonance angiography (MRA) after 4 weeks and conventional angiography after 6 months. Feasibility, complications, clinical outcome, early 1-month MRA and 6 months conventional angiographic follow-up results were analyzed. Of the five aneurysms treated, four were in the anterior circulation and one in the posterior circulation. All five patients were treated with a single PED in each, and additionally coils were used in one patient. At 1-month MRA follow-up, complete occlusion was seen in 2 (40%) of the five cases. Post 6 months conventional angiography showed complete occlusion of the aneurysm sac in all five cases (100%). Side branch ostia were covered in three patients, all of which were patent (100%). There was no incidence of major neurological morbidity or mortality. One patient (20%) who had basilar top aneurysm experienced minor neurological disability after 5 days which partially improved. Pipeline embolization device for complex and recurrent aneurysms is technically feasible, safe, offers low complication rate, and definitive vascular reconstruction. PED can be used without fear of occlusion of covered eloquent side branches and perforators.

  8. Optimization of memory use of fragment extension-based protein-ligand docking with an original fast minimum cost flow algorithm.

    Science.gov (United States)

    Yanagisawa, Keisuke; Komine, Shunta; Kubota, Rikuto; Ohue, Masahito; Akiyama, Yutaka

    2018-03-16

    The need to accelerate large-scale protein-ligand docking in virtual screening against a huge compound database led researchers to propose a strategy that entails memorizing the evaluation result of the partial structure of a compound and reusing it to evaluate other compounds. However, the previous method required frequent disk accesses, resulting in insufficient acceleration. Thus, more efficient memory usage can be expected to lead to further acceleration, and optimal memory usage could be achieved by solving the minimum cost flow problem. In this research, we propose a fast algorithm for the minimum cost flow problem utilizing the characteristics of the graph generated for this problem as constraints. The proposed algorithm, which optimized memory usage, was approximately seven times faster compared to existing minimum cost flow algorithms. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Unified analysis of ensemble and single-complex optical spectral data from light-harvesting complex-2 chromoproteins for gaining deeper insight into bacterial photosynthesis

    Science.gov (United States)

    Pajusalu, Mihkel; Kunz, Ralf; Rätsep, Margus; Timpmann, Kõu; Köhler, Jürgen; Freiberg, Arvi

    2015-11-01

    Bacterial light-harvesting pigment-protein complexes are very efficient at converting photons into excitons and transferring them to reaction centers, where the energy is stored in a chemical form. Optical properties of the complexes are known to change significantly in time and also vary from one complex to another; therefore, a detailed understanding of the variations on the level of single complexes and how they accumulate into effects that can be seen on the macroscopic scale is required. While experimental and theoretical methods exist to study the spectral properties of light-harvesting complexes on both individual complex and bulk ensemble levels, they have been developed largely independently of each other. To fill this gap, we simultaneously analyze experimental low-temperature single-complex and bulk ensemble optical spectra of the light-harvesting complex-2 (LH2) chromoproteins from the photosynthetic bacterium Rhodopseudomonas acidophila in order to find a unique theoretical model consistent with both experimental situations. The model, which satisfies most of the observations, combines strong exciton-phonon coupling with significant disorder, characteristic of the proteins. We establish a detailed disorder model that, in addition to containing a C2-symmetrical modulation of the site energies, distinguishes between static intercomplex and slow conformational intracomplex disorders. The model evaluations also verify that, despite best efforts, the single-LH2-complex measurements performed so far may be biased toward complexes with higher Huang-Rhys factors.

  10. Spin-polarized transport through single-molecule magnet Mn6 complexes

    KAUST Repository

    Cremades, Eduard; Pemmaraju, C. D.; Sanvito, Stefano; Ruiz, Eliseo

    2013-01-01

    The coherent transport properties of a device, constructed by sandwiching a Mn6 single-molecule magnet between two gold surfaces, are studied theoretically by using the non-equilibrium Green's function approach combined with density functional theory. Two spin states of such Mn6 complexes are explored, namely the ferromagnetically coupled configuration of the six MnIII cations, leading to the S = 12 ground state, and the low S = 4 spin state. For voltages up to 1 volt the S = 12 ground state shows a current one order of magnitude larger than that of the S = 4 state. Furthermore this is almost completely spin-polarized, since the Mn6 frontier molecular orbitals for S = 12 belong to the same spin manifold. As such the high-anisotropy Mn6 molecule appears as a promising candidate for implementing, at the single molecular level, both spin-switches and low-temperature spin-valves. © 2013 The Royal Society of Chemistry.

  11. Electrical manipulation of spin states in a single electrostatically gated transition-metal complex

    DEFF Research Database (Denmark)

    Osorio, Edgar A; Moth-Poulsen, Kasper; van der Zant, Herre S J

    2010-01-01

    -field on the Mn-atom. Adding a single electron thus stabilizes the low-spin configuration and the corresponding sequential tunnelling current is suppressed by spin-blockade. From low-temperature inelastic cotunneling spectroscopy, we infer the magnetic excitation spectrum of the molecule and uncover also...... a strongly gate-dependent singlet-triplet splitting on the low-spin side. The measured bias-spectroscopy is shown to be consistent with an exact diagonalization of the Mn-complex, and an interpretation of the data is given in terms of a simplified effective model....

  12. Direct measurement and modulation of single-molecule coordinative bonding forces in a transition metal complex

    DEFF Research Database (Denmark)

    Hao, Xian; Zhu, Nan; Gschneidtner, Tina

    2013-01-01

    remain a daunting challenge. Here we demonstrate an interdisciplinary and systematic approach that enables measurement and modulation of the coordinative bonding forces in a transition metal complex. Terpyridine is derived with a thiol linker, facilitating covalent attachment of this ligand on both gold...... substrate surfaces and gold-coated atomic force microscopy tips. The coordination and bond breaking between terpyridine and osmium are followed in situ by electrochemically controlled atomic force microscopy at the single-molecule level. The redox state of the central metal atom is found to have...

  13. Hydrogen-related complexes in Li-diffused ZnO single crystals

    Science.gov (United States)

    Corolewski, Caleb D.; Parmar, Narendra S.; Lynn, Kelvin G.; McCluskey, Matthew D.

    2016-07-01

    Zinc oxide (ZnO) is a wide band gap semiconductor and a potential candidate for next generation white solid state lighting applications. In this work, hydrogen-related complexes in lithium diffused ZnO single crystals were studied. In addition to the well-known Li-OH complex, several other hydrogen defects were observed. When a mixture of Li2O and ZnO is used as the dopant source, zinc vacancies are suppressed and the bulk Li concentration is very high (>1019 cm-3). In that case, the predominant hydrogen complex has a vibrational frequency of 3677 cm-1, attributed to surface O-H species. When Li2CO3 is used, a structured blue luminescence band and O-H mode at 3327 cm-1 are observed at 10 K. These observations, along with positron annihilation measurements, suggest a zinc vacancy-hydrogen complex, with an acceptor level ˜0.3 eV above the valence-band maximum. This relatively shallow acceptor could be beneficial for p-type ZnO.

  14. Hydrogen-related complexes in Li-diffused ZnO single crystals

    International Nuclear Information System (INIS)

    Corolewski, Caleb D.; Parmar, Narendra S.; Lynn, Kelvin G.; McCluskey, Matthew D.

    2016-01-01

    Zinc oxide (ZnO) is a wide band gap semiconductor and a potential candidate for next generation white solid state lighting applications. In this work, hydrogen-related complexes in lithium diffused ZnO single crystals were studied. In addition to the well-known Li-OH complex, several other hydrogen defects were observed. When a mixture of Li_2O and ZnO is used as the dopant source, zinc vacancies are suppressed and the bulk Li concentration is very high (>10"1"9" cm"−"3). In that case, the predominant hydrogen complex has a vibrational frequency of 3677 cm"−"1, attributed to surface O-H species. When Li_2CO_3 is used, a structured blue luminescence band and O-H mode at 3327 cm"−"1 are observed at 10 K. These observations, along with positron annihilation measurements, suggest a zinc vacancy–hydrogen complex, with an acceptor level ∼0.3 eV above the valence-band maximum. This relatively shallow acceptor could be beneficial for p-type ZnO.

  15. Hydrogen-related complexes in Li-diffused ZnO single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Corolewski, Caleb D. [Materials Science and Engineering Program, Washington State University, Pullman, Washington 99164-2814 (United States); Parmar, Narendra S.; Lynn, Kelvin G. [Center for Materials Research, Washington State University, Pullman, Washington 99164-2814 (United States); McCluskey, Matthew D., E-mail: mattmcc@wsu.edu [Materials Science and Engineering Program, Washington State University, Pullman, Washington 99164-2814 (United States); Department of Physics and Astronomy, Washington State University, Pullman, Washington 99164-2814 (United States)

    2016-07-21

    Zinc oxide (ZnO) is a wide band gap semiconductor and a potential candidate for next generation white solid state lighting applications. In this work, hydrogen-related complexes in lithium diffused ZnO single crystals were studied. In addition to the well-known Li-OH complex, several other hydrogen defects were observed. When a mixture of Li{sub 2}O and ZnO is used as the dopant source, zinc vacancies are suppressed and the bulk Li concentration is very high (>10{sup 19 }cm{sup −3}). In that case, the predominant hydrogen complex has a vibrational frequency of 3677 cm{sup −1}, attributed to surface O-H species. When Li{sub 2}CO{sub 3} is used, a structured blue luminescence band and O-H mode at 3327 cm{sup −1} are observed at 10 K. These observations, along with positron annihilation measurements, suggest a zinc vacancy–hydrogen complex, with an acceptor level ∼0.3 eV above the valence-band maximum. This relatively shallow acceptor could be beneficial for p-type ZnO.

  16. Synthesis and Characterization of Hexahapto-Chromium Complexes of Single-Walled Carbon Nanotubes

    KAUST Repository

    Kalinina, Irina

    2016-12-17

    This chapter employs purified pristine single-walled carbon nanotubes (SWNTs) and octadecylaminefunctionalized-SWNTs. These SWNTs are employed for investigate the potential of the SWNT sidewall to function as a hexahapto ligand for chromium (Cr), with in-depth characterization of the products using some of the techniques, such as thermogravimetric analysis (TGA), transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS). Purified electric arc (EA)-produced SWNTs (P2-SWNT) and octadecylaminefunctionalized SWNTs were obtained from Carbon Solutions, Inc. The TEM images show the removal of the Cr particles from the outer surface of the SWNT bundles in the SWNT-Cr complexes after decomplexation; Cr attachment to the surface of the as-prepared complexes (η6-SWNT)Cr(CO)3 and (η6-SWNT-CONH(CH2)17CH3)Cr(CO)3 is clearly evident. The positions of the bands in the Raman spectra of SWNTs are sensitive to doping and thus the chapter examines the effect of complexation of the Cr(CO)3 and Cr(η6-benzene) units on the position of the G and 2D bands in the (η6-SWNT)Cr(CO)3 and (η6-SWNT)Cr(η6-benzene) complexes.

  17. Single-molecule magnet behavior in 2,2’-bipyrimidine-bridged dilanthanide complexes

    Directory of Open Access Journals (Sweden)

    Wen Yu

    2016-01-01

    Full Text Available A series of 2,2’-bipyrimidine-bridged dinuclear lanthanide complexes with the general formula [Ln(tmhd3]2bpm (tmhd = 2,2,6,6-tetramethyl-3,5-heptanedionate, bpm = 2,2’-bipyrimidine, Ln = Gd(III, 1; Tb(III, 2; Dy(III, 3; Ho(III, 4 and Er(III, 5 has been synthesized and characterized. Sublimation of [Tb(tmhd3]2bpm onto a Au(111 surface leads to the formation of a homogeneous film with hexagonal pattern, which was studied by scanning tunneling microscopy (STM. The bulk magnetic properties of all complexes have been studied comprehensively. The dynamic magnetic behavior of the Dy(III and Er(III compounds clearly exhibits single molecule magnet (SMM characteristics with an energy barrier of 97 and 25 K, respectively. Moreover, micro-SQUID measurements on single crystals confirm their SMM behavior with the presence of hysteresis loops.

  18. Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing

    Directory of Open Access Journals (Sweden)

    Yu-Chih Tsai

    2016-02-01

    Full Text Available Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for de novo reconstruction of genomes from these communities. However, the resultant “genomes” are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT sequencing to reconstruct a high-quality, closed genome of a previously uncharacterized Corynebacterium simulans and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short-read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this C. simulans in its skin community at single-nucleotide resolution, we observed a dominant C. simulans strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation.

  19. Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing

    Science.gov (United States)

    Tsai, Yu-Chih; Deming, Clayton; Segre, Julia A.; Kong, Heidi H.; Korlach, Jonas

    2016-01-01

    ABSTRACT Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for de novo reconstruction of genomes from these communities. However, the resultant “genomes” are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT) sequencing to reconstruct a high-quality, closed genome of a previously uncharacterized Corynebacterium simulans and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short-read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this C. simulans in its skin community at single-nucleotide resolution, we observed a dominant C. simulans strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation. PMID:26861018

  20. Lower extremity fatigue increases complexity of postural control during a single-legged stance

    Directory of Open Access Journals (Sweden)

    Bailey Jerry J

    2011-08-01

    Full Text Available Abstract Background Non-linear approaches to assessment of postural control can provide insight that compliment linear approaches. Control entropy (CE is a recently developed statistical tool from non-linear dynamical systems used to assess the complexity of non-stationary signals. We have previously used CE of high resolution accelerometry in running to show decreased complexity with exhaustive exercise. The purpose of this study was to determine if complexity of postural control decreases following fatiguing exercise using CE. Methods Ten subjects (5 M/5 F; 25 ± 3 yr; 169.4 ± 11.7 cm; 79.0 ± 16.9 kg consented to participation approved by Western Oregon University IRB and completed two trials separated by 2-7 days. Trials consisted of two single-legged balance tests separated by two Wingate anaerobic tests (WAnT; PreFat/PostFat, or rest period (PreRest/PostRest. Balance tests consisted of a series of five single-legged stances, separated by 30 s rest, performed while standing on the dominant leg for 15-s with the participant crossing the arms over the chest and flexing the non-dominant knee to 90 degrees. High resolution accelerometers (HRA were fixed superficial to L3/L4 at the approximate center of mass (COM. Triaxial signals from the HRA were streamed in real time at 625 Hz. COM accelerations were recorded in g's for vertical (VT, medial/lateral (ML, and anterior/posterior (AP axes. A newly developed statistic (R-test was applied to group response shapes generated by Karhunen Loeve (KL transform modes resulting from Control Entropy (CE analysis. Results R-tests showed a significant mean vector difference (p p p p Conclusions These data indicate that fatiguing exercise eliminates the differential complexity response between axes, but increases complexity in all axes compared to the non-fatigued condition. This has implications with regard to the effects of fatigue on strategies of the control system to maintain postural control.

  1. Genetic and biochemical identification of a novel single-stranded DNA binding complex in Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Amy eStroud

    2012-06-01

    Full Text Available Single-stranded DNA binding proteins play an essential role in DNA replication and repair. They use oligosaccharide-binding folds, a five-stranded ß-sheet coiled into a closed barrel, to bind to single-stranded DNA thereby protecting and stabilizing the DNA. In eukaryotes the single-stranded DNA binding protein is known as replication protein A (RPA and consists of three distinct subunits that function as a heterotrimer. The bacterial homolog is termed single-stranded DNA-binding protein (SSB and functions as a homotetramer. In the archaeon Haloferax volcanii there are three genes encoding homologs of RPA. Two of the rpa genes (rpa1 and rpa3 exist in operons with a novel gene specific to Euryarchaeota, this gene encodes a protein that we have termed rpa-associated protein (RPAP. The rpap genes encode proteins belonging to COG3390 group and feature oligosaccharide-binding folds, suggesting that they might cooperate with RPA in binding to single-stranded DNA. Our genetic analysis showed that rpa1 and rpa3 deletion mutants have differing phenotypes; only ∆rpa3 strains are hypersensitive to DNA damaging agents. Deletion of the rpa3-associated gene rpap3 led to similar levels of DNA damage sensitivity, as did deletion of the rpa3 operon, suggesting that RPA3 and RPAP3 function in the same pathway. Protein pull-downs involving recombinant hexahistidine-tagged RPAs showed that RPA3 co-purifies with RPAP3, and RPA1 co-purifies with RPAP1. This indicates that the RPAs interact only with their respective associated proteins; this was corroborated by the inability to construct rpa1 rpap3 and rpa3 rpap1 double mutants. This is the first report investigating the individual function of the archaeal COG3390 RPA-associated proteins. We have shown genetically and biochemically that the RPAPs interact with their respective RPAs, and have uncovered a novel single-stranded DNA binding complex that is unique to Euryarchaeota.

  2. Max-Min SINR in Large-Scale Single-Cell MU-MIMO: Asymptotic Analysis and Low Complexity Transceivers

    KAUST Repository

    Sifaou, Houssem; Kammoun, Abla; Sanguinetti, Luca; Debbah, Merouane; Alouini, Mohamed-Slim

    2016-01-01

    This work focuses on the downlink and uplink of large-scale single-cell MU-MIMO systems in which the base station (BS) endowed with M antennas communicates with K single-antenna user equipments (UEs). Particularly, we aim at reducing the complexity

  3. Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study.

    Science.gov (United States)

    Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D

    2013-06-01

    The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including establishing a safe therapeutic environment, reprocessing the trauma, constructing a new narrative, and managing emotional dysregulation. Therapeutic Assessment (TA) is a semistructured, brief intervention that uses psychological testing to promote positive change. The case study of Kelly, a middle-aged woman with a history of repeated interpersonal trauma, illustrates delivery of the TA model for CPTSD. Results of this single-case time-series experiment indicate statistically significant symptom improvement as a result of participating in TA. We discuss the implications of these findings for assessing and treating trauma-related concerns, such as CPTSD.

  4. Cp2 TiX Complexes for Sustainable Catalysis in Single-Electron Steps.

    Science.gov (United States)

    Richrath, Ruben B; Olyschläger, Theresa; Hildebrandt, Sven; Enny, Daniel G; Fianu, Godfred D; Flowers, Robert A; Gansäuer, Andreas

    2018-04-25

    We present a combined electrochemical, kinetic, and synthetic study with a novel and easily accessible class of titanocene catalysts for catalysis in single-electron steps. The tailoring of the electronic properties of our Cp 2 TiX-catalysts that are prepared in situ from readily available Cp 2 TiX 2 is achieved by varying the anionic ligand X. Of the complexes investigated, Cp 2 TiOMs proved to be either equal or substantially superior to the best catalysts developed earlier. The kinetic and thermodynamic properties pertinent to catalysis have been determined. They allow a mechanistic understanding of the subtle interplay of properties required for an efficient oxidative addition and reduction. Therefore, our study highlights that efficient catalysts do not require the elaborate covalent modification of the cyclopentadienyl ligands. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Protein dynamics revealed in the excitonic spectra of single LH2 complexes

    International Nuclear Information System (INIS)

    Valkunas, Leonas; Janusonis, Julius; Rutkauskas, Danielis; Grondelle, Rienk van

    2007-01-01

    The fluorescence emission spectrum of single peripheral light-harvesting (LH2) complexes of the photosynthetic purple bacterium Rhodopseudomonas acidophila exhibits remarkable dynamics on a time scale of several minutes. Often the spectral properties are quasi-stable; sometimes large spectral jumps to the blue or to the red are observed. To explain the dynamics, every pigment is proposed to be in two conformational substates with different excitation energies, which originate from the conformational state of the protein as a result of pigment-protein interaction. Due to the excitonic coupling in the ring of 18 pigments, the two-state assumption generates a substantial amount of distinct spectroscopic states, which reflect part of the inhomogeneous distributed spectral properties of LH2. To describe the observed dynamics, spontaneous and light-induced transitions are introduced between the two states. For each 'realization of the disorder', the spectral properties are calculated using a disordered exciton model combined with the modified Redfield theory to obtain realistic spectral line shapes. The single-molecule fluorescence peak (FLP) distribution, the distribution dependence on the excitation intensity, and the FLP time traces are well described within the framework of this model

  6. Spin-polarized transport through single-molecule magnet Mn6 complexes

    KAUST Repository

    Cremades, Eduard

    2013-01-01

    The coherent transport properties of a device, constructed by sandwiching a Mn6 single-molecule magnet between two gold surfaces, are studied theoretically by using the non-equilibrium Green\\'s function approach combined with density functional theory. Two spin states of such Mn6 complexes are explored, namely the ferromagnetically coupled configuration of the six MnIII cations, leading to the S = 12 ground state, and the low S = 4 spin state. For voltages up to 1 volt the S = 12 ground state shows a current one order of magnitude larger than that of the S = 4 state. Furthermore this is almost completely spin-polarized, since the Mn6 frontier molecular orbitals for S = 12 belong to the same spin manifold. As such the high-anisotropy Mn6 molecule appears as a promising candidate for implementing, at the single molecular level, both spin-switches and low-temperature spin-valves. © 2013 The Royal Society of Chemistry.

  7. Single-particle fusion of influenza viruses reveals complex interactions with target membranes

    Science.gov (United States)

    van der Borg, Guus; Braddock, Scarlett; Blijleven, Jelle S.; van Oijen, Antoine M.; Roos, Wouter H.

    2018-05-01

    The first step in infection of influenza A virus is contact with the host cell membrane, with which it later fuses. The composition of the target bilayer exerts a complex influence on both fusion efficiency and time. Here, an in vitro, single-particle approach is used to study this effect. Using total internal reflection fluorescence (TIRF) microscopy and a microfluidic flow cell, the hemifusion of single virions is visualized. Hemifusion efficiency and kinetics are studied while altering target bilayer cholesterol content and sialic-acid donor. Cholesterol ratios tested were 0%, 10%, 20%, and 40%. Sialic-acid donors GD1a and GYPA were used. Both cholesterol ratio and sialic-acid donors proved to have a significant effect on hemifusion efficiency. Furthermore, comparison between GD1a and GYPA conditions shows that the cholesterol dependence of the hemifusion time is severely affected by the sialic-acid donor. Only GD1a shows a clear increasing trend in hemifusion efficiency and time with increasing cholesterol concentration of the target bilayer with maximum rates for GD1A and 40% cholesterol. Overall our results show that sialic acid donor and target bilayer composition should be carefully chosen, depending on the desired hemifusion time and efficiency in the experiment.

  8. Simplified paraboloid phase model-based phase tracker for demodulation of a single complex fringe.

    Science.gov (United States)

    He, A; Deepan, B; Quan, C

    2017-09-01

    A regularized phase tracker (RPT) is an effective method for demodulation of single closed-fringe patterns. However, lengthy calculation time, specially designed scanning strategy, and sign-ambiguity problems caused by noise and saddle points reduce its effectiveness, especially for demodulating large and complex fringe patterns. In this paper, a simplified paraboloid phase model-based regularized phase tracker (SPRPT) is proposed. In SPRPT, first and second phase derivatives are pre-determined by the density-direction-combined method and discrete higher-order demodulation algorithm, respectively. Hence, cost function is effectively simplified to reduce the computation time significantly. Moreover, pre-determined phase derivatives improve the robustness of the demodulation of closed, complex fringe patterns. Thus, no specifically designed scanning strategy is needed; nevertheless, it is robust against the sign-ambiguity problem. The paraboloid phase model also assures better accuracy and robustness against noise. Both the simulated and experimental fringe patterns (obtained using electronic speckle pattern interferometry) are used to validate the proposed method, and a comparison of the proposed method with existing RPT methods is carried out. The simulation results show that the proposed method has achieved the highest accuracy with less computational time. The experimental result proves the robustness and the accuracy of the proposed method for demodulation of noisy fringe patterns and its feasibility for static and dynamic applications.

  9. Max-min SINR low complexity transceiver design for single cell massive MIMO

    KAUST Repository

    Sifaou, Houssem

    2016-08-11

    This work focuses on large scale multi-user MIMO systems in which the base station (BS) outfitted with M antennas communicates with K single antenna user equipments (UEs). In particular, we aim at designing the linear precoder and receiver that maximizes the minimum signal-to-interference-plus-noise ratio (SINR) subject to a given power constraint. To gain insights into the structure of the optimal precoder and receiver as well as to reduce the computational complexity for their implementation, we analyze the asymptotic regime where M and K grow large with a given ratio and make use of random matrix theory (RMT) tools to compute accurate approximations. Although simpler, the implementation of the asymptotic precoder and receiver requires fast inversions of large matrices in every coherence period. To overcome this issue, we apply the truncated polynomial expansion (TPE) technique to the precoding and receiving vector of each UE and make use of RMT to determine the optimal weighting coefficients that asymptotically solve the max-min SINR problem. Numerical results are used to show that the proposed TPE-based precoder and receiver almost achieve the same performance as the optimal ones while requiring a lower complexity.

  10. Rational design of single-ion magnets and spin qubits based on mononuclear lanthanoid complexes.

    Science.gov (United States)

    Baldoví, José J; Cardona-Serra, Salvador; Clemente-Juan, Juan M; Coronado, Eugenio; Gaita-Ariño, Alejandro; Palii, Andrew

    2012-11-19

    Here we develop a general approach to calculating the energy spectrum and the wave functions of the low-lying magnetic levels of a lanthanoid ion submitted to the crystal field created by the surrounding ligands. This model allows us to propose general criteria for the rational design of new mononuclear lanthanoid complexes behaving as single-molecule magnets (SMMs) or acting as robust spin qubits. Three typical environments exhibited by these metal complexes are considered, namely, (a) square antiprism, (b) triangular dodecahedron, and (c) trigonal prism. The developed model is used to explain the properties of some representative examples showing these geometries. Key questions in this area, such as the chemical tailoring of the superparamagnetic energy barrier, tunneling gap, or spin relaxation time, are discussed. Finally, in order to take into account delocalization and/or covalent effects of the ligands, this point-charge model is complemented with ab initio calculations, which provide accurate information on the charge distribution around the metal, allowing for an explanation of the SMM behavior displayed by some sandwich-type organometallic compounds.

  11. Complex antioxidants in a randomized single-blinded study of memory in seniors.

    Science.gov (United States)

    Summers, William K; Martin, Roy L; Liu, Yimeng; Peña, Bernice; Marsh, Gary M

    2018-04-01

    Oxidative injury to the brain and aging are theoretical co-causes of Alzheimer's Disease (AD). Amyloid plaques and tangles are then secondary phenomenon. The preclinical state would then be 'normal' elderly. A potent complex antioxidant (antiOx) was tested against a popular one-a-day multivitamin (mV) in a randomized single blind design in 'normal' senior subjects over 6 months. Memory testing was done at baseline, 1, 3, and 6 months. The generalized estimating equation (GEE) approach was used to compare the change score of NLT 100 and 20 WR between two groups over time. Analysis of the antiOx group (30 subjects) demonstrated significant improvement in declarative memory (change score for NLT 100 at month 6 = 6.36 p working memory (change score for 20 WR at month 6 = 3.23, p < 0.0001). A change-score analysis over 6 months suggests possible neurogenesis in the antiOx group. The mV group (33 subjects) had a change score of the NLT 100 and 20WR on the sixth month of 2.20 and 0.32 (p = 0.07, 0.35). A complex antioxidant blend, sold as an over-the-counter (OTC) supplement, can improve memory in elder subjects. Antioxidants may be beneficial in AD and other neurodegerative diseases.

  12. ESR study of irradiated single crystals of the cocrystalline complex of cytidine: Salicylic acid

    International Nuclear Information System (INIS)

    Close, D.M.; Sagstuen, E.

    1983-01-01

    Irradiation at 77 K of single crystals of the 1:1 complex of cytidine and salicylic acid produces a phenoxyl radical formed by oxidation of the salicylic acid. Anisotropic hyperfine coupling tensors have been determined for this radical which are associated with the para and ortho hydrogens. No cytidine oxidation products (alkoxy or hydroxyalkyl radicals) were observed at 77 K. Following the decay of the phenoxyl radical at room temperature, four radicals were detected. These include the cytosine 5--yl and 6--yl radicals, formed by H addition to the cytosine ring, and an anisotropic doublet. By UV irradiation at room temperature, it is possible to convert a significant fraction of 6-yl radicals into 5-yl radicals. Hyperfine coupling and g tensors determined for the anisotropic doublet indicate that this radical is formed in the C/sub 1'/-C/sub 2'/ region of the sugar moiety. These results indicate a shift in radiation damage away from the salicylic acid upon warming, and show that the radiation chemistry of the cocrystalline complex is different from that of the isolated bases

  13. Assignment of Streptococcus agalactiae isolates to clonal complexes using a small set of single nucleotide polymorphisms.

    Science.gov (United States)

    Honsa, Erin; Fricke, Thomas; Stephens, Alex J; Ko, Danny; Kong, Fanrong; Gilbert, Gwendolyn L; Huygens, Flavia; Giffard, Philip M

    2008-08-19

    Streptococcus agalactiae (Group B Streptococcus (GBS)) is an important human pathogen, particularly of newborns. Emerging evidence for a relationship between genotype and virulence has accentuated the need for efficient and well-defined typing methods. The objective of this study was to develop a single nucleotide polymorphism (SNP) based method for assigning GBS isolates to multilocus sequence typing (MLST)-defined clonal complexes. It was found that a SNP set derived from the MLST database on the basis of maximization of Simpsons Index of Diversity provided poor resolution and did not define groups concordant with the population structure as defined by eBURST analysis of the MLST database. This was interpreted as being a consequence of low diversity and high frequency horizontal gene transfer. Accordingly, a different approach to SNP identification was developed. This entailed use of the "Not-N" bioinformatic algorithm that identifies SNPs diagnostic for groups of known sequence variants, together with an empirical process of SNP testing. This yielded a four member SNP set that divides GBS into 10 groups that are concordant with the population structure. A fifth SNP was identified that increased the sensitivity for the clinically significant clonal complex 17 to 100%. Kinetic PCR methods for the interrogation of these SNPs were developed, and used to genotype 116 well characterized isolates. A five SNP method for dividing GBS into biologically valid groups has been developed. These SNPs are ideal for high throughput surveillance activities, and combining with more rapidly evolving loci when additional resolution is required.

  14. Modern possibilities of radiotherapy in the complex and single treatment of panaris

    International Nuclear Information System (INIS)

    Kolipiliev, V.; Momchev, M.

    1979-01-01

    Results are reported of the treatment of 282 patients with different forms of panaris: 39 per cent received radiotherapy alone, in the remaining radiotherapy was combined with surgical management, antibiotics and local treatment. Two different radiotherapy schemes were attempted: 49% of the patients received rather high single (50-80 rad) and total (300-600 rad) doses in the local site at a regimen of superficial (100 kV, 4 mm Al) or deep (180-200 kV, 0.5-1 mm Cu) roentgentherapy, with size of field 4/4 cm or 4/6 cm and 30-40 cm distance. In the remaining 51% of patients radiotherapy was characterized by dynamic fractionation and longer duration of procedures with significantly lower single (30-40 rad) and total (160-320 rad) doses. In recent years the second scheme has been preferred and has gain wide acceptance. Irradiation dose and rate invariably conformed to the type of inflammatory process. Patients with panaritium paronychium and panaritium subcutaneum admitted for treatment in the first few days of development of the digital infection required only several procedures on alternate days to achieve complete cure in a week. In the event of pus collection, 1 or 2 irradiation procedures accelerated abscess formation; this was followed by surgical intervention with postoperative radiotherapy to hasten the granulation process. Treatment of bone-and-joint forms of panaris was complex with initially higher single doses, followed by lower ones, applied up to twice weekly. The following advantages of the method are pointed out: shortening of treatment, respectively of the disability period; easy to perform, painless and practically innocuous manipulation. Complete cure could not be achieved only in advanced, torpid cases. (A.B.)

  15. SCAP-82, Single Scattering, Albedo Scattering, Point-Kernel Analysis in Complex Geometry

    International Nuclear Information System (INIS)

    Disney, R.K.; Vogtman, S.E.

    1987-01-01

    1 - Description of problem or function: SCAP solves for radiation transport in complex geometries using the single or albedo scatter point kernel method. The program is designed to calculate the neutron or gamma ray radiation level at detector points located within or outside a complex radiation scatter source geometry or a user specified discrete scattering volume. Geometry is describable by zones bounded by intersecting quadratic surfaces within an arbitrary maximum number of boundary surfaces per zone. Anisotropic point sources are describable as pointwise energy dependent distributions of polar angles on a meridian; isotropic point sources may also be specified. The attenuation function for gamma rays is an exponential function on the primary source leg and the scatter leg with a build- up factor approximation to account for multiple scatter on the scat- ter leg. The neutron attenuation function is an exponential function using neutron removal cross sections on the primary source leg and scatter leg. Line or volumetric sources can be represented as a distribution of isotropic point sources, with un-collided line-of-sight attenuation and buildup calculated between each source point and the detector point. 2 - Method of solution: A point kernel method using an anisotropic or isotropic point source representation is used, line-of-sight material attenuation and inverse square spatial attenuation between the source point and scatter points and the scatter points and detector point is employed. A direct summation of individual point source results is obtained. 3 - Restrictions on the complexity of the problem: - The SCAP program is written in complete flexible dimensioning so that no restrictions are imposed on the number of energy groups or geometric zones. The geometric zone description is restricted to zones defined by boundary surfaces defined by the general quadratic equation or one of its degenerate forms. The only restriction in the program is that the total

  16. "Switching on" the properties of single-molecule magnetism in triangular manganese(III) complexes.

    Science.gov (United States)

    Stamatatos, Theocharis C; Foguet-Albiol, Dolos; Lee, Sheng-Chiang; Stoumpos, Constantinos C; Raptopoulou, Catherine P; Terzis, Aris; Wernsdorfer, Wolfgang; Hill, Stephen O; Perlepes, Spyros P; Christou, George

    2007-08-01

    The reaction between oxide-centered, triangular [MnIII3O(O2CR)6(py)3](ClO4) (R = Me (1), Et (2), Ph (3)) compounds and methyl 2-pyridyl ketone oxime (mpkoH) affords a new family of Mn/carboxylato/oximato complexes, [MnIII3O(O2CR)3(mpko)3](ClO4) [R = Me (4), Et (5), and Ph (6)]. As in 1-3, the cations of 4-6 contain an [MnIII3(mu3-O)]7+ triangular core, but with each Mn2 edge now bridged by an eta1:eta1:mu-RCO2- and an eta1:eta1:eta1:mu-mpko- group. The tridentate binding mode of the latter causes a buckling of the formerly planar [MnIII3(mu3-O)]7+ core, resulting in a relative twisting of the three MnIII octahedra and the central O2- ion now lying approximately 0.3 A above the Mn3 plane. This structural distortion leads to ferromagnetic exchange interactions within the molecule and a resulting S = 6 ground state. Fits of dc magnetization data for 4-6 collected in the 1.8-10.0 K and 10-70 kG ranges confirmed S = 6 ground states, and gave the following D and g values: -0.34 cm(-1) and 1.92 for 4, -0.34 cm(-1) and 1.93 for 5, and -0.35 cm(-1) and 1.99 for 6, where D is the axial zero-field splitting (anisotropy) parameter. Complexes 4-6 all exhibit frequency-dependent out-of-phase (chi" M) ac susceptibility signals suggesting them possibly to be single-molecule magnets (SMMs). Relaxation rate vs T data for complex 4 down to 1.8 K obtained from the chi" M vs T studies were supplemented with rate vs T data measured to 0.04 K via magnetization vs time decay studies, and these were used to construct Arrhenius plots from which was obtained the effective barrier to relaxation (Ueff) of 10.9 K. Magnetization vs dc field sweeps on single-crystals of 4.3CH2Cl2 displayed hysteresis loops exhibiting steps due to quantum tunneling of magnetization (QTM). The loops were essentially temperature-independent below approximately 0.3 K, indicating only ground-state QTM between the lowest-lying Ms = +/-6 levels. Complexes 4-6 are thus confirmed as the first triangular SMMs. High

  17. Superior Performance of the SQM/COSMO Scoring Functions in Native Pose Recognition of Diverse Protein-Ligand Complexes in Cognate Docking

    Czech Academy of Sciences Publication Activity Database

    Ajani, Haresh; Pecina, Adam; Eyrilmez, Saltuk M.; Fanfrlík, Jindřich; Haldar, Susanta; Řezáč, Jan; Hobza, Pavel; Lepšík, Martin

    2017-01-01

    Roč. 2, č. 7 (2017), s. 4022-4029 ISSN 2470-1343 R&D Projects: GA ČR(CZ) GBP208/12/G016; GA ČR(CZ) GJ16-11321Y Institutional support: RVO:61388963 Keywords : aldose reductase inhibition * biological applications * mechanical calculations Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry https://pubs.acs.org/doi/full/10.1021/acsomega.7b00503

  18. Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.

    Science.gov (United States)

    Duffy, Bryan C; Liu, Shuang; Martin, Gregory S; Wang, Ruifang; Hsia, Ming Min; Zhao, He; Guo, Cheng; Ellis, Michael; Quinn, John F; Kharenko, Olesya A; Norek, Karen; Gesner, Emily M; Young, Peter R; McLure, Kevin G; Wagner, Gregory S; Lakshminarasimhan, Damodharan; White, Andre; Suto, Robert K; Hansen, Henrik C; Kitchen, Douglas B

    2015-07-15

    Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low μM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Ranking docking poses by graph matching of protein-ligand interactions: lessons learned from the D3R Grand Challenge 2

    Science.gov (United States)

    da Silva Figueiredo Celestino Gomes, Priscila; Da Silva, Franck; Bret, Guillaume; Rognan, Didier

    2018-01-01

    A novel docking challenge has been set by the Drug Design Data Resource (D3R) in order to predict the pose and affinity ranking of a set of Farnesoid X receptor (FXR) agonists, prior to the public release of their bound X-ray structures and potencies. In a first phase, 36 agonists were docked to 26 Protein Data Bank (PDB) structures of the FXR receptor, and next rescored using the in-house developed GRIM method. GRIM aligns protein-ligand interaction patterns of docked poses to those of available PDB templates for the target protein, and rescore poses by a graph matching method. In agreement with results obtained during the previous 2015 docking challenge, we clearly show that GRIM rescoring improves the overall quality of top-ranked poses by prioritizing interaction patterns already visited in the PDB. Importantly, this challenge enables us to refine the applicability domain of the method by better defining the conditions of its success. We notably show that rescoring apolar ligands in hydrophobic pockets leads to frequent GRIM failures. In the second phase, 102 FXR agonists were ranked by decreasing affinity according to the Gibbs free energy of the corresponding GRIM-selected poses, computed by the HYDE scoring function. Interestingly, this fast and simple rescoring scheme provided the third most accurate ranking method among 57 contributions. Although the obtained ranking is still unsuitable for hit to lead optimization, the GRIM-HYDE scoring scheme is accurate and fast enough to post-process virtual screening data.

  20. 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)

    2012-02-21

    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.

  1. Complex Parts, Complex Data: Why You Need to Understand What Radiation Single Event Testing Data Does and Doesn't Show and the Implications Thereof

    Science.gov (United States)

    LaBel, Kenneth A.; Berg, Melanie D.

    2015-01-01

    Electronic parts (integrated circuits) have grown in complexity such that determining all failure modes and risks from single particle event testing is impossible. In this presentation, the authors will present why this is so and provide some realism on what this means. Its all about understanding actual risks and not making assumptions.

  2. Single ICMEs and Complex Transient Structures in the Solar Wind in 2010 - 2011

    Science.gov (United States)

    Rodkin, D.; Slemzin, V.; Zhukov, A. N.; Goryaev, F.; Shugay, Y.; Veselovsky, I.

    2018-05-01

    the single-source and multi-source solar wind structures and compared them with the ICME signatures determined from the kinematic and magnetic field parameters of the solar wind. In single-source events, the ion charge state, as a rule, has a one-peak enhancement with an average duration of about one day, which is similar to the mean ICME duration of 1.12 days derived from the Richardson and Cane list. In the multi-source events, the total profile of the ion charge state consists of a sequence of enhancements that is associated with the interaction between the participating streams. On average, the total duration of the complex structures that appear as a result of the CME-CME and CME-HSS interactions as determined from their ion composition is 2.4 days, which is more than twice longer than that of the single-source events.

  3. Size versus polarizability in protein-ligand interactions: binding of noble gases within engineered cavities in phage T4 lysozyme.

    Science.gov (United States)

    Quillin, M L; Breyer, W A; Griswold, I J; Matthews, B W

    2000-09-29

    To investigate the relative importance of size and polarizability in ligand binding within proteins, we have determined the crystal structures of pseudo wild-type and cavity-containing mutant phage T4 lysozymes in the presence of argon, krypton, and xenon. These proteins provide a representative sample of predominantly apolar cavities of varying size and shape. Even though the volumes of these cavities range up to the equivalent of five xenon atoms, the noble gases bind preferentially at highly localized sites that appear to be defined by constrictions in the walls of the cavities, coupled with the relatively large radii of the noble gases. The cavities within pseudo wild-type and L121A lysozymes each bind only a single atom of noble gas, while the cavities within mutants L133A and F153A have two independent binding sites, and the L99A cavity has three interacting sites. The binding of noble gases within two double mutants was studied to characterize the additivity of binding at such sites. In general, when a cavity in a protein is created by a "large-to-small" substitution, the surrounding residues relax somewhat to reduce the volume of the cavity. The binding of xenon and, to a lesser degree, krypton and argon, tend to expand the volume of the cavity and to return it closer to what it would have been had no relaxation occurred. In nearly all cases, the extent of binding of the noble gases follows the trend xenon>krypton>argon. Pressure titrations of the L99A mutant have confirmed that the crystallographic occupancies accurately reflect fractional saturation of the binding sites. The trend in noble gas affinity can be understood in terms of the effects of size and polarizability on the intermolecular potential. The plasticity of the protein matrix permits repulsion due to increased ligand size to be more than compensated for by attraction due to increased ligand polarizability. These results have implications for the mechanism of general anesthesia, the migration

  4. Excitation energy transfer in natural photosynthetic complexes and chlorophyll trefoils: hole-burning and single complex/trefoil spectroscopic studies

    Energy Technology Data Exchange (ETDEWEB)

    Ryszard Jankowiak, Kansas State University, Department of Chemistry, CBC Bldg., Manhattan KS, 66505; Phone: (785) 532-6785

    2012-09-12

    In this project we studied both natural photosynthetic antenna complexes and various artificial systems (e.g. chlorophyll (Chl) trefoils) using high resolution hole-burning (HB) spectroscopy and excitonic calculations. Results obtained provided more insight into the electronic (excitonic) structure, inhomogeneity, electron-phonon coupling strength, vibrational frequencies, and excitation energy (or electron) transfer (EET) processes in several antennas and reaction centers. For example, our recent work provided important constraints and parameters for more advanced excitonic calculations of CP43, CP47, and PSII core complexes. Improved theoretical description of HB spectra for various model systems offers new insight into the excitonic structure and composition of low-energy absorption traps in very several antenna protein complexes and reaction centers. We anticipate that better understanding of HB spectra obtained for various photosynthetic complexes and their simultaneous fits with other optical spectra (i.e. absorption, emission, and circular dichroism spectra) provides more insight into the underlying electronic structures of these important biological systems. Our recent progress provides a necessary framework for probing the electronic structure of these systems via Hole Burning Spectroscopy. For example, we have shown that the theoretical description of non-resonant holes is more restrictive (in terms of possible site energies) than those of absorption and emission spectra. We have demonstrated that simultaneous description of linear optical spectra along with HB spectra provides more realistic site energies. We have also developed new algorithms to describe both nonresonant and resonant hole-burn spectra using more advanced Redfield theory. Simultaneous description of various optical spectra for complex biological system, e.g. artificial antenna systems, FMO protein complexes, water soluble protein complexes, and various mutants of reaction centers

  5. Measuring kinetics of complex single ion channel data using mean-variance histograms.

    Science.gov (United States)

    Patlak, J B

    1993-07-01

    The measurement of single ion channel kinetics is difficult when those channels exhibit subconductance events. When the kinetics are fast, and when the current magnitudes are small, as is the case for Na+, Ca2+, and some K+ channels, these difficulties can lead to serious errors in the estimation of channel kinetics. I present here a method, based on the construction and analysis of mean-variance histograms, that can overcome these problems. A mean-variance histogram is constructed by calculating the mean current and the current variance within a brief "window" (a set of N consecutive data samples) superimposed on the digitized raw channel data. Systematic movement of this window over the data produces large numbers of mean-variance pairs which can be assembled into a two-dimensional histogram. Defined current levels (open, closed, or sublevel) appear in such plots as low variance regions. The total number of events in such low variance regions is estimated by curve fitting and plotted as a function of window width. This function decreases with the same time constants as the original dwell time probability distribution for each of the regions. The method can therefore be used: 1) to present a qualitative summary of the single channel data from which the signal-to-noise ratio, open channel noise, steadiness of the baseline, and number of conductance levels can be quickly determined; 2) to quantify the dwell time distribution in each of the levels exhibited. In this paper I present the analysis of a Na+ channel recording that had a number of complexities. The signal-to-noise ratio was only about 8 for the main open state, open channel noise, and fast flickers to other states were present, as were a substantial number of subconductance states. "Standard" half-amplitude threshold analysis of these data produce open and closed time histograms that were well fitted by the sum of two exponentials, but with apparently erroneous time constants, whereas the mean

  6. Single-molecule exploration of photoprotective mechanisms in light-harvesting complexes

    Science.gov (United States)

    Yang, Hsiang-Yu; Schlau-Cohen, Gabriela S.; Gwizdala, Michal; Krüger, Tjaart; Xu, Pengqi; Croce, Roberta; van Grondelle, Rienk; Moerner, W. E.

    2015-03-01

    Plants harvest sunlight by converting light energy to electron flow through the primary events in photosynthesis. One important question is how the light harvesting machinery adapts to fluctuating sunlight intensity. As a result of various regulatory processes, efficient light harvesting and photoprotection are balanced. Some of the biological steps in the photoprotective processes have been extensively studied and physiological regulatory factors have been identified. For example, the effect of lumen pH in changing carotenoid composition has been explored. However, the importance of photophysical dynamics in the initial light-harvesting steps and its relation to photoprotection remain poorly understood. Conformational and excited-state dynamics of multi-chromophore pigment-protein complexes are often difficult to study and limited information can be extracted from ensemble-averaged measurements. To address the problem, we use the Anti-Brownian ELectrokinetic (ABEL) trap to investigate the fluorescence from individual copies of light-harvesting complex II (LHCII), the primary antenna protein in higher plants, in a solution-phase environment. Perturbative surface immobilization or encapsulation schemes are avoided, and therefore the intrinsic dynamics and heterogeneity in the fluorescence of individual proteins are revealed. We perform simultaneous measurements of fluorescence intensity (brightness), excited-state lifetime, and emission spectrum of single trapped proteins. By analyzing the correlated changes between these observables, we identify forms of LHCII with different fluorescence intensities and excited-state lifetimes. The distinct forms may be associated with different energy dissipation mechanisms in the energy transfer chain. Changes of relative populations in response to pH and carotenoid composition are observed, which may extend our understanding of the molecular mechanisms of photoprotection.

  7. Assignment of Streptococcus agalactiae isolates to clonal complexes using a small set of single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Gilbert Gwendolyn L

    2008-08-01

    Full Text Available Abstract Background Streptococcus agalactiae (Group B Streptococcus (GBS is an important human pathogen, particularly of newborns. Emerging evidence for a relationship between genotype and virulence has accentuated the need for efficient and well-defined typing methods. The objective of this study was to develop a single nucleotide polymorphism (SNP based method for assigning GBS isolates to multilocus sequence typing (MLST-defined clonal complexes. Results It was found that a SNP set derived from the MLST database on the basis of maximisation of Simpsons Index of Diversity provided poor resolution and did not define groups concordant with the population structure as defined by eBURST analysis of the MLST database. This was interpreted as being a consequence of low diversity and high frequency horizontal gene transfer. Accordingly, a different approach to SNP identification was developed. This entailed use of the "Not-N" bioinformatic algorithm that identifies SNPs diagnostic for groups of known sequence variants, together with an empirical process of SNP testing. This yielded a four member SNP set that divides GBS into 10 groups that are concordant with the population structure. A fifth SNP was identified that increased the sensitivity for the clinically significant clonal complex 17 to 100%. Kinetic PCR methods for the interrogation of these SNPs were developed, and used to genotype 116 well characterized isolates. Conclusion A five SNP method for dividing GBS into biologically valid groups has been developed. These SNPs are ideal for high throughput surveillance activities, and combining with more rapidly evolving loci when additional resolution is required.

  8. Complex single step skull reconstruction in Gorham's disease - a technical report and review of the literature.

    Science.gov (United States)

    Ohla, Victoria; Bayoumi, Ahmed B; Hefty, Markus; Anderson, Matthew; Kasper, Ekkehard M

    2015-03-11

    Gorham's disease is a rare osteolytic disorder characterized by progressive resorption of bone and replacement of osseous matrix by a proliferative non-neoplastic vascular or lymphatic tissue. A standardized treatment protocol has not yet been defined due to the unpredictable natural history of the disease and variable clinical presentations. No single treatment has proven to be superior in arresting the course of the disease. Trials have included surgery, radiation and medical therapies using drugs such as calcium salts, vitamin D supplements and hormones. We report on our advantageous experience in the management of this osteolyic disorder in a case when it affected only the skull vault. A brief review of pertinent literature about Gorham's disease with skull involvement is provided. A 25-year-old Caucasian male presented with a skull depression over the left fronto-temporal region. He noticed progressive enlargement of the skull defect associated with local pain and mild headache. Physical examination revealed a tender palpable depression of the fronto-temporal convexity. Conventional X-ray of the skull showed widespread loss of bone substance. Subsequent CT scans showed features of patchy erosions indicative of an underlying osteolysis. MRI also revealed marginal enhancement at the site of the defect. The patient was in need of a pathological diagnosis as well as complex reconstruction of the afflicted area. A density graded CT scan was done to determine the variable degrees of osteolysis and a custom made allograft was designed for cranioplasty preoperatively to allow for a single step excisional craniectomy with synchronous skull repair. Gorham's disease was diagnosed based on histopathological examination. No neurological deficit or wound complications were reported postoperatively. Over a two-year follow up period, the patient had no evidence of local recurrence or other systemic involvement. A single step excisional craniectomy and cranioplasty can be an

  9. Impacts of Coulomb Interactions on the Magnetic Responses of Excitonic Complexes in Single Semiconductor Nanostructures

    Directory of Open Access Journals (Sweden)

    Fu Ying-Jhe

    2010-01-01

    Full Text Available Abstract We report on the diamagnetic responses of different exciton complexes in single InAs/GaAs self-assembled quantum dots (QDs and quantum rings (QRs. For QDs, the imbalanced magnetic responses of inter-particle Coulomb interactions play a crucial role in the diamagnetic shifts of excitons (X, biexcitons (XX, and positive trions (X−. For negative trions (X− in QDs, anomalous magnetic responses are observed, which cannot be described by the conventional quadratic energy shift with the magnetic field. The anomalous behavior is attributed to the apparent change in the electron wave function extent after photon emission due to the strong Coulomb attraction by the hole in its initial state. In QRs, the diamagnetic responses of X and XX also show different behaviors. Unlike QDs, the diamagnetic shift of XX in QRs is considerably larger than that of X. The inherent structural asymmetry combined with the inter-particle Coulomb interactions makes the wave function distribution of XX very different from that of X in QRs. Our results suggest that the phase coherence of XX in QRs may survive from the wave function localization due to the structural asymmetry or imperfections.

  10. Capturing complex human behaviors in representative sports contexts with a single camera.

    Science.gov (United States)

    Duarte, Ricardo; Araújo, Duarte; Fernandes, Orlando; Fonseca, Cristina; Correia, Vanda; Gazimba, Vítor; Travassos, Bruno; Esteves, Pedro; Vilar, Luís; Lopes, José

    2010-01-01

    In the last years, several motion analysis methods have been developed without considering representative contexts for sports performance. The purpose of this paper was to explain and underscore a straightforward method to measure human behavior in these contexts. Procedures combining manual video tracking (with TACTO device) and bidimensional reconstruction (through direct linear transformation) using a single camera were used in order to capture kinematic data required to compute collective variable(s) and control parameter(s). These procedures were applied to a 1vs1 association football task as an illustrative subphase of team sports and will be presented in a tutorial fashion. Preliminary analysis of distance and velocity data identified a collective variable (difference between the distance of the attacker and the defender to a target defensive area) and two nested control parameters (interpersonal distance and relative velocity). Findings demonstrated that the complementary use of TACTO software and direct linear transformation permit to capture and reconstruct complex human actions in their context in a low dimensional space (information reduction).

  11. Single conversion audio amplifier and DC-AC converters with high performance and low complexity control scheme

    DEFF Research Database (Denmark)

    Poulsen, Søren; Andersen, Michael Andreas E.

    2004-01-01

    This paper proposes a novel control topology for a mains isolated single conversion audio amplifier and DC-AC converters. The topology is made for use in audio applications, and differs from prior art in terms of significantly reduced distortion as well as lower system complexity. The topology can...

  12. Development of a Single Locus Sequence Typing (SLST) Scheme for Typing Bacterial Species Directly from Complex Communities.

    Science.gov (United States)

    Scholz, Christian F P; Jensen, Anders

    2017-01-01

    The protocol describes a computational method to develop a Single Locus Sequence Typing (SLST) scheme for typing bacterial species. The resulting scheme can be used to type bacterial isolates as well as bacterial species directly from complex communities using next-generation sequencing technologies.

  13. Low-Complexity Model Predictive Control of Single-Phase Three-Level Rectifiers with Unbalanced Load

    DEFF Research Database (Denmark)

    Ma, Junpeng; Song, Wensheng; Wang, Xiongfei

    2018-01-01

    The fluctuation of the neutral-point potential in single-phase three-level rectifiers leads to coupling between the line current regulation and dc-link voltage balancing, deteriorating the quality of line current. For addressing this issue, this paper proposes a low-complexity model predictive...

  14. Tunable complex-valued multi-tap microwave photonic filter based on single silicon-oninsulator microring resonator

    DEFF Research Database (Denmark)

    Lloret, Juan; Sancho, Juan; Pu, Minhao

    2011-01-01

    A complex-valued multi-tap tunable microwave photonic filter based on single silicon-on-insulator microring resonator is presented. The degree of tunability of the approach involving two, three and four taps is theoretical and experimentally characterized, respectively. The constraints of exploit...

  15. Detailed Investigation of the Structural, Thermal, and Electronic Properties of Gold Isocyanide Complexes with Mechano-Triggered Single-Crystal-to-Single-Crystal Phase Transitions.

    Science.gov (United States)

    Seki, Tomohiro; Sakurada, Kenta; Muromoto, Mai; Seki, Shu; Ito, Hajime

    2016-02-01

    Mechano-induced phase transitions in organic crystalline materials, which can alter their properties, have received much attention. However, most mechano-responsive molecular crystals exhibit crystal-to-amorphous phase transitions, and the intermolecular interaction patterns in the daughter phase are difficult to characterize. We have investigated phenyl(phenylisocyanide)gold(I) (1) and phenyl(3,5-dimethylphenylisocyanide)gold(I) (2) complexes, which exhibit a mechano-triggered single-crystal-to-single-crystal phase transition. Previous reports of complexes 1 and 2 have focused on the relationships between the crystalline structures and photoluminescence properties; in this work we have focused on other aspects. The face index measurements of complexes 1 and 2 before and after the mechano-induced phase transitions have indicated that they undergo non-epitaxial phase transitions without a rigorous orientational relationship between the mother and daughter phases. Differential scanning calorimetry analyses revealed the phase transition of complex 1 to be enthalpically driven by the formation of new aurophilic interactions. In contrast, the phase transition of complex 2 was found to be entropically driven, with the closure of an empty void in the mother phase. Scanning electron microscopy observation showed that the degree of the charging effect of both complexes 1 and 2 was changed by the phase transitions, which suggests that the formation of the aurophilic interactions affords more effective conductive pathways. Moreover, flash-photolysis time-resolved microwave conductivity measurements revealed that complex 1 increased in conductivity after the phase change, whereas the conductivity of complex 2 decreased. These contrasting results were explained by the different patterns in the aurophilic interactions. Finally, an intriguing disappearing polymorphism of complex 2 has been reported, in which a polymorph form could not be obtained again after some period of time

  16. Terbutaline causes immobilization of single β2-adrenergic receptor-ligand complexes in the plasma membrane of living A549 cells as revealed by single-molecule microscopy

    Science.gov (United States)

    Sieben, Anne; Kaminski, Tim; Kubitscheck, Ulrich; Häberlein, Hanns

    2011-02-01

    G-protein-coupled receptors are important targets for various drugs. After signal transduction, regulatory processes, such as receptor desensitization and internalization, change the lateral receptor mobility. In order to study the lateral diffusion of β2-adrenergic receptors (β2AR) complexed with fluorescently labeled noradrenaline (Alexa-NA) in plasma membranes of A549 cells, trajectories of single receptor-ligand complexes were monitored using single-particle tracking. We found that a fraction of 18% of all β2ARs are constitutively immobile. About 2/3 of the β2ARs moved with a diffusion constant of D2 = 0.03+/-0.001 μm2/s and about 17% were diffusing five-fold faster (D3 = 0.15+/-0.02 μm2/s). The mobile receptors moved within restricted domains and also showed a discontinuous diffusion behavior. Analysis of the trajectory lengths revealed two different binding durations with τ1 = 77+/-1 ms and τ2 = 388+/-11 ms. Agonistic stimulation of the β2AR-Alexa-NA complexes with 1 μM terbutaline caused immobilization of almost 50% of the receptors within 35 min. Simultaneously, the mean area covered by the mobile receptors decreased significantly. Thus, we demonstrated that agonistic stimulation followed by cell regulatory processes results in a change in β2AR mobility suggesting that different receptor dynamics characterize different receptor states.

  17. TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize.

    Science.gov (United States)

    Garcia, Nelson; Messing, Joachim

    2017-01-01

    The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90) to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs). Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

  18. In Planta Single-Molecule Pull-Down Reveals Tetrameric Stoichiometry of HD-ZIPIII:LITTLE ZIPPER Complexes.

    Science.gov (United States)

    Husbands, Aman Y; Aggarwal, Vasudha; Ha, Taekjip; Timmermans, Marja C P

    2016-08-01

    Deciphering complex biological processes markedly benefits from approaches that directly assess the underlying biomolecular interactions. Most commonly used approaches to monitor protein-protein interactions typically provide nonquantitative readouts that lack statistical power and do not yield information on the heterogeneity or stoichiometry of protein complexes. Single-molecule pull-down (SiMPull) uses single-molecule fluorescence detection to mitigate these disadvantages and can quantitatively interrogate interactions between proteins and other compounds, such as nucleic acids, small molecule ligands, and lipids. Here, we establish SiMPull in plants using the HOMEODOMAIN LEUCINE ZIPPER III (HD-ZIPIII) and LITTLE ZIPPER (ZPR) interaction as proof-of-principle. Colocalization analysis of fluorophore-tagged HD-ZIPIII and ZPR proteins provides strong statistical evidence of complex formation. In addition, we use SiMPull to directly quantify YFP and mCherry maturation probabilities, showing these differ substantially from values obtained in mammalian systems. Leveraging these probabilities, in conjunction with fluorophore photobleaching assays on over 2000 individual complexes, we determined HD-ZIPIII:ZPR stoichiometry. Intriguingly, these complexes appear as heterotetramers, comprising two HD-ZIPIII and two ZPR molecules, rather than heterodimers as described in the current model. This surprising result raises new questions about the regulation of these key developmental factors and is illustrative of the unique contribution SiMPull is poised to make to in planta protein interaction studies. © 2016 American Society of Plant Biologists. All rights reserved.

  19. TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize

    Directory of Open Access Journals (Sweden)

    Nelson Garcia

    2017-11-01

    Full Text Available The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90 to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs. Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

  20. Tunable complex-valued multi-tap microwave photonic filter based on single silicon-on-insulator microring resonator.

    Science.gov (United States)

    Lloret, Juan; Sancho, Juan; Pu, Minhao; Gasulla, Ivana; Yvind, Kresten; Sales, Salvador; Capmany, José

    2011-06-20

    A complex-valued multi-tap tunable microwave photonic filter based on single silicon-on-insulator microring resonator is presented. The degree of tunability of the approach involving two, three and four taps is theoretical and experimentally characterized, respectively. The constraints of exploiting the optical phase transfer function of a microring resonator aiming at implementing complex-valued multi-tap filtering schemes are also reported. The trade-off between the degree of tunability without changing the free spectral range and the number of taps is studied in-depth. Different window based scenarios are evaluated for improving the filter performance in terms of the side-lobe level.

  1. Max-min SINR low complexity transceiver design for single cell massive MIMO

    KAUST Repository

    Sifaou, Houssem; Kammoun, Abla; Sanguinetti, Luca; Debbah, Mé rouane; Alouini, Mohamed-Slim

    2016-01-01

    This work focuses on large scale multi-user MIMO systems in which the base station (BS) outfitted with M antennas communicates with K single antenna user equipments (UEs). In particular, we aim at designing the linear precoder and receiver

  2. A single cognitive heuristic process meets the complexity of domain-specific moral heuristics.

    Science.gov (United States)

    Dubljević, Veljko; Racine, Eric

    2014-10-01

    The inherence heuristic (a) offers modest insights into the complex nature of both the is-ought tension in moral reasoning and moral reasoning per se, and (b) does not reflect the complexity of domain-specific moral heuristics. Formal and general in nature, we contextualize the process described as "inherence heuristic" in a web of domain-specific heuristics (e.g., agent specific; action specific; consequences specific).

  3. Outcomes of the single-stent versus kissing-stents technique in asymmetric complex aortoiliac bifurcation lesions.

    Science.gov (United States)

    Suh, Yongsung; Ko, Young-Guk; Shin, Dong-Ho; Kim, Jung-Sun; Kim, Byeong-Keuk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

    2015-07-01

    This study investigated the outcomes of single-stent vs kissing-stents techniques in asymmetric complex aortoiliac bifurcation (ACAB) lesions. We retrospectively investigated 80 consecutive patients (69 males, 66.6 ± 8.7 years) treated with a single stent and 30 patients (26 males, 67.1 ± 7.7 years) treated with kissing stents for ACAB between January 2005 and December 2012 from a single-center cohort. A ACAB lesion was defined as a symptomatic unilateral common iliac artery stenosis (>50%) combined with intermediate stenosis (30%-50%) in the contralateral common iliac artery ostium. The primary end point was the primary patency of the ACAB. The baseline clinical characteristics did not differ significantly between the single-stent and the kissing-stents group. Technical success was achieved in all patients. The single-stent group required fewer stents (1.3 ± 0.5 vs 2.3 ± 0.8; P stent group (3%) required bailout kissing stents because of plaque shift to the contralateral side. The major complication rates were 8% in single-stent vs 13% in the kissing-stent group, which was similar (P = .399). At 3 years, the single-stent and kissing-stents group had similar rates of primary patency (89% vs 87%; P = .916) and target lesion revascularization-free survival (93% vs 87%; P = .462). The single-stent technique in ACAB was safe and showed midterm outcomes comparable with those of kissing stents. Considering the benefits, such as fewer stents, less bilateral femoral access, and the availability of contralateral access for future intervention, the single-stent technique may be an advantageous treatment option in ACAB. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  4. Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

    Science.gov (United States)

    Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

    2014-11-24

    Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Ultrafast single-molecule photonics: Excited state dynamics in coherently coupled complexes

    International Nuclear Information System (INIS)

    Hernando, Jordi; Hoogenboom, Jacob; Dijk, Erik van; Garcia-Parajo, Maria; Hulst, Niek F. van

    2008-01-01

    We present a single-molecule study on femtosecond dynamics in multichromophoric systems, combining fs pump-probe, emission-spectra and fluorescence-lifetime analysis. The ultrafast fs approach gives direct information on the initial exciton dynamics after excitation. The lifetime data show superradiance, a direct measure for the extent of the coherent coupling and static disorder. The spectra finally reveal the role of exciton-phonon coupling. At the single-molecule level a wide range of exciton delocalization lengths and energy redistribution times is revealed

  6. Ultrafast single-molecule photonics: Excited state dynamics in coherently coupled complexes

    Energy Technology Data Exchange (ETDEWEB)

    Hernando, Jordi [Dept. de Quimica, Universitat Autonoma Barcelona, 08193 Cerdanyola del Valles (Spain); Hoogenboom, Jacob [ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona (Spain); Dijk, Erik van [Applied Optics Group, MESA Institute for Nanotechnology, University of Twente, 7500AE Enschede (Netherlands); Garcia-Parajo, Maria [IBEC-Institute of BioEngineering of Catalunya, 08028 Barcelona (Spain); ICREA-Institucio Catalana de Recerca i Estudis Avancats, 08015 Barcelona (Spain); Hulst, Niek F. van [ICFO-Institut de Ciencies Fotoniques, Mediterranean Technology Park, 08860 Castelldefels, Barcelona (Spain) and ICREA-Institucio Catalana de Recerca i Estudis Avancats, 08015 Barcelona (Spain)], E-mail: Niek.vanHulst@ICFO.es

    2008-05-15

    We present a single-molecule study on femtosecond dynamics in multichromophoric systems, combining fs pump-probe, emission-spectra and fluorescence-lifetime analysis. The ultrafast fs approach gives direct information on the initial exciton dynamics after excitation. The lifetime data show superradiance, a direct measure for the extent of the coherent coupling and static disorder. The spectra finally reveal the role of exciton-phonon coupling. At the single-molecule level a wide range of exciton delocalization lengths and energy redistribution times is revealed.

  7. A single frequency component-based re-estimated MUSIC algorithm for impact localization on complex composite structures

    International Nuclear Information System (INIS)

    Yuan, Shenfang; Bao, Qiao; Qiu, Lei; Zhong, Yongteng

    2015-01-01

    The growing use of composite materials on aircraft structures has attracted much attention for impact monitoring as a kind of structural health monitoring (SHM) method. Multiple signal classification (MUSIC)-based monitoring technology is a promising method because of its directional scanning ability and easy arrangement of the sensor array. However, for applications on real complex structures, some challenges still exist. The impact-induced elastic waves usually exhibit a wide-band performance, giving rise to the difficulty in obtaining the phase velocity directly. In addition, composite structures usually have obvious anisotropy, and the complex structural style of real aircrafts further enhances this performance, which greatly reduces the localization precision of the MUSIC-based method. To improve the MUSIC-based impact monitoring method, this paper first analyzes and demonstrates the influence of measurement precision of the phase velocity on the localization results of the MUSIC impact localization method. In order to improve the accuracy of the phase velocity measurement, a single frequency component extraction method is presented. Additionally, a single frequency component-based re-estimated MUSIC (SFCBR-MUSIC) algorithm is proposed to reduce the localization error caused by the anisotropy of the complex composite structure. The proposed method is verified on a real composite aircraft wing box, which has T-stiffeners and screw holes. Three typical categories of 41 impacts are monitored. Experimental results show that the SFCBR-MUSIC algorithm can localize impact on complex composite structures with an obviously improved accuracy. (paper)

  8. Complex Pattern Formation from Current-Driven Dynamics of Single-Layer Homoepitaxial Islands on Crystalline Conducting Substrates

    Science.gov (United States)

    Kumar, Ashish; Dasgupta, Dwaipayan; Maroudas, Dimitrios

    2017-07-01

    We report a systematic study of complex pattern formation resulting from the driven dynamics of single-layer homoepitaxial islands on surfaces of face-centered-cubic (fcc) crystalline conducting substrates under the action of an externally applied electric field. The analysis is based on an experimentally validated nonlinear model of mass transport via island edge atomic diffusion, which also accounts for edge diffusional anisotropy. We analyze the morphological stability and simulate the field-driven evolution of rounded islands for an electric field oriented along the fast edge diffusion direction. For larger-than-critical island sizes on {110 } and {100 } fcc substrates, we show that multiple necking instabilities generate complex island patterns, including not-simply-connected void-containing islands mediated by sequences of breakup and coalescence events and distributed symmetrically with respect to the electric field direction. We analyze the dependence of the formed patterns on the original island size and on the duration of application of the external field. Starting from a single large rounded island, we characterize the evolution of the number of daughter islands and their average size and uniformity. The evolution of the average island size follows a universal power-law scaling relation, and the evolution of the total edge length of the islands in the complex pattern follows Kolmogorov-Johnson-Mehl-Avrami kinetics. Our study makes a strong case for the use of electric fields, as precisely controlled macroscopic forcing, toward surface patterning involving complex nanoscale features.

  9. Lutzomyia longipalpis in Brazil: a complex or a single species? A mini-review

    Directory of Open Access Journals (Sweden)

    Luiz GSR Bauzer

    2007-02-01

    Full Text Available Lutzomyia longipalpis is the main vector of Leishmania infantum chagasi, the causative agent of American visceral leishmaniasis (AVL. Although there is strong evidence that Lu. longipalpis is a species complex, not all data concerning populations from Brazil support this hypothesis. The issue is still somewhat controversial for this large part of Lu. longipalpis distribution range even though that it is the Latin American region contributing to most of the cases of AVL. In this mini-review we consider in detail the current data for the Brazilian populations and conclude that Lu. longipalpis is a complex of incipient vector species with a complexity similar to Anopheles gambiae s.s. in Africa.

  10. Reducing assembly complexity of microbial genomes with single-molecule sequencing

    Science.gov (United States)

    Genome assembly algorithms cannot fully reconstruct microbial chromosomes from the DNA reads output by first or second-generation sequencing instruments. Therefore, most genomes are left unfinished due to the significant resources required to manually close gaps left in the draft assemblies. Single-...

  11. Mass transfer with complex reversible chemical reactions—I. Single reversible chemical reaction

    NARCIS (Netherlands)

    Versteeg, G.F.; Kuipers, J.A.M.; Beckum, F.P.H. van; Swaaij, W.P.M. van

    1989-01-01

    An improved numerical technique was used in order to develop an absorption model with which it is possible to calculate rapidly absorption rates for the phenomenon of mass transfer accompanied by a complex reversible chemical reaction. This model can be applied for the calculation of the mass

  12. Management of complex urethral stricture disease: Algorithm and experience from a single institute

    Directory of Open Access Journals (Sweden)

    Yu-Hua Shau

    2015-09-01

    Conclusion: Complex urethral strictures can be managed by a variety of surgical techniques according to specific stricture locations. However, a careful postoperative follow-up for recurrences is mandatory, since ∼40% of patients undergoing buccal mucosal graft-augmented urethroplasties were expected to have additional procedures after the index urethroplasty.

  13. Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study

    OpenAIRE

    Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D.

    2013-01-01

    The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including es...

  14. Single-stage soft tissue reconstruction and orbital fracture repair for complex facial injuries.

    Science.gov (United States)

    Wu, Peng Sen; Matoo, Reshvin; Sun, Hong; Song, Li Yuan; Kikkawa, Don O; Lu, Wei

    2017-02-01

    Orbital fractures with open periorbital wounds cause significant morbidity. Timing of debridement with fracture repair and soft tissue reconstruction is controversial. This study focuses on the efficacy of early single-stage repair in combined bony and soft tissue injuries. Retrospective review. Twenty-three patients with combined open soft tissue wounds and orbital fractures were studied for single-stage orbital reconstruction and periorbital soft tissue repair. Inclusion criteria were open soft tissue wounds with clinical and radiographic evidence of orbital fractures and repair performed within 48 h after injury. Surgical complications and reconstructive outcomes were assessed over 6 months. The main outcome measures were enophthalmos, pre- and post-CT imaging of orbits, scar evaluation, presence of diplopia, and eyelid position. Enophthalmos was corrected in 16/19 cases and improved in 3/19 cases. 3D reconstruction of CT images showed markedly improved orbital alignment with objective measurements of the optic foramen to cornea distance (mm) in reconstructed orbits relative to intact orbits of 0.66, 95% confidence interval [CI] (lower 0.33, upper 0.99) mm. The mean baseline of Stony Brook Scar Evaluation Scale was 0.6, 95%CI (0.30-0.92), and for 6 months, the mean score was 3.4, 95%CI (3.05-3.73). Residual diplopia in secondary gazes was present in two patients; one patient had ectropion. Complications included one case of local wound infection. An early single-stage repair of combined soft tissue and orbital fractures yields satisfactory functional and aesthetic outcomes. Complications are low and likely related to trauma severity. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    OpenAIRE

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show ...

  16. Mapping the q-voter model: From a single chain to complex networks

    Science.gov (United States)

    Jȩdrzejewski, Arkadiusz; Sznajd-Weron, Katarzyna; Szwabiński, Janusz

    2016-03-01

    We propose and compare six different ways of mapping the modified q-voter model to complex networks. Considering square lattices, Barabási-Albert, Watts-Strogatz and real Twitter networks, we ask the question if always a particular choice of the group of influence of a fixed size q leads to different behavior at the macroscopic level. Using Monte Carlo simulations we show that the answer depends on the relative average path length of the network and for real-life topologies the differences between the considered mappings may be negligible.

  17. Hydrophobic Interaction Chromatography for Bottom-Up Proteomics Analysis of Single Proteins and Protein Complexes.

    Science.gov (United States)

    Rackiewicz, Michal; Große-Hovest, Ludger; Alpert, Andrew J; Zarei, Mostafa; Dengjel, Jörn

    2017-06-02

    Hydrophobic interaction chromatography (HIC) is a robust standard analytical method to purify proteins while preserving their biological activity. It is widely used to study post-translational modifications of proteins and drug-protein interactions. In the current manuscript we employed HIC to separate proteins, followed by bottom-up LC-MS/MS experiments. We used this approach to fractionate antibody species followed by comprehensive peptide mapping as well as to study protein complexes in human cells. HIC-reversed-phase chromatography (RPC)-mass spectrometry (MS) is a powerful alternative to fractionate proteins for bottom-up proteomics experiments making use of their distinct hydrophobic properties.

  18. Methods for the preparation of large quantities of complex single-stranded oligonucleotide libraries.

    Science.gov (United States)

    Murgha, Yusuf E; Rouillard, Jean-Marie; Gulari, Erdogan

    2014-01-01

    Custom-defined oligonucleotide collections have a broad range of applications in fields of synthetic biology, targeted sequencing, and cytogenetics. Also, they are used to encode information for technologies like RNA interference, protein engineering and DNA-encoded libraries. High-throughput parallel DNA synthesis technologies developed for the manufacture of DNA microarrays can produce libraries of large numbers of different oligonucleotides, but in very limited amounts. Here, we compare three approaches to prepare large quantities of single-stranded oligonucleotide libraries derived from microarray synthesized collections. The first approach, alkaline melting of double-stranded PCR amplified libraries with a biotinylated strand captured on streptavidin coated magnetic beads results in little or no non-biotinylated ssDNA. The second method wherein the phosphorylated strand of PCR amplified libraries is nucleolyticaly hydrolyzed is recommended when small amounts of libraries are needed. The third method combining in vitro transcription of PCR amplified libraries to reverse transcription of the RNA product into single-stranded cDNA is our recommended method to produce large amounts of oligonucleotide libraries. Finally, we propose a method to remove any primer binding sequences introduced during library amplification.

  19. Circular dichroism measured on single chlorosomal light-harvesting complexes of green photosynthetic bacteria

    KAUST Repository

    Furumaki, Shu

    2012-12-06

    We report results on circular dichroism (CD) measured on single immobilized chlorosomes of a triple mutant of green sulfur bacterium Chlorobaculum tepidum. The CD signal is measured by monitoring chlorosomal bacteriochlorphyll c fluorescence excited by alternate left and right circularly polarized laser light with a fixed wavelength of 733 nm. The excitation wavelength is close to a maximum of the negative CD signal of a bulk solution of the same chlorosomes. The average CD dissymmetry parameter obtained from an ensemble of individual chlorosomes was gs = -0.025, with an intrinsic standard deviation (due to variations between individual chlorosomes) of 0.006. The dissymmetry value is about 2.5 times larger than that obtained at the same wavelength in the bulk solution. The difference can be satisfactorily explained by taking into account the orientation factor in the single-chlorosome experiments. The observed distribution of the dissymmetry parameter reflects the well-ordered nature of the mutant chlorosomes. © 2012 American Chemical Society.

  20. Circular dichroism measured on single chlorosomal light-harvesting complexes of green photosynthetic bacteria

    KAUST Repository

    Furumaki, Shu; Yabiku, Yu; Habuchi, Satoshi; Tsukatani, Yusuke; Bryant, Donald A.; Vá cha, Martin

    2012-01-01

    We report results on circular dichroism (CD) measured on single immobilized chlorosomes of a triple mutant of green sulfur bacterium Chlorobaculum tepidum. The CD signal is measured by monitoring chlorosomal bacteriochlorphyll c fluorescence excited by alternate left and right circularly polarized laser light with a fixed wavelength of 733 nm. The excitation wavelength is close to a maximum of the negative CD signal of a bulk solution of the same chlorosomes. The average CD dissymmetry parameter obtained from an ensemble of individual chlorosomes was gs = -0.025, with an intrinsic standard deviation (due to variations between individual chlorosomes) of 0.006. The dissymmetry value is about 2.5 times larger than that obtained at the same wavelength in the bulk solution. The difference can be satisfactorily explained by taking into account the orientation factor in the single-chlorosome experiments. The observed distribution of the dissymmetry parameter reflects the well-ordered nature of the mutant chlorosomes. © 2012 American Chemical Society.

  1. Single-Sided Deafness: Impact of Cochlear Implantation on Speech Perception in Complex Noise and on Auditory Localization Accuracy.

    Science.gov (United States)

    Döge, Julia; Baumann, Uwe; Weissgerber, Tobias; Rader, Tobias

    2017-12-01

    To assess auditory localization accuracy and speech reception threshold (SRT) in complex noise conditions in adult patients with acquired single-sided deafness, after intervention with a cochlear implant (CI) in the deaf ear. Nonrandomized, open, prospective patient series. Tertiary referral university hospital. Eleven patients with late-onset single-sided deafness (SSD) and normal hearing in the unaffected ear, who received a CI. All patients were experienced CI users. Unilateral cochlear implantation. Speech perception was tested in a complex multitalker equivalent noise field consisting of multiple sound sources. Speech reception thresholds in noise were determined in aided (with CI) and unaided conditions. Localization accuracy was assessed in complete darkness. Acoustic stimuli were radiated by multiple loudspeakers distributed in the frontal horizontal plane between -60 and +60 degrees. In the aided condition, results show slightly improved speech reception scores compared with the unaided condition in most of the patients. For 8 of the 11 subjects, SRT was improved between 0.37 and 1.70 dB. Three of the 11 subjects showed deteriorations between 1.22 and 3.24 dB SRT. Median localization error decreased significantly by 12.9 degrees compared with the unaided condition. CI in single-sided deafness is an effective treatment to improve the auditory localization accuracy. Speech reception in complex noise conditions is improved to a lesser extent in 73% of the participating CI SSD patients. However, the absence of true binaural interaction effects (summation, squelch) impedes further improvements. The development of speech processing strategies that respect binaural interaction seems to be mandatory to advance speech perception in demanding listening situations in SSD patients.

  2. Validation of single-plane fluoroscopy and 2D/3D shape-matching for quantifying shoulder complex kinematics.

    Science.gov (United States)

    Lawrence, Rebekah L; Ellingson, Arin M; Ludewig, Paula M

    2018-02-01

    Fluoroscopy and 2D/3D shape-matching has emerged as the standard for non-invasively quantifying kinematics. However, its accuracy has not been well established for the shoulder complex when using single-plane fluoroscopy. The purpose of this study was to determine the accuracy of single-plane fluoroscopy and 2D/3D shape-matching for quantifying full shoulder complex kinematics. Tantalum markers were implanted into the clavicle, humerus, and scapula of four cadaveric shoulders. Biplane radiographs were obtained with the shoulder in five humerothoracic elevation positions (arm at the side, 30°, 60°, 90°, maximum). Images from both systems were used to perform marker tracking, while only those images acquired with the primary fluoroscopy system were used to perform 2D/3D shape-matching. Kinematics errors due to shape-matching were calculated as the difference between marker tracking and 2D/3D shape-matching and expressed as root mean square (RMS) error, bias, and precision. Overall RMS errors for the glenohumeral joint ranged from 0.7 to 3.3° and 1.2 to 4.2 mm, while errors for the acromioclavicular joint ranged from 1.7 to 3.4°. Errors associated with shape-matching individual bones ranged from 1.2 to 3.2° for the humerus, 0.5 to 1.6° for the scapula, and 0.4 to 3.7° for the clavicle. The results of the study demonstrate that single-plane fluoroscopy and 2D/3D shape-matching can accurately quantify full shoulder complex kinematics in static positions. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  3. Investigation of the complex electroviscous effects on electrolyte (single and multiphase) flow in porous medi.

    Science.gov (United States)

    Bolet, A. J. S.; Linga, G.; Mathiesen, J.

    2017-12-01

    Surface charge is an important control parameter for wall-bounded flow of electrolyte solution. The electroviscous effect has been studied theoretically in model geometries such as infinite capillaries. However, in more complex geometries a quantification of the electroviscous effect is a non-trival task due to strong non-linarites of the underlying equations. In general, one has to rely on numerical methods. Here we present numerical studies of the full three-dimensional steady state Stokes-Poisson-Nernst-Planck problem in order to model electrolyte transport in artificial porous samples. The simulations are performed using the finite element method. From the simulation, we quantity how the electroviscous effect changes the general flow permeability in complex three-dimensional porous media. The porous media we consider are mostly generated artificially by connecting randomly dispersed cylindrical pores. Furthermore, we present results of electric driven two-phase immiscible flow in two dimensions. The simulations are performed by augmenting the above equations with a phase field model to handle and track the interaction between the two fluids (using parameters corresponding to oil-water interfaces, where oil non-polar). In particular, we consider the electro-osmotic effect on imbibition due to charged walls and electrolyte-solution.

  4. Thorium–phosphorus triamidoamine complexes containing Th–P single- and multiple-bond interactions

    Science.gov (United States)

    Wildman, Elizabeth P.; Balázs, Gábor; Wooles, Ashley J.; Scheer, Manfred; Liddle, Stephen T.

    2016-01-01

    Despite the burgeoning field of uranium-ligand multiple bonds, analogous complexes involving other actinides remain scarce. For thorium, under ambient conditions only a few multiple bonds to carbon, nitrogen, oxygen, sulfur, selenium and tellurium are reported, and no multiple bonds to phosphorus are known, reflecting a general paucity of synthetic methodologies and also problems associated with stabilising these linkages at the large thorium ion. Here we report structurally authenticated examples of a parent thorium(IV)–phosphanide (Th–PH2), a terminal thorium(IV)–phosphinidene (Th=PH), a parent dithorium(IV)–phosphinidiide (Th–P(H)-Th) and a discrete actinide–phosphido complex under ambient conditions (Th=P=Th). Although thorium is traditionally considered to have dominant 6d-orbital contributions to its bonding, contrasting to majority 5f-orbital character for uranium, computational analyses suggests that the bonding of thorium can be more nuanced, in terms of 5f- versus 6d-orbital composition and also significant involvement of the 7s-orbital and how this affects the balance of 5f- versus 6d-orbital bonding character. PMID:27682617

  5. Stability and Hopf Bifurcation of Fractional-Order Complex-Valued Single Neuron Model with Time Delay

    Science.gov (United States)

    Wang, Zhen; Wang, Xiaohong; Li, Yuxia; Huang, Xia

    2017-12-01

    In this paper, the problems of stability and Hopf bifurcation in a class of fractional-order complex-valued single neuron model with time delay are addressed. With the help of the stability theory of fractional-order differential equations and Laplace transforms, several new sufficient conditions, which ensure the stability of the system are derived. Taking the time delay as the bifurcation parameter, Hopf bifurcation is investigated and the critical value of the time delay for the occurrence of Hopf bifurcation is determined. Finally, two representative numerical examples are given to show the effectiveness of the theoretical results.

  6. Luminescent single-ion magnets from Lanthanoid(III) complexes with monodentate ketone ligands

    Energy Technology Data Exchange (ETDEWEB)

    Kanetomo, Takuya; Ishida, Takayuki, E-mail: takayuki.ishida@uec.ac.jp [Department of Engineering Science, The University of Electro-Communications, Tokyo (Japan)

    2016-02-01

    We synthesized [Ln{sup III}(hfac){sub 3}(H{sub 2}O)(L)] (abbreviated as Ln-L; Ln = Gd, Tb, Eu; L = DTBK (di-t-butyl ketone), BP (benzophenone)), in which the carbonyl oxygen atom was coordinated to the Ln ion center, despite of such bulky substituents. Their crystal structures were determined by means of X-ray diffraction study. Gd-DTBK is completely isomorphous to the di-t-butyl nitroxide derivative and accordingly can be regarded as a model with the ligand spin masked. The ac magnetic susceptibility measurements on Tb-DTBK and -BP showed frequency dependence, characteristic of single-ion magnets. They also displayed photoluminescence in the solid state at room temperature. The quantum yields of the luminescence of Tb-DTBK and -BP (λ{sub ex} = 360 nm) were improved to 57 and 35%, respectively, from that of the starting material [TbI{sup III}(hfac){sub 3}(H{sub 2}O){sub 2}] (28% at λ{sub ex} = 370 nm). Similarly, the quantum yields for Eu-DTBK and -BP were 8 and 15%, respectively, with λ{sub ex} = 400 nm, while that of the starting material [EuI{sup III}(hfac){sub 3}(H{sub 2}O){sub 2}] was 4% at λ{sub ex}=400 nm.

  7. Complex Pattern Formation from Current-Driven Dynamics of Single-Layer Epitaxial Islands on Crystalline Conducting Substrates

    Science.gov (United States)

    Kumar, Ashish; Dasgupta, Dwaipayan; Maroudas, Dimitrios

    We report a systematic study of complex pattern formation resulting from the driven dynamics of single-layer homoepitaxial islands on face-centered cubic (FCC) crystalline conducting substrate surfaces under the action of an externally applied electric field. The analysis is based on an experimentally validated nonlinear model of mass transport via island edge atomic diffusion, which also accounts for edge diffusional anisotropy. We analyze the morphological stability and simulate the field-driven evolution of rounded islands for an electric field oriented along the fast diffusion direction. For larger than critical island sizes on {110} and {100} FCC substrates, we show that multiple necking instabilities generate complex island patterns, including void-containing islands, mediated by sequences of breakup and coalescence events and distributed symmetrically with respect to the electric field direction. We analyze the dependence of the formed patterns on the original island size and on the duration of application of the external field. Starting from a single large rounded island, we characterize the evolution of the number of daughter islands and their average size and uniformity. The analysis reveals that the pattern formation kinetics follows a universal scaling relation. Division of Materials Sciences & Engineering, Office of Basic Energy Sciences, U.S. Department of Energy (Award No.: DE-FG02-07ER46407).

  8. Identification of Zn-vacancy-hydrogen complexes in ZnO single crystals: A challenge to positron annihilation spectroscopy

    Science.gov (United States)

    Brauer, G.; Anwand, W.; Grambole, D.; Grenzer, J.; Skorupa, W.; Čížek, J.; Kuriplach, J.; Procházka, I.; Ling, C. C.; So, C. K.; Schulz, D.; Klimm, D.

    2009-03-01

    A systematic study of various, nominally undoped ZnO single crystals, either hydrothermally grown (HTG) or melt grown (MG), has been performed. The crystal quality has been assessed by x-ray diffraction, and a comprehensive estimation of the detailed impurity and hydrogen contents by inductively coupled plasma mass spectrometry and nuclear reaction analysis, respectively, has been made also. High precision positron lifetime experiments show that a single positron lifetime is observed in all crystals investigated, which clusters at 180-182 ps and 165-167 ps for HTG and MG crystals, respectively. Furthermore, hydrogen is detected in all crystals in a bound state with a high concentration (at least 0.3at.% ), whereas the concentrations of other impurities are very small. From ab initio calculations it is suggested that the existence of Zn-vacancy-hydrogen complexes is the most natural explanation for the given experimental facts at present. Furthermore, the distribution of H at a metal/ZnO interface of a MG crystal, and the H content of a HTG crystal upon annealing and time afterward has been monitored, as this is most probably related to the properties of electrical contacts made at ZnO and the instability in p -type conductivity observed at ZnO nanorods in literature. All experimental findings and presented theoretical considerations support the conclusion that various types of Zn-vacancy-hydrogen complexes exist in ZnO and need to be taken into account in future studies, especially for HTG materials.

  9. [Single procedure treatment of complex nephrolithiasis: about a modern series of anatrophic nephrolithotomy].

    Science.gov (United States)

    Lunardi, P; Timsit, M O; Roumiguie, M; Dariane, C; N'Guyen, K; Beauval, J B; Leroux, S

    2015-02-01

    Advances in endourology have significantly reduced indications of open surgery in the treatment of staghorn calculi. However, in our experience, open surgery is still the treatment of choice in some cases. This study presents the results of a series of selected patients and discusses the results in terms of efficacy and morbidity. A cohort of 26 patients underwent anatrophic nephrolithotomy by lombotomy to treat a complex staghorn calculus. The mean stone size was 68,5mm, 70% were complete staghorn calculi. The operative time was 100minutes. Blood loss was 225mL, with a postoperative transfusion rate of 15.4%. The hospital stay was 8.4 days. The stone free rate following the procedure was 92%. The creatinine clearance (MDRD) at 3 months was improved from 5.9mL/min/m(2) on average over the entire series. There are clearly still indications for open surgery in staghorn stones management, with good results in this contemporary series on both stone removal and nephronic preservation. Yet, it appears that this technique is no longer taught. 5. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Hybrid Nanomaterials with Single-Site Catalysts by Spatially Controllable Immobilization of Nickel Complexes via Photoclick Chemistry for Alkene Epoxidation.

    Science.gov (United States)

    Ghosh, Dwaipayan; Febriansyah, Benny; Gupta, Disha; Ng, Leonard Kia-Sheun; Xi, Shibo; Du, Yonghua; Baikie, Tom; Dong, ZhiLi; Soo, Han Sen

    2018-05-22

    Catalyst deactivation is a persistent problem not only for the scientific community but also in industry. Isolated single-site heterogeneous catalysts have shown great promise to overcome these problems. Here, a versatile anchoring strategy for molecular complex immobilization on a broad range of semiconducting or insulating metal oxide ( e. g., titanium dioxide, mesoporous silica, cerium oxide, and tungsten oxide) nanoparticles to synthesize isolated single-site catalysts has been studied systematically. An oxidatively stable anchoring group, maleimide, is shown to form covalent linkages with surface hydroxyl functionalities of metal oxide nanoparticles by photoclick chemistry. The nanocomposites have been thoroughly characterized by techniques including UV-visible diffuse reflectance spectroscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, infrared spectroscopy, and X-ray absorption spectroscopy (XAS). The IR spectroscopic studies confirm the covalent linkages between the maleimide group and surface hydroxyl functionalities of the oxide nanoparticles. The hybrid nanomaterials function as highly efficient catalysts for essentially quantitative oxidations of terminal and internal alkenes and show molecular catalyst product selectivities even in more eco-friendly solvents. XAS studies verify the robustness of the catalysts after several catalytic cycles. We have applied the photoclick anchoring methodology to precisely control the deposition of a luminescent variant of our catalyst on the metal oxide nanoparticles. Overall, we demonstrate a general approach to use irradiation to anchor molecular complexes on oxide nanoparticles to create recyclable, hybrid, single-site catalysts that function with high selectivity in a broad range of solvents. We have achieved a facile, spatially and temporally controllable photoclick method that can potentially be extended to other ligands, catalysts, functional molecules, and surfaces.

  11. The MARVEL domain protein, Singles Bar, is required for progression past the pre-fusion complex stage of myoblast fusion.

    Science.gov (United States)

    Estrada, Beatriz; Maeland, Anne D; Gisselbrecht, Stephen S; Bloor, James W; Brown, Nicholas H; Michelson, Alan M

    2007-07-15

    Multinucleated myotubes develop by the sequential fusion of individual myoblasts. Using a convergence of genomic and classical genetic approaches, we have discovered a novel gene, singles bar (sing), that is essential for myoblast fusion. sing encodes a small multipass transmembrane protein containing a MARVEL domain, which is found in vertebrate proteins involved in processes such as tight junction formation and vesicle trafficking where--as in myoblast fusion--membrane apposition occurs. sing is expressed in both founder cells and fusion competent myoblasts preceding and during myoblast fusion. Examination of embryos injected with double-stranded sing RNA or embryos homozygous for ethane methyl sulfonate-induced sing alleles revealed an identical phenotype: replacement of multinucleated myofibers by groups of single, myosin-expressing myoblasts at a stage when formation of the mature muscle pattern is complete in wild-type embryos. Unfused sing mutant myoblasts form clusters, suggesting that early recognition and adhesion of these cells are unimpaired. To further investigate this phenotype, we undertook electron microscopic ultrastructural studies of fusing myoblasts in both sing and wild-type embryos. These experiments revealed that more sing mutant myoblasts than wild-type contain pre-fusion complexes, which are characterized by electron-dense vesicles paired on either side of the fusing plasma membranes. In contrast, embryos mutant for another muscle fusion gene, blown fuse (blow), have a normal number of such complexes. Together, these results lead to the hypothesis that sing acts at a step distinct from that of blow, and that sing is required on both founder cell and fusion-competent myoblast membranes to allow progression past the pre-fusion complex stage of myoblast fusion, possibly by mediating fusion of the electron-dense vesicles to the plasma membrane.

  12. Max-Min SINR in Large-Scale Single-Cell MU-MIMO: Asymptotic Analysis and Low Complexity Transceivers

    KAUST Repository

    Sifaou, Houssem

    2016-12-28

    This work focuses on the downlink and uplink of large-scale single-cell MU-MIMO systems in which the base station (BS) endowed with M antennas communicates with K single-antenna user equipments (UEs). Particularly, we aim at reducing the complexity of the linear precoder and receiver that maximize the minimum signal-to-interference-plus-noise ratio subject to a given power constraint. To this end, we consider the asymptotic regime in which M and K grow large with a given ratio. Tools from random matrix theory (RMT) are then used to compute, in closed form, accurate approximations for the parameters of the optimal precoder and receiver, when imperfect channel state information (modeled by the generic Gauss-Markov formulation form) is available at the BS. The asymptotic analysis allows us to derive the asymptotically optimal linear precoder and receiver that are characterized by a lower complexity (due to the dependence on the large scale components of the channel) and, possibly, by a better resilience to imperfect channel state information. However, the implementation of both is still challenging as it requires fast inversions of large matrices in every coherence period. To overcome this issue, we apply the truncated polynomial expansion (TPE) technique to the precoding and receiving vector of each UE and make use of RMT to determine the optimal weighting coefficients on a per- UE basis that asymptotically solve the max-min SINR problem. Numerical results are used to validate the asymptotic analysis in the finite system regime and to show that the proposed TPE transceivers efficiently mimic the optimal ones, while requiring much lower computational complexity.

  13. Malachite green mediates homodimerization of antibody VL domains to form a fluorescent ternary complex with singular symmetric interfaces

    Science.gov (United States)

    Szent-Gyorgyi, Chris; Stanfield, Robyn L.; Andreko, Susan; Dempsey, Alison; Ahmed, Mushtaq; Capek, Sara; Waggoner, Alan; Wilson, Ian A.; Bruchez, Marcel P.

    2013-01-01

    We report that a symmetric small molecule ligand mediates the assembly of antibody light chain variable domains (VLs) into a correspondent symmetric ternary complex with novel interfaces. The L5* Fluorogen Activating Protein (FAP) is a VL domain that binds malachite green dye (MG) to activate intense fluorescence. Crystallography of liganded L5* reveals a 2:1 protein:ligand complex with inclusive C2 symmetry, where MG is almost entirely encapsulated between an antiparallel arrangement of the two VL domains. Unliganded L5* VL domains crystallize as a similar antiparallel VL/VL homodimer. The complementarity determining regions (CDRs) are spatially oriented to form novel VL/VL and VL/ligand interfaces that tightly constrain a propeller conformer of MG. Binding equilibrium analysis suggests highly cooperative assembly to form a very stable VL/MG/VL complex, such that MG behaves as a strong chemical inducer of dimerization. Fusion of two VL domains into a single protein tightens MG binding over 1,000-fold to low picomolar affinity without altering the large binding enthalpy, suggesting that bonding interactions with ligand and restriction of domain movements make independent contributions to binding. Fluorescence activation of a symmetrical fluorogen provides a selection mechanism for the isolation and directed evolution of ternary complexes where unnatural symmetric binding interfaces are favored over canonical antibody interfaces. As exemplified by L5*, these self-reporting complexes may be useful as modulators of protein association or as high affinity protein tags and capture reagents. PMID:23978698

  14. Response of single bacterial cells to stress gives rise to complex history dependence at the population level

    Science.gov (United States)

    Mathis, Roland; Ackermann, Martin

    2016-01-01

    Most bacteria live in ever-changing environments where periods of stress are common. One fundamental question is whether individual bacterial cells have an increased tolerance to stress if they recently have been exposed to lower levels of the same stressor. To address this question, we worked with the bacterium Caulobacter crescentus and asked whether exposure to a moderate concentration of sodium chloride would affect survival during later exposure to a higher concentration. We found that the effects measured at the population level depended in a surprising and complex way on the time interval between the two exposure events: The effect of the first exposure on survival of the second exposure was positive for some time intervals but negative for others. We hypothesized that the complex pattern of history dependence at the population level was a consequence of the responses of individual cells to sodium chloride that we observed: (i) exposure to moderate concentrations of sodium chloride caused delays in cell division and led to cell-cycle synchronization, and (ii) whether a bacterium would survive subsequent exposure to higher concentrations was dependent on the cell-cycle state. Using computational modeling, we demonstrated that indeed the combination of these two effects could explain the complex patterns of history dependence observed at the population level. Our insight into how the behavior of single cells scales up to processes at the population level provides a perspective on how organisms operate in dynamic environments with fluctuating stress exposure. PMID:26960998

  15. Self-assembly of a 3d-5f trinuclear single-molecule magnet from a pentavalent uranyl complex

    International Nuclear Information System (INIS)

    Chatelain, Lucile; Pecaut, Jacques; Walsh, James P.S.; Tuna, Floriana; Mazzanti, Marinella

    2014-01-01

    Mixed-metal uranium compounds are very attractive candidates in the design of single-molecule magnets (SMMs), but only one 3d-5f hetero-polymetallic SMM containing a uranium center is known. Herein, we report two trimeric heterodimetallic 3d-5f complexes self-assembled by cation-cation interactions between a uranyl(V) complex and a TPA-capped M II complex (M=Mn (1), Cd (2); TPA=tris(2-pyridylmethyl)amine). The metal centers were strategically chosen to promote the formation of discrete molecules rather than extended chains. Compound 1, which contains an almost linear {Mn-O=U=O-Mn} core, exhibits SMM behavior with a relaxation barrier of 81±0.5 K - the highest reported for a mono-uranium system - arising from intramolecular Mn-U exchange interactions combined with the high Ising anisotropy of the uranyl(V) moiety. Compound 1 also exhibits an open magnetic hysteresis loop at temperatures less than 3 K, with a significant coercive field of 1.9 T at 1.8 K.

  16. Self-assembly of a 3d-5f trinuclear single-molecule magnet from a pentavalent uranyl complex

    Energy Technology Data Exchange (ETDEWEB)

    Chatelain, Lucile; Pecaut, Jacques [CEA-Grenoble (France). Lab. de Reconnaissance Ionique et Chimie de Coordination SCIB; Walsh, James P.S.; Tuna, Floriana [Manchester Univ. (United Kingdom). School of Chemistry and Photon Science Inst.; Mazzanti, Marinella [Ecole Polytechnique Federale de Lausanne (EPFL) (Switzerland). Inst. de Sciences et Ingenierie Chimiques

    2014-12-01

    Mixed-metal uranium compounds are very attractive candidates in the design of single-molecule magnets (SMMs), but only one 3d-5f hetero-polymetallic SMM containing a uranium center is known. Herein, we report two trimeric heterodimetallic 3d-5f complexes self-assembled by cation-cation interactions between a uranyl(V) complex and a TPA-capped M{sup II} complex (M=Mn (1), Cd (2); TPA=tris(2-pyridylmethyl)amine). The metal centers were strategically chosen to promote the formation of discrete molecules rather than extended chains. Compound 1, which contains an almost linear {Mn-O=U=O-Mn} core, exhibits SMM behavior with a relaxation barrier of 81±0.5 K - the highest reported for a mono-uranium system - arising from intramolecular Mn-U exchange interactions combined with the high Ising anisotropy of the uranyl(V) moiety. Compound 1 also exhibits an open magnetic hysteresis loop at temperatures less than 3 K, with a significant coercive field of 1.9 T at 1.8 K.

  17. Post-cardiotomy extracorporeal cardiopulmonary resuscitation in neonates with complex single ventricle: analysis of outcomes.

    Science.gov (United States)

    Polimenakos, Anastasios C; Wojtyla, Patrice; Smith, Pamela J; Rizzo, Vincent; Nater, Melissa; El Zein, Chawki F; Ilbawi, Michel N

    2011-12-01

    Extracorporeal cardiopulmonary resuscitation (ECPR) in children with cardiac arrest refractory to conventional cardiopulmonary resuscitation (CPR) has been reported with encouraging results. We sought to review outcomes of neonates with functional single ventricle (FSV) receiving post-cardiotomy ECPR. Forty-eight patients who required post-cardiotomy extracorporeal membrane oxygenation (ECMO) since the introduction of our ECPR protocol (January 2007-December 2009) were identified. Twenty-seven were neonates. Review of records and survival analysis were conducted. Of 27 neonates receiving post-cardiotomy ECMO 20 had FSV. Fourteen had ECPR. Ten underwent Norwood operation (NO) for hypoplastic left heart syndrome (HLHS). Four had FSV other than HLHS. Three underwent Damus-Kay-Stansel or modified NO with systemic-to-pulmonary shunt (SPS) and one SPS with anomalous pulmonary venous connection repair. Mean age and weight were 7.8 ± 2.9 days and 3.44 ± 1.78 kg, respectively. ECMO median duration was 6 days (interquartile range (IQR) 3-14). Survival to ECMO discontinuation was 79% (11 of 14 patients) and at hospital discharge was 57% (8 of 14 patients). The most common cause of death was multi-organ failure (four of six deaths). At last follow-up (median: 11 months (1-34)) 43% of patients were alive. CPR mean duration for patients with favorable versus unfavorable outcome was 38.6 ± 6.3 versus 42.1 ± 7.7 min (p = 0.12). Previously reported determinants for poorer prognosis in conventional non-rescue ECMO (such as pre-ECMO pH0.05). ECMO support in neonates with FSV requiring ECPR can result in favorable outcome in more than half of patients at hospital discharge. Aggressive strategy toward timely application of ECPR is justified. Expeditious ECPR deployment after proper patients' selection, refinement of CPR quality and use of adjunctive neuroprotective interventions, such as induced hypothermia, might further improve outcomes. Copyright © 2011 European Association for

  18. Single-shot ultrabroadband two-dimensional electronic spectroscopy of the light-harvesting complex LH2.

    Science.gov (United States)

    Harel, Elad; Long, Phillip D; Engel, Gregory S

    2011-05-01

    Here we present two-dimensional (2D) electronic spectra of the light-harvesting complex LH2 from purple bacteria using coherent pulses with bandwidth of over 100 nm FWHM. This broadband excitation and detection has allowed the simultaneous capture of both the B800 and B850 bands using a single light source. We demonstrate that one laser pulse is sufficient to capture the entire 2D electronic spectrum with a high signal-to-noise ratio. At a waiting time of 800 fs, we observe population transfer from the B800 to B850 band as manifested by a prominent cross peak. These results will enable observation of the dynamics of biological systems across both ultrafast (1 ms) timescales simultaneously.

  19. Hiding the Complexity: Building a Distributed ATLAS Tier-2 with a Single Resource Interface using ARC Middleware

    International Nuclear Information System (INIS)

    Purdie, S; Stewart, G; Skipsey, S; Washbrook, A; Bhimji, W; Filipcic, A; Kenyon, M

    2011-01-01

    Since their inception, Grids for high energy physics have found management of data to be the most challenging aspect of operations. This problem has generally been tackled by the experiment's data management framework controlling in fine detail the distribution of data around the grid and the careful brokering of jobs to sites with co-located data. This approach, however, presents experiments with a difficult and complex system to manage as well as introducing a rigidity into the framework which is very far from the original conception of the grid. In this paper we describe how the ScotGrid distributed Tier-2, which has sites in Glasgow, Edinburgh and Durham, was presented to ATLAS as a single, unified resource using the ARC middleware stack. In this model the ScotGrid 'data store' is hosted at Glasgow and presented as a single ATLAS storage resource. As jobs are taken from the ATLAS PanDA framework, they are dispatched to the computing cluster with the fastest response time. An ARC compute element at each site then asynchronously stages the data from the data store into a local cache hosted at each site. The job is then launched in the batch system and accesses data locally. We discuss the merits of this system compared to other operational models and consider, from the point of view of the resource providers (sites), and from the resource consumers (experiments); and consider issues involved in transitions to this model.

  20. Illuminant direction estimation for a single image based on local region complexity analysis and average gray value.

    Science.gov (United States)

    Yi, Jizheng; Mao, Xia; Chen, Lijiang; Xue, Yuli; Compare, Angelo

    2014-01-10

    Illuminant direction estimation is an important research issue in the field of image processing. Due to low cost for getting texture information from a single image, it is worthwhile to estimate illuminant direction by employing scenario texture information. This paper proposes a novel computation method to estimate illuminant direction on both color outdoor images and the extended Yale face database B. In our paper, the luminance component is separated from the resized YCbCr image and its edges are detected with the Canny edge detector. Then, we divide the binary edge image into 16 local regions and calculate the edge level percentage in each of them. Afterward, we use the edge level percentage to analyze the complexity of each local region included in the luminance component. Finally, according to the error function between the measured intensity and the calculated intensity, and the constraint function for an infinite light source model, we calculate the illuminant directions of the luminance component's three local regions, which meet the requirements of lower complexity and larger average gray value, and synthesize them as the final illuminant direction. Unlike previous works, the proposed method requires neither all of the information of the image nor the texture that is included in the training set. Experimental results show that the proposed method works better at the correct rate and execution time than the existing ones.

  1. Application of X-ray single crystal diffractometry to investigation of Np(5) complexes with n-donor ligands

    International Nuclear Information System (INIS)

    Andreev, G.

    2007-01-01

    Full text of publication follows. We present here some results of application of conventional X-ray single crystal diffractometry to the research on the interaction of Np(V) with N-donor ligands. Compounds that can coordinate to actinides through one or several nitrogen atoms are of a great variety and occur widely in the biosphere. For example, imidazole, pyridine and their derivatives are the building blocks of many biologically important molecules; triazines are known to occur in some aquatic plants. The presence of anthropogenic organic agents like amine-N-carboxylic acids in surface waters has the potential to re-mobilize metals from sediments and aquifers and to influence their bioavailability. The interaction of radionuclides with such ligands needs to be studied in detail to give fundamental understanding the conditions of the incorporation of long lived a-emitters (Np and Pu primarily) into the food chain. Another aspect of the same problem is the design of new chelating ligands for selective co-ordination of actinide ions as an alternative to the traditional sequestering agents. The problem of the separation of long-lived minor actinides and their transmutation also calls for design of new highly selective ligands for solvent extraction. Polydentate N-donor ligands are now considered to be very promising. A detailed study of structural chemistry is crucial for understanding the relationship between the architecture of the ligands and their binding affinity for actinides. The X-ray single crystal diffractometry became conventional technique as applied to the investigation of actinides in spite of difficulties regarding safe handling of radionuclides. This technique provides unambiguous information about modes of the ligand co-ordination to the metal ion and geometrical parameters of complexes. Moreover, the employment of a synchrotron radiation shows considerable promise for determination of solid state structures as well as obtaining structural

  2. Combination of binaural and harmonic masking release effects in the detection of a single component in complex tones.

    Science.gov (United States)

    Klein-Hennig, Martin; Dietz, Mathias; Hohmann, Volker

    2018-03-01

    Both harmonic and binaural signal properties are relevant for auditory processing. To investigate how these cues combine in the auditory system, detection thresholds for an 800-Hz tone masked by a diotic (i.e., identical between the ears) harmonic complex tone were measured in six normal-hearing subjects. The target tone was presented either diotically or with an interaural phase difference (IPD) of 180° and in either harmonic or "mistuned" relationship to the diotic masker. Three different maskers were used, a resolved and an unresolved complex tone (fundamental frequency: 160 and 40 Hz) with four components below and above the target frequency and a broadband unresolved complex tone with 12 additional components. The target IPD provided release from masking in most masker conditions, whereas mistuning led to a significant release from masking only in the diotic conditions with the resolved and the narrowband unresolved maskers. A significant effect of mistuning was neither found in the diotic condition with the wideband unresolved masker nor in any of the dichotic conditions. An auditory model with a single analysis frequency band and different binaural processing schemes was employed to predict the data of the unresolved masker conditions. Sensitivity to modulation cues was achieved by including an auditory-motivated modulation filter in the processing pathway. The predictions of the diotic data were in line with the experimental results and literature data in the narrowband condition, but not in the broadband condition, suggesting that across-frequency processing is involved in processing modulation information. The experimental and model results in the dichotic conditions show that the binaural processor cannot exploit modulation information in binaurally unmasked conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Advantages of conducting in-situ U-Pb age dating of multiple U-bearing minerals from a single complex: Case in point - the Oka Carbonatite Complex

    Science.gov (United States)

    Chen, W.; Simonetti, A.

    2012-12-01

    sample. The niocalite for a carbonatite sample Oka153 defines a bimodal age distribution, with weighted average 206Pb/238U ages of 110.1 ±5.0 and 133.2 ±6.1 Ma. Apatite from the same sample also records a similar bimodal age distribution of 111.4 ±2.8 and 126.9 ±1.8 Ma. The combined in situ U-Pb dating results for apatite, pervoskite, niocalite from Oka clearly support a protracted history of magmatic activity (~30 Myr) for this carbonatite complex. Of importance, the U-Pb results from this study clearly indicate the significance of conducting a thorough geochronological investigation rather than defining the age of any one alkaline complex solely on the basis of a single radiometric age determination.

  4. Highly selective single-use fluoride ion optical sensor based on aluminum(III)-salen complex in thin polymeric film

    International Nuclear Information System (INIS)

    Badr, Ibrahim H.A.; Meyerhoff, Mark E.

    2005-01-01

    A highly selective optical sensor for fluoride ion based on the use of an aluminum(III)-salen complex as an ionophore within a thin polymeric film is described. The sensor is prepared by embedding the aluminum(III)-salen ionophore and a suitable lipophilic pH-sensitive indicator (ETH-7075) in a plasticized poly(vinyl chloride) (PVC) film. Optical response to fluoride occurs due to fluoride extraction into the polymer via formation of a strong complex with the aluminum(III)-salen species. Co-extraction of protons occurs simultaneously, with protonation of the indicator dye yielding the optical response at 529 nm. Films prepared using dioctylsebacate (DOS) are shown to exhibit better response (e.g., linear range, detection limit, and optical signal stability) compared to those prepared using ortho-nitrophenyloctyl ether (o-NPOE). Films formulated with aluminum(III)-salen and ETH-7075 indicator in 2 DOS:1 PVC, exhibit a significantly enhanced selectivity for fluoride over a wide range of lipophilic anions including salicylate, perchlorate, nitrate, and thiocyanate. The optimized films exhibit a sub-micromolar detection limit, using glycine-phosphate buffer, pH 3.00, as the test sample. The response times of the fluoride optical sensing films are in the range of 1-10 min depending on the fluoride ion concentration in the sample. The sensor exhibits very poor reversibility owing to a high co-extraction constant (log K = 8.5 ± 0.4), indicating that it can best be employed as a single-use transduction device. The utility of the aluminum(III)-salen based fluoride sensitive films as single-use sensors is demonstrated by casting polymeric films on the bottom of standard polypropylene microtiter plate wells (96 wells/plate). The modified microtiter plate optode format sensors exhibit response characteristics comparable to the classical optode films cast on quartz slides. The modified microtiter is utilized for the analysis of fluoride in diluted anti-cavity fluoride rinse

  5. Analysis of Proteins, Protein Complexes, and Organellar Proteomes Using Sheathless Capillary Zone Electrophoresis - Native Mass Spectrometry

    Science.gov (United States)

    Belov, Arseniy M.; Viner, Rosa; Santos, Marcia R.; Horn, David M.; Bern, Marshall; Karger, Barry L.; Ivanov, Alexander R.

    2017-12-01

    Native mass spectrometry (MS) is a rapidly advancing field in the analysis of proteins, protein complexes, and macromolecular species of various types. The majority of native MS experiments reported to-date has been conducted using direct infusion of purified analytes into a mass spectrometer. In this study, capillary zone electrophoresis (CZE) was coupled online to Orbitrap mass spectrometers using a commercial sheathless interface to enable high-performance separation, identification, and structural characterization of limited amounts of purified proteins and protein complexes, the latter with preserved non-covalent associations under native conditions. The performance of both bare-fused silica and polyacrylamide-coated capillaries was assessed using mixtures of protein standards known to form non-covalent protein-protein and protein-ligand complexes. High-efficiency separation of native complexes is demonstrated using both capillary types, while the polyacrylamide neutral-coated capillary showed better reproducibility and higher efficiency for more complex samples. The platform was then evaluated for the determination of monoclonal antibody aggregation and for analysis of proteomes of limited complexity using a ribosomal isolate from E. coli. Native CZE-MS, using accurate single stage and tandem-MS measurements, enabled identification of proteoforms and non-covalent complexes at femtomole levels. This study demonstrates that native CZE-MS can serve as an orthogonal and complementary technique to conventional native MS methodologies with the advantages of low sample consumption, minimal sample processing and losses, and high throughput and sensitivity. This study presents a novel platform for analysis of ribosomes and other macromolecular complexes and organelles, with the potential for discovery of novel structural features defining cellular phenotypes (e.g., specialized ribosomes). [Figure not available: see fulltext.

  6. Giant crystal-electric-field effect and complex magnetic behavior in single-crystalline CeRh3Si2

    Science.gov (United States)

    Pikul, A. P.; Kaczorowski, D.; Gajek, Z.; Stȩpień-Damm, J.; Ślebarski, A.; Werwiński, M.; Szajek, A.

    2010-05-01

    Single-crystalline CeRh3Si2 was investigated by means of x-ray diffraction, magnetic susceptibility, magnetization, electrical resistivity, and specific-heat measurements carried out in wide temperature and magnetic field ranges. Moreover, the electronic structure of the compound was studied at room temperature by cerium core-level x-ray photoemission spectroscopy (XPS). The physical properties were analyzed in terms of crystalline electric field and compared with results of ab initio band-structure calculations performed within the density-functional theory approach. The compound was found to crystallize in the orthorhombic unit cell of the ErRh3Si2 type (space group Imma No.74, Pearson symbol: oI24 ) with the lattice parameters a=7.1330(14)Å , b=9.7340(19)Å , and c=5.6040(11)Å . Analysis of the magnetic and XPS data revealed the presence of well-localized magnetic moments of trivalent cerium ions. All the physical properties were found to be highly anisotropic over the whole temperature range studied and influenced by exceptionally strong crystalline electric field with the overall splitting of the 4f1 ground multiplet exceeding 5700 K. Antiferromagnetic order of the cerium magnetic moments at TN=4.70(1)K and their subsequent spin rearrangement at Tt=4.48(1)K manifest themselves as distinct anomalies in the temperature characteristic of all the physical properties investigated and exhibit complex evolution in an external magnetic field. A tentative magnetic B-T phase diagram, constructed for B parallel to the b axis being the easy magnetization direction, shows very complex magnetic behavior of CeRh3Si2 , similar to that recently reported for an isostructural compound CeIr3Si2 . The electronic band-structure calculations corroborated the antiferromagnetic ordering of the cerium magnetic moments and well-reproduced the experimental XPS valence-band spectrum.

  7. Development of novel strategy for the synthesis of organometallic compounds usable as protein ligands: application to the human cyclophilin hCyp-18

    International Nuclear Information System (INIS)

    Clavaud, C.

    2006-02-01

    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.)

  8. Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization

    Science.gov (United States)

    Turchin, Peter; Currie, Thomas E.; Whitehouse, Harvey; François, Pieter; Feeney, Kevin; Mullins, Daniel; Hoyer, Daniel; Collins, Christina; Grohmann, Stephanie; Mendel-Gleason, Gavin; Turner, Edward; Dupeyron, Agathe; Cioni, Enrico; Reddish, Jenny; Levine, Jill; Jordan, Greine; Brandl, Eva; Williams, Alice; Cesaretti, Rudolf; Krueger, Marta; Ceccarelli, Alessandro; Figliulo-Rosswurm, Joe; Tuan, Po-Ju; Peregrine, Peter; Marciniak, Arkadiusz; Preiser-Kapeller, Johannes; Kradin, Nikolay; Korotayev, Andrey; Palmisano, Alessio; Baker, David; Bidmead, Julye; Bol, Peter; Christian, David; Cook, Connie; Covey, Alan; Feinman, Gary; Júlíusson, Árni Daníel; Kristinsson, Axel; Miksic, John; Mostern, Ruth; Petrie, Cameron; Rudiak-Gould, Peter; ter Haar, Barend; Wallace, Vesna; Mair, Victor; Xie, Liye; Baines, John; Bridges, Elizabeth; Manning, Joseph; Lockhart, Bruce; Bogaard, Amy; Spencer, Charles

    2018-01-01

    Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as “Seshat: Global History Databank.” We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history. PMID:29269395

  9. Structural Complexity and Ecosystem Functions in a Natural Mixed Forest under a Single-Tree Selection Silviculture

    Directory of Open Access Journals (Sweden)

    Toshiya Yoshida

    2017-11-01

    Full Text Available The objective of forest management has become broader, and it is essential to harmonize timber production with conservation of the forest ecosystem. Selection cutting is recognized as a major alternative of clear-cutting, because it can maintain the complexity and heterogeneity of a natural forest; however, its long-term evaluations are limited. This study compared various attributes of stand structures, which are indicators of biodiversity and ecosystem carbon stock between managed and unmanaged blocks (12.6 ha area in total in a natural mixed forest in Hokkaido, the northernmost island of Japan. We found that 30 years’ implementation of single-tree selection did not affect the volume, size structure, species diversity nor spatial distribution of overstory trees in the managed stands. Also, the total carbon stock in the managed stands was almost equal to that of the unmanaged stands. In contrast, several structural attributes and indicator elements that are significant for biodiversity (such as large-diameter live trees, dead trees, cavities, epiphytic bryophytes, and some avian guilds showed marked decrease in the managed stands. We conclude that it is required to leave these structures and elements to some extent for deriving the merit of the management as an alternative silvicultural regime in the region.

  10. Regio- and Enantioselective N-Allylations of Imidazole, Benzimidazole, and Purine Heterocycles Catalyzed by Single-Component Metallacyclic Iridium Complexes

    Science.gov (United States)

    Stanley, Levi M.

    2010-01-01

    Highly regio- and enantioselective iridium-catalyzed N-allylations of benzimidazoles, imidazoles, and purines have been developed. N-Allylated benzimidazoles and imidazoles were isolated in high yields (up to 97%) with high branched-to-linear selectivity (up to 99:1) and enantioselectivity (up to 98% ee) from the reactions of benzimidazole and imidazole nucleophiles with unsymmetrical allylic carbonates in the presence of single component, ethylene-bound, metallacyclic iridium catalysts. N-Allylated purines were also obtained in high yields (up to 91%) with high N9:N7 selectivity (up to 96:4), high branched-to-linear selectivity (98:2), and high enantioselectivity (up to 98% ee) under similar conditions. The reactions encompass a range of benzimidazole, imidazole, and purine nucleophiles, as well as a variety of unsymmetrical aryl, heteroaryl, and aliphatic allylic carbonates. Competition experiments between common amine nucleophiles and the heterocyclic nitrogen nucleophiles studied in this work illustrate the effect of nucleophile pKa on the rate of iridium-catalyzed N-allylation reactions. Kinetic studies on the allylation of benzimidazole catalyzed by metallacyclic iridium-phosphoramidite complexes, in combination with studies on the deactivation of these catalysts in the presence of heterocyclic nucleophiles, provide insight into the effects of the structure of the phosphoramidite ligands on the stability of the metallacyclic catalysts. The data obtained from these studies has led to the development of N-allylations of benzimidazoles and imidazoles in the absence of an exogenous base. PMID:19480431

  11. Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.

    Science.gov (United States)

    Mandal, Kalyaneswar; Uppalapati, Maruti; Ault-Riché, Dana; Kenney, John; Lowitz, Joshua; Sidhu, Sachdev S; Kent, Stephen B H

    2012-09-11

    Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF(165) to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form of VEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 Å. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 Å(2) in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2.

  12. Multi-tap complex-coefficient incoherent microwave photonic filters based on optical single-sideband modulation and narrow band optical filtering.

    Science.gov (United States)

    Sagues, Mikel; García Olcina, Raimundo; Loayssa, Alayn; Sales, Salvador; Capmany, José

    2008-01-07

    We propose a novel scheme to implement tunable multi-tap complex coefficient filters based on optical single sideband modulation and narrow band optical filtering. A four tap filter is experimentally demonstrated to highlight the enhanced tuning performance provided by complex coefficients. Optical processing is performed by the use of a cascade of four phase-shifted fiber Bragg gratings specifically fabricated for this purpose.

  13. Size-dependent binding energies and fine-structure splitting of excitonic complexes in single InAs/GaAs quantum dots

    International Nuclear Information System (INIS)

    Rodt, S.; Seguin, R.; Schliwa, A.; Guffarth, F.; Poetschke, K.; Pohl, U.W.; Bimberg, D.

    2007-01-01

    A systematic study of excitonic complexes confined in single InAs/GaAs quantum dots is presented. Emphasis is placed on the recombination energies of the excitonic complexes and on the fine-structure splitting of the bright exciton ground state. The values depend in a characteristic way on the size of the respective quantum dot which controls the number of bound hole states and the piezoelectric potential

  14. Genetic and Biochemical Identification of a Novel Single-Stranded DNA-Binding Complex in Haloferax volcanii.

    Science.gov (United States)

    Stroud, Amy; Liddell, Susan; Allers, Thorsten

    2012-01-01

    Single-stranded DNA (ssDNA)-binding proteins play an essential role in DNA replication and repair. They use oligonucleotide/oligosaccharide-binding (OB)-folds, a five-stranded β-sheet coiled into a closed barrel, to bind to ssDNA thereby protecting and stabilizing the DNA. In eukaryotes the ssDNA-binding protein (SSB) is known as replication protein A (RPA) and consists of three distinct subunits that function as a heterotrimer. The bacterial homolog is termed SSB and functions as a homotetramer. In the archaeon Haloferax volcanii there are three genes encoding homologs of RPA. Two of the rpa genes (rpa1 and rpa3) exist in operons with a novel gene specific to Euryarchaeota; this gene encodes a protein that we have termed RPA-associated protein (rpap). The rpap genes encode proteins belonging to COG3390 group and feature OB-folds, suggesting that they might cooperate with RPA in binding to ssDNA. Our genetic analysis showed that rpa1 and rpa3 deletion mutants have differing phenotypes; only Δrpa3 strains are hypersensitive to DNA damaging agents. Deletion of the rpa3-associated gene rpap3 led to similar levels of DNA damage sensitivity, as did deletion of the rpa3 operon, suggesting that RPA3 and RPAP3 function in the same pathway. Protein pull-downs involving recombinant hexahistidine-tagged RPAs showed that RPA3 co-purifies with RPAP3, and RPA1 co-purifies with RPAP1. This indicates that the RPAs interact only with their respective associated proteins; this was corroborated by the inability to construct rpa1 rpap3 and rpa3 rpap1 double mutants. This is the first report investigating the individual function of the archaeal COG3390 RPA-associated proteins (RPAPs). We have shown genetically and biochemically that the RPAPs interact with their respective RPAs, and have uncovered a novel single-stranded DNA-binding complex that is unique to Euryarchaeota.

  15. Accurate prediction of complex free surface flow around a high speed craft using a single-phase level set method

    Science.gov (United States)

    Broglia, Riccardo; Durante, Danilo

    2017-11-01

    This paper focuses on the analysis of a challenging free surface flow problem involving a surface vessel moving at high speeds, or planing. The investigation is performed using a general purpose high Reynolds free surface solver developed at CNR-INSEAN. The methodology is based on a second order finite volume discretization of the unsteady Reynolds-averaged Navier-Stokes equations (Di Mascio et al. in A second order Godunov—type scheme for naval hydrodynamics, Kluwer Academic/Plenum Publishers, Dordrecht, pp 253-261, 2001; Proceedings of 16th international offshore and polar engineering conference, San Francisco, CA, USA, 2006; J Mar Sci Technol 14:19-29, 2009); air/water interface dynamics is accurately modeled by a non standard level set approach (Di Mascio et al. in Comput Fluids 36(5):868-886, 2007a), known as the single-phase level set method. In this algorithm the governing equations are solved only in the water phase, whereas the numerical domain in the air phase is used for a suitable extension of the fluid dynamic variables. The level set function is used to track the free surface evolution; dynamic boundary conditions are enforced directly on the interface. This approach allows to accurately predict the evolution of the free surface even in the presence of violent breaking waves phenomena, maintaining the interface sharp, without any need to smear out the fluid properties across the two phases. This paper is aimed at the prediction of the complex free-surface flow field generated by a deep-V planing boat at medium and high Froude numbers (from 0.6 up to 1.2). In the present work, the planing hull is treated as a two-degree-of-freedom rigid object. Flow field is characterized by the presence of thin water sheets, several energetic breaking waves and plungings. The computational results include convergence of the trim angle, sinkage and resistance under grid refinement; high-quality experimental data are used for the purposes of validation, allowing to

  16. Synthesis, characterization, single crystal X-ray determination, fluorescence and electrochemical studies of new dinuclear nickel(II) and oxovanadium(IV) complexes containing double Schiff base ligands

    Science.gov (United States)

    Shafaatian, Bita; Ozbakzaei, Zahra; Notash, Behrouz; Rezvani, S. Ahmad

    2015-04-01

    A series of new bimetallic complexes of nickel(II) and vanadium(IV) have been synthesized by the reaction of the new double bidentate Schiff base ligands with nickel acetate and vanadyl acetylacetonate in 1:1 M ratio. In nickel and also vanadyl complexes the ligands were coordinated to the metals via the imine N and enolic O atoms. The complexes have been found to possess 1:1 metals to ligands stoichiometry and the molar conductance data revealed that the metal complexes were non-electrolytes. The nickel and vanadyl complexes exhibited distorted square planar and square pyramidal coordination geometries, respectively. The emission spectra of the ligands and their complexes were studied in methanol. Electrochemical properties of the ligands and their metal complexes were also investigated in DMSO solvent at 150 mV s-1 scan rate. The ligands and metal complexes showed both quasi-reversible and irreversible processes at this scan rate. The Schiff bases and their complexes have been characterized by FT-IR, 1H NMR, UV/Vis spectroscopies, elemental analysis and conductometry. The crystal structure of the nickel complex has been determined by single crystal X-ray diffraction.

  17. Single-row versus double-row capsulolabral repair: a comparative evaluation of contact pressure and surface area in the capsulolabral complex-glenoid bone interface.

    Science.gov (United States)

    Kim, Doo-Sup; Yoon, Yeo-Seung; Chung, Hoi-Jeong

    2011-07-01

    Despite the attention that has been paid to restoration of the capsulolabral complex anatomic insertion onto the glenoid, studies comparing the pressurized contact area and mean interface pressure at the anatomic insertion site between a single-row repair and a double-row labral repair have been uncommon. The purpose of our study was to compare the mean interface pressure and pressurized contact area at the anatomic insertion site of the capsulolabral complex between a single-row repair and a double-row repair technique. Controlled laboratory study. Thirty fresh-frozen cadaveric shoulders (mean age, 61 ± 8 years; range, 48-71 years) were used for this study. Two types of repair were performed on each specimen: (1) a single-row repair and (2) a double-row repair. Using pressure-sensitive films, we examined the interface contact area and contact pressure. The mean interface pressure was greater for the double-row repair technique (0.29 ± 0.04 MPa) when compared with the single-row repair technique (0.21 ± 0.03 MPa) (P = .003). The mean pressurized contact area was also significantly greater for the double-row repair technique (211.8 ± 18.6 mm(2), 78.4% footprint) compared with the single-row repair technique (106.4 ± 16.8 mm(2), 39.4% footprint) (P = .001). The double-row repair has significantly greater mean interface pressure and pressurized contact area at the insertion site of the capsulolabral complex than the single-row repair. The double-row repair may be advantageous compared with the single-row repair in restoring the native footprint area of the capsulolabral complex.

  18. 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.

    Science.gov (United States)

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

    2001-12-15

    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. (c)2001 Elsevier Science.

  19. Single particle ICP-MS combined with a data evaluastion tool as a routine techique for the analysis of nanoparticles in complex matrices

    NARCIS (Netherlands)

    Peters, R.J.B.; Herrera-Rivera, Z.; Undas, A.K.; Lee, van der M.K.; Marvin, H.J.P.; Bouwmeester, H.; Weigel, S.

    2015-01-01

    Detection and characterization of nanoparticles (NPs) in complex media as consumer products, food and toxicological test media is an essential part of understanding the potential benefits and risks of the application of nanoparticles. Single particle ICP-MS (spICP-MS) was studied as a screening tool

  20. Diethylenetriamine/diamines/copper (II complexes [Cu(dien(NN]Br2: Synthesis, solvatochromism, thermal, electrochemistry, single crystal, Hirshfeld surface analysis and antibacterial activity

    Directory of Open Access Journals (Sweden)

    Fatima Abu Saleemh

    2017-09-01

    Full Text Available Two dicationic water soluble mixed triamine/diamine copper (II complexes, of general formula [Cu(dienNN]Br2 (1–2 [dien = diethelenetriamine and NN is en = ethylenediamine or Me4en = N,N′,N,N′-tetramethylethylenediamine] were prepared under ultrasonic mode with a relatively high yield. These complexes were characterized by elemental microanalysis, UV visible IR spectroscopy, and thermal and electrochemical techniques. In addition, complex 2 structure was solved by X-ray single crystal and Hirshfeld surface analysis. The complex exhibits a distorted square pyramidal coordination environment around Cu(II centre. The solvatochromism of the desired complexes was investigated in water and other suitable organic solvents. The results show that the Guttmann’s DN parameter values of the solvents have mainly contributed to the shift of the d–d absorption band towards the linear increase in the wavelength of the absorption maxima of the complexes. The complex 1 showed higher antibacterial activity against the studied microorganisms compared to complex 2. Both complexes revealed promising antibacterial activities.

  1. Diffusion, capture and recycling of SCAR/WAVE and Arp2/3 complexes observed in cells by single-molecule imaging

    Science.gov (United States)

    Millius, Arthur; Watanabe, Naoki; Weiner, Orion D.

    2012-01-01

    The SCAR/WAVE complex drives lamellipodium formation by enhancing actin nucleation by the Arp2/3 complex. Phosphoinositides and Rac activate the SCAR/WAVE complex, but how SCAR/WAVE and Arp2/3 complexes converge at sites of nucleation is unknown. We analyzed the single-molecule dynamics of WAVE2 and p40 (subunits of the SCAR/WAVE and Arp2/3 complexes, respectively) in XTC cells. We observed lateral diffusion of both proteins and captured the transition of p40 from diffusion to network incorporation. These results suggest that a diffusive 2D search facilitates binding of the Arp2/3 complex to actin filaments necessary for nucleation. After nucleation, the Arp2/3 complex integrates into the actin network and undergoes retrograde flow, which results in its broad distribution throughout the lamellipodium. By contrast, the SCAR/WAVE complex is more restricted to the cell periphery. However, with single-molecule imaging, we also observed WAVE2 molecules undergoing retrograde motion. WAVE2 and p40 have nearly identical speeds, lifetimes and sites of network incorporation. Inhibition of actin retrograde flow does not prevent WAVE2 association and disassociation with the membrane but does inhibit WAVE2 removal from the actin cortex. Our results suggest that membrane binding and diffusion expedites the recruitment of nucleation factors to a nucleation site independent of actin assembly, but after network incorporation, ongoing actin polymerization facilitates recycling of SCAR/WAVE and Arp2/3 complexes. PMID:22349699

  2. Strong antenna-enhanced fluorescence of a single light-harvesting complex shows photon anti-bunching

    NARCIS (Netherlands)

    Wientjes, E.; Renger, J.; Curto, A.G.; Cogdell, R.; Hulst, van N.F.

    2014-01-01

    The nature of the highly efficient energy transfer in photosynthetic light-harvesting complexes is a subject of intense research. Unfortunately, the low fluorescence efficiency and limited photostability hampers the study of individual light-harvesting complexes at ambient conditions. Here we

  3. Dynamics of water around the complex structures formed between the KH domains of far upstream element binding protein and single-stranded DNA molecules

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Kaushik; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in [Molecular Modeling Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India)

    2015-07-28

    Single-stranded DNA (ss-DNA) binding proteins specifically bind to the single-stranded regions of the DNA and protect it from premature annealing, thereby stabilizing the DNA structure. We have carried out atomistic molecular dynamics simulations of the aqueous solutions of two DNA binding K homology (KH) domains (KH3 and KH4) of the far upstream element binding protein complexed with two short ss-DNA segments. Attempts have been made to explore the influence of the formation of such complex structures on the microscopic dynamics and hydrogen bond properties of the interfacial water molecules. It is found that the water molecules involved in bridging the ss-DNA segments and the protein domains form a highly constrained thin layer with extremely retarded mobility. These water molecules play important roles in freezing the conformational oscillations of the ss-DNA oligomers and thereby forming rigid complex structures. Further, it is demonstrated that the effect of complexation on the slow long-time relaxations of hydrogen bonds at the interface is correlated with hindered motions of the surrounding water molecules. Importantly, it is observed that the highly restricted motions of the water molecules bridging the protein and the DNA components in the complexed forms originate from more frequent hydrogen bond reformations.

  4. Three Cyanide-Bridged One-Dimensional Single Chain Co"I"I"I-Mn"I"I Complexes: Rational Design, Synthesis, Crystal Structures and Magnetic Properties

    International Nuclear Information System (INIS)

    Zhang, Daopeng; Zhao, Zengdian; Wang, Ping; Chen, Xia

    2012-01-01

    Two pyridinecarboxamide dicyanidecobalt(III) building blocks and two mononuclear seven-coordinated macrocycle manganese(II) compounds have been rationally selected to assemble cyanide-bridged heterobimetallic complexes, resulting in three cyanide-bridged Co"I"I"I-Mn"I"I complexes. Single X-ray diffraction analysis show that these complexes {[Mn(L"1)][Co(bpb)]}ClO_4·CH_3OH·0.5H_2O (1), {[Mn(L"2)][Co(bpb)]}ClO_4·0.5CH_3OH (2) and {[Mn(L"1)][Cobpmb]}ClO_4·H_2O (3) (L"1 = 3,6-diazaoctane-1,8-diamine, L"2 = 3,6-dioxaoctano-1,8- diamine: bpb"2"- = 1,2-bis(pyridine-2-carboxamido)benzenate, bpmb"2"- = 1,2-bis(pyridine-2-carboxamido)-4- methyl-benzenate) all present predictable one-dimensional single chain structures. The molecular structures of these one-dimensional complexes consists of alternating units of [Mn(L)]"2"+ (L = L"1 or L"2) and [Co(L')(CN)_2]"- (L' = bpb"2"-, or bpmb"2"-), forming a cyanide-bridged cationic polymeric chain with free ClO_4"- as the balance anion. The coordination geometry of manganese(II) ion in the three one-dimensional complexes is a slightly distorted pentagonal-bipyrimidal with two cyanide nitrogen atoms at the trans positions and N_5 or N_3O_2 coordinating mode at the equatorial plane from ligand L"1 or L"2. Investigation over magnetic properties of these complexes reveals that the very weak magnetic coupling between neighboring Mn(II) ions connected by the diamagnetic dicyanidecobalt(III) building block. A best-fit to the magnetic susceptibility of complex 1 leads to the magnetic coupling constants J = .0.084(3) cm"-"1

  5. Time-dependent inhibition of Na+/K+-ATPase induced by single and simultaneous exposure to lead and cadmium

    Science.gov (United States)

    Vasić, V.; Kojić, D.; Krinulović, K.; Čolović, M.; Vujačić, A.; Stojić, D.

    2007-09-01

    Time-dependent interactions of Na+/K+-ATPase, isolated from rat brain synaptic plasma membranes (SPMs), with Cd2+ and Pb2+ ions in a single exposure and in a mixture were investigated in vitro. The interference of the enzyme with these metal ions was studied as a function of different protein concentrations and exposure time. The aim of the work was to investigate the possibility of selective recognition of Cd2+ and Pb2+ ions in a mixture, on the basis of the different rates of their protein-ligand interactions. Decreasing protein concentration increased the sensitivity of Na+/K+-ATPase toward both metals. The selectivity in protein-ligand interactions was obtained by variation of preincubation time (incubation before starting the enzymatic reaction).

  6. ZnS, CdS and HgS Nanoparticles via Alkyl-Phenyl Dithiocarbamate Complexes as Single Source Precursors

    OpenAIRE

    Onwudiwe, Damian C.; Ajibade, Peter A.

    2011-01-01

    The synthesis of II-VI semiconductor nanoparticles obtained by the thermolysis of certain group 12 metal complexes as precursors is reported. Thermogravimetric analysis of the single source precursors showed sharp decomposition leading to their respective metal sulfides. The structural and optical properties of the prepared nanoparticles were characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) UV-Vis and photoluminescen...

  7. Low-temperature protein dynamics of the B800 molecules in the LH2 light-harvesting complex: spectral hole burning study and comparison with single photosynthetic complex spectroscopy.

    Science.gov (United States)

    Grozdanov, Daniel; Herascu, Nicoleta; Reinot, Tõnu; Jankowiak, Ryszard; Zazubovich, Valter

    2010-03-18

    Previously published and new spectral hole burning (SHB) data on the B800 band of LH2 light-harvesting antenna complex of Rps. acidophila are analyzed in light of recent single photosynthetic complex spectroscopy (SPCS) results (for a review, see Berlin et al. Phys. Life Rev. 2007, 4, 64.). It is demonstrated that, in general, SHB-related phenomena observed for the B800 band are in qualitative agreement with the SPCS data and the protein models involving multiwell multitier protein energy landscapes. Regarding the quantitative agreement, we argue that the single-molecule behavior associated with the fastest spectral diffusion (smallest barrier) tier of the protein energy landscape is inconsistent with the SHB data. The latter discrepancy can be attributed to SPCS probing not only the dynamics of of the protein complex per se, but also that of the surrounding amorphous host and/or of the host-protein interface. It is argued that SHB (once improved models are developed) should also be able to provide the average magnitudes and probability distributions of light-induced spectral shifts and could be used to determine whether SPCS probes a set of protein complexes that are both intact and statistically relevant. SHB results are consistent with the B800 --> B850 energy-transfer models including consideration of the whole B850 density of states.

  8. A high-throughput 2D-analytical technique to obtain single protein parameters from complex cell lysates for in silico process development of ion exchange chromatography.

    Science.gov (United States)

    Kröner, Frieder; Elsäßer, Dennis; Hubbuch, Jürgen

    2013-11-29

    The accelerating growth of the market for biopharmaceutical proteins, the market entry of biosimilars and the growing interest in new, more complex molecules constantly pose new challenges for bioseparation process development. In the presented work we demonstrate the application of a multidimensional, analytical separation approach to obtain the relevant physicochemical parameters of single proteins in a complex mixture for in silico chromatographic process development. A complete cell lysate containing a low titre target protein was first fractionated by multiple linear salt gradient anion exchange chromatography (AEC) with varying gradient length. The collected fractions were subsequently analysed by high-throughput capillary gel electrophoresis (HT-CGE) after being desalted and concentrated. From the obtained data of the 2D-separation the retention-volumes and the concentration of the single proteins were determined. The retention-volumes of the single proteins were used to calculate the related steric-mass action model parameters. In a final evaluation experiment the received parameters were successfully applied to predict the retention behaviour of the single proteins in salt gradient AEC. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Synthesis, crystal growth and characterization of bioactive material: 2-amino-1H-benzo[d]imidazol-3-ium salicylate single crystal-a proton transfer molecular complex

    Science.gov (United States)

    Fathima, K. Saiadali; Anitha, K.

    2017-05-01

    The 1:1 molecular adducts 2-aminobenzimidazolium salicylate (ABIS) single crystal was synthesized and grown from 2-aminobenzimidazole (ABI) as a donor and salicylic acid (SA) as an acceptor. The cell parameter was determined using single crystal X-Ray diffraction method and the complex ABIS belongs to monoclinic system. The spectroscopic studies showed that ABIS crystal was an ion pair complex. The FTIR and Raman spectra showed that the presence of O-H, C=N, C=O vibration which confirms the proton transfer from SA to ABI. The UV-Vis spectrum exhibited a visible band at 359nm for ABIS due to the salicylate anion of the molecule. Further the antimicrobial activity of ABIS complex against Staphylococcus aureus, klebsiella pneumonia, Pseudomonas eruginos and E.coli pathogens was investigated. So the complex molecule inhibits both Gram positive and Gram negative bacterial. It is found that benzimidazole with aminogroup at position 2 increases the general antimicrobial activities of ABIS crystal.

  10. Microscopic models for proton transfer in water and strongly hydrogen-bonded complexes with a single-well proton potential

    DEFF Research Database (Denmark)

    Kuznetsov, A.M.; Ulstrup, Jens

    2004-01-01

    A new mechanism and formalism for proton transfer in donor-acceptor complexes with long hydrogen bonds introduced recently [1], is applied to a proton transfer in liquid water. "Structural diffusion" of hydroxonium ions is regarded as totally adiabatic process, with synchronous hindered translation...... of two closest water molecules to and from the reaction complex as crucial steps. The water molecules induce a "gated" shift of the proton from the donor to the acceptor in the double-well potential with simultaneous breaking/formation of hydrogen bonds between these molecules and the proton donor...... and acceptor. The short-range and long-range proton transfer as "structural diffusion" of Zundel complexes is also considered. The theoretical formalism is illustrated with the use of Morse, exponential, and harmonic molecular potentials. This approach is extended to proton transfer in strongly hydrogen...

  11. Lanthanide Single-Molecule Magnets Framed by Alkali Metals & Magnetic and Spectroscopic Studies of 3d Transition Metal Complexes

    DEFF Research Database (Denmark)

    Konstantatos, Andreas

    -molecule magnets (SMMs). Starting from the archetype SMM Mn12 we present the details of the mechanisms governing the relaxation of the magnetization of these systems. In Chapter 2 we present our work on the coordination chemistry of lanthanides with a new Schiff-base ligand, H3L [(E)-3-((2-hydroxyphenyl...... complexes of M3+ or M2+ metal ions (M: 3d transition metal) with the preference to either approximate octahedral or trigonal prismatic coordination geometry. A detailed magnetic characterization for most of the complexes is presented where a trinuclear Co2+ cluster stands out for its pronounced SMM...

  12. Single-molecule magnetism in three related {Co(III)2Dy(III)2}-acetylacetonate complexes with multiple relaxation mechanisms.

    Science.gov (United States)

    Langley, Stuart K; Chilton, Nicholas F; Moubaraki, Boujemaa; Murray, Keith S

    2013-06-17

    Three new heterometallic complexes with formulas of [Dy(III)2Co(III)2(OMe)2(teaH)2(acac)4(NO3)2] (1), [Dy(III)2Co(III)2(OH)2(teaH)2(acac)4(NO3)2]·4H2O (2), and [Dy(III)2Co(III)2(OMe)2(mdea)2(acac)4(NO3)2] (3) were characterized by single-crystal X-ray diffraction and by dc and ac magnetic susceptibility measurements. All three complexes have an identical "butterfly"-type metallic core that consists of two Dy(III) ions occupying the "body" position and two diamagnetic low-spin Co(III) ions occupying the outer "wing-tips". Each complex displays single-molecule magnet (SMM) behavior in zero applied magnetic field, with thermally activated anisotropy barriers of 27, 28, and 38 K above 7.5 K for 1-3, respectively, as well as observing a temperature-independent mechanism of relaxation below 5 K for 1 and 2 and at 3 K for 3, indicating fast quantum tunneling of magnetization (QTM). A second, faster thermally activated relaxation mechanism may also be active under a zero applied dc field as derived from the Cole-Cole data. Interestingly, these complexes demonstrate further relaxation modes that are strongly dependent upon the application of a static dc magnetic field. Dilution experiments that were performed on 1, in the {Y(III)2Co(III)2} diamagnetic analog, show that the slow magnetic relaxation is of a single-ion origin, but it was found that the neighboring ion also plays an important role in the overall relaxation dynamics.

  13. Detecting gait abnormalities after concussion or mild traumatic brain injury: A systematic review of single-task, dual-task, and complex gait.

    Science.gov (United States)

    Fino, Peter C; Parrington, Lucy; Pitt, Will; Martini, Douglas N; Chesnutt, James C; Chou, Li-Shan; King, Laurie A

    2018-05-01

    While a growing number of studies have investigated the effects of concussion or mild traumatic brain injury (mTBI) on gait, many studies use different experimental paradigms and outcome measures. The path for translating experimental studies for objective clinical assessments of gait is unclear. This review asked 2 questions: 1) is gait abnormal after concussion/mTBI, and 2) what gait paradigms (single-task, dual-task, complex gait) detect abnormalities after concussion. Data sources included MEDLINE/PubMed, Scopus, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) accessed on March 14, 2017. Original research articles reporting gait outcomes in people with concussion or mTBI were included. Studies of moderate, severe, or unspecified TBI, and studies without a comparator were excluded. After screening 233 articles, 38 studies were included and assigned to one or more sections based on the protocol and reported outcomes. Twenty-six articles reported single-task simple gait outcomes, 24 reported dual-task simple gait outcomes, 21 reported single-task complex gait outcomes, and 10 reported dual-task complex gait outcomes. Overall, this review provides evidence for two conclusions: 1) gait is abnormal acutely after concussion/mTBI but generally resolves over time; and 2) the inconsistency of findings, small sample sizes, and small number of studies examining homogenous measures at the same time-period post-concussion highlight the need for replication across independent populations and investigators. Future research should concentrate on dual-task and complex gait tasks, as they showed promise for detecting abnormal locomotor function outside of the acute timeframe. Additionally, studies should provide detailed demographic and clinical characteristics to enable more refined comparisons across studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Thermodynamics of complex structures formed between single-stranded DNA oligomers and the KH domains of the far upstream element binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Kaushik; Sinha, Sudipta Kumar; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in [Molecular Modeling Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India)

    2016-05-28

    The noncovalent interaction between protein and DNA is responsible for regulating the genetic activities in living organisms. The most critical issue in this problem is to understand the underlying driving force for the formation and stability of the complex. To address this issue, we have performed atomistic molecular dynamics simulations of two DNA binding K homology (KH) domains (KH3 and KH4) of the far upstream element binding protein (FBP) complexed with two single-stranded DNA (ss-DNA) oligomers in aqueous media. Attempts have been made to calculate the individual components of the net entropy change for the complexation process by adopting suitable statistical mechanical approaches. Our calculations reveal that translational, rotational, and configurational entropy changes of the protein and the DNA components have unfavourable contributions for this protein-DNA association process and such entropy lost is compensated by the entropy gained due to the release of hydration layer water molecules. The free energy change corresponding to the association process has also been calculated using the Free Energy Perturbation (FEP) method. The free energy gain associated with the KH4–DNA complex formation has been found to be noticeably higher than that involving the formation of the KH3–DNA complex.

  15. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Mustafa, A S; Amoudy, H A; Wiker, H G

    1998-01-01

    GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN...

  16. Virtual screening with AutoDock Vina and the common pharmacophore engine of a low diversity library of fragments and hits against the three allosteric sites of HIV integrase: participation in the SAMPL4 protein-ligand binding challenge.

    Science.gov (United States)

    Perryman, Alexander L; Santiago, Daniel N; Forli, Stefano; Martins, Diogo Santos; Olson, Arthur J

    2014-04-01

    To rigorously assess the tools and protocols that can be used to understand and predict macromolecular recognition, and to gain more structural insight into three newly discovered allosteric binding sites on a critical drug target involved in the treatment of HIV infections, the Olson and Levy labs collaborated on the SAMPL4 challenge. This computational blind challenge involved predicting protein-ligand binding against the three allosteric sites of HIV integrase (IN), a viral enzyme for which two drugs (that target the active site) have been approved by the FDA. Positive control cross-docking experiments were utilized to select 13 receptor models out of an initial ensemble of 41 different crystal structures of HIV IN. These 13 models of the targets were selected using our new "Rank Difference Ratio" metric. The first stage of SAMPL4 involved using virtual screens to identify 62 active, allosteric IN inhibitors out of a set of 321 compounds. The second stage involved predicting the binding site(s) and crystallographic binding mode(s) for 57 of these inhibitors. Our team submitted four entries for the first stage that utilized: (1) AutoDock Vina (AD Vina) plus visual inspection; (2) a new common pharmacophore engine; (3) BEDAM replica exchange free energy simulations, and a Consensus approach that combined the predictions of all three strategies. Even with the SAMPL4's very challenging compound library that displayed a significantly lower amount of structural diversity than most libraries that are conventionally employed in prospective virtual screens, these approaches produced hit rates of 24, 25, 34, and 27 %, respectively, on a set with 19 % declared binders. Our only entry for the second stage challenge was based on the results of AD Vina plus visual inspection, and it ranked third place overall according to several different metrics provided by the SAMPL4 organizers. The successful results displayed by these approaches highlight the utility of the computational

  17. Virtual screening with AutoDock Vina and the common pharmacophore engine of a low diversity library of fragments and hits against the three allosteric sites of HIV integrase: participation in the SAMPL4 protein-ligand binding challenge

    Science.gov (United States)

    Perryman, Alexander L.; Santiago, Daniel N.; Forli, Stefano; Santos-Martins, Diogo; Olson, Arthur J.

    2014-04-01

    To rigorously assess the tools and protocols that can be used to understand and predict macromolecular recognition, and to gain more structural insight into three newly discovered allosteric binding sites on a critical drug target involved in the treatment of HIV infections, the Olson and Levy labs collaborated on the SAMPL4 challenge. This computational blind challenge involved predicting protein-ligand binding against the three allosteric sites of HIV integrase (IN), a viral enzyme for which two drugs (that target the active site) have been approved by the FDA. Positive control cross-docking experiments were utilized to select 13 receptor models out of an initial ensemble of 41 different crystal structures of HIV IN. These 13 models of the targets were selected using our new "Rank Difference Ratio" metric. The first stage of SAMPL4 involved using virtual screens to identify 62 active, allosteric IN inhibitors out of a set of 321 compounds. The second stage involved predicting the binding site(s) and crystallographic binding mode(s) for 57 of these inhibitors. Our team submitted four entries for the first stage that utilized: (1) AutoDock Vina (AD Vina) plus visual inspection; (2) a new common pharmacophore engine; (3) BEDAM replica exchange free energy simulations, and a Consensus approach that combined the predictions of all three strategies. Even with the SAMPL4's very challenging compound library that displayed a significantly lower amount of structural diversity than most libraries that are conventionally employed in prospective virtual screens, these approaches produced hit rates of 24, 25, 34, and 27 %, respectively, on a set with 19 % declared binders. Our only entry for the second stage challenge was based on the results of AD Vina plus visual inspection, and it ranked third place overall according to several different metrics provided by the SAMPL4 organizers. The successful results displayed by these approaches highlight the utility of the computational

  18. Single-molecule conductance of a chemically modified, π-extended tetrathiafulvalene and its charge-transfer complex with F4TCNQ

    Directory of Open Access Journals (Sweden)

    Raúl García

    2015-06-01

    Full Text Available We describe the synthesis and single-molecule electrical transport properties of a molecular wire containing a π-extended tetrathiafulvalene (exTTF group and its charge-transfer complex with F4TCNQ. We form single-molecule junctions using the in situ break junction technique using a homebuilt scanning tunneling microscope with a range of conductance between 10 G0 down to 10−7 G0. Within this range we do not observe a clear conductance signature of the neutral parent molecule, suggesting either that its conductance is too low or that it does not form a stable junction. Conversely, we do find a clear conductance signature in the experiments carried out on the charge-transfer complex. Due to the fact we expected this species to have a higher conductance than the neutral molecule, we believe this supports the idea that the conductance of the neutral molecule is very low, below our measurement sensitivity. This idea is further supported by theoretical calculations. To the best of our knowledge, these are the first reported single-molecule conductance measurements on a molecular charge-transfer species.

  19. Temporal evolution of multi-carrier complexes in single GaN/AlGaN quantum dots

    International Nuclear Information System (INIS)

    Surowiecka, K.; Wysmolek, A.; Stepniewski, R.; Bozek, R.; Pakula, K.; Baranowski, J.M.

    2005-01-01

    Micro photoluminescence of low-density GaN/Al x Ga 1-x N quantum dots grown by metal-organic vapor phase epitaxy using in situ etching of AlGaN is presented. The narrow lines in the micro photoluminescence spectra due to the single quantum dots are observed. Both energy and intensity of these lines show temporal fluctuations. Statistical analysis based on the correlation matrix allowed us to identify objects, which are affected by photo-induced electric field fluctuations. Relations between emission lines participating in the spectrum are discussed. (author)

  20. A Low-Complexity Joint Synchronization and Detection Algorithm for Single-Band DS-CDMA UWB Communications

    Directory of Open Access Journals (Sweden)

    Christensen Lars PB

    2005-01-01

    Full Text Available The problem of asynchronous direct-sequence code-division multiple-access (DS-CDMA detection over the ultra-wideband (UWB multipath channel is considered. A joint synchronization, channel-estimation, and multiuser detection scheme based on the adaptive linear minimum mean square error (LMMSE receiver is presented and evaluated. Further, a novel nonrecursive least-squares algorithm capable of reducing the complexity of the adaptation in the receiver while preserving the advantages of the recursive least-squares (RLS algorithm is presented.

  1. Three-Year Major Clinical Outcomes of Angiography-Guided Single Stenting Technique in Non-Complex Left Main Coronary Artery Diseases.

    Science.gov (United States)

    Kim, Yong Hoon; Her, Ae-Young; Rha, Seung-Woon; Choi, Byoung Geol; Shim, Minsuk; Choi, Se Yeon; Byun, Jae Kyeong; Li, Hu; Kim, Woohyeun; Kang, Jun Hyuk; Choi, Jah Yeon; Park, Eun Jin; Park, Sung Hun; Lee, Sunki; Na, Jin Oh; Choi, Cheol Ung; Lim, Hong Euy; Kim, Eung Ju; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo

    2017-10-12

    There is limited long-term comparative clinical outcome data concerning angiography- versus intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in non-complex left main coronary artery (LMCA) disease treated with the single stenting technique in the drug-eluting stent (DES) era.The aim of this study was to investigate whether angiography-guided stenting is comparable to IVUS-guided stenting during 3-year clinical follow-up periods in patients with non-complex LM disease treated with the single stenting technique.A total of 196 patients treated with either angiography-guided (n = 74) or IVUS-guided (n = 122) PCI were included. The primary outcome was the occurrence of major adverse cardiac events (MACE) defined as total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-target vessel revascularization (Non-TVR). To adjust for any potential confounders, propensity score (PS) adjusted analysis was performed.During 3-year follow-up, the PS adjusted Cox-proportional hazard ratio (HR) was not significantly different between the two groups for total death, cardiac death, and MI. Also, TLR and the combined rates of TVR and non-TVR were not significantly different. Finally, MACE was not significantly different between the two groups (HR: 0.63, 95% Confidence interval (CI): 0.33-1.17; P = 0.149).Angiography-guided PCI for non-complex LMCA diseases treated with the single stenting technique showed comparable results compared with IVUS-guided PCI in reducing clinical events during 3-year clinical follow-up in the DES era. Although IVUS guided PCI is the ideal strategy, angiography-guided PCI can be an option for LMCA PCI in some selected cases.

  2. Automatic sleep stage classification of single-channel EEG by using complex-valued convolutional neural network.

    Science.gov (United States)

    Zhang, Junming; Wu, Yan

    2018-03-28

    Many systems are developed for automatic sleep stage classification. However, nearly all models are based on handcrafted features. Because of the large feature space, there are so many features that feature selection should be used. Meanwhile, designing handcrafted features is a difficult and time-consuming task because the feature designing needs domain knowledge of experienced experts. Results vary when different sets of features are chosen to identify sleep stages. Additionally, many features that we may be unaware of exist. However, these features may be important for sleep stage classification. Therefore, a new sleep stage classification system, which is based on the complex-valued convolutional neural network (CCNN), is proposed in this study. Unlike the existing sleep stage methods, our method can automatically extract features from raw electroencephalography data and then classify sleep stage based on the learned features. Additionally, we also prove that the decision boundaries for the real and imaginary parts of a complex-valued convolutional neuron intersect orthogonally. The classification performances of handcrafted features are compared with those of learned features via CCNN. Experimental results show that the proposed method is comparable to the existing methods. CCNN obtains a better classification performance and considerably faster convergence speed than convolutional neural network. Experimental results also show that the proposed method is a useful decision-support tool for automatic sleep stage classification.

  3. Comparison of antigen-specific T-cell responses of tuberculosis patients using complex or single antigens of Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Mustafa, A S; Amoudy, H A; Wiker, H G

    1998-01-01

    We have screened peripheral blood mononuclear cells (PBMC) from tuberculosis (TB) patients for proliferative reactivity and interferon-gamma (IFN-gamma) secretion against a panel of purified recombinant (r) and natural (n) culture filtrate (rESAT-6, nMPT59, nMPT64 and nMPB70) and somatic-derived (r......GroES, rPstS, rGroEL and rDnaK) antigens of Mycobacterium tuberculosis. The responses of PBMC to these defined antigens were compared with the corresponding results obtained with complex antigens, such as whole-cell M. tuberculosis, M. tuberculosis culture filtrate (MT-CF) and cell wall antigens, as well...... as the vaccine strain, Mycobacterium bovis bacillus Calmette-Guerin (BCG). In addition, M. tuberculosis and MT-CF-induced T-cell lines were tested in the same assays against the panel of purified and complex antigens. The compiled data from PBMC and T-cell lines tested for antigen-induced proliferation and IFN...

  4. Synthesis, characterization and single crystal x-ray analysis of a complex of iron(II) bis(2,4-dimethylphenyl)dithiophosphate with 4-ethylpyridine

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Sandeep; Andotra, Savit; Kaur, Mandeep [University of Jammu, Department of Chemistry (India); Gupta, Vivek K.; Kant, Rajni [Department of Physics and Electronics, University of Jammu, X-ray Crystallographic Laboratory (India); Pandey, Sushil K., E-mail: kpsushil@rediffmail.com [University of Jammu, Department of Chemistry (India)

    2016-09-15

    Complex of iron(II) bis(2,4-dimethylphenyl)dithiophosphate with 4-ethylpyridine [((2,4- (CH{sub 3}){sub 2}C{sub 6}H{sub 3}O)2PS2)2Fe(NC{sub 5}H{sub 4}(C{sub 2}H{sub 5})-4){sub 2}] is synthesized and characterized by elemental analysis, magnetic moment, IR spectroscopy and single crystal X-ray analysis. Complex crystallizes in the monoclinic sp. gr. P2{sub 1}/n, Z = 2. Crystal structure consists of mononuclear units with Fe(II) ion chelated by four S atoms of the two diphenyldithiophosphate ligands in bidentate manner. N atoms from two 4-ethylpyridine ligands are axially coordinated to the Fe(II) atom leading to an octahedral geometry.

  5. Associated equilibria with participatian of single and mixed silver, lead and cadmium halide complexes in mixtures of molten alkali and alkaline earth metal nitrates

    International Nuclear Information System (INIS)

    Gouk, Kh.S.; Gupta, R.K.; Vekma, K.V.

    1983-01-01

    Associated equilibria in the systems, which contain single and mixed silver, cadmium and lead halide complexes in the KNO 3 -Ba(N0 3 ) 2 (87.6:12.4 and 89:11 mol.%) and NaNO 3 -Ba(NO 3 ) 2 (94.2-5.8 mol%) melts in the temperature range from 568.2 up to 698.2 K are investigated. Applicability of equations derivated on the base of quasi-lattice model to description of temperature coefficients of association constants is analized

  6. Rolling cycle amplification based single-color quantum dots–ruthenium complex assembling dyads for homogeneous and highly selective detection of DNA

    Energy Technology Data Exchange (ETDEWEB)

    Su, Chen; Liu, Yufei; Ye, Tai; Xiang, Xia; Ji, Xinghu; He, Zhike, E-mail: zhkhe@whu.edu.cn

    2015-01-01

    Graphical abstract: A universal, label-free, homogeneous, highly sensitive, and selective fluorescent biosensor for DNA detection is developed by using rolling-circle amplification (RCA) based single-color quantum dots–ruthenium complex (QDs–Ru) assembling dyads. - Highlights: • The single-color QDs–Ru assembling dyads were applied in homogeneous DNA assay. • This biosensor exhibited high selectivity against base mismatched sequences. • This biosensor could be severed as universal platform for the detection of ssDNA. • This sensor could be used to detect the target in human serum samples. • This DNA sensor had a good selectivity under the interference of other dsDNA. - Abstract: In this work, a new, label-free, homogeneous, highly sensitive, and selective fluorescent biosensor for DNA detection is developed by using rolling-circle amplification (RCA) based single-color quantum dots–ruthenium complex (QDs–Ru) assembling dyads. This strategy includes three steps: (1) the target DNA initiates RCA reaction and generates linear RCA products; (2) the complementary DNA hybridizes with the RCA products to form long double-strand DNA (dsDNA); (3) [Ru(phen){sub 2}(dppx)]{sup 2+} (dppx = 7,8-dimethyldipyrido [3,2-a:2′,3′-c] phenanthroline) intercalates into the long dsDNA with strong fluorescence emission. Due to its strong binding propensity with the long dsDNA, [Ru(phen){sub 2}(dppx)]{sup 2+} is removed from the surface of the QDs, resulting in restoring the fluorescence of the QDs, which has been quenched by [Ru(phen){sub 2}(dppx)]{sup 2+} through a photoinduced electron transfer process and is overlaid with the fluorescence of dsDNA bonded Ru(II) polypyridyl complex (Ru-dsDNA). Thus, high fluorescence intensity is observed, and is related to the concentration of target. This sensor exhibits not only high sensitivity for hepatitis B virus (HBV) ssDNA with a low detection limit (0.5 pM), but also excellent selectivity in the complex matrix. Moreover

  7. Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process.

    Science.gov (United States)

    Rudrangi, Shashi Ravi Suman; Kaialy, Waseem; Ghori, Muhammad U; Trivedi, Vivek; Snowden, Martin J; Alexander, Bruce David

    2016-07-01

    The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11±0.09% dissolving at the end of 60min, while the binary mixtures processed by supercritical carbon dioxide at 45°C and 200bar released 99.39±2.34% of the drug at the end of 30min. All the binary mixtures processed by supercritical carbon dioxide at 45°C exhibited a drug release of more than 80% within the first 10min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. A novel non-enzymatic hydrogen peroxide sensor based on single walled carbon nanotubes-manganese complex modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Salimi, Abdollah, E-mail: absalimi@uok.ac.i [Department of Chemistry, University of Kurdistan, P.O. Box 416, Sanandaj (Iran, Islamic Republic of); Research Center for Nanotechnology, University of Kurdistan, P.O. Box 416, Sanandaj (Iran, Islamic Republic of); Mahdioun, Monierosadat; Noorbakhsh, Abdollah [Department of Chemistry, University of Kurdistan, P.O. Box 416, Sanandaj (Iran, Islamic Republic of); Abdolmaleki, Amir [Department of Chemistry, Isfahan University of Technology, Isfahan, 84156/83111 (Iran, Islamic Republic of); Ghavami, Raoof [Department of Chemistry, University of Kurdistan, P.O. Box 416, Sanandaj (Iran, Islamic Republic of)

    2011-03-30

    A simple procedure was developed to prepare a glassy carbon (GC) electrode modified with single wall carbon nanotubes (SWCNTs) and phenazine derivative of Mn-complex. With immersing the GC/CNTs modified electrode into Mn-complex solution for a short period of time 20-100 s, a stable thin layer of the complex was immobilized onto electrode surface. Modified electrode showed a well defined redox couples at wide pH range (1-12). The surface coverages and heterogeneous electron transfer rate constants (k{sub s}) of immobilized Mn-complex were approximately 1.58 x 10{sup -10} mole cm{sup -2} and 48.84 s{sup -1}. The modified electrode showed excellent electrocatalytic activity toward H{sub 2}O{sub 2} reduction. Detection limit, sensitivity, linear concentration range and k{sub cat} for H{sub 2}O{sub 2} were, 0.2 {mu}M and 692 nA {mu}M{sup -1} cm{sup -2}, 1 {mu}M to 1.5 mM and 7.96({+-}0.2) x 10{sup 3} M{sup -1} s{sup -1}, respectively. Compared to other modified electrodes, this electrode has many advantageous such as remarkable catalytic activity, good reproducibility, simple preparation procedure and long term stability.

  9. A novel non-enzymatic hydrogen peroxide sensor based on single walled carbon nanotubes-manganese complex modified glassy carbon electrode

    International Nuclear Information System (INIS)

    Salimi, Abdollah; Mahdioun, Monierosadat; Noorbakhsh, Abdollah; Abdolmaleki, Amir; Ghavami, Raoof

    2011-01-01

    A simple procedure was developed to prepare a glassy carbon (GC) electrode modified with single wall carbon nanotubes (SWCNTs) and phenazine derivative of Mn-complex. With immersing the GC/CNTs modified electrode into Mn-complex solution for a short period of time 20-100 s, a stable thin layer of the complex was immobilized onto electrode surface. Modified electrode showed a well defined redox couples at wide pH range (1-12). The surface coverages and heterogeneous electron transfer rate constants (k s ) of immobilized Mn-complex were approximately 1.58 x 10 -10 mole cm -2 and 48.84 s -1 . The modified electrode showed excellent electrocatalytic activity toward H 2 O 2 reduction. Detection limit, sensitivity, linear concentration range and k cat for H 2 O 2 were, 0.2 μM and 692 nA μM -1 cm -2 , 1 μM to 1.5 mM and 7.96(±0.2) x 10 3 M -1 s -1 , respectively. Compared to other modified electrodes, this electrode has many advantageous such as remarkable catalytic activity, good reproducibility, simple preparation procedure and long term stability.

  10. Laser desorption single-conformation UV and IR spectroscopy of the sulfonamide drug sulfanilamide, the sulfanilamide-water complex, and the sulfanilamide dimer.

    Science.gov (United States)

    Uhlemann, Thomas; Seidel, Sebastian; Müller, Christian W

    2017-06-07

    We have studied the conformational preferences of the sulfonamide drug sulfanilamide, its dimer, and its monohydrated complex through laser desorption single-conformation UV and IR spectroscopy in a molecular beam. Based on potential energy curves for the inversion of the anilinic and the sulfonamide NH 2 groups calculated at DFT level, we suggest that the zero-point level wave function of the sulfanilamide monomer is appreciably delocalized over all four conformer wells. The sulfanilamide dimer, and the monohydrated complex each exhibit a single isomer in the molecular beam. The isomeric structures of the sulfanilamide dimer and the monohydrated sulfanilamide complex were assigned based on their conformer-specific IR spectra in the NH and OH stretch region. Quantum Theory of Atoms in Molecules (QTAIM) analysis of the calculated electron density in the water complex suggests that the water molecule is bound side-on in a hydrogen bonding pocket, donating one O-HO[double bond, length as m-dash]S hydrogen bond and accepting two hydrogen bonds, a NHO and a CHO hydrogen bond. QTAIM analysis of the dimer electron density suggests that the C i symmetry dimer structure exhibits two dominating N-HO[double bond, length as m-dash]S hydrogen bonds, and three weaker types of interactions: two CHO bonds, two CHN bonds, and a chalcogen OO interaction. Most interestingly, the molecular beam dimer structure closely resembles the R dimer unit - the dimer unit with the greatest interaction energy - of the α, γ, and δ crystal polymorphs. Interacting Quantum Atoms analysis provides evidence that the total intermolecular interaction in the dimer is dominated by the short-range exchange-correlation contribution.

  11. Turn-on fluorescence sensor based on single-walled-carbon-nanohorn-peptide complex for the detection of thrombin.

    Science.gov (United States)

    Zhu, Shuyun; Liu, Zhongyuan; Hu, Lianzhe; Yuan, Yali; Xu, Guobao

    2012-12-14

    Proteases play a central role in several widespread diseases. Thus, there is a great need for the fast and sensitive detection of various proteolytic enzymes. Herein, we have developed a carbon nanotube (CNT)-based protease biosensing platform that uses peptides as a fluorescence probe for the first time. Single-walled carbon nanohorns (SWCNHs) and thrombin were used to demonstrate this detection strategy. SWCNHs can adsorb a fluorescein-based dye (FAM)-labeled peptide (FAM-pep) and quench the fluorescence of FAM. In contrast, thrombin can cleave FAM-pep on SWCNHs and recover the fluorescence of FAM, which allows the sensitive detection of thrombin. This biosensor has a high sensitivity and selectivity toward thrombin, with a detection limit of 100 pM. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Toward The Reconstitution of the Maturation of Okazaki Fragments Multiprotein Complex in Human At The Single Molecule Level

    KAUST Repository

    Joudeh, Luay

    2017-04-01

    The maturation of Okazaki fragments on the lagging strand in eukaryotes is mediated by a highly coordinated multistep process involving several proteins that ensure the accurate and efficient replication of genomic DNA. Human proliferating cell nuclear antigen (PCNA) that slides on double-stranded DNA is the key player that coordinates the access of various proteins to the different intermediary steps in this process. In this study, I am focusing on characterizing how PCNA recruits and stimulates the structure specific flap endonuclease 1 (FEN1) to process the aberrant double flap (DF) structures that are produced during maturation of Okazaki fragments. FEN1 distorts the DF structures into a bent conformer to place the scissile phosphate into the active site for cleavage. The product is a nick substrate that can be sealed by DNA ligase I whose recruitment is also mediated by its interaction with PCNA. Using single-molecule Förster resonance energy transfer (smFRET) measurements that simultaneously monitored bending and cleavage of various DF substrates by FEN1 alone or in the presence of PCNA, we found that FEN1 and PCNA bends cognate and non-cognate substrates but display remarkable selectivity to stabilize the bent conformer in cognate substrate while promoting the dissociation of non-cognate substrates. This mechanism provides efficiency and accuracy for FEN1 and PCNA to cleave the correct substrate while avoiding the deleterious cleavage of incorrect substrates. This work provides a true molecular level understanding of the key step during the maturation of Okazaki fragment and contributes towards the reconstitution of its entire activity at the single molecule level.

  13. Apparent change in cardiac geometry during single-photon emission tomography thallium-201 acquisition: a complex phenomenon

    International Nuclear Information System (INIS)

    Eisner, R.L.; Aaron, A.M.; Worthy, M.R.; Boyers, A.S.; Leon, A.R.; Fajman, W.A.; Patterson, R.E.; Emory Univ., Atlanta, GA

    1993-01-01

    We investigated the frequency and extent of changes in heart positon and geometry independent of body motion during stress single-photon emission tomography (SPET) thallium-201 myocardial perfusion imaging. Following an exercise treadmill test, patients had a 22.1-min SPET acquisition which was followed immediately by a static image acquisition for 1 min with the camera position identical to the first fiew of the SPET study. Point sources were placed on the body to monitor patient motion. Cardiac motion was assessed by an approach which mimicked a cross-correlation technique applied to cardia count profiles along the horizontal and vertical directions from the first view of the SPET study and the static image. A large percentage (87.5%) of cases had some degree of horizontal or vertical motion. Pixel shifts in caridac position of ≥2 pixels (12 mm) occurred in 60% of patients. In 37% of patients who moved the caridac motion was consistent with simple translation of the heart and thus amenable to correction using proposed SPET motion-correction programs. The peak heart rate achieved during stress and the ratio of the heart rate immediately before SPET acquisition to the resting heart rate were determined to be independent predictors of patient motion during SPET acquisition. Cardiac motion changes were minimal at (13.3±2.2) min after cessation of exercise. The implications of these findings for the accuracy of SPET 201 TI require further investigation. (orig.)

  14. Covalent lanthanide(III) macrocyclic complexes: the bonding nature and optical properties of a promising single antenna molecule.

    Science.gov (United States)

    Rabanal-León, Walter A; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro

    2014-12-21

    The present work is focused on the elucidation of the electronic structure, bonding nature and optical properties of a series of low symmetry (C2) coordination compounds of type [Ln(III)HAM](3+), where "Ln(III)" are the trivalent lanthanide ions: La(3+), Ce(3+), Eu(3+) and Lu(3+), while "HAM" is the neutral six-nitrogen donor macrocyclic ligand [C22N6H26]. This systematic study has been performed in the framework of the Relativistic Density Functional Theory (R-DFT) and also using a multi-reference approach via the Complete Active Space (CAS) wavefunction treatment with the aim of analyzing their ground state and excited state electronic structures as well as electronic correlation. Furthermore, the use of the energy decomposition scheme proposed by Morokuma-Ziegler and the electron localization function (ELF) allows us to characterize the bonding between the lanthanide ions and the macrocyclic ligand, obtaining as a result a dative-covalent interaction. Due to a great deal of lanthanide optical properties and their technological applications, the absorption spectra of this set of coordination compounds were calculated using the time-dependent density functional theory (TD-DFT), where the presence of the intense Ligand to Metal Charge Transfer (LMCT) bands in the ultraviolet and visible region and the inherent f-f electronic transitions in the Near-Infra Red (NIR) region for some lanthanide ions allow us to propose these systems as "single antenna molecules" with potential applications in NIR technologies.

  15. Simplifying the complex 1H NMR spectra of fluorine-substituted benzamides by spin system filtering and spin-state selection: multiple-quantum-single-quantum correlation.

    Science.gov (United States)

    Baishya, Bikash; Reddy, G N Manjunatha; Prabhu, Uday Ramesh; Row, T N Guru; Suryaprakash, N

    2008-10-23

    The proton NMR spectra of fluorine-substituted benzamides are very complex (Figure 1) due to severe overlap of (1)H resonances from the two aromatic rings, in addition to several short and long-range scalar couplings experienced by each proton. With no detectable scalar couplings between the inter-ring spins, the (1)H NMR spectra can be construed as an overlap of spectra from two independent phenyl rings. In the present study we demonstrate that it is possible to separate the individual spectrum for each aromatic ring by spin system filtering employing the multiple-quantum-single-quantum correlation methodology. Furthermore, the two spin states of fluorine are utilized to simplify the spectrum corresponding to each phenyl ring by the spin-state selection. The demonstrated technique reduces spectral complexity by a factor of 4, in addition to permitting the determination of long-range couplings of less than 0.2 Hz and the relative signs of heteronuclear couplings. The technique also aids the judicious choice of the spin-selective double-quantum-single-quantum J-resolved experiment to determine the long-range homonuclear couplings of smaller magnitudes.

  16. The approximate entropy concept extended to three dimensions for calibrated, single parameter structural complexity interrogation of volumetric images.

    Science.gov (United States)

    Moore, Christopher; Marchant, Thomas

    2017-07-12

    Reconstructive volumetric imaging permeates medical practice because of its apparently clear depiction of anatomy. However, the tell tale signs of abnormality and its delineation for treatment demand experts work at the threshold of visibility for hints of structure. Hitherto, a suitable assistive metric that chimes with clinical experience has been absent. This paper develops the complexity measure approximate entropy (ApEn) from its 1D physiological origin into a three-dimensional (3D) algorithm to fill this gap. The first 3D algorithm for this is presented in detail. Validation results for known test arrays are followed by a comparison of fan-beam and cone-beam x-ray computed tomography image volumes used in image guided radiotherapy for cancer. Results show the structural detail down to individual voxel level, the strength of which is calibrated by the ApEn process itself. The potential for application in machine assisted manual interaction and automated image processing and interrogation, including radiomics associated with predictive outcome modeling, is discussed.

  17. The approximate entropy concept extended to three dimensions for calibrated, single parameter structural complexity interrogation of volumetric images

    Science.gov (United States)

    Moore, Christopher; Marchant, Thomas

    2017-08-01

    Reconstructive volumetric imaging permeates medical practice because of its apparently clear depiction of anatomy. However, the tell tale signs of abnormality and its delineation for treatment demand experts work at the threshold of visibility for hints of structure. Hitherto, a suitable assistive metric that chimes with clinical experience has been absent. This paper develops the complexity measure approximate entropy (ApEn) from its 1D physiological origin into a three-dimensional (3D) algorithm to fill this gap. The first 3D algorithm for this is presented in detail. Validation results for known test arrays are followed by a comparison of fan-beam and cone-beam x-ray computed tomography image volumes used in image guided radiotherapy for cancer. Results show the structural detail down to individual voxel level, the strength of which is calibrated by the ApEn process itself. The potential for application in machine assisted manual interaction and automated image processing and interrogation, including radiomics associated with predictive outcome modeling, is discussed.

  18. Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

    Directory of Open Access Journals (Sweden)

    Gu YJ

    2011-11-01

    Full Text Available Yan-Juan Gu1,2,*, Jinping Cheng2,*, Jiefu Jin3, Shuk Han Cheng2, Wing-Tak Wong11Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, 2Department of Biology and Chemistry, The City University of Hong Kong, 3Department of Chemistry, The University of Hong Kong, Hong Kong, China*These authors contributed equally to this workAbstract: Single-walled carbon nanotubes (SWNTs have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2. Hydrazinobenzoic acid (HBA was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study.Keywords: carbon nanotubes, drug delivery, controlled release, SWNTs

  19. Structural models of increasing complexity for icosahedral boron carbide with compositions throughout the single-phase region from first principles

    Science.gov (United States)

    Ektarawong, A.; Simak, S. I.; Alling, B.

    2018-05-01

    We perform first-principles calculations to investigate the phase stability of boron carbide, concentrating on the recently proposed alternative structural models composed not only of the regularly studied B11Cp (CBC) and B12(CBC), but also of B12(CBCB) and B12( B4 ). We find that a combination of the four structural motifs can result in low-energy electron precise configurations of boron carbide. Among several considered configurations within the composition range of B10.5C and B4C , we identify in addition to the regularly studied B11Cp (CBC) at the composition of B4C two low-energy configurations, resulting in a new view of the B-C convex hull. Those are [B12 (CBC)]0.67[B12(B4)] 0.33 and [B12 (CBC)]0.67[ B12 (CBCB)]0.33, corresponding to compositions of B10.5C and B6.67C , respectively. As a consequence, B12(CBC) at the composition of B6.5C , previously suggested in the literature as a stable configuration of boron carbide, is no longer part of the B -C convex hull. By inspecting the electronic density of states as well as the elastic moduli, we find that the alternative models of boron carbide can provide a reasonably good description for electronic and elastic properties of the material in comparison with the experiments, highlighting the importance of considering B12(CBCB) and B12( B4 ), together with the previously proposed B11Cp (CBC) and B12(CBC), as the crucial ingredients for modeling boron carbide with compositions throughout the single-phase region.

  20. From the Earliest Evidence of Life to Complex Single-cell Organisms: The First 3 Gyr on Earth

    Science.gov (United States)

    Buick, Roger

    2006-12-01

    a failed attempt at complex multicellular evolution.

  1. Transition metal redox switches for reversible "on/off" and "slow/fast" single-molecule magnet behaviour in dysprosium and erbium bis-diamidoferrocene complexes.

    Science.gov (United States)

    Dickie, Courtney M; Laughlin, Alexander L; Wofford, Joshua D; Bhuvanesh, Nattamai S; Nippe, Michael

    2017-12-01

    Single-molecule magnets (SMMs) are considered viable candidates for next-generation data storage and quantum computing. Systems featuring switchability of their magnetization dynamics are particularly interesting with respect to accessing more complex logic gates and device architectures. Here we show that transition metal based redox events can be exploited to enable reversible switchability of slow magnetic relaxation of magnetically anisotropic lanthanide ions. Specifically, we report anionic homoleptic bis-diamidoferrocene complexes of Dy 3+ (oblate) and Er 3+ (prolate) which can be reversibly oxidized by one electron to yield their respective charge neutral redox partners (Dy: [1] - , 1 ; Er: [2] - , 2 ). Importantly, compounds 1 and 2 are thermally stable which allowed for detailed studies of their magnetization dynamics. We show that the Dy 3+ [1] - / 1 system can function as an "on"/"off" or a "slow"/"fast" redox switchable SMM system in the absence or presence of applied dc fields, respectively. The Er 3+ based [2] - / 2 system features "on"/"off" switchability of SMM properties in the presence of applied fields. Results from electrochemical investigations, UV-vis-NIR spectroscopy, and 57 Fe Mössbauer spectroscopy indicate the presence of significant electronic communication between the mixed-valent Fe ions in 1 and 2 in both solution and solid state. This comparative evaluation of redox-switchable magnetization dynamics in low coordinate lanthanide complexes may be used as a potential blueprint toward the development of future switchable magnetic materials.

  2. Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex

    Science.gov (United States)

    Feng, Mei; Bell, David R.; Zhou, Ruhong

    2017-12-01

    The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

  3. The 2006 July 17 Java (Indonesia) tsunami from satellite imagery and numerical modelling: a single or complex source?

    Science.gov (United States)

    Hébert, H.; Burg, P.-E.; Binet, R.; Lavigne, F.; Allgeyer, S.; Schindelé, F.

    2012-12-01

    The Mw 7.8 2006 July 17 earthquake off the southern coast of Java, Indonesia, has been responsible for a very large tsunami causing more than 700 casualties. The tsunami has been observed on at least 200 km of coastline in the region of Pangandaran (West Java), with run-up heights from 5 to more than 20 m. Such a large tsunami, with respect to the source magnitude, has been attributed to the slow character of the seismic rupture, defining the event as a so-called tsunami earthquake, but it has also been suggested that the largest run-up heights are actually the result of a second local landslide source. Here we test whether a single slow earthquake source can explain the tsunami run-up, using a combination of new detailed data in the region of the largest run-ups and comparison with modelled run-ups for a range of plausible earthquake source models. Using high-resolution satellite imagery (SPOT 5 and Quickbird), the coastal impact of the tsunami is refined in the surroundings of the high-security Permisan prison on Nusa Kambangan island, where 20 m run-up had been recorded directly after the event. These data confirm the extreme inundation lengths close to the prison, and extend the area of maximum impact further along the Nusa Kambangan island (about 20 km of shoreline), where inundation lengths reach several hundreds of metres, suggesting run-up as high as 10-15 m. Tsunami modelling has been conducted in detail for the high run-up Permisan area (Nusa Kambangan) and the PLTU power plant about 25 km eastwards, where run-up reached only 4-6 m and a video recording of the tsunami arrival is available. For the Permisan prison a high-resolution DEM was built from stereoscopic satellite imagery. The regular basin of the PLTU plant was designed using photographs and direct observations. For the earthquake's mechanism, both static (infinite) and finite (kinematic) ruptures are investigated using two published source models. The models account rather well for the sea level

  4. Hippocampal and neocortical metabolite ratio in patients with complex partial seizure: short TE and long TE techniques using single voxel proton MR spectroscopy

    International Nuclear Information System (INIS)

    Chung, Jin Il; Kim, Dong Ik; Lee, Byung In; Lee, Seung Ik; Yoon, Pyeong Ho

    2000-01-01

    To compare hippocampal and neocortical metabolite ratios using single-voxel proton MR spectroscopy with different echo times in patients with complex partial seizure. Using a GE Signa 1.5T scanner with STEAM and PRESS sequences, automated single voxel proton MRS was used to determine metabolite ratio differences in the hippocampus and neocortex of nine complex partial seizure patients (mesial temporal sclerosis (n=3D5), status epilepticus (n=3D1), tumor (n=3D1), cortical dysplasia (n=3D1), occipital lobe epilepsy (n=3D1)). A total of 20 examinations were performed in the region of the hippocampus (n=3D17), temporal neocortex (n=3D1), and parieto-occipital gray matter (n=3D1). Voxel size range was 5.2-17.4 cm 3 . The calculated creatine (Cr) peak was employed as an internal reference and the relative ratio of N-acetylaspartate (NAA) and choline (Cho) was calculated for both short and long echo times using an automated PROBE/SV (GE Medical Systems) package. Each NAA/Cho ratio obtained using both PRESS and STEAM techniques was compared by means of statistical analysis (paired Student t-test). Using PRESS (long TE, 272 ms), NAA/Cho ratios were successfully calculated in 16 of 20 examinations; in four this was not possible due to noise levels of the Cr and Cho peaks. Using STEAM (short TE, 30 ms) NAA/Cho ratios were successfully calculated in 19 of 20 examinations; in one, the Cho peak could not be measured. Using PRESS and STEAM, mean and standard deviations for the NAA/Cho ratio were 1.22±0.50 and 1.16±0.36, respectively. There were no statistically significant differences in this ratio between the short and long TE method (p less than 0.01). In complex partial seizure patients, no significant metabolite differences were found between short and long echo times of single voxel proton MR spectroscopy. The metabolite ratio at different echo times can be reliably obtained using this simplified and automated PROBE/SV quantitation method. (author)

  5. Hippocampal and neocortical metabolite ratio in patients with complex partial seizure: short TE and long TE techniques using single voxel proton MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jin Il; Kim, Dong Ik; Lee, Byung In; Lee, Seung Ik; Yoon, Pyeong Ho [Medical College, Yonsei University, Seoul (Korea, Republic of)

    2000-08-01

    To compare hippocampal and neocortical metabolite ratios using single-voxel proton MR spectroscopy with different echo times in patients with complex partial seizure. Using a GE Signa 1.5T scanner with STEAM and PRESS sequences, automated single voxel proton MRS was used to determine metabolite ratio differences in the hippocampus and neocortex of nine complex partial seizure patients (mesial temporal sclerosis (n=3D5), status epilepticus (n=3D1), tumor (n=3D1), cortical dysplasia (n=3D1), occipital lobe epilepsy (n=3D1)). A total of 20 examinations were performed in the region of the hippocampus (n=3D17), temporal neocortex (n=3D1), and parieto-occipital gray matter (n=3D1). Voxel size range was 5.2-17.4 cm{sup 3}. The calculated creatine (Cr) peak was employed as an internal reference and the relative ratio of N-acetylaspartate (NAA) and choline (Cho) was calculated for both short and long echo times using an automated PROBE/SV (GE Medical Systems) package. Each NAA/Cho ratio obtained using both PRESS and STEAM techniques was compared by means of statistical analysis (paired Student t-test). Using PRESS (long TE, 272 ms), NAA/Cho ratios were successfully calculated in 16 of 20 examinations; in four this was not possible due to noise levels of the Cr and Cho peaks. Using STEAM (short TE, 30 ms) NAA/Cho ratios were successfully calculated in 19 of 20 examinations; in one, the Cho peak could not be measured. Using PRESS and STEAM, mean and standard deviations for the NAA/Cho ratio were 1.22{+-}0.50 and 1.16{+-}0.36, respectively. There were no statistically significant differences in this ratio between the short and long TE method (p less than 0.01). In complex partial seizure patients, no significant metabolite differences were found between short and long echo times of single voxel proton MR spectroscopy. The metabolite ratio at different echo times can be reliably obtained using this simplified and automated PROBE/SV quantitation method. (author)

  6. Analysis of Single-Hole and Cross-Hole Tracer Tests Conducted at the Nye County Earl Warning Drilling Program Well Complex, Nye County, Nevada

    International Nuclear Information System (INIS)

    A. Umari; J.D. Earle; M.F. Fahy

    2006-01-01

    As part of the effort to understand the flow and transport characteristics downgradient from the proposed high-level radioactive waste geologic repository at Yucca Mountain, Nevada, single- and cross-hole tracer tests were conducted from December 2004 through October 2005 in boreholes at the Nye County 22 well complex. The results were analyzed for transport properties using both numerical and analytical solutions of the governing advection dispersion equation. Preliminary results indicate effective flow porosity values ranging from 1.0 x 10 -2 for an individual flow path to 2.0 x 10 -1 for composite flow paths, longitudinal dispersivity ranging from 0.3 to 3 m, and a transverse horizontal dispersivity of 0.03 m. Individual flow paths identified from the cross-hole testing indicate some solute diffusion into the stagnant portion of the alluvial aquifer

  7. Dye sensitized solar cell applications of CdTiO{sub 3}–TiO{sub 2} composite thin films deposited from single molecular complex

    Energy Technology Data Exchange (ETDEWEB)

    Ehsan, Muhammad Ali [Nanotechnology and Catalysis Centre (NANOCAT), University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Khaledi, Hamid [Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Pandikumar, Alagarsamy; Huang, Nay Ming [Department of Physics, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Arifin, Zainudin [Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia); Mazhar, Muhammad, E-mail: mazhar42pk@yahoo.com [Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur (Malaysia)

    2015-10-15

    A heterobimetallic complex [Cd{sub 2}Ti{sub 4}(μ-O){sub 6}(TFA){sub 8}(THF){sub 6}]·1.5THF (1) (TFA=trifluoroacetato, THF=tetrahydrofuran) comprising of Cd:Ti (1:2) ratio was synthesized by a chemical reaction of cadmium (II) acetate with titanium (IV) isopropoxide and triflouroacetic acid in THF. The stoichiometry of (1) was recognized by single crystal X-ray diffraction, spectroscopic and elemental analyses. Thermal studies revealed that (1) neatly decomposes at 450 °C to furnish 1:1 ratio of cadmium titanate:titania composite oxides material. The thin films of CdTiO{sub 3}–TiO{sub 2} composite oxides were deposited at 550 °C on fluorine doped tin oxide coated conducting glass substrate in air ambient. The micro-structure, crystallinity, phase identification and chemical composition of microspherical architectured CdTiO{sub 3}–TiO{sub 2} composite thin film have been determined by scanning electron microscopy, X-ray diffraction, Raman spectroscopy and energy dispersive X-ray analysis. The scope of composite thin film having band gap of 3.1 eV was explored as photoanode for dye-sensitized solar cell application. - Graphical abstarct: Microspherical designed CdTiO{sub 3}–TiO{sub 2} composite oxides photoanode film has been fabricated from single source precursor [Cd{sub 2}Ti{sub 4}(μ-O){sub 6}(TFA){sub 8}(THF){sub 6}]·1.5THF via aerosol assisted chemical vapor deposition technique for dye sensitized solar cell application. - Highlights: • Synthesis and characterization of a heterobimetallic Cd–Ti complex. • Fabrication of CdTiO{sub 3}–TiO{sub 2} thin film photoelectrode. • Application as dye sensitized photoanode for solar application.

  8. Socioeconomic status and overweight prevalence in polish adolescents: the impact of single factors and a complex index of socioeconomic status in respect to age and sex.

    Science.gov (United States)

    Kowalkowska, Joanna; Wadolowska, Lidia; Weronika Wuenstel, Justyna; Słowińska, Małgorzata Anna; Niedźwiedzka, Ewa

    2014-07-01

    The aim of this study was to analyze the association between overweight prevalence and socioeconomic status (SES) measured by complex SES index and single SES factors in Polish adolescents in respect to age and sex. This cross-sectional study was conducted in 2010-2011. A total of 1,176 adolescents aged 13.0-18.9 years were included. The respondents were students of junior-high and high schools from northern, eastern and central Poland. Quota sampling by sex and age was used. The SES was determined by: place of residence, self-declared economic situation, and parental education level. Respondents with low, average or high SES index (SESI) were identified. The level of overweight was assessed using Polish and international standards. The odds ratio (OR) for overweight prevalence in the oldest girls (aged 17.0-18.9 years) with high SESI was 0.34 (95%CI:0.13-0.92; P single SES factors were not significant for overweight prevalence. The relationship between socioeconomic status and prevalence of overweight was related to sex and age. The high socioeconomic status strongly lowered the risk of overweight prevalence in the oldest girls, but not in boys, irrespective of age. Maternal education level lowered risk of overweight prevalence in girls.

  9. Synthesis, crystal growth and characterization of bioactive material: 2- Amino-1H-benzimidazolium pyridine-3-carboxylate single crystal- a proton transfer molecular complex

    Science.gov (United States)

    Fathima, K. Saiadali; Kavitha, P.; Anitha, K.

    2017-09-01

    The 1:1 molecular adducts 2- Amino-1H-benzimidazolium pyridine-3-carboxylate (2ABPC) was synthesized and grown as single crystal where 2-aminobenzimidazole (ABI) acts as a donor and nicotinic acid (NA) acts as an acceptor. The presence of proton and carbon were predicted using 1H and 13C NMR spectral analysis. The molecular structure of the crystal was elucidated by subjecting the grown crystals to the single crystal x-ray diffraction analysis and was refined by full matrix least-squares method to R = 0.038 for 2469 reflections. The vibrational modes of functional group have been studied using FTIR and Raman spectroscopic analysis. The UV-Vis spectrum exhibited a visible band at 246 nm for 2ABPC due to the nicotinate anion of the molecule. Further, the antimicrobial activity of 2ABPC complex against B. subtilis, klebsiella pneumonia, Pseudomonas eruginos and E. coli pathogens was investigated. Minimum Inhibitory Concentration (MIC) for this crystal was obtained using UV spectrometer against MRSA pathogen. It was found that the benzimidazole with aminogroup at position 2 increases the general antimicrobial activities of 2ABPC crystal.

  10. Electrosorption of Os(III)-complex at single-wall carbon nanotubes immobilized on a glassy carbon electrode: Application to nanomolar detection of bromate, periodate and iodate

    International Nuclear Information System (INIS)

    Salimi, Abdollah; Kavosi, Begard; Babaei, Ali; Hallaj, Rahman

    2008-01-01

    A simple procedure was developed to prepare a glassy carbon electrode modified with single-wall carbon nanotubes (SWCNTs) and Os(III)-complex. The glassy carbon (GC) electrode modified with CNTs was immersed into Os(III)-complex solution (direct deposition) for a short period of time (60 s). 1,4,8,12-Tetraazacyclotetradecane osmium(III) chloride, (Os(III)LCl 2 ).ClO 4 , irreversibly and strongly adsorbed on SWCNTs immobilized on the surface of GC electrode. Cyclic voltammograms of the Os(III)-complex-incorporated-SWCNTs indicate a pair of well defined and nearly reversible redox couple with surface confined characteristic at wide pH range (1-8). The surface coverage (Γ) and charge transfer rate constant (k s ) of the immobilized Os-complex on SWCNTs were 3.07 x 10 -9 mol cm -2 , 5.5 (±0.2) s -1 , 2.94 x 10 -9 mol cm -2 , 7.3 (±0.3) s -1 at buffer solution with pH 2 and 7, respectively, indicate high loading ability of SWCNTs for Os(III) complex and great facilitation of the electron transfer between electroactive redox center and carbon nanotubes immobilized on the electrode surface. Modified electrodes showed higher electrocatalytic activity toward reduction of BrO 3 - , IO 3 - and IO 4 - in acidic solutions. The catalytic rate constants for catalytic reduction bromate, periodate and iodate were 3.79 (±0.2) x 10 3 , 7.32 (±0.2) x 10 3 and 1.75 (±0.2) x 10 3 M -1 s -1 , respectively. The hydrodynamic amperometry of rotating modified electrode at constant potential (0.3 V) was used for nanomolar detection of selected analytes. Excellent electrochemical reversibility of the redox couple, good reproducibility, high stability, low detection limit, long life time, fast amperometric response time, wide linear concentration range, technical simplicity and possibility of rapid preparation are great advantage of this sensor

  11. Single-molecule spectroscopy reveals that individual low-light LH2 complexes from Rhodopseudomonas palustris 2.1.6. have a heterogeneous polypeptide composition.

    Science.gov (United States)

    Brotosudarmo, Tatas H P; Kunz, Ralf; Böhm, Paul; Gardiner, Alastair T; Moulisová, Vladimíra; Cogdell, Richard J; Köhler, Jürgen

    2009-09-02

    Rhodopseudomonas palustris belongs to the group of purple bacteria that have the ability to produce LH2 complexes with unusual absorption spectra when they are grown at low-light intensity. This ability is often related to the presence of multiple genes encoding the antenna apoproteins. Here we report, for the first time to our knowledge, direct evidence that individual low-light LH2 complexes have a heterogeneous alphabeta-apoprotein composition that modulates the site energies of Bchl a molecules, producing absorption bands at 800, 820, and 850 nm. The arrangement of the Bchl a molecules in the "tightly coupled ring" can be modeled by nine alphabeta-Bchls dimers, such that the Bchls bound to six alphabeta-pairs have B820-like site energies and the remaining Bchl a molecules have B850-like site energies. Furthermore, the experimental data can only be satisfactorily modeled when these six alphabeta-pairs with B820 Bchl a molecules are distributed such that the symmetry of the assembly is reduced to C(3). It is also clear from the measured single-molecule spectra that the energies of the electronically excited states in the mixed B820/850 ring are mainly influenced by diagonal disorder.

  12. Exchange coupling and magnetic anisotropy of exchanged-biased quantum tunnelling single-molecule magnet Ni3Mn2 complexes using theoretical methods based on Density Functional Theory.

    Science.gov (United States)

    Gómez-Coca, Silvia; Ruiz, Eliseo

    2012-03-07

    The magnetic properties of a new family of single-molecule magnet Ni(3)Mn(2) complexes were studied using theoretical methods based on Density Functional Theory (DFT). The first part of this study is devoted to analysing the exchange coupling constants, focusing on the intramolecular as well as the intermolecular interactions. The calculated intramolecular J values were in excellent agreement with the experimental data, which show that all the couplings are ferromagnetic, leading to an S = 7 ground state. The intermolecular interactions were investigated because the two complexes studied do not show tunnelling at zero magnetic field. Usually, this exchange-biased quantum tunnelling is attributed to the presence of intermolecular interactions calculated with the help of theoretical methods. The results indicate the presence of weak intermolecular antiferromagnetic couplings that cannot explain the ferromagnetic value found experimentally for one of the systems. In the second part, the goal is to analyse magnetic anisotropy through the calculation of the zero-field splitting parameters (D and E), using DFT methods including the spin-orbit effect.

  13. Single-electron transfer in palladium complexes of 1,4-naphthoquinone-containing bis(pyrazol-1-yl)methane ligands.

    Science.gov (United States)

    Scheuermann, Sebastian; Sarkar, Biprajit; Bolte, Michael; Bats, Jan W; Lerner, Hans-Wolfram; Wagner, Matthias

    2009-10-05

    A 1,4-naphthoquinone-substituted bis(pyrazol-1-yl)methane ligand (N--N) has been synthesized and transformed into its corresponding Pd(II) chelate complex [(N--N)PdCl(2)]. Both N--N and [(N--N)PdCl(2)] have been fully characterized by NMR spectroscopy, spectro-electrochemistry, and X-ray crystallography. After treatment of [(N--N)PdCl(2)] with NEt(3), the signature of a 1,4-naphthosemiquinonate radical is visible in the UV-vis- and electron paramagnetic resonance (EPR) spectrum of the reaction mixture; the free ligand N--N does not react with NEt(3) under the conditions applied. It is therefore concluded that NEt(3) first reduces the Pd(II)-ion of [(N--N)PdCl(2)] to the zero-valent state and that this reaction is followed by a single-electron transfer from the metal atom to the 1,4-naphthoquinone moiety. The complex has been specifically designed to disfavor any direct Pd-to-naphthoquinone coordination. Electron transfer thus proceeds through space or, less likely, via sigma-bonds of the ligand framework.

  14. FRET structure with non-radiative acceptor provided by dye-linker-glass surface complex and single-molecule photodynamics by TIRFM-polarized imaging

    International Nuclear Information System (INIS)

    Tani, Toshiro; Mashimo, Kei; Suzuki, Tetsu; Horiuchi, Hiromi; Oda, Masaru

    2008-01-01

    We present our recent study of microscopic single-molecule imaging on the artificial complex of tetramethylrhodamine linked with a propyl chain onto silica glass surface, i.e. an asymmetric fluorescence resonance energy transfer (FRET) structure with non-radiative acceptor. In the synthesis of the complex, we used a mixture of two kinds of isomers to introduce rather small photodynamic difference among them. This isomeric structure change will provide more or less a distinctive photophysical change in e.g. non-radiative relaxation rate. Our recent observation at room temperatures, so far, shows that such contributions can be discriminated in the histograms of the fluorescent spot intensities; broad but distinctive multi-components appear. To identify the isomeric difference as a cause of structures, some configurational assumptions are necessary. One such basic prerequisite is that the transition dipoles of the chromophores should be oriented almost parallel to the glass surface. In order to make clear the modeling, we also provide preliminary experiments on the polarization dependence of the imaging under rotating polarization in epi-illumination

  15. TrackArt: the user friendly interface for single molecule tracking data analysis and simulation applied to complex diffusion in mica supported lipid bilayers.

    Science.gov (United States)

    Matysik, Artur; Kraut, Rachel S

    2014-05-01

    Single molecule tracking (SMT) analysis of fluorescently tagged lipid and protein probes is an attractive alternative to ensemble averaged methods such as fluorescence correlation spectroscopy (FCS) or fluorescence recovery after photobleaching (FRAP) for measuring diffusion in artificial and plasma membranes. The meaningful estimation of diffusion coefficients and their errors is however not straightforward, and is heavily dependent on sample type, acquisition method, and equipment used. Many approaches require advanced computing and programming skills for their implementation. Here we present TrackArt software, an accessible graphic interface for simulation and complex analysis of multiple particle paths. Imported trajectories can be filtered to eliminate spurious or corrupted tracks, and are then analyzed using several previously described methodologies, to yield single or multiple diffusion coefficients, their population fractions, and estimated errors. We use TrackArt to analyze the single-molecule diffusion behavior of a sphingolipid analog SM-Atto647N, in mica supported DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) bilayers. Fitting with a two-component diffusion model confirms the existence of two separate populations of diffusing particles in these bilayers on mica. As a demonstration of the TrackArt workflow, we characterize and discuss the effective activation energies required to increase the diffusion rates of these populations, obtained from Arrhenius plots of temperature-dependent diffusion. Finally, TrackArt provides a simulation module, allowing the user to generate models with multiple particle trajectories, diffusing with different characteristics. Maps of domains, acting as impermeable or permeable obstacles for particles diffusing with given rate constants and diffusion coefficients, can be simulated or imported from an image. Importantly, this allows one to use simulated data with a known diffusion behavior as a comparison for results

  16. Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

    Directory of Open Access Journals (Sweden)

    Brafman-Kennedy Barbara

    2011-05-01

    Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

  17. First example of a reversible single-crystal-to-single-crystal polymerization-depolymerization accompanied by a magnetic anomaly for a transition-metal complex with an organic radical.

    Science.gov (United States)

    Ovcharenko, Victor I; Fokin, Sergey V; Kostina, Elvina T; Romanenko, Galina V; Bogomyakov, Artem S; Tretyakov, Eugene V

    2012-11-19

    The reaction of copper(II) hexafluoroacetylacetonate [Cu(hfac)2] with the stable nitronyl nitroxide 2-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (L(a)) resulted in a paired heterospin complex [[Cu(hfac)2]3(μ-O,N-L(a))2][Cu(hfac)2(O-L(a))2]. The crystals of the compound were found to be capable of a reversible single-crystal-to-single-crystal (SC-SC) transformation initiated by the variation of temperature. At room temperature, the molecular structure of [[Cu(hfac)2]3(μ-O,N-L(a))2][Cu(hfac)2(O-L(a))2] is formed by the alternating fragments of the pair complex. Cooling the crystals of the complex below 225 K caused considerable mutual displacements of adjacent molecules, which ended in a transformation of the molecular structure into a polymer chain structure. A reversible topotactic polymerization-depolymerization coordination reaction actually takes place in the solid during repeated cooling-heating cycles: [[Cu(hfac)2]3(μ-O,N-L(a))2][Cu(hfac)2(O-L(a))2] ⇌ Cu(hfac)2(μ-O,N-L(a))]∞. Polymerization during cooling is the result of the anomalously great shortening of intermolecular distances (from 4.403 Å at 295 K to 2.460 Å at 150 K; Δd = 1.943 Å) between the terminal Cu atoms of the trinuclear fragments {[[Cu(hfac)2]3(μ-O,N-L(a))2]} and the noncoordinated N atoms of the pyrazole rings of the mononuclear {[Cu(hfac)2(O-L(a))2]} fragments. When the low-temperature phase was heated above 270 K, the polymer chain structure was destroyed and the compound was again converted to the pair molecular complex. The specifics of the given SC-SC transformation lies in the fact that the process is accompanied by a magnetic anomaly, because the intracrystalline displacements of molecules lead to a considerable change in the mutual orientation of the paramagnetic centers, which, in turn, causes modulation of the exchange interaction between the odd electrons of the Cu(2+) ion and nitroxide. On the temperature curve of

  18. Revealing Ligand Binding Sites and Quantifying Subunit Variants of Noncovalent Protein Complexes in a Single Native Top-Down FTICR MS Experiment

    Science.gov (United States)

    Li, Huilin; Wongkongkathep, Piriya; Van Orden, Steve L.; Ogorzalek Loo, Rachel R.; Loo, Joseph A.

    2014-12-01

    "Native" mass spectrometry (MS) has been proven to be increasingly useful for structural biology studies of macromolecular assemblies. Using horse liver alcohol dehydrogenase (hADH) and yeast alcohol dehydrogenase (yADH) as examples, we demonstrate that rich information can be obtained in a single native top-down MS experiment using Fourier transform ion cyclotron mass spectrometry (FTICR MS). Beyond measuring the molecular weights of the protein complexes, isotopic mass resolution was achieved for yeast ADH tetramer (147 kDa) with an average resolving power of 412,700 at m/z 5466 in absorption mode, and the mass reflects that each subunit binds to two zinc atoms. The N-terminal 89 amino acid residues were sequenced in a top-down electron capture dissociation (ECD) experiment, along with the identifications of the zinc binding site at Cys46 and a point mutation (V58T). With the combination of various activation/dissociation techniques, including ECD, in-source dissociation (ISD), collisionally activated dissociation (CAD), and infrared multiphoton dissociation (IRMPD), 40% of the yADH sequence was derived directly from the native tetramer complex. For hADH, native top-down ECD-MS shows that both E and S subunits are present in the hADH sample, with a relative ratio of 4:1. Native top-down ISD of the hADH dimer shows that each subunit (E and S chains) binds not only to two zinc atoms, but also the NAD/NADH ligand, with a higher NAD/NADH binding preference for the S chain relative to the E chain. In total, 32% sequence coverage was achieved for both E and S chains.

  19. 2D MI-DRAGON: a new predictor for protein-ligands interactions and theoretic-experimental studies of US FDA drug-target network, oxoisoaporphine inhibitors for MAO-A and human parasite proteins.

    Science.gov (United States)

    Prado-Prado, Francisco; García-Mera, Xerardo; Escobar, Manuel; Sobarzo-Sánchez, Eduardo; Yañez, Matilde; Riera-Fernandez, Pablo; González-Díaz, Humberto

    2011-12-01

    There are many pairs of possible Drug-Proteins Interactions that may take place or not (DPIs/nDPIs) between drugs with high affinity/non-affinity for different proteins. This fact makes expensive in terms of time and resources, for instance, the determination of all possible ligands-protein interactions for a single drug. In this sense, we can use Quantitative Structure-Activity Relationships (QSAR) models to carry out rational DPIs prediction. Unfortunately, almost all QSAR models predict activity against only one target. To solve this problem we can develop multi-target QSAR (mt-QSAR) models. In this work, we introduce the technique 2D MI-DRAGON a new predictor for DPIs based on two different well-known software. We use the software MARCH-INSIDE (MI) to calculate 3D structural parameters for targets and the software DRAGON was used to calculated 2D molecular descriptors all drugs showing known DPIs present in the Drug Bank (US FDA benchmark dataset). Both classes of parameters were used as input of different Artificial Neural Network (ANN) algorithms to seek an accurate non-linear mt-QSAR predictor. The best ANN model found is a Multi-Layer Perceptron (MLP) with profile MLP 21:21-31-1:1. This MLP classifies correctly 303 out of 339 DPIs (Sensitivity = 89.38%) and 480 out of 510 nDPIs (Specificity = 94.12%), corresponding to training Accuracy = 92.23%. The validation of the model was carried out by means of external predicting series with Sensitivity = 92.18% (625/678 DPIs; Specificity = 90.12% (730/780 nDPIs) and Accuracy = 91.06%. 2D MI-DRAGON offers a good opportunity for fast-track calculation of all possible DPIs of one drug enabling us to re-construct large drug-target or DPIs Complex Networks (CNs). For instance, we reconstructed the CN of the US FDA benchmark dataset with 855 nodes 519 drugs+336 targets). We predicted CN with similar topology (observed and predicted values of average distance are equal to 6.7 vs. 6.6). These CNs can be used to explore

  20. Formation of a dinuclear copper(II) complex through the cleavage of CSingle-Bond' name='Single-Bond' value='Single-Bond'/>N bond of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole

    Energy Technology Data Exchange (ETDEWEB)

    Shardin, Rosidah; Pui, Law Kung; Yamin, Bohari M. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM 43600 Bangi, Selangor (Malaysia); Kassim, Mohammad B. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM 43600 Bangi, Selangor, Malaysia and Fuel Cell Institute, Universiti Kebangsaan Malaysia, UKM 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    A simple mononuclear octahedral copper(II) complex was attempted from the reaction of three moles of 1-benzoyl-3-(pyridin-2-yl)-1H-pyrazole and one mole of copper(II) perchlorate hexahydrate in methanol. However, the product of the reaction was confirmed to be a dinuclear copper(II) complex with μ-(3-(pyridin-2-yl)-pyrazolato) and 3-(pyridin-2-yl)-1H-pyrazole ligands attached to each of the Cu(II) centre atom. The copper(II) ion assisted the cleavage of the C{sub benzoyl}Single-Bond' name='Single-Bond' value='Single-Bond'/>N bond afforded a 3-(pyridin-2-yl)-1H-pyrazole molecule. Deprotonation of the 3-(pyridin-2-yl)-1H-pyrazole gave a 3-(pyridin-2-yl)-pyrazolato, which subsequently reacted with the Cu(II) ion to give the (3-(pyridin-2-yl)-pyrazolato)(3-(pyridin-2-yl)-1H-pyrazole)Cu(II) product moiety. The structure of the dinuclear complex was confirmed by x-ray crystallography. The complex crystallized in a monoclinic crystal system with P2(1)/n space group and cell dimensions of a = 12.2029(8) Å, b = 11.4010(7) Å, c = 14.4052(9) Å and β = 102.414(2)°. The compound was further characterized by mass spectrometry, CHN elemental analysis, infrared and UV-visible spectroscopy and the results concurred with the x-ray structure. The presence of d-d transition at 671 nm (ε = 116 dm{sup 3} mol{sup −1} cm{sup −1}) supports the presence of Cu(II) centres.

  1. ZnS, CdS and HgS nanoparticles via alkyl-phenyl dithiocarbamate complexes as single source precursors.

    Science.gov (United States)

    Onwudiwe, Damian C; Ajibade, Peter A

    2011-01-01

    The synthesis of II-VI semiconductor nanoparticles obtained by the thermolysis of certain group 12 metal complexes as precursors is reported. Thermogravimetric analysis of the single source precursors showed sharp decomposition leading to their respective metal sulfides. The structural and optical properties of the prepared nanoparticles were characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) UV-Vis and photoluminescence spectroscopy. The X-ray diffraction pattern showed that the prepared ZnS nanoparticles have a cubic sphalerite structure; the CdS indicates a hexagonal phase and the HgS show the presence of metacinnabar phase. The TEM image demonstrates that the ZnS nanoparticles are dot-shaped, the CdS and the HgS clearly showed a rice and spherical morphology respectively. The UV-Vis spectra exhibited a blue-shift with respect to that of the bulk samples which is attributed to the quantum size effect. The band gap of the samples have been calculated from absorption spectra and werefound to be about 4.33 eV (286 nm), 2.91 eV (426 nm) and 4.27 eV (290 nm) for the ZnS, CdS and HgS samples respectively.

  2. ZnS, CdS and HgS Nanoparticles via Alkyl-Phenyl Dithiocarbamate Complexes as Single Source Precursors

    Directory of Open Access Journals (Sweden)

    Peter A. Ajibade

    2011-08-01

    Full Text Available The synthesis of II-VI semiconductor nanoparticles obtained by the thermolysis of certain group 12 metal complexes as precursors is reported. Thermogravimetric analysis of the single source precursors showed sharp decomposition leading to their respective metal sulfides. The structural and optical properties of the prepared nanoparticles were characterized by means of X-ray diffraction (XRD, transmission electron microscopy (TEM, scanning electron microscopy (SEM UV-Vis and photoluminescence spectroscopy. The X-ray diffraction pattern showed that the prepared ZnS nanoparticles have a cubic sphalerite structure; the CdS indicates a hexagonal phase and the HgS show the presence of metacinnabar phase. The TEM image demonstrates that the ZnS nanoparticles are dot-shaped, the CdS and the HgS clearly showed a rice and spherical morphology respectively. The UV-Vis spectra exhibited a blue-shift with respect to that of the bulk samples which is attributed to the quantum size effect. The band gap of the samples have been calculated from absorption spectra and werefound to be about 4.33 eV (286 nm, 2.91 eV (426 nm and 4.27 eV (290 nm for the ZnS, CdS and HgS samples respectively.

  3. Invasive cyprinid fish in Europe originate from the single introduction of an admixed source population followed by a complex pattern of spread.

    Directory of Open Access Journals (Sweden)

    Andrea Simon

    Full Text Available The Asian cyprinid fish, the topmouth gudgeon (Pseudorasbora parva, was introduced into Europe in the 1960s. A highly invasive freshwater fish, it is currently found in at least 32 countries outside its native range. Here we analyse a 700 base pair fragment of the mitochondrial cytochrome b gene to examine different models of colonisation and spread within the invasive range, and to investigate the factors that may have contributed to their invasion success. Haplotype and nucleotide diversity of the introduced populations from continental Europe was higher than that of the native populations, although two recently introduced populations from the British Isles showed low levels of variability. Based on coalescent theory, all introduced and some native populations showed a relative excess of nucleotide diversity compared to haplotype diversity. This suggests that these populations are not in mutation-drift equilibrium, but rather that the relative inflated level of nucleotide diversity is consistent with recent admixture. This study elucidates the colonisation patterns of P. parva in Europe and provides an evolutionary framework of their invasion. It supports the hypothesis that their European colonisation was initiated by their introduction to a single location or small geographic area with subsequent complex pattern of spread including both long distance and stepping-stone dispersal. Furthermore, it was preceded by, or associated with, the admixture of genetically diverse source populations that may have augmented its invasive-potential.

  4. Socioeconomic Status and Overweight Prevalence in Polish Adolescents: The Impact of Single Factors and a Complex Index of Socioeconomic Status in Respect to Age and Sex

    Science.gov (United States)

    KOWALKOWSKA, Joanna; WADOLOWSKA, Lidia; WERONIKA WUENSTEL, Justyna; SŁOWIŃSKA, Małgorzata Anna; NIEDŹWIEDZKA, Ewa

    2014-01-01

    Abstract Background The aim of this study was to analyze the association between overweight prevalence and socioeconomic status (SES) measured by complex SES index and single SES factors in Polish adolescents in respect to age and sex. Methods This cross-sectional study was conducted in 2010-2011. A total of 1,176 adolescents aged 13.0-18.9 years were included. The respondents were students of junior-high and high schools from northern, eastern and central Poland. Quota sampling by sex and age was used. The SES was determined by: place of residence, self-declared economic situation, and parental education level. Respondents with low, average or high SES index (SESI) were identified. The level of overweight was assessed using Polish and international standards. Results The odds ratio (OR) for overweight prevalence in the oldest girls (aged 17.0-18.9 years) with high SESI was 0.34 (95%CI:0.13-0.92; P socioeconomic status and prevalence of overweight was related to sex and age. The high socioeconomic status strongly lowered the risk of overweight prevalence in the oldest girls, but not in boys, irrespective of age. Maternal education level lowered risk of overweight prevalence in girls. PMID:25909059

  5. Association of a specific major histocompatibility complex class IIβ single nucleotide polymorphism with resistance to lactococcosis in rainbow trout, Oncorhynchus mykiss (Walbaum).

    Science.gov (United States)

    Colussi, S; Prearo, M; Bertuzzi, S A; Scanzio, T; Peletto, S; Favaro, L; Modesto, P; Maniaci, M G; Ru, G; Desiato, R; Acutis, P L

    2015-01-01

    Major histocompatibility complex (MHC) loci encode glycoproteins that bind to foreign peptides and initiate immune responses through their interaction with T cells. MHC class II molecules are heterodimers consisting of α and β chains encoded by extremely variable genes; variation in exon 2 is responsible for the majority of observed polymorphisms, mostly concentrated in the codons specifying the peptide-binding region. Lactococcus garvieae is the causative agent of lactococcosis, a warm-water bacterial infection pathogenic for cultured freshwater and marine fish. It causes considerable economic losses, limiting the profitability and development of fish industries in general and the intensive production of rainbow trout, Oncorhynchus mykiss (Walbaum), in particular. The disease is currently controlled with vaccines and antibiotics; however, vaccines have short-term efficacy, and increasing concerns regarding antibiotic residues have called for alternative strategies. To explore the involvement of the MHC class II β-1 domain as a candidate gene for resistance to lactococcosis, we exposed 400 rainbow trout to naturally contaminated water. One single nucleotide polymorphism (SNP) and one haplotype were associated with resistance (P trout resistant to lactococcosis. © 2014 John Wiley & Sons Ltd.

  6. Improving the SMM and luminescence properties of lanthanide complexes with LnO9 cores in the presence of ZnII: an emissive Zn2Dy single ion magnet.

    Science.gov (United States)

    Fondo, Matilde; Corredoira-Vázquez, Julio; Herrera-Lanzós, Antía; García-Deibe, Ana M; Sanmartín-Matalobos, Jesús; Herrera, Juan Manuel; Colacio, Enrique; Nuñez, Cristina

    2017-12-12

    Mononuclear complexes of stoichiometry [Ln(H 3 L)(H 2 O)(NO 3 )](NO 3 ) 2 (Ln = Tb, 1; Dy, 2, Er, 3), which crystallise with different solvates, and the heterotrinuclear compound [Zn 2 Dy(L)(NO 3 ) 3 (OH)] (4) can be obtained with the same H 3 L compartmental ligand. The single X-ray crystal structure of the mononuclear complexes shows a LnO 9 core with a muffin-like disposition while the geometry of the DyO 9 core in 4 seems to be closer to spherical capped square antiprism. The analysis of the magnetic properties of all the complexes demonstrates that the mononuclear lanthanide compounds do not show slow relaxation of the magnetization, even when the samples are diluted with a diamagnetic matrix and subjected to a dc applied field of 1000 Oe. Nevertheless, the heterotrinuclear dysprosium complex 4·3H 2 O is a field-induced single ion magnet, with an estimated U eff barrier of 59 K. The luminescence characterisation of all the metal complexes in methanol solution at 298 K also shows a notable increase in the fluorescence emission of the heterotrinuclear complex with respect to the mononuclear ones, in such a way that 4 can be defined as a fluorescent single ion magnet.

  7. Two modes of interaction of the single-stranded DNA-binding protein of bacteriophage T7 with the DNA polymerase-thioredoxin complex

    KAUST Repository

    Ghosh, Sharmistha; Hamdan, Samir; Richardson, Charles C.

    2010-01-01

    The DNA polymerase encoded by bacteriophage T7 has low processivity. Escherichia coli thioredoxin binds to a segment of 76 residues in the thumb subdomain of the polymerase and increases the processivity. The binding of thioredoxin leads to the formation of two basic loops, loops A and B, located within the thioredoxin-binding domain (TBD). Both loops interact with the acidic C terminus of the T7 helicase. A relatively weak electrostatic mode involves the C-terminal tail of the helicase and the TBD, whereas a high affinity interaction that does not involve the C-terminal tail occurs when the polymerase is in a polymerization mode. T7 gene 2.5 single-stranded DNA-binding protein (gp2.5) also has an acidic C-terminal tail. gp2.5 also has two modes of interaction with the polymerase, but both involve the C-terminal tail of gp2.5. An electrostatic interaction requires the basic residues in loops A and B, and gp2.5 binds to both loops with similar affinity as measured by surface plasmon resonance. When the polymerase is in a polymerization mode, the C terminus of gene 2.5 protein interacts with the polymerase in regions outside the TBD.gp2.5 increases the processivity of the polymerase-helicase complex during leading strand synthesis. When loop B of the TBD is altered, abortive DNA products are observed during leading strand synthesis. Loop B appears to play an important role in communication with the helicase and gp2.5, whereas loop A plays a stabilizing role in these interactions. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

    Directory of Open Access Journals (Sweden)

    Abhijeet Kapoor

    Full Text Available Human dopamine β-hydroxylase (DBH is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering.Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function.The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and

  9. Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

    Science.gov (United States)

    Kapoor, Abhijeet; Shandilya, Manish; Kundu, Suman

    2011-01-01

    Human dopamine β-hydroxylase (DBH) is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs) have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering. Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function. The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and provides

  10. Two modes of interaction of the single-stranded DNA-binding protein of bacteriophage T7 with the DNA polymerase-thioredoxin complex

    KAUST Repository

    Ghosh, Sharmistha

    2010-04-06

    The DNA polymerase encoded by bacteriophage T7 has low processivity. Escherichia coli thioredoxin binds to a segment of 76 residues in the thumb subdomain of the polymerase and increases the processivity. The binding of thioredoxin leads to the formation of two basic loops, loops A and B, located within the thioredoxin-binding domain (TBD). Both loops interact with the acidic C terminus of the T7 helicase. A relatively weak electrostatic mode involves the C-terminal tail of the helicase and the TBD, whereas a high affinity interaction that does not involve the C-terminal tail occurs when the polymerase is in a polymerization mode. T7 gene 2.5 single-stranded DNA-binding protein (gp2.5) also has an acidic C-terminal tail. gp2.5 also has two modes of interaction with the polymerase, but both involve the C-terminal tail of gp2.5. An electrostatic interaction requires the basic residues in loops A and B, and gp2.5 binds to both loops with similar affinity as measured by surface plasmon resonance. When the polymerase is in a polymerization mode, the C terminus of gene 2.5 protein interacts with the polymerase in regions outside the TBD.gp2.5 increases the processivity of the polymerase-helicase complex during leading strand synthesis. When loop B of the TBD is altered, abortive DNA products are observed during leading strand synthesis. Loop B appears to play an important role in communication with the helicase and gp2.5, whereas loop A plays a stabilizing role in these interactions. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells

    Science.gov (United States)

    Knies, Diana; Klobuch, Sebastian; Xue, Shao-An; Birtel, Matthias; Echchannaoui, Hakim; Yildiz, Oezlem; Omokoko, Tana; Guillaume, Philippe; Romero, Pedro; Stauss, Hans; Sahin, Ugur; Herr, Wolfgang; Theobald, Matthias; Thomas, Simone; Voss, Ralf-Holger

    2016-01-01

    Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells. PMID:27028870

  12. Significance of fragmented QRS complexes for identifying culprit lesions in patients with non-ST-elevation myocardial infarction: a single-center, retrospective analysis of 183 cases

    Directory of Open Access Journals (Sweden)

    Guo Rong

    2012-06-01

    Full Text Available Abstract Background Fragmented QRS (fQRS complexes are novel electrocardiographic signals, which reflect myocardial conduction delays in patients with coronary artery disease (CAD. The importance of fQRS complexes in identifying culprit vessels was evaluated in this retrospective study. Methods A 12-lead surface electrocardiogram was obtained in 183 patients who had non-ST-elevation myocardial infarction (NSTEMI and subsequently underwent coronary angiography (CAG. On the basis of the frequency of fQRS complexes, indices such as sensitivity, specificity, positive and negative predictive values, and likelihood ratio were evaluated to determine the ability of fQRS complexes to identify the culprit vessels. Results Among the patients studied, elderly patients (age ≥ 65 years and those with diabetes had a significantly higher frequency of fQRS complexes (p = 0.005, p = 0.003, respectively. The fQRS complexes recorded in the 4 precordial leads had the highest specificity (81.8% for indentifying the culprit vessel (left anterior descending artery. However, the specificity of fQRS complexes to identify lesions in the left circumflex and right coronary arteries was lower for the inferior and lateral leads than for the limb leads (65.5% versus 71.7%; however, the limb leads had higher sensitivity (92.3% versus 89.4%. And the total sensitivity and specificity of fQRS (77.1% and 71.5% were higher than those values for ischemic T-waves. Conclusions The frequency of fQRS complexes was higher in elderly and diabetic patients with NSTEMI. The frequency of fQRS complexes recorded in each of the ECG leads can be used to identify culprit vessels in patients with NSTEMI.

  13. The effects of complex exercise on shoulder range of motion and pain for women with breast cancer-related lymphedema: a single-blind, randomized controlled trial.

    Science.gov (United States)

    Park, Jin-Hyuck

    2017-07-01

    This study was to investigate the effects of complex exercise on shoulder range of motion and pain for women with breast cancer-related lymphedema. 69 women participated in this study and then they were randomly allocated to complex exercise group (n = 35) or the conventional decongestive therapy group (n = 34). All subjects received 8 sessions for 4 weeks. To identify the effects on shoulder range of motion and pain, goniometer and visual analog scale were used, respectively. The outcome measurements were performed before and after the 4 week intervention. After 4 weeks, complex exercise group had greater improvements in shoulder range of motion and pain compared with the conventional decongestive therapy group (p women with breast cancer-related lymphedema. Complex exercise would be useful to improve shoulder range of motion and pain of the women with breast cancer-related lymphedema.

  14. Series of isostructural planar lanthanide complexes [Ln(III)4(mu3-OH)2(mdeaH)2(piv)8] with single molecule magnet behavior for the Dy4 analogue.

    Science.gov (United States)

    Abbas, Ghulam; Lan, Yanhua; Kostakis, George E; Wernsdorfer, Wolfgang; Anson, Christopher E; Powell, Annie K

    2010-09-06

    A series of five isostructural tetranuclear lanthanide complexes of formula [Ln(4)(mu(3)-OH)(2)(mdeaH)(2)(piv)(8)], (mdeaH(2) = N-methyldiethanolamine; piv = pivalate; Ln = Tb (1), Dy (2), Ho (3), Er (4), and Tm (5)) have been synthesized and characterized. These clusters have a planar "butterfly" Ln(4) core. Magnetically, the Ln(III) ions are weakly coupled in all cases; the Dy(4) compound 2 shows Single Molecule Magnet (SMM) behavior.

  15. Crystallization and preliminary crystallographic studies of the single-chain variable fragment of antibody chA21 in complex with an N-terminal fragment of ErbB2

    International Nuclear Information System (INIS)

    Liu, Yang; Zhou, Huihao; Zhu, Juanjuan; Gao, Yongxiang; Niu, Liwen; Liu, Jing; Teng, Maikun

    2009-01-01

    An antibody–antigen complex consisting of a single-chain variable fragment of the potential therapeutic antibody chA21 and an N-terminal fragment (residues 1–192) of the human ErbB2 extracellular domain was expressed, purified and crystallized. X-ray diffraction data were collected to 2.45 Å resolution. ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes abnormality and disorder in cell signalling and leads to cell transformation. Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was developed. Here, an antibody–antigen complex consisting of the single-chain variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1–192, named EP I) of the ErbB2 extracellular domain was crystallized using the sitting-drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45 Å resolution from a single flash-cooled crystal; the crystal belonged to space group P2 1 2 1 2 1

  16. Syntheses, structures, and properties of imidazolate-bridged Cu(II)-Cu(II) and Cu(II)-Zn(II) dinuclear complexes of a single macrocyclic ligand with two hydroxyethyl pendants.

    Science.gov (United States)

    Li, Dongfeng; Li, Shuan; Yang, Dexi; Yu, Jiuhong; Huang, Jin; Li, Yizhi; Tang, Wenxia

    2003-09-22

    The imidazolate-bridged homodinuclear Cu(II)-Cu(II) complex, [(CuimCu)L]ClO(4).0.5H(2)O (1), and heterodinuclear Cu(II)-Zn(II) complex, [(CuimZnL(-)(2H))(CuimZnL(-)(H))](ClO(4))(3) (2), of a single macrocyclic ligand with two hydroxyethyl pendants, L (L = 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)tricyclo[22,2,2,2(11,14)]triaconta-1,11,13,24,27,29-hexaene), have been synthesized as possible models for copper-zinc superoxide dismutase (Cu(2),Zn(2)-SOD). Their crystal structures analyzed by X-ray diffraction methods have shown that the structures of the two complexes are markedly different. Complex 1 crystallizes in the orthorhombic system, containing an imidazolate-bridged dicopper(II) [Cu-im-Cu](3+) core, in which the two copper(II) ions are pentacoordinated by virtue of an N4O environment with a Cu.Cu distance of 5.999(2) A, adopting the geometry of distorted trigonal bipyramid and tetragonal pyramid, respectively. Complex 2 crystallizes in the triclinic system, containing two similar Cu-im-Zn cores in the asymmetric unit, in which both the Cu(II) and Zn(II) ions are pentacoordinated in a distorted trigonal bipyramid geometry, with the Cu.Zn distance of 5.950(1)/5.939(1) A, respectively. Interestingly, the macrocyclic ligand with two arms possesses a chairlike (anti) conformation in complex 1, but a boatlike (syn) conformation in complex 2. Magnetic measurements and ESR spectroscopy of complex 1 have revealed the presence of an antiferromagnetic exchange interaction between the two Cu(II) ions. The ESR spectrum of the Cu(II)-Zn(II) heterodinuclear complex 2 displayed a typical signal for mononuclear trigonal bipyramidal Cu(II) complexes. From pH-dependent ESR and electronic spectroscopic studies, the imidazolate bridges in the two complexes have been found to be stable over broad pH ranges. The cyclic voltammograms of the two complexes have been investigated. Both of the two complexes can catalyze the dismutation of superoxide and show rather high activity.

  17. Relation between sedimentation behaviour of DNA-membrane complexes and DNA single- and double-strand breaks after irradiation with gamma-rays, pulse neutrons and 12C ions

    International Nuclear Information System (INIS)

    Erzgraber, G.; Lapidus, I.L.

    1985-01-01

    The experimental data on sedimentation behaviour of DNA-membrane complexes at radiation of the Chinese hamster cells (V79-4) in a wide dose range of 127 Cs γ-rays, pulse neutrons (reactor IBR-2, Laboratory of Neutron Physics, JINR, Dubna) are accelerated 12 C ions (cyclotron U-200, Laboratory of Nuclear Reactions, JINR, Dubna) are presented An assumption on the role of DNA single- and double-strend breaks in changing the sedimentation properties of DNA-membrane complexes has been confirmed by the experiments with radiation of different quality. The possibility of estimating induction and repair of DNA breaks on the basis of dependence of the relative sedimentation velocity of complexes on the irradiation does is discussed

  18. Non-covalent interactions in 2-methylimidazolium copper(II) complex (MeImH)2[Cu(pfbz)4]: Synthesis, characterization, single crystal X-ray structure and packing analysis

    Science.gov (United States)

    Sharma, Raj Pal; Saini, Anju; Kumar, Santosh; Kumar, Jitendra; Sathishkumar, Ranganathan; Venugopalan, Paloth

    2017-01-01

    A new anionic copper(II) complex, (MeImH)2 [Cu(pfbz)4] (1) where, MeImH = 2-methylimidazolium and pfbz = pentafluorobenzoate has been isolated by reacting copper(II) sulfate pentahydrate, pentafluorobenzoic acid and 2-methylimidazole in ethanol: water mixture in 1:2:2 molar ratio. This complex 1 has been characterized by elemental analysis, thermogravimetric analysis, spectroscopic techniques (UV-Vis, FT-IR) and conductance measurements. The complex salt crystallizes in monoclinic crystal system with space group C2/c. Single crystal X-ray structure determination revealed the presence of discrete ions: [Cu(pfbz)4]2- anion and two 2-methylimidazolium cation (C4H7N2)+. The crystal lattice is stabilized by strong hydrogen bonding and F⋯F interactions between cationic-anionic and the anionic-anionic moieties respectively, besides π-π interactions.

  19. FIELD IMPLEMENTATION OF A WINSOR TYPE I SURFACTANT/ALCOHOL MIXTURE FOR IN SITU SOLUBILIZATION OF A COMPLEX LNAPL AS A SINGLE-PHASE MICROEMULSION

    Science.gov (United States)

    A Winsor Type I surfactant/alcohol mixture was used as an in situ flushing agent to solubilize a muticomponent nonaqueous phase liquid (NAPL) as a single-phase microemulsion (SPME) in a hydraulically isolated test cell at Hill Air Force Base (AFB), Utah. The surfactant (polyoxye...

  20. Immobilization of [Cu(bpy)2]Br2 complex onto a glassy carbon electrode modified with alpha-SiMo12O40(4-) and single walled carbon nanotubes: application to nanomolar detection of hydrogen peroxide and bromate.

    Science.gov (United States)

    Salimi, Abdollah; Korani, Aazam; Hallaj, Rahman; Khoshnavazi, Roshan; Hadadzadeh, Hasan

    2009-03-02

    A simple procedure has been used for preparation of modified glassy carbon electrode with carbon nanotubes and copper complex. Copper complex [Cu(bpy)(2)]Br(2) was immobilized onto glassy carbon (GC) electrode modified with silicomolybdate, alpha-SiMo(12)O(40)(4-) and single walled carbon nanotubes (SWCNTs). Copper complex and silicomolybdate irreversibly and strongly adsorbed onto GC electrode modified with CNTs. Electrostatic interactions between polyoxometalates (POMs) anions and Cu-complex, cations mentioned as an effective method for fabrication of three-dimensional structures. The modified electrode shows three reversible redox couples for polyoxometalate and one redox couple for Cu-complex at wide range of pH values. The electrochemical behavior, stability and electron transfer kinetics of the adsorbed redox couples were investigated using cyclic voltammetry. Due to electrostatic interaction, copper complex immobilized onto GC/CNTs/alpha-SiMo(12)O(40)(4-) electrode shows more stable voltammetric response compared to GC/CNTs/Cu-complex modified electrode. In comparison to GC/CNTs/Cu-complex the GC/CNTs/alpha-SiMo(12)O(40)(4-) modified electrodes shows excellent electrocatalytic activity toward reduction H(2)O(2) and BrO(3)(-) at more reduced overpotential. The catalytic rate constants for catalytic reduction hydrogen peroxide and bromate were 4.5(+/-0.2)x10(3) M(-1) s(-1) and 3.0(+/-0.10)x10(3) M(-1) s(-1), respectively. The hydrodynamic amperommetry technique at 0.08 V was used for detection of nanomolar concentration of hydrogen peroxide and bromate. Detection limit, sensitivity and linear concentration range proposed sensor for bromate and hydrogen peroxide detection were 1.1 nM and 6.7 nA nM(-1), 10 nM-20 microM, 1 nM, 5.5 nA nM(-1) and 10 nM-18 microM, respectively.

  1. Synthesis and Characterization of a Ru(II Complex with Functionalized Phenanthroline Ligands Having Single-Double Linked Anthracenyl and 1-Methoxy-1-buten-3-yne Moieties

    Directory of Open Access Journals (Sweden)

    Adewale O. Adeloye

    2010-10-01

    Full Text Available Two series of bidentate polypyridine ligands, made of phenanthroline chelating subunits having substituted mono-and di-anthracenyl groups, and 1-methoxy-1-buten-3-yne at the 4 and 7-positions with the corresponding heteroleptic Ru(II complex have been synthesized and characterized. The complex is formulated as [(Ru(L1(L2(NCS2], (where L1 = 4-(9-dianthracenyl-10-(2,3-dimethylacrylic acid-7-(9-anthracenyl-10-(2,3-dimethylacrylic acid-1,10-phenanthroline and L2 = 4,7-bis(1-methoxy-1-buten-3-yne-1,10-phenanthroline. The Ru(II complex shows characteristic broad and intense metal-to-ligand charge transfer (MLCT bands absorption and appreciable photoluminescence spanning the visible region. The ligands and complex were characterized by FT-IR, 1H, 13C NMR spectroscopy, UV-Vis, photoluminescence and elemental analysis (see in supplementary materials. The anchoring groups in both ligands have allowed an extended delocalization of acceptor orbital of the metal-to-ligand charge-transfer (MLCT excited state.

  2. ”Are CRT upgrade procedures more complex and associated with more complications than de novo CRT implantations?” A single centre experience

    NARCIS (Netherlands)

    Ter Horst, I. A H; Kuijpers, Y.; van t Sant, Jetske; Tuinenburg, A. E.; Cramer, M. J.; Meine, M.

    2016-01-01

    Objective The objective of the study was to examine whether cardiac resynchronisation therapy upgrade procedures are more complex and associated with more complications than de novo implantations. Method We retrospectively compared 134 upgrade procedures performed between 2006-2012 with a random,

  3. Studying anti-oxidative properties of inclusion complexes of α-lipoic acid with γ-cyclodextrin in single living fission yeast by confocal Raman microspectroscopy

    Science.gov (United States)

    Noothalapati, Hemanth; Ikarashi, Ryo; Iwasaki, Keita; Nishida, Tatsuro; Kaino, Tomohiro; Yoshikiyo, Keisuke; Terao, Keiji; Nakata, Daisuke; Ikuta, Naoko; Ando, Masahiro; Hamaguchi, Hiro-o.; Kawamukai, Makoto; Yamamoto, Tatsuyuki

    2018-05-01

    α-lipoic acid (ALA) is an essential cofactor for many enzyme complexes in aerobic metabolism, especially in mitochondria of eukaryotic cells where respiration takes place. It also has excellent anti-oxidative properties. The acid has two stereo-isomers, R- and S- lipoic acid (R-LA and S-LA), but only the R-LA has biological significance and is exclusively produced in our body. A mutant strain of fission yeast, Δdps1, cannot synthesize coenzyme Q10, which is essential during yeast respiration, leading to oxidative stress. Therefore, it shows growth delay in the minimal medium. We studied anti-oxidant properties of ALA in its free form and their inclusion complexes with γ-cyclodextrin using this mutant yeast model. Both free forms R- and S-LA as well as 1:1 inclusion complexes with γ-cyclodextrin recovered growth of Δdps1 depending on the concentration and form. However, it has no effect on the growth of wild type fission yeast strain at all. Raman microspectroscopy was employed to understand the anti-oxidant property at the molecular level. A sensitive Raman band at 1602 cm-1 was monitored with and without addition of ALAs. It was found that 0.5 mM and 1.0 mM concentrations of ALAs had similar effect in both free and inclusion forms. At 2.5 mM ALAs, free forms inhibited the growth while inclusion complexes helped in recovered. 5.0 mM ALA showed inhibitory effect irrespective of form. Our results suggest that the Raman band at 1602 cm-1 is a good measure of oxidative stress in fission yeast.

  4. Impact of Surgihoney Reactive Oxygen on surgical site infection (SSI after complex abdominal wall reconstruction (AWR of grade 3 and 4 ventral Hernias: A single arm pilot study

    Directory of Open Access Journals (Sweden)

    Sam Parker

    2017-01-01

    Conclusions: This study will provide an assessment of methods and feasibility of recruiting and following up patients who are treated with SHRO. On the basis of this pilot trial, a full trial may be proposed in the future which will provide additional, robust evidence on the clinical and cost effectiveness of SHRO in wound management following AWR. This may act as a model for the management of wounds in complex patients undergoing AWR.

  5. Ruthenium(II) bipyridine complexes bearing quinoline-azoimine (NN'N″) tridentate ligands: synthesis, spectral characterization, electrochemical properties and single-crystal X-ray structure analysis.

    Science.gov (United States)

    Al-Noaimi, Mousa; Abdel-Rahman, Obadah S; Fasfous, Ismail I; El-khateeb, Mohammad; Awwadi, Firas F; Warad, Ismail

    2014-05-05

    Four octahedral ruthenium(II) azoimine-quinoline complexes having the general molecular formula [Ru(II)(L-Y)(bpy)Cl](PF6) {L-Y=YC6H4N=NC(COCH3)=NC9H6N, Y=H (1), CH3 (2), Br (3), NO2 (4) and bpy=2,2'-bipyrdine} were synthesized. The azoimine-quinoline based ligands behave as NN'N″ tridentate donors and coordinated to ruthenium via azo-N', imine-N' and quinolone-N″ nitrogen atoms. The composition of the complexes has been established by elemental analysis, spectral methods (FT-IR, electronic, (1)H NMR, UV/Vis and electrochemical (cyclic voltammetry) techniques. The crystal structure of complex 1 is reported. The Ru(II) oxidation state is greatly stabilized by the novel tridentate ligands, showing Ru(III/II) couples ranging from 0.93-1.27 V vs. Cp2Fe/Cp2Fe(+). The absorption spectrum of 1 in dichloromethane was modeled by time-dependent density functional theory (TD-DFT). Copyright © 2014 Elsevier B.V. All rights reserved.

  6. From a Dy(III) single molecule magnet (SMM) to a ferromagnetic [Mn(II)Dy(III)Mn(II)] trinuclear complex.

    Science.gov (United States)

    Bhunia, Asamanjoy; Gamer, Michael T; Ungur, Liviu; Chibotaru, Liviu F; Powell, Annie K; Lan, Yanhua; Roesky, Peter W; Menges, Fabian; Riehn, Christoph; Niedner-Schatteburg, Gereon

    2012-09-17

    The Schiff base compound 2,2'-{[(2-aminoethyl)imino]bis[2,1-ethanediyl-nitriloethylidyne]}bis-2-hydroxy-benzoic acid (H(4)L) as a proligand was prepared in situ. This proligand has three potential coordination pockets which make it possible to accommodate from one to three metal ions allowing for the possible formation of mono-, di-, and trinuclear complexes. Reaction of in situ prepared H(4)L with Dy(NO(3))(3)·5H(2)O resulted in the formation of a mononuclear complex [Dy(H(3)L)(2)](NO(3))·(EtOH)·8(H(2)O) (1), which shows SMM behavior. In contrast, reaction of in situ prepared H(4)L with Mn(ClO(4))(2)·6H(2)O and Dy(NO(3))(3)·5H(2)O in the presence of a base resulted in a trinuclear mixed 3d-4f complex (NHEt(3))(2)[Dy{Mn(L)}(2)](ClO(4))·2(H(2)O) (2). At low temperatures, compound 2 is a weak ferromagnet. Thus, the SMM behavior of compound 1 can be switched off by incorporating two Mn(II) ions in close proximity either side of the Dy(III). This quenching behavior is ascribed to the presence of the weak ferromagnetic interactions between the Mn(II) and Dy(III) ions, which at T > 2 K act as a fluctuating field causing the reversal of magnetization on the dysprosium ion. Mass spectrometric ion signals related to compounds 1 and 2 were both detected in positive and negative ion modes via electrospray ionization mass spectrometry. Hydrogen/deuterium exchange (HDX) reactions with ND(3) were performed in a FT-ICR Penning-trap mass spectrometer.

  7. A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study.

    Science.gov (United States)

    Patel, Manish V; Patel, Kalapi B; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S

    2015-01-01

    Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda). The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA). In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

  8. Slow magnetic relaxation and single-molecule toroidal behaviour in a family of heptanuclear {Cr"I"I"ILn"I"I"I_6} (Ln=Tb, Ho, Er) complexes

    Energy Technology Data Exchange (ETDEWEB)

    Vignesh, Kuduva R. [IITB-Monash Research Academy, IIT Bombay, Powai, Mumbai (India); Langley, Stuart K. [School of Science and the Environment, Division of Chemistry, Manchester Metropolitan University, Manchester (United Kingdom); Swain, Abinash; Rajaraman, Gopalan [Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai (India); Moubaraki, Boujemaa; Murray, Keith S. [School of Chemistry, Monash University, Clayton, VIC (Australia); Damjanovic, Marko; Wernsdorfer, Wolfgang [Institute Neel, CNRS, Universite Grenoble Alpes, Grenoble (France); Institute of Nanotechnology (INT), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen (Germany)

    2018-01-15

    The synthesis, magnetic properties, and theoretical studies of three heterometallic {Cr"I"I"ILn"I"I"I_6} (Ln=Tb, Ho, Er) complexes, each containing a metal topology consisting of two Ln{sub 3} triangles connected via a Cr{sup III} linker, are reported. The {CrTb_6} and {CrEr_6} analogues display slow relaxation of magnetization in a 3000 Oe static magnetic field. Single-crystal measurements reveal opening up of the hysteresis loop for {CrTb_6} and {CrHo_6} molecules at low temperatures. Ab initio calculations predict toroidal magnetic moments in the two Ln{sub 3} triangles, which are found to couple, stabilizing a con-rotating ferrotoroidal ground state in Tb and Ho examples and extend the possibility of observing toroidal behaviour in non Dy{sup III} complexes for the first time. (copyright 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Type 2 Active Galactic Nuclei with Double-peaked [O III] Lines. II. Single AGNs with Complex Narrow-line Region Kinematics are More Common than Binary AGNs

    Science.gov (United States)

    Shen, Yue; Liu, Xin; Greene, Jenny E.; Strauss, Michael A.

    2011-07-01

    Approximately 1% of low-redshift (z interpreted as either due to kinematics, such as biconical outflows and/or disk rotation of the narrow line region (NLR) around single black holes, or due to the relative motion of two distinct NLRs in a merging pair of AGNs. Here, we report follow-up near-infrared (NIR) imaging and optical slit spectroscopy of 31 double-peaked [O III] type 2 AGNs drawn from the Sloan Digital Sky Survey (SDSS) parent sample presented in Liu et al. The NIR imaging traces the old stellar population in each galaxy, while the optical slit spectroscopy traces the NLR gas. These data reveal a mixture of origins for the double-peaked feature. Roughly 10% of our objects are best explained by binary AGNs at (projected) kpc-scale separations, where two stellar components with spatially coincident NLRs are seen. ~50% of our objects have [O III] emission offset by a few kpc, corresponding to the two velocity components seen in the SDSS spectra, but there are no spatially coincident double stellar components seen in the NIR imaging. For those objects with sufficiently high-quality slit spectra, we see velocity and/or velocity dispersion gradients in [O III] emission, suggestive of the kinematic signatures of a single NLR. The remaining ~40% of our objects are ambiguous and will need higher spatial resolution observations to distinguish between the two scenarios. Our observations therefore favor the kinematics scenario with a single AGN for the majority of these double-peaked [O III] type 2 AGNs. We emphasize the importance of combining imaging and slit spectroscopy in identifying kpc-scale binary AGNs, i.e., in no cases does one of these alone allow an unambiguous identification. We estimate that ~0.5%-2.5% of the z ~ 150 km s-1. Based in part on observations obtained with the 6.5 m Magellan telescopes located at Las Campanas Observatory, Chile, and with the Apache Point Observatory 3.5 m telescope, which is owned and operated by the Astrophysical Research

  10. Analysis of Magnetic Anisotropy and the Role of Magnetic Dilution in Triggering Single-Molecule Magnet (SMM) Behavior in a Family of CoII YIII Dinuclear Complexes with Easy-Plane Anisotropy.

    Science.gov (United States)

    Palacios, María A; Nehrkorn, Joscha; Suturina, Elizaveta A; Ruiz, Eliseo; Gómez-Coca, Silvia; Holldack, Karsten; Schnegg, Alexander; Krzystek, Jurek; Moreno, José M; Colacio, Enrique

    2017-08-25

    Three new closely related Co II Y III complexes of general formula [Co(μ-L)(μ-X)Y(NO 3 ) 2 ] (X - =NO 3 - 1, benzoate 2, or 9-anthracenecarboxylato 3) have been prepared with the compartmental ligand N,N',N''-trimethyl-N,N''-bis(2-hydroxy-3-methoxy-5-methylbenzyl)diethylenetriamine (H 2 L). In these complexes, Co II and Y III are triply bridged by two phenoxide groups belonging to the di-deprotonated ligand (L 2- ) and one ancillary anion X - . The change of the ancillary bridging group connecting Co II and Y III ions induces small differences in the trigonally distorted CoN 3 O 3 coordination sphere with a concomitant tuning of the magnetic anisotropy and intermolecular interactions. Direct current magnetic, high-frequency and -field EPR (HFEPR), frequency domain Fourier transform THz electron paramagnetic resonance (FD-FT THz-EPR) measurements, and ab initio theoretical calculations demonstrate that Co II ions in compounds 1-3 have large and positive D values (≈50 cm -1 ), which decrease with increasing the distortion of the pseudo-octahedral Co II coordination sphere. Dynamic ac magnetic susceptibility measurements indicate that compound 1 exhibits field-induced single-molecule magnet (SMM) behavior, whereas compounds 2 and 3 only display this behavior when they are magnetically diluted with diamagnetic Zn II (Zn/Co=10:1). In view of this, it is always advisable to use magnetically diluted complexes, in which intermolecular interactions and quantum tunneling of magnetism (QTM) would be at least partly suppressed, so that "hidden single-ion magnet (SIM)" behavior could emerge. Field- and temperature-dependence of the relaxation times indicate the prevalence of the Raman process in all these complexes above approximately 3 K. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Invariant protection of high-voltage electric motors of technological complexes at industrial enterprises at partial single-phase ground faults

    Science.gov (United States)

    Abramovich, B. N.; Sychev, Yu A.; Pelenev, D. N.

    2018-03-01

    Development results of invariant protection of high-voltage motors at incomplete single-phase ground faults are observed in the article. It is established that current protections have low action selectivity because of an inadmissible decrease in entrance signals during the shirt circuit occurrence in the place of transient resistance. The structural functional scheme and an algorithm of protective actions where correction of automatic zero sequence currents signals of the protected accessions implemented according to the level of incompleteness of ground faults are developed. It is revealed that automatic correction of zero sequence currents allows one to provide the invariance of sensitivity factor for protection under the variation conditions of a transient resistance in the place of damage. Application of invariant protection allows one to minimize damages in 6-10 kV electrical installations of industrial enterprises for a cause of infringement of consumers’ power supply and their system breakdown due to timely localization of emergency of ground faults modes.

  12. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking

    International Nuclear Information System (INIS)

    Rossier, Olivier; Giannone, Grégory

    2016-01-01

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells.

  13. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking

    Energy Technology Data Exchange (ETDEWEB)

    Rossier, Olivier; Giannone, Grégory [Univ. Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux (France); CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux (France)

    2016-04-10

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells.

  14. Complex refractive index measurements for BaF 2 and CaF 2 via single-angle infrared reflectance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kelly-Gorham, Molly Rose K.; DeVetter, Brent M.; Brauer, Carolyn S.; Cannon, Bret D.; Burton, Sarah D.; Bliss, Mary; Johnson, Timothy J.; Myers, Tanya L.

    2017-10-01

    We have re-investigated the optical constants n and k for the homologous series of inorganic salts barium fluoride (BaF2) and calcium fluoride (CaF2) using a single-angle near-normal incidence reflectance device in combination with a calibrated Fourier transform infrared (FTIR) spectrometer. Our results are in good qualitative agreement with most previous works. However, certain features of the previously published data near the reststrahlen band exhibit distinct differences in spectral characteristics. Notably, our measurements of BaF2 do not include a spectral feature in the ~250 cm-1 reststrahlen band that was previously published. Additionally, CaF2 exhibits a distinct wavelength shift relative to the model derived from previously published data. We confirmed our results with recently published works that use significantly more modern instrumentation and data reduction techniques

  15. Solvent phase characterisation of lanthanide(3) and americium(3) complexes with malonamide (tema) and ter-pyridine ligands by EXAFS: comparison with single crystals

    International Nuclear Information System (INIS)

    Den Auwer, C.; Presson, M.T.; Grigoriev, M.; Madic, C.; Nierlich, M.; Thuery, P.; David, F.; Hubert, S.; Drew, M.G.B.; Hudson, M.J.; Iveson, P.B.; Russell, M.L.

    2002-01-01

    In order to develop molecules that will be good candidates for the extractive separation of the various elements contained within nuclear fuels, 4f and 5f molecular chemistry has been the subject of numerous studies. Thus, to better understand the ligand to cation interaction and to fine tune the theoretical models, precise knowledge about the cation co-ordination sphere must be obtained. More precisely, both structural and electronic data must be acquired in order to define the role of the cation frontier orbitals within the complex. To do so, various structural probes must be used, from vibrational and nuclear techniques to X-ray spectroscopies. In the field of actinide solvent extraction, the species of interest are in the solvent phase and both solid state diffraction methods and solvent phase X-ray absorption spectroscopy have become of primary importance lately. A number of Ln(III) and Am(III) complexes of the type M(NO 3 ) 3 L 1,2 (where M is either Ln 3+ or Am 3+ and L is either the 2,2',6',2 - ter-pyridine (Tpy) or the N,N,N',N' tetraethyl-malonamide (TEMA) ligand) have been crystallographically characterised in the solid state. In order to obtain structural information in the solvent phase, EXAFS L III edge measurements have been performed on the cation (DCI ring at the LURE facility). The overall contraction (-0.05 Angstrom) of the cation co-ordination sphere from Nd 3+ to Lu 3+ reflects the decrease in the lanthanide ionic radii. With the TEMA ligand, this steric constraint generates the elongation of one nitrate bond, leading to one formally monodendate nitrate for the late Ln ions. Comparison is made with the Tpy ligand. In the case of Am 3+ cation, comparison with isostructural Nd 3+ shows that similar co-ordination spheres are obtained, either with the TEMA or the Tpy ligands. (authors)

  16. NMR Studies of Protein Hydration and Protein-Ligand Interactions

    Science.gov (United States)

    Chong, Yuan

    Water on the surface of a protein is called hydration water. Hydration water is known to play a crucial role in a variety of biological processes including protein folding, enzymatic activation, and drug binding. Although the significance of hydration water has been recognized, the underlying mechanism remains far from being understood. This dissertation employs a unique in-situ nuclear magnetic resonance (NMR) technique to study the mechanism of protein hydration and the role of hydration in alcohol-protein interactions. Water isotherms in proteins are measured at different temperatures via the in-situ NMR technique. Water is found to interact differently with hydrophilic and hydrophobic groups on the protein. Water adsorption on hydrophilic groups is hardly affected by the temperature, while water adsorption on hydrophobic groups strongly depends on the temperature around 10 C, below which the adsorption is substantially reduced. This effect is induced by the dramatic decrease in the protein flexibility below 10 C. Furthermore, nanosecond to microsecond protein dynamics and the free energy, enthalpy, and entropy of protein hydration are studied as a function of hydration level and temperature. A crossover at 10 C in protein dynamics and thermodynamics is revealed. The effect of water at hydrophilic groups on protein dynamics and thermodynamics shows little temperature dependence, whereas water at hydrophobic groups has stronger effect above 10 C. In addition, I investigate the role of water in alcohol binding to the protein using the in-situ NMR detection. The isotherms of alcohols are first measured on dry proteins, then on proteins with a series of controlled hydration levels. The free energy, enthalpy, and entropy of alcohol binding are also determined. Two distinct types of alcohol binding are identified. On the one hand, alcohols can directly bind to a few specific sites on the protein. This type of binding is independent of temperature and can be facilitated by hydration. On the other hand, alcohols can bind to many nonspecific sites on the protein. In dry proteins, this type of binding only occurs above a threshold of alcohol vapor pressure. Such a threshold is gradually reduced by increasing the hydration level and can be removed above a critical hydration level. Hydration also shifts the nonspecific alcohol binding from an entropy-driven to an enthalpy-driven process. This dissertation reveals the mechanism of protein hydration and the detailed roles of hydration in ligand binding, with important implications for the understanding of protein functions.

  17. Nanoparticle-based receptors mimic protein-ligand recognition

    OpenAIRE

    Riccardi, Laura; Gabrielli, Luca; Sun, Xiaohuan; Biasi, Federico De; Rastrelli, Federico; Mancin, Fabrizio; De Vivo, Marco

    2017-01-01

    Summary The self-assembly of a monolayer of ligands on the surface of noble-metal nanoparticles dictates the fundamental nanoparticle's behavior and its functionality. In this combined computational-experimental study, we analyze the structure, organization, and dynamics of functionalized coating thiols in monolayer-protected gold nanoparticles (AuNPs). We explain how functionalized coating thiols self-organize through a delicate and somehow counterintuitive balance of interactions within the...

  18. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

    Science.gov (United States)

    Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

    2008-01-01

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

  19. Assembly of oligomeric death domain complexes during Toll receptor signaling.

    Science.gov (United States)

    Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

    2008-11-28

    The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

  20. Preparation of detergent-lipase complexes utilizing water-soluble amphiphiles in single aqueous phase and catalysis of transesterifications in homogeneous organic solvents.

    Science.gov (United States)

    Mine, Y; Fukunaga, K; Maruoka, N; Nakao, K; Sugimura, Y

    2000-01-01

    A novel method of preparing detergent-enzyme complexes that can be employed in organic media was developed utilizing newly synthesized water-soluble nonionic gemini-type detergents, N,N-bis(3-D-gluconamidopropyl)-3-(dialkyl-L-glutamatecarbonyl)propanamides (BIG2CnCA: n = 10,12,14,16,18) and N,N-bis(3-D-lactonamidopropyl)-3-(dialkyl-L-glutamatecarbonyl)propanamides (BIL2CnCA: n = 16,18), and nonionic twin-headed detergents, N,N-bis(3-D-gluconamidopropyl)alkanamides (BIG1Cn: n = 12,14,16,18,delta9). This method simply entails mixing a selected enzyme with an appropriate detergent in an aqueous solution followed by lyophilization, and it offers the advantages of enhanced enzymatic activity in organic solvents and eliminates both enzyme loss and the necessity for an organic solvent in the preparation stage. Using various modified lipases originating from Aspergillus niger (Lipase A), Candida rugosa (Lipase C), Pseudomonas cepacia (Lipase P), and porcine pancreas (PPL), prepared using the novel method and detergents, including conventional synthesized nonionic detergents such as dialkyl N-D-glucona-L-glutamates (2CnGE: n = 12,18delta9) and octanoyl-N-methylglucamide (MEGA-8), enantioselective transesterifications of 6-methyl-5-hepten-2-ol (sulcatol) and 2,2-dimethyl-1,3-dioxolane-4-methanol (solketal) with a vinyl or isopropenyl carboxylate were carried out in an organic solvent. The modified lipase activity was influenced by both the lipases and the structure of the detergents. The value for the hydrophile-lipophile balance (HLB) of the detergent provided a means of correlating the structure and the obtained modified lipase activity. For detergents of the same class with a HLB value of approximately 9 and 12, the highest activity was obtained for Lipase A and Lipase P, and Lipase C and PPL, respectively. Among detergents of the same HLB value tested, the gemini-type detergents possessing the most bulky head and tail were most effective as a modifier for lipases of all

  1. A Single Atom Antenna

    International Nuclear Information System (INIS)

    Trinter, Florian; Williams, Joshua B; Weller, Miriam; Waitz, Markus; Pitzer, Martin; Voigtsberger, Jörg; Schober, Carl; Kastirke, Gregor; Müller, Christian; Goihl, Christoph; Burzynski, Phillip; Wiegandt, Florian; Wallauer, Robert; Kalinin, Anton; Schmidt, Lothar Ph H; Schöffler, Markus S; Jahnke, Till; Dörner, Reinhard; Chiang, Ying-Chih; Gokhberg, Kirill

    2015-01-01

    Here we demonstrate the smallest possible implementation of an antenna-receiver complex which consists of a single (helium) atom acting as the antenna and a second (neon) atom acting as a receiver. (paper)

  2. Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

    Science.gov (United States)

    Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

    2013-01-01

    A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

  3. The journey of integrins and partners in a complex interactions landscape studied by super-resolution microscopy and single protein tracking.

    Science.gov (United States)

    Rossier, Olivier; Giannone, Grégory

    2016-04-10

    Cells adjust their adhesive and cytoskeletal organizations according to changes in the biochemical and physical nature of their surroundings. In return, by adhering and generating forces on the extracellular matrix (ECM) cells organize their microenvironment. Integrin-dependent focal adhesions (FAs) are the converging zones integrating biochemical and biomechanical signals arising from the ECM and the actin cytoskeleton. Thus, integrin-mediated adhesion and mechanotransduction, the conversion of mechanical forces into biochemical signals, are involved in critical cellular functions such as migration, proliferation and differentiation, and their deregulation contributes to pathologies including cancer. A challenging problem is to decipher how stochastic protein movements and interactions lead to formation of dynamic architecture such as integrin-dependent adhesive structures. In this review, we will describe recent advances made possible by super-resolution microscopies and single molecule tracking approaches that provided new understanding on the organization and the dynamics of integrins and intracellular regulators at the nanoscale in living cells. Copyright © 2015. Published by Elsevier Inc.

  4. Fear of movement modulates the feedforward motor control of the affected limb in complex regional pain syndrome (CRPS): A single-case study.

    Science.gov (United States)

    Osumi, Michihiro; Sumitani, Masahiko; Otake, Yuko; Morioka, Shu

    2018-01-01

    Pain-related fear can exacerbate physical disability and pathological pain in complex regional pain syndrome (CRPS) patients. We conducted a kinematic analysis of grasping movements with a pediatric patient suffering from CRPS in an upper limb to investigate how pain-related fear affects motor control. Using a three-dimensional measurement system, we recorded the patient's movement while grasping three vertical bars of different diameters (thin, middle, thick) with the affected and intact hands. We analyzed the maximum grasp distance between the thumb and the index finger (MGD), the peak velocity of the grasp movement (PV), and the time required for the finger opening phase (TOP) and closing phase (TCP). Consequently, the MGD and PV of grasp movements in the affected hand were significantly smaller than those of the intact hand when grasping the middle and thick bars. This might reflect pain-related fear against visual information of the target size which evokes sensation of difficulty in opening fingers widely to grasp the middle and thick bars. Although MGD and PV increased with target size, the TOP was longer in the affected hand when grasping the thick bar. These findings indicate that pain-related fear impairs motor commands that are sent to the musculoskeletal system, subsequently disrupting executed movements and their sensory feedback. Using kinematic analysis, we objectively demonstrated that pain-related fear affects the process of sending motor commands towards the musculoskeletal system in the CRPS-affected hand, providing a possible explanatory model of pathological pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. A framework for the use of single-chemical transcriptomics data in predicting the hazards associated with complex mixtures of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Labib, Sarah; Williams, Andrew; Kuo, Byron; Yauk, Carole L; White, Paul A; Halappanavar, Sabina

    2017-07-01

    The assumption of additivity applied in the risk assessment of environmental mixtures containing carcinogenic polycyclic aromatic hydrocarbons (PAHs) was investigated using transcriptomics. MutaTMMouse were gavaged for 28 days with three doses of eight individual PAHs, two defined mixtures of PAHs, or coal tar, an environmentally ubiquitous complex mixture of PAHs. Microarrays were used to identify differentially expressed genes (DEGs) in lung tissue collected 3 days post-exposure. Cancer-related pathways perturbed by the individual or mixtures of PAHs were identified, and dose-response modeling of the DEGs was conducted to calculate gene/pathway benchmark doses (BMDs). Individual PAH-induced pathway perturbations (the median gene expression changes for all genes in a pathway relative to controls) and pathway BMDs were applied to models of additivity [i.e., concentration addition (CA), generalized concentration addition (GCA), and independent action (IA)] to generate predicted pathway-specific dose-response curves for each PAH mixture. The predicted and observed pathway dose-response curves were compared to assess the sensitivity of different additivity models. Transcriptomics-based additivity calculation showed that IA accurately predicted the pathway perturbations induced by all mixtures of PAHs. CA did not support the additivity assumption for the defined mixtures; however, GCA improved the CA predictions. Moreover, pathway BMDs derived for coal tar were comparable to BMDs derived from previously published coal tar-induced mouse lung tumor incidence data. These results suggest that in the absence of tumor incidence data, individual chemical-induced transcriptomics changes associated with cancer can be used to investigate the assumption of additivity and to predict the carcinogenic potential of a mixture.

  6. Single gene deletions of mrpA to mrpG and mrpE point mutations affect activity of the Mrp Na+/H+ antiporter of alkaliphilic Bacillus and formation of hetero-oligomeric Mrp complexes.

    Science.gov (United States)

    Morino, Masato; Natsui, Shinsuke; Swartz, Talia H; Krulwich, Terry A; Ito, Masahiro

    2008-06-01

    Mrp antiporters catalyze secondary Na(+)(Li(+))/H(+) antiport and/or K(+)/H(+) antiport that is physiologically important in diverse bacteria. An additional capacity for anion flux has been observed for a few systems. Mrp is unique among antiporters in that it requires all six or seven hydrophobic gene products (MrpA to MrpG) of the mrp operon for full antiporter activity, but MrpE has been reported to be dispensable. Here, the membrane complexes formed by Mrp proteins were examined using a cloned mrp operon from alkaliphilic Bacillus pseudofirmus OF4. The operon was engineered so that the seven Mrp proteins could be detected in single samples. Membrane extracts of an antiporter-deficient Escherichia coli strain expressing this construct were analyzed by blue native-sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Mrp complexes of two sizes were identified containing all seven Mrp proteins. Studies of the single nonpolar mrp gene deletions in the construct showed that a subcomplex of MrpA, MrpB, MrpC, and MrpD was formed in the absence of MrpE, MrpF, or MrpG. By contrast, MrpE, MrpF, and MrpG were not observed in membranes lacking MrpA, MrpB, MrpC, or MrpD. Although MrpA and MrpD have been hypothesized to be the antiporter proteins, the MrpA-to-D complex was inactive. Every Mrp protein was required for an activity level near that of the wild-type Na(+)/H(+) antiporter, but a very low activity level was observed in the absence of MrpE. The introduction of an MrpE(P114G) mutation into the full Mrp complex led to antiport activity with a greatly increased apparent K(m) value for Na(+). The results suggested that interactions among the proteins of heterooligomeric Mrp complexes strongly impact antiporter properties.

  7. ComplexRec 2017

    DEFF Research Database (Denmark)

    a single step in the user's more complex background need. These background needs can often place a variety of constraints on which recommendations are interesting to the user and when they are appropriate. However, relatively little research has been done on these complex recommendation scenarios....... The ComplexRec 2017 workshop addressed this by providing an interactive venue for discussing approaches to recommendation in complex scenarios that have no simple one-size-fits-all-solution....

  8. Four-factor prothrombin complex concentrate improves thrombin generation and prothrombin time in patients with bleeding complications related to rivaroxaban: a single-center pilot trial.

    Science.gov (United States)

    Schenk, Bettina; Goerke, Stephanie; Beer, Ronny; Helbok, Raimund; Fries, Dietmar; Bachler, Mirjam

    2018-01-01

    Direct oral anticoagulants (DOACs) pose a great challenge for physicians in life-threatening bleeding events. The aim of this study was to test the efficacy of reversing the DOAC rivaroxaban using four-factor PCC (prothrombin complex concentrate), a non-specific reversing agent. Patients with life-threatening bleeding events during rivaroxaban treatment were included and administered 25 U kg -1 of PCC. Blood samples were collected immediately prior to as well as after PCC treatment at predefined time intervals. The primary endpoint was defined as the difference in thrombin generation (TG) parameters ETP (endogenous thrombin potential) and C max (peak thrombin generation) prior to and ten minutes subsequent to PCC treatment. Thirteen patients, of whom the majority suffered from intra-cranial haemorrhage (ICH) or subdural haemorrhage (SDH), were included and administered PCC. The results show that the ETP (TG) significantly ( p  = 0.001) improved by 68% and C max (TG) by 54% (p = 0.001) during PCC treatment. In addition, the Quick value (prothrombin time: Quick PT ) significantly improved by 28% and the activated partial thromboplastin time (aPTT) was decreased by 7% ten minutes after PCC administration. C max was reduced at baseline, but not ETP, aPTT or Quick PT . Lag time until initiation (TG, t lag ), thromboelastometry clotting time (CT EXTEM ) and time to peak (TG, t max ) correlated best with measured rivaroxaban levels and were out of normal ranges at baseline, but did not improve after PCC administration. In 77% of the patients bleeding (ICH/SDH-progression) ceased following PCC administration. During the study three participants passed away due to other complications not related to PCC treatment. The possibility of thrombosis formation was also evaluated seven days after administering PCC and no thromboses were found. This study shows that use of PCC improved ETP, C max, Quick PT and aPTT. However, of these parameters, only C max was reduced at the

  9. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  10. Trace detection of organic compounds in complex sample matrixes by single photon ionization ion trap mass spectrometry: real-time detection of security-relevant compounds and online analysis of the coffee-roasting process.

    Science.gov (United States)

    Schramm, Elisabeth; Kürten, Andreas; Hölzer, Jasper; Mitschke, Stefan; Mühlberger, Fabian; Sklorz, Martin; Wieser, Jochen; Ulrich, Andreas; Pütz, Michael; Schulte-Ladbeck, Rasmus; Schultze, Rainer; Curtius, Joachim; Borrmann, Stephan; Zimmermann, Ralf

    2009-06-01

    An in-house-built ion trap mass spectrometer combined with a soft ionization source has been set up and tested. As ionization source, an electron beam pumped vacuum UV (VUV) excimer lamp (EBEL) was used for single-photon ionization. It was shown that soft ionization allows the reduction of fragmentation of the target analytes and the suppression of most matrix components. Therefore, the combination of photon ionization with the tandem mass spectrometry (MS/MS) capability of an ion trap yields a powerful tool for molecular ion peak detection and identification of organic trace compounds in complex matrixes. This setup was successfully tested for two different applications. The first one is the detection of security-relevant substances like explosives, narcotics, and chemical warfare agents. One test substance from each of these groups was chosen and detected successfully with single photon ionization ion trap mass spectrometry (SPI-ITMS) MS/MS measurements. Additionally, first tests were performed, demonstrating that this method is not influenced by matrix compounds. The second field of application is the detection of process gases. Here, exhaust gas from coffee roasting was analyzed in real time, and some of its compounds were identified using MS/MS studies.

  11. The DFT Calculations of Structures and EPR Parameters for the Dinuclear Paddle-Wheel Copper(II) Complex {Cu2(μ2-O2CCH3)4}(OCNH2CH3) as Powder or Single Crystal

    Science.gov (United States)

    Ding, Chang-Chun; Wu, Shao-Yi; Xu, Yong-Qiang; Zhang, Li-Juan; Zhang, Zhi-Hong; Zhu, Qin-Sheng; Wu, Ming-He; Teng, Bao-Hua

    2017-10-01

    Density functional theory (DFT) calculations of the structures and the Cu2+ g factors (gx, gy and gz ) and hyperfine coupling tensor A (Ax , Ay and Az ) were performed for the paddle-wheel (PW)-type binuclear copper(II) complex {Cu2(μ2-O2CCH3)4}(OCNH2CH3) powder and single crystal. Calculations were carried out with the ORCA software using the functionals BHandHlyp, B3P86 and B3LYP with five different basis sets: 6-311g, 6-311g(d,p), VTZ, def-2 and def2-TZVP. Results were tested by the MPAD analysis to find the most suitable functional and basis sets. The electronic structure and covalency between copper and oxygen were investigated by the electron localisation function and the localised orbital locator as well as the Mayer bond order for the [CuO5] group. The optical spectra were theoretically calculated by the time-dependent DFT module and plotted by the Multiwfn program for the [CuO5] group and reasonably associated with the local structure in the vicinity of the central ion copper. In addition, the interactions between the OCNH2CH3, NH3 and H2O molecules and the uncoordinated PW copper(II) complex were studied, and the corresponding adsorption energies, the frequency shifts with respect to the free molecules and the changes of the Cu-Cu distances were calculated and compared with the relevant systems.

  12. A complex small RNA repertoire is generated by a plant/fungal-like machinery and effected by a metazoan-like Argonaute in the single-cell human parasite Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Laurence Braun

    2010-05-01

    Full Text Available In RNA silencing, small RNAs produced by the RNase-III Dicer guide Argonaute-like proteins as part of RNA-induced silencing complexes (RISC to regulate gene expression transcriptionally or post-transcriptionally. Here, we have characterized the RNA silencing machinery and exhaustive small RNAome of Toxoplasma gondii, member of the Apicomplexa, a phylum of animal- and human-infecting parasites that cause extensive health and economic damages to human populations worldwide. Remarkably, the small RNA-generating machinery of Toxoplasma is phylogenetically and functionally related to that of plants and fungi, and accounts for an exceptionally diverse array of small RNAs. This array includes conspicuous populations of repeat-associated small interfering RNA (siRNA, which, as in plants, likely generate and maintain heterochromatin at DNA repeats and satellites. Toxoplasma small RNAs also include many microRNAs with clear metazoan-like features whose accumulation is sometimes extremely high and dynamic, an unexpected finding given that Toxoplasma is a unicellular protist. Both plant-like heterochromatic small RNAs and metazoan-like microRNAs bind to a single Argonaute protein, Tg-AGO. Toxoplasma miRNAs co-sediment with polyribosomes, and thus, are likely to act as translational regulators, consistent with the lack of catalytic residues in Tg-AGO. Mass spectrometric analyses of the Tg-AGO protein complex revealed a common set of virtually all known RISC components so far characterized in human and Drosophila, as well as novel proteins involved in RNA metabolism. In agreement with its loading with heterochromatic small RNAs, Tg-AGO also associates substoichiometrically with components of known chromatin-repressing complexes. Thus, a puzzling patchwork of silencing processor and effector proteins from plant, fungal and metazoan origin accounts for the production and action of an unsuspected variety of small RNAs in the single-cell parasite Toxoplasma and

  13. Low Complexity Bayesian Single Channel Source Separation

    DEFF Research Database (Denmark)

    Beierholm, Thomas; Pedersen, Brian Dam; Winther, Ole

    2004-01-01

    can be estimated quite precisely using ML-II, but the estimation is quite sensitive to the accuracy of the priors as opposed to the source separation quality for known mixing coefficients, which is quite insensitive to the accuracy of the priors. Finally, we discuss how to improve our approach while...

  14. Complex dynamics

    CERN Document Server

    Carleson, Lennart

    1993-01-01

    Complex dynamics is today very much a focus of interest. Though several fine expository articles were available, by P. Blanchard and by M. Yu. Lyubich in particular, until recently there was no single source where students could find the material with proofs. For anyone in our position, gathering and organizing the material required a great deal of work going through preprints and papers and in some cases even finding a proof. We hope that the results of our efforts will be of help to others who plan to learn about complex dynamics and perhaps even lecture. Meanwhile books in the field a. re beginning to appear. The Stony Brook course notes of J. Milnor were particularly welcome and useful. Still we hope that our special emphasis on the analytic side will satisfy a need. This book is a revised and expanded version of notes based on lectures of the first author at UCLA over several \\Vinter Quarters, particularly 1986 and 1990. We owe Chris Bishop a great deal of gratitude for supervising the production of cour...

  15. Nogo-receptor 1 antagonization in combination with neurotrophin-4/5 is not superior to single factor treatment in promoting survival and morphological complexity of cultured dopaminergic neurons.

    Science.gov (United States)

    Seiler, Stefanie; Di Santo, Stefano; Sahli, Sebastian; Andereggen, Lukas; Widmer, Hans Rudolf

    2017-08-01

    Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures. We investigated whether a combination of both treatments offers a novel tool to further improve dopaminergic neuron survival. Rat embryonic ventral mesencephalic neurons grown as organotypic free-floating roller tube or primary dissociated cultures were exposed to neurotrophin-4/5 and NEP1-40. The combined and single factor treatment resulted in significantly higher numbers of tyrosine hydroxylase positive neurons compared to controls. Significantly stronger tyrosine hydroxylase signal intensity was detected by Western blotting in the combination-treated cultures compared to controls but not compared to single factor treatments. Neurotrophin-4/5 and the combined treatment showed significantly higher signals for the neuronal marker microtubule-associated protein 2 in Western blots compared to control while no effects were observed for the astroglial marker glial fibrillary acidic protein between groups, suggesting that neurotrophin-4/5 targets mainly neuronal cells. Finally, NEP1-40 and the combined treatment significantly augmented tyrosine hydroxylase positive neurite length. Summarizing, our findings substantiate that antagonization of the Nogo-receptor 1 promotes dopaminergic neurons but does not further increase the yield of dopaminergic neurons and their morphological complexity when combined with neurotrophin-4/5 hinting to the idea that these treatments might exert their effects by activating common

  16. Stabilization of Proteins and Noncovalent Protein Complexes during Electrospray Ionization by Amino Acid Additives.

    Science.gov (United States)

    Zhang, Hua; Lu, Haiyan; Chingin, Konstantin; Chen, Huanwen

    2015-07-21

    Ionization of proteins and noncovalent protein complexes with minimal disturbance to their native structure presents a great challenge for biological mass spectrometry (MS). In living organisms, the native structure of intracellular proteins is commonly stabilized by solute amino acids (AAs) accumulated in cells at very high concentrations. Inspired by nature, we hypothesized that AAs could also pose a stabilizing effect on the native structure of proteins and noncovalent protein complexes during ionization. To test this hypothesis, here we explored MS response for various protein complexes upon the addition of free AAs at mM concentrations into the electrospray ionization (ESI) solution. Thermal activation of ESI droplets in the MS inlet capillary was employed as a model destabilizing factor during ionization. Our results indicate that certain AAs, in particular proline (Pro), pose considerable positive effect on the stability of noncovalent protein complexes in ESI-MS without affecting the signal intensity of protein ions and original protein-ligand equilibrium, even when added at the 20 mM concentration. The data suggest that the degree of protein stabilization is primarily determined by the osmolytic and ampholytic characteristics of AA solutes. The highest stability and visibility of noncovalent protein complexes in ESI-MS are achieved using AA additives with neutral isoelectric point, moderate proton affinity, and unfavorable interaction with the native protein state. Overall, our results indicate that the simple addition of free amino acids into the working solution can notably improve the stability and accuracy of protein analysis by native ESI-MS.

  17. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  18. Complex chemistry

    International Nuclear Information System (INIS)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-01

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  19. Beyond the Single Story

    Science.gov (United States)

    McKenney, Yekaterina

    2016-01-01

    Teachers of world literature have the opportunity to help students explore the more complex reality behind the stereotypes that they often see in the media. If we don't encourage students to challenge one-dimensional "single stories" that characterize an entire people--whether Muslims, Russians, Mexicans, African Americans, Chinese,…

  20. Effect of a single prophylactic preoperative oral antibiotic dose on surgical site infection following complex dermatological procedures on the nose and ear: a prospective, randomised, controlled, double-blinded trial.

    Science.gov (United States)

    Rosengren, Helena; Heal, Clare F; Buttner, Petra G

    2018-04-19

    There is limited published research studying the effect of antibiotic prophylaxis on surgical site infection (SSI) in dermatological surgery, and there is no consensus for its use in higher-risk cases. The objective of this study was to determine the effectiveness of a single oral preoperative 2 g dose of cephalexin in preventing SSI following flap and graft dermatological closures on the nose and ear. Prospective double-blinded, randomised, placebo-controlled trial testing for difference in infection rates. Primary care skin cancer clinics in North Queensland, Australia, were randomised to 2 g oral cephalexin or placebo 40-60 min prior to skin incision. 154 consecutive eligible patients booked for flap or graft closure following skin cancer excision on the ear and nose. 2 g dose of cephalexin administered 40-60 min prior to surgery. Overall 8/69 (11.6%) controls and 1/73 (1.4%) in the intervention group developed SSI (p=0.015; absolute SSI reduction 10.2%; number needed to treat (NNT) for benefit 9.8, 95% CI 5.5 to 45.5). In males, 7/44 controls and 0/33 in the intervention group developed SSI (p=0.018; absolute SSI reduction 15.9%; NNT for benefit 6.3, 95% CI 3.8 to 19.2). SSI was much lower in female controls (1/25) and antibiotic prophylaxis did not further reduce this (p=1.0). There was no difference between the study groups in adverse symptoms attributable to high-dose antibiotic administration (p=0.871). A single oral 2 g dose of cephalexin given before complex skin closure on the nose and ear reduced SSI. ANZCTR 365115; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Surface-Induced Dissociation of Protein Complexes in a Hybrid Fourier Transform Ion Cyclotron Resonance Mass Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Jing; Zhou, Mowei; Gilbert, Joshua D.; Wolff, Jeremy J.; Somogyi, Árpád; Pedder, Randall E.; Quintyn, Royston S.; Morrison, Lindsay J.; Easterling, Michael L.; Paša-Tolić, Ljiljana; Wysocki, Vicki H.

    2017-01-03

    Mass spectrometry continues to develop as a valuable tool in the analysis of proteins and protein complexes. In protein complex mass spectrometry studies, surface-induced dissociation (SID) has been successfully applied in quadrupole time-of-flight (Q-TOF) instruments. SID provides structural information on non-covalent protein complexes that is complementary to other techniques. However, the mass resolution of Q-TOF instruments can limit the information that can be obtained for protein complexes by SID. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) provides ultrahigh resolution and ultrahigh mass accuracy measurements. In this study, an SID device was designed and successfully installed in a hybrid FT-ICR instrument in place of the standard gas collision cell. The SID-FT-ICR platform has been tested with several protein complex systems (homooligomers, a heterooligomer, and a protein-ligand complex, ranging from 53 kDa to 85 kDa), and the results are consistent with data previously acquired on Q-TOF platforms, matching predictions from known protein interface information. SID fragments with the same m/z but different charge states are well-resolved based on distinct spacing between adjacent isotope peaks, and the addition of metal cations and ligands can also be isotopically resolved with the ultrahigh mass resolution available in FT-ICR.

  2. single crystals

    Indian Academy of Sciences (India)

    2018-05-18

    May 18, 2018 ... Abstract. 4-Nitrobenzoic acid (4-NBA) single crystals were studied for their linear and nonlinear optical ... studies on the proper growth, linear and nonlinear optical ..... between the optic axes and optic sign of the biaxial crystal.

  3. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  4. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  5. Single-Arc IMRT?

    International Nuclear Information System (INIS)

    Bortfeld, Thomas; Webb, Steve

    2009-01-01

    The idea of delivering intensity-modulated radiation therapy (IMRT) with a multileaf collimator in a continuous dynamic mode during a single rotation of the gantry has recently gained momentum both in research and industry. In this note we investigate the potential of this Single-Arc IMRT technique at a conceptual level. We consider the original theoretical example case from Brahme et al that got the field of IMRT started. Using analytical methods, we derive deliverable intensity 'landscapes' for Single-Arc as well as standard IMRT and Tomotherapy. We find that Tomotherapy provides the greatest flexibility in shaping intensity landscapes and that it allows one to deliver IMRT in a way that comes close to the ideal case in the transverse plane. Single-Arc and standard IMRT make compromises in different areas. Only in relatively simple cases that do not require substantial intensity modulation will Single-Arc be dosimetrically comparable to Tomotherapy. Compared with standard IMRT, Single-Arc could be dosimetrically superior in certain cases if one is willing to accept the spreading of low dose values over large volumes of normal tissue. In terms of treatment planning, Single-Arc poses a more challenging optimization problem than Tomotherapy or standard IMRT. We conclude that Single-Arc holds potential as an efficient IMRT technique especially for relatively simple cases. In very complex cases, Single-Arc may unduly compromise the quality of the dose distribution, if one tries to keep the treatment time below 2 min or so. As with all IMRT techniques, it is important to explore the tradeoff between plan quality and the efficiency of its delivery carefully for each individual case. (note)

  6. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  7. Analysis of various types of single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complexes and their allosteric receptor–receptor interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Toshio, E-mail: kamiya@z2.keio.jp [Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526 (Japan); Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526 (Japan); Cell Biology Laboratory, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502 (Japan); Yoshioka, Kazuaki; Nakata, Hiroyasu [Department of Molecular Cell Signaling, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526 (Japan)

    2015-01-09

    Highlights: • Various scA{sub 2A}R/D{sub 2}R constructs, with spacers between the two receptors, were created. • Using whole cell binding assay, constructs were examined for their binding activity. • Although the apparent ratio of A{sub 2A}R to D{sub 2}R binding sites should be 1, neither was 1. • Counter agonist-independent binding cooperativity occurred in context of scA{sub 2A}R/D{sub 2}R. - Abstract: Adenosine A{sub 2A} receptor (A{sub 2A}R) heteromerizes with dopamine D{sub 2} receptor (D{sub 2}R). However, these class A G protein-coupled receptor (GPCR) dimers are not fully formed, but depend on the equilibrium between monomer and dimer. In order to stimulate the heteromerization, we have previously shown a successful design for a fusion receptor, single-polypeptide-chain (sc) heterodimeric A{sub 2A}R/D{sub 2}R complex. Here, using whole cell binding assay, six more different scA{sub 2A}R/D{sub 2}R constructs were examined. Not only in scA{sub 2A}R/D{sub 2}R ‘liberated’ with longer spacers between the two receptors, which confer the same configuration as the prototype, the A{sub 2A}R-odr4TM-D{sub 2L}R, but differ in size (Forms 1–3), but also in scA{sub 2A}R/D{sub 2L}R (Form 6) fused with a transmembrane (TM) of another type II TM protein, instead of odr4TM, neither of their fixed stoichiometry (the apparent ratios of A{sub 2A}R to D{sub 2}R binding sites) was 1, suggesting their compact folding. This suggests that type II TM, either odr4 or another, facilitates the equilibrial process of the dimer formation between A{sub 2A}R and D{sub 2L}R, resulting in the higher-order oligomer formation from monomer of scA{sub 2A}R/D{sub 2L}R itself. Also, in the reverse type scA{sub 2A}R/D{sub 2L}R, i.e., the D{sub 2L}R-odr4TM-A{sub 2A}R, counter agonist-independent binding cooperativity (cooperative folding) was found to occur (Forms 4 and 5). In this way, the scA{sub 2A}R/D{sub 2L}R system has unveiled the cellular phenomenon as a snapshot of the

  8. Single Site Mutations in the Hetero-oligomeric Mrp Antiporter from Alkaliphilic Bacillus pseudofirmus OF4 That Affect Na+/H+ Antiport Activity, Sodium Exclusion, Individual Mrp Protein Levels, or Mrp Complex Formation*

    OpenAIRE

    Morino, Masato; Natsui, Shinsuke; Ono, Tomohiro; Swartz, Talia H.; Krulwich, Terry A.; Ito, Masahiro

    2010-01-01

    Mrp systems are widely distributed and structurally complex cation/proton antiporters. Antiport activity requires hetero-oligomeric complexes of all six or seven hydrophobic Mrp proteins (MrpA–MrpG). Here, a panel of site-directed mutants in conserved or proposed motif residues was made in the Mrp Na+(Li+)/H+ antiporter from an alkaliphilic Bacillus. The mutant operons were expressed in antiporter-deficient Escherichia coli KNabc and assessed for antiport properties, support of sodium resista...

  9. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

  10. Single site mutations in the hetero-oligomeric Mrp antiporter from alkaliphilic Bacillus pseudofirmus OF4 that affect Na+/H+ antiport activity, sodium exclusion, individual Mrp protein levels, or Mrp complex formation.

    Science.gov (United States)

    Morino, Masato; Natsui, Shinsuke; Ono, Tomohiro; Swartz, Talia H; Krulwich, Terry A; Ito, Masahiro

    2010-10-01

    Mrp systems are widely distributed and structurally complex cation/proton antiporters. Antiport activity requires hetero-oligomeric complexes of all six or seven hydrophobic Mrp proteins (MrpA-MrpG). Here, a panel of site-directed mutants in conserved or proposed motif residues was made in the Mrp Na(+)(Li(+))/H(+) antiporter from an alkaliphilic Bacillus. The mutant operons were expressed in antiporter-deficient Escherichia coli KNabc and assessed for antiport properties, support of sodium resistance, membrane levels of each Mrp protein, and presence of monomeric and dimeric Mrp complexes. Antiport did not depend on a VFF motif or a conserved tyrosine pair, but a role for a conserved histidine in a potential quinone binding site of MrpA was supported. The importance of several acidic residues for antiport was confirmed, and the importance of additional residues was demonstrated (e.g. three lysine residues conserved across MrpA, MrpD, and membrane-bound respiratory Complex I subunits (NuoL/M/N)). The results extended indications that MrpE is required for normal membrane levels of other Mrp proteins and for complex formation. Moreover, mutations in several other Mrp proteins lead to greatly reduced membrane levels of MrpE. Thus, changes in either of the two Mrp modules, MrpA-MrpD and MrpE-MrpG, influence the other. Two mutants, MrpB-P37G and MrpC-Q70A, showed a normal phenotype but lacked the MrpA-MrpG monomeric complex while retaining the dimeric hetero-oligomeric complex. Finally, MrpG-P81A and MrpG-P81G mutants exhibited no antiport activity but supported sodium resistance and a low [Na(+)](in). Such mutants could be used to screen hypothesized but uncharacterized sodium efflux functions of Mrp apart from Na(+) (Li(+))/H(+) antiport.

  11. Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation.

    Science.gov (United States)

    Iida, Shinji; Nakamura, Haruki; Higo, Junichi

    2016-06-15

    We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein-protein or protein-ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks. © 2016 The Author(s).

  12. Singled out?

    Science.gov (United States)

    Waller, Frank

    2004-03-01

    The increasing use of single use medical devices is being driven by a growing awareness of iatrogenic (from the Greek; caused by the doctor) and nosocomial infections. Public health perceptions relating to transmissible spongiform encephalopathies, specifically variant Creutzfeldt-Jakob disease (vCJD), the Human Immunodeficiency Virus (HIV) and Hepatitis B are high on the political agenda and a matter of concern to healthcare professionals.

  13. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    and into French. The complexity of the undertaking proved to be a central element in the students' learning, as the collaboration closely resembles the complexity of international documentation workplaces of language service providers. © Association of Teachers of Technical Writing.......This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dutch...

  14. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  15. Softball Complex

    Science.gov (United States)

    Ellis, Jim

    1977-01-01

    The Parks and Recreation Department of Montgomery, Alabama, has developed a five-field softball complex as part of a growing community park with facilities for camping, golf, aquatics, tennis, and picnicking. (MJB)

  16. Lecithin Complex

    African Journals Online (AJOL)

    1Department of Food Science and Engineering, Xinyang College of Agriculture and ... Results: The UV and IR spectra of the complex showed an additive effect of polydatin-lecithin, in which .... Monochromatic Cu Ka radiation (wavelength =.

  17. Advances in single chain technology.

    Science.gov (United States)

    Gonzalez-Burgos, Marina; Latorre-Sanchez, Alejandro; Pomposo, José A

    2015-10-07

    The recent ability to manipulate and visualize single atoms at atomic level has given rise to modern bottom-up nanotechnology. Similar exquisite degree of control at the individual polymeric chain level for producing functional soft nanoentities is expected to become a reality in the next few years through the full development of so-called "single chain technology". Ultra-small unimolecular soft nano-objects endowed with useful, autonomous and smart functions are the expected, long-term valuable output of single chain technology. This review covers the recent advances in single chain technology for the construction of soft nano-objects via chain compaction, with an emphasis in dynamic, letter-shaped and compositionally unsymmetrical single rings, complex multi-ring systems, single chain nanoparticles, tadpoles, dumbbells and hairpins, as well as the potential end-use applications of individual soft nano-objects endowed with useful functions in catalysis, sensing, drug delivery and other uses.

  18. 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

    2006-02-15

    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.)

  19. Changes in body composition, blood lipid profile, and growth factor hormone in a patient with Prader-willi syndrome during 24 weeks of complex exercise: a single case study.

    Science.gov (United States)

    Joung, Hee Joung; Lim, In Soo

    2018-03-30

    Prader-Willi syndrome (PWS) is a genetic disorder characterized by excessive appetite with progressive obesity and growth hormone (GH) deficiency. Excessive eating causes progressive obesity with increased risk of morbidities and mortality. Although GH treatment has beneficial effects on patients with PWS, adverse events have occurred during GH treatment. Exercise potentially has a positive effect on obesity management. The purpose of this research was to examine the effects of 24-week complex exercise program on changes in body composition, blood lipid profiles, and growth factor hormone levels in a patient with PWS. The case study participant was a 23-year-old man with PWS who also had type II diabetes mellitus because of extreme obesity. Complex exercises, including strength and aerobic exercises, were conducted 5 times one week for 60 minutes per session, over 24 weeks. Blood sampling was conducted five times: before and at 8, 16, 20, and 24 weeks after commencement of the exercise program. Weight, fat mass, triglycerides/high-density lipoprotein (TG/HDL) ratio, mean blood glucose, and GH decreased after training. Blood insulin and insulin-like growth factor (IGF-1) levels increased after training. At 15 and 20 weeks, insulin injection was discontinued. Insulin levels increased and average blood glucose decreased to normal levels; IGF-1 increased continuously during the 24-week exercise program. Conclusion] Twenty-four weeks of complex exercises had a positive effect on obesity and diabetes in the patient with PWS. Therefore, long-period complex exercises might be an effective intervention for improvement of metabolic factors in PWS patients. ©2018 The Korean Society for Exercise Nutrition.

  20. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  1. Subgroup complexes

    CERN Document Server

    Smith, Stephen D

    2011-01-01

    This book is intended as an overview of a research area that combines geometries for groups (such as Tits buildings and generalizations), topological aspects of simplicial complexes from p-subgroups of a group (in the spirit of Brown, Quillen, and Webb), and combinatorics of partially ordered sets. The material is intended to serve as an advanced graduate-level text and partly as a general reference on the research area. The treatment offers optional tracks for the reader interested in buildings, geometries for sporadic simple groups, and G-equivariant equivalences and homology for subgroup complexes.

  2. Complex manifolds

    CERN Document Server

    Morrow, James

    2006-01-01

    This book, a revision and organization of lectures given by Kodaira at Stanford University in 1965-66, is an excellent, well-written introduction to the study of abstract complex (analytic) manifolds-a subject that began in the late 1940's and early 1950's. It is largely self-contained, except for some standard results about elliptic partial differential equations, for which complete references are given. -D. C. Spencer, MathSciNet The book under review is the faithful reprint of the original edition of one of the most influential textbooks in modern complex analysis and geometry. The classic

  3. Genomic Functionalization: The Next Revolution In Biology

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Peter [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Schoeniger, Joseph S. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Imbro, Paula M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2014-07-01

    We have implemented a ligand-alignment algorithm into our developed computational pipeline for identifying specificity-determining features (SDFs) in protein-ligand complexes. Given a set of protein-ligand complex structures, the algorithm aligns the complexes by ligand rather than by the C -RMSD or standard approach, providing a single reference frame for extracting SDFs. We anticipate that this ligand-alignment capability will be highly useful for protein function prediction. We already have a database containing > 20 K ligand-protein complex crystal structures taken from the Protein Data Bank. By aligning these proteins to single reference frames using ligand alignment, we can submit the complexes to our pipeline for SDF extraction. The SDFs derived from this training procedure can be used as thumbprints that are hallmarks of individual enzyme classes. These SDF thumbprints may then serve as guides to the prediction of function of new unknown proteins.

  4. Complex Networks

    CERN Document Server

    Evsukoff, Alexandre; González, Marta

    2013-01-01

    In the last decade we have seen the emergence of a new inter-disciplinary field focusing on the understanding of networks which are dynamic, large, open, and have a structure sometimes called random-biased. The field of Complex Networks is helping us better understand many complex phenomena such as the spread of  deseases, protein interactions, social relationships, to name but a few. Studies in Complex Networks are gaining attention due to some major scientific breakthroughs proposed by network scientists helping us understand and model interactions contained in large datasets. In fact, if we could point to one event leading to the widespread use of complex network analysis is the availability of online databases. Theories of Random Graphs from Erdös and Rényi from the late 1950s led us to believe that most networks had random characteristics. The work on large online datasets told us otherwise. Starting with the work of Barabási and Albert as well as Watts and Strogatz in the late 1990s, we now know th...

  5. A single-chain fusion molecule consisting of peptide, major histocompatibility gene complex class I heavy chain and beta2-microglobulin can fold partially correctly, but binds peptide inefficiently

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Buus, S

    1999-01-01

    of a recombinant murine MHC-I molecule, which could be produced in large amounts in bacteria. The recombinant MHC-I protein was expressed as a single molecule (PepSc) consisting of the antigenic peptide linked to the MHC-I heavy chain and further linked to human beta2-microglobulin (hbeta2m). The PepSc molecule...... electrophoresis (SDS-PAGE). Serological analysis revealed the presence of some, but not all, MHC-I-specific epitopes. Biochemically, PepSc could bind peptide, however, rather ineffectively. We suggest that a partially correctly refolded MHC-I has been obtained....

  6. Characterization, stoichiometry, and stability of salivary protein-tannin complexes by ESI-MS and ESI-MS/MS.

    Science.gov (United States)

    Canon, Francis; Paté, Franck; Meudec, Emmanuelle; Marlin, Thérèse; Cheynier, Véronique; Giuliani, Alexandre; Sarni-Manchado, Pascale

    2009-12-01

    Numerous protein-polyphenol interactions occur in biological and food domains particularly involving proline-rich proteins, which are representative of the intrinsically unstructured protein group (IUP). Noncovalent protein-ligand complexes are readily detected by electrospray ionization mass spectrometry (ESI-MS), which also gives access to ligand binding stoichiometry. Surprisingly, the study of interactions between polyphenolic molecules and proteins is still an area where ESI-MS has poorly benefited, whereas it has been extensively applied to the detection of noncovalent complexes. Electrospray ionization mass spectrometry has been applied to the detection and the characterization of the complexes formed between tannins and a human salivary proline-rich protein (PRP), namely IB5. The study of the complex stability was achieved by low-energy collision-induced dissociation (CID) measurements, which are commonly implemented using triple quadrupole, hybrid quadrupole time-of-flight, or ion trap instruments. Complexes composed of IB5 bound to a model polyphenol EgCG have been detected by ESI-MS and further analyzed by MS/MS. Mild ESI interface conditions allowed us to observe intact noncovalent PRP-tannin complexes with stoichiometries ranging from 1:1 to 1:5. Thus, ESI-MS shows its efficiency for (1) the study of PRP-tannin interactions, (2) the determination of stoichiometry, and (3) the study of complex stability. We were able to establish unambiguously both their stoichiometries and their overall subunit architecture via tandem mass spectrometry and solution disruption experiments. Our results prove that IB5.EgCG complexes are maintained intact in the gas phase.

  7. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

    Science.gov (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

    2012-04-30

    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

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

  9. Expanded potential of seleno-carbohydrates as a molecular tool for X-ray structural determination of a carbohydrate-protein complex with single/multi-wavelength anomalous dispersion phasing.

    Science.gov (United States)

    Suzuki, Tatsuya; Makyio, Hisayoshi; Ando, Hiromune; Komura, Naoko; Menjo, Masanori; Yamada, Yusuke; Imamura, Akihiro; Ishida, Hideharu; Wakatsuki, Soichi; Kato, Ryuichi; Kiso, Makoto

    2014-04-01

    Seleno-lactoses have been successfully synthesized as candidates for mimicking carbohydrate ligands for human galectin-9 N-terminal carbohydrate recognition domain (NCRD). Selenium was introduced into the mono- or di-saccharides using p-methylselenobenzoic anhydride (Tol2Se) as a novel selenating reagent. The TolSe-substituted monosaccharides were converted into selenoglycosyl donors or acceptors, which were reacted with coupling partners to afford seleno-lactoses. The seleno-lactoses were converted to the target compounds. The structure of human galectin-9 NCRD co-crystallized with 6-MeSe-lactose was determined with single/multi-wavelength anomalous dispersion (SAD/MAD) phasing and was similar to that of the co-crystal with natural lactose. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. An integrated in silico approach to analyze the involvement of single amino acid polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 complex.

    Science.gov (United States)

    Doss, C George Priya; Nagasundaram, N

    2014-11-01

    Fanconi anemia (FA) is an autosomal recessive human disease characterized by genomic instability and a marked increase in cancer risk. The importance of FANCD1 gene is manifested by the fact that deleterious amino acid substitutions were found to confer susceptibility to hereditary breast and ovarian cancers. Attaining experimental knowledge about the possible disease-associated substitutions is laborious and time consuming. The recent introduction of genome variation analyzing in silico tools have the capability to identify the deleterious variants in an efficient manner. In this study, we conducted in silico variation analysis of deleterious non-synonymous SNPs at both functional and structural level in the breast cancer and FA susceptibility gene BRCA2/FANCD1. To identify and characterize deleterious mutations in this study, five in silico tools based on two different prediction methods namely pathogenicity prediction (SIFT, PolyPhen, and PANTHER), and protein stability prediction (I-Mutant 2.0 and MuStab) were analyzed. Based on the deleterious scores that overlap in these in silico approaches, and the availability of three-dimensional structures, structure analysis was carried out with the major mutations that occurred in the native protein coded by FANCD1/BRCA2 gene. In this work, we report the results of the first molecular dynamics (MD) simulation study performed to analyze the structural level changes in time scale level with respect to the native and mutated protein complexes (G25R, W31C, W31R in FANCD1/BRCA2-PALB2, and F1524V, V1532F in FANCD1/BRCA2-RAD51). Analysis of the MD trajectories indicated that predicted deleterious variants alter the structural behavior of BRCA2-PALB2 and BRCA2-RAD51 protein complexes. In addition, statistical analysis was employed to test the significance of these in silico tool predictions. Based on these predictions, we conclude that the identification of disease-related SNPs by in silico methods, in combination with MD

  11. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  12. COMPLEX PROMOTIONSIN RETAIL

    Directory of Open Access Journals (Sweden)

    O. Yusupova

    2015-10-01

    Full Text Available Complex promotions used by retailers introduce to the consumers several rules that must be satisfied in order to get some benefits and usually refer to multiple products (e.g. “buy two, get one free”. Rules of complex promotions can be quite sophisticated and complicated themselves. Since diversity of complex promotions limited only by marketers’ imagination we can observe broad variety of promotions’ rules and representa¬tions of those rules in retailers’ commercials. Such diversification makes no good for fellow scientist who’s trying to sort all type of promotions into the neatly organized classification. Although we can simple add every single set of rules offered by retailers as a separate form of sales promotion it seems not to be the best way of dealing with such a problem. The better way is to realize that mechanisms underlying that variety of promotions are basically the same, namely changes in demand or quantity demanded. Those two concepts alone provide powerful insight into classification of complex promotions and allow us to comprehend the variety of promotions offered by marketers nowadays.

  13. Unifying Complexity and Information

    Science.gov (United States)

    Ke, Da-Guan

    2013-04-01

    Complex systems, arising in many contexts in the computer, life, social, and physical sciences, have not shared a generally-accepted complexity measure playing a fundamental role as the Shannon entropy H in statistical mechanics. Superficially-conflicting criteria of complexity measurement, i.e. complexity-randomness (C-R) relations, have given rise to a special measure intrinsically adaptable to more than one criterion. However, deep causes of the conflict and the adaptability are not much clear. Here I trace the root of each representative or adaptable measure to its particular universal data-generating or -regenerating model (UDGM or UDRM). A representative measure for deterministic dynamical systems is found as a counterpart of the H for random process, clearly redefining the boundary of different criteria. And a specific UDRM achieving the intrinsic adaptability enables a general information measure that ultimately solves all major disputes. This work encourages a single framework coving deterministic systems, statistical mechanics and real-world living organisms.

  14. Workshop on Recommendation in Complex Scenarios (ComplexRec 2017)

    DEFF Research Database (Denmark)

    Bogers, Toine; Koolen, Marijn; Mobasher, Bamshad

    2017-01-01

    Recommendation algorithms for ratings prediction and item ranking have steadily matured during the past decade. However, these state-of-the-art algorithms are typically applied in relatively straightforward scenarios. In reality, recommendation is often a more complex problem: it is usually just...... a single step in the user's more complex background need. These background needs can often place a variety of constraints on which recommendations are interesting to the user and when they are appropriate. However, relatively little research has been done on these complex recommendation scenarios....... The ComplexRec 2017 workshop addressed this by providing an interactive venue for discussing approaches to recommendation in complex scenarios that have no simple one-size-fits-all-solution....

  15. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  16. Heterolytic cleavage of ammonia N-H bond by bifunctional activation in silica-grafted single site Ta(V) imido amido surface complex. Importance of the outer sphere NH3 assistance

    KAUST Repository

    Gouré, Eric

    2011-01-01

    Ammonia N-H bond is cleaved at room temperature by the silica-supported tantalum imido amido complex [(≡SiO)2Ta(NH)(-NH2)], 2, if excess ammonia is present, but requires 150 °C to achieve the same reaction if only one equivalent NH3 is added to 2. MAS solid-state 15N NMR and in situ IR spectroscopic studies of the reaction of either 15N or 2H labeled ammonia with 2 show that initial coordination of the ammonia is followed by scrambling of either 15N or 2H among ammonia, amido and imido groups. Density functional theory (DFT) calculations with a cluster model [{(μ-O)[(H3SiO) 2SiO]2}Ta(NH)(-NH2)(NH3)], 2 q·NH3, show that the intramolecular H transfer from Ta-NH2 to TaNH is ruled out, but the H transfers from the coordinated ammonia to the amido and imido groups have accessible energy barriers. The energy barrier for the ammonia N-H activation by the Ta-amido group is energetically preferred relative to the Ta-imido group. The importance of excess NH3 for getting full isotope scrambling is rationalized by an outer sphere assistance of ammonia acting as proton transfer agent, which equalizes the energy barriers for H transfer from coordinated ammonia to the amido and imido groups. In contrast, additional coordinated ammonia does not favor significantly the H transfer. These results rationalize the experimental conditions used. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011.

  17. Analysis of protein-protein docking decoys using interaction fingerprints: application to the reconstruction of CaM-ligand complexes

    Directory of Open Access Journals (Sweden)

    Uchikoga Nobuyuki

    2010-05-01

    Full Text Available Abstract Background Protein-protein docking for proteins with large conformational changes was analyzed by using interaction fingerprints, one of the scales for measuring similarities among complex structures, utilized especially for searching near-native protein-ligand or protein-protein complex structures. Here, we have proposed a combined method for analyzing protein-protein docking by taking large conformational changes into consideration. This combined method consists of ensemble soft docking with multiple protein structures, refinement of complexes, and cluster analysis using interaction fingerprints and energy profiles. Results To test for the applicability of this combined method, various CaM-ligand complexes were reconstructed from the NMR structures of unbound CaM. For the purpose of reconstruction, we used three known CaM-ligands, namely, the CaM-binding peptides of cyclic nucleotide gateway (CNG, CaM kinase kinase (CaMKK and the plasma membrane Ca2+ ATPase pump (PMCA, and thirty-one structurally diverse CaM conformations. For each ligand, 62000 CaM-ligand complexes were generated in the docking step and the relationship between their energy profiles and structural similarities to the native complex were analyzed using interaction fingerprint and RMSD. Near-native clusters were obtained in the case of CNG and CaMKK. Conclusions The interaction fingerprint method discriminated near-native structures better than the RMSD method in cluster analysis. We showed that a combined method that includes the interaction fingerprint is very useful for protein-protein docking analysis of certain cases.

  18. Increase of Organization in Complex Systems

    OpenAIRE

    Georgiev, Georgi Yordanov; Daly, Michael; Gombos, Erin; Vinod, Amrit; Hoonjan, Gajinder

    2013-01-01

    Measures of complexity and entropy have not converged to a single quantitative description of levels of organization of complex systems. The need for such a measure is increasingly necessary in all disciplines studying complex systems. To address this problem, starting from the most fundamental principle in Physics, here a new measure for quantity of organization and rate of self-organization in complex systems based on the principle of least (stationary) action is applied to a model system -...

  19. Lanthanide single molecule magnets

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry

    2015-10-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

  20. Lanthanide single molecule magnets

    CERN Document Server

    Tang, Jinkui

    2015-01-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

  1. Going Vertical To Improve the Accuracy of Atomic Force Microscopy Based Single-Molecule Force Spectroscopy.

    Science.gov (United States)

    Walder, Robert; Van Patten, William J; Adhikari, Ayush; Perkins, Thomas T

    2018-01-23

    Single-molecule force spectroscopy (SMFS) is a powerful technique to characterize the energy landscape of individual proteins, the mechanical properties of nucleic acids, and the strength of receptor-ligand interactions. Atomic force microscopy (AFM)-based SMFS benefits from ongoing progress in improving the precision and stability of cantilevers and the AFM itself. Underappreciated is that the accuracy of such AFM studies remains hindered by inadvertently stretching molecules at an angle while measuring only the vertical component of the force and extension, degrading both measurements. This inaccuracy is particularly problematic in AFM studies using double-stranded DNA and RNA due to their large persistence length (p ≈ 50 nm), often limiting such studies to other SMFS platforms (e.g., custom-built optical and magnetic tweezers). Here, we developed an automated algorithm that aligns the AFM tip above the DNA's attachment point to a coverslip. Importantly, this algorithm was performed at low force (10-20 pN) and relatively fast (15-25 s), preserving the connection between the tip and the target molecule. Our data revealed large uncorrected lateral offsets for 100 and 650 nm DNA molecules [24 ± 18 nm (mean ± standard deviation) and 180 ± 110 nm, respectively]. Correcting this offset yielded a 3-fold improvement in accuracy and precision when characterizing DNA's overstretching transition. We also demonstrated high throughput by acquiring 88 geometrically corrected force-extension curves of a single individual 100 nm DNA molecule in ∼40 min and versatility by aligning polyprotein- and PEG-based protein-ligand assays. Importantly, our software-based algorithm was implemented on a commercial AFM, so it can be broadly adopted. More generally, this work illustrates how to enhance AFM-based SMFS by developing more sophisticated data-acquisition protocols.

  2. Herding Complex Networks

    KAUST Repository

    Ruf, Sebastian F.

    2018-04-12

    The problem of controlling complex networks is of interest to disciplines ranging from biology to swarm robotics. However, controllability can be too strict a condition, failing to capture a range of desirable behaviors. Herdability, which describes the ability to drive a system to a specific set in the state space, was recently introduced as an alternative network control notion. This paper considers the application of herdability to the study of complex networks. The herdability of a class of networked systems is investigated and two problems related to ensuring system herdability are explored. The first is the input addition problem, which investigates which nodes in a network should receive inputs to ensure that the system is herdable. The second is a related problem of selecting the best single node from which to herd the network, in the case that a single node is guaranteed to make the system is herdable. In order to select the best herding node, a novel control energy based herdability centrality measure is introduced.

  3. Thiolato-technetium complexes. 5. Synthesis, characterization, and electrochemical properties of bis(o-phenylenebis(dimethylarsine))technetium(II) and -technetium(III) complexes with thiolato ligands. Single-crystal structural analyses of trans-[Tc(SCH3)2(DIARS)2]PF6 and trans-[Tc(SC6H5)2(DIARS)2]0

    International Nuclear Information System (INIS)

    Konno, Takumi; Heineman, W.R.; Deutsch, E.; Kirchhoff, J.R.; Heeg, M.J.; Stuckey, J.A.

    1992-01-01

    Three different thiols have been brought into reaction with trans-[Tc(OH)(O)(DIARS) 2 ] 2+ to produce initially the Tc(II) complex, [Tc(SR) 2 (DIARS) 2 ] 0 , which can be oxidized to the Tc(III) complex, [Tc(SR) 2 (DIARS) 2 ] + (DIARS = o-phenylenebis(dimethylarsine)). In the case of SR = SCH 3 and SCH 2 C 6 H 5 , the Tc(II) and Tc(III) products were found to be in the trans geometry, while for SR = SC 6 H 5 , both cis and trans isomers were generated. Two of the complexes were structurally characterized by X-ray diffraction. trans-[Tc(SCH 3 ) 2 (DIARS) 2 ]PF 6 , chemical formula TcAs 4 S 2 PF 6 C 22 H 38 , crystallizes in the monoclinic space group. The Tc atom occupies an inversion center. Representative elemental analyses, FAB mass spectra, and visible-UV spectra are reported. Electrochemical and spectroelectrochemical measurements were taken on trans-[Tc(SCH 3 ) 2 (DIARS) 2 ] + , trans-[Tc(SCH 2 C 6 H 5 ) 2 (DIARS) 2 ] + , and cis-[Tc(SC 6 H 5 ) 2 (DIARS) 2 ] + , which exhibit a reversible Tc(III/II) redox couple in the range -0.32 to -0.47 V vs. Ag/AgCl. Another redox couple is present in the range -1.22 to -1.70 V; this is ascribed to Tc(II/I) and is reversible only for SR = SCH 2 C 6 H 5 at 20C. At room temperature, chemically irreversible couples are exhibited at ca. +1.0 V for Tc(IV/III)

  4. Convenient method for resolving degeneracies due to symmetry of the magnetic susceptibility tensor and its application to pseudo contact shift-based protein-protein complex structure determination

    Energy Technology Data Exchange (ETDEWEB)

    Kobashigawa, Yoshihiro; Saio, Tomohide [Hokkaido University, Department of Structural Biology, Faculty of Advanced Life Science (Japan); Ushio, Masahiro [Hokkaido University, Graduate School of Life Science (Japan); Sekiguchi, Mitsuhiro [Astellas Pharma Inc., Analysis and Pharmacokinetics Research Labs, Department of Drug Discovery (Japan); Yokochi, Masashi; Ogura, Kenji; Inagaki, Fuyuhiko, E-mail: finagaki@pharm.hokudai.ac.jp [Hokkaido University, Department of Structural Biology, Faculty of Advanced Life Science (Japan)

    2012-05-15

    Pseudo contact shifts (PCSs) induced by paramagnetic lanthanide ions fixed in a protein frame provide long-range distance and angular information, and are valuable for the structure determination of protein-protein and protein-ligand complexes. We have been developing a lanthanide-binding peptide tag (hereafter LBT) anchored at two points via a peptide bond and a disulfide bond to the target proteins. However, the magnetic susceptibility tensor displays symmetry, which can cause multiple degenerated solutions in a structure calculation based solely on PCSs. Here we show a convenient method for resolving this degeneracy by changing the spacer length between the LBT and target protein. We applied this approach to PCS-based rigid body docking between the FKBP12-rapamycin complex and the mTOR FRB domain, and demonstrated that degeneracy could be resolved using the PCS restraints obtained from two-point anchored LBT with two different spacer lengths. The present strategy will markedly increase the usefulness of two-point anchored LBT for protein complex structure determination.

  5. Chemistry and structure of technetium complexes

    International Nuclear Information System (INIS)

    Baldas, J.; Boas, J.F.; Bonnyman, J.; Williams, G.A.

    1983-01-01

    The structures of tris(2-aminobenzenethiolato) technetium(VI) and dichlorobis(diethyldithiocarbamato) thionitrosyltechnetium(V) have been determined by single crystal x-ray diffraction analysis. The preparation and chemistry of thiocyanato complexes of technetium have been investigated

  6. Fluorido complexes of technetium

    International Nuclear Information System (INIS)

    Mariappan Balasekaran, Samundeeswari

    2013-01-01

    Fluorine chemistry has received considerable interest during recent years due to its significant role in the life sciences, especially for drug development. Despite the great nuclear medicinal importance of the radioactive metal technetium in radiopharmaceuticals, its coordination chemistry with the fluorido ligand is by far less explored than that of other ligands. Up to now, only a few technetium fluorides are known. This thesis contains the synthesis, spectroscopic and structural characterization of novel technetium fluorides in the oxidation states ''+1'', ''+2'', ''+4'' and ''+6''. In the oxidation state ''+6'', the fluoridotechnetates were synthesized either from nitridotechnetic(VI) acid or from pertechnetate by using reducing agent and have been isolated as cesium or tetraethylammonium salts. The compounds were characterized spectroscopically and structurally. In the intermediate oxidation state ''+4'', hexafluoridotechnetate(IV) was known for long time and studied spectroscopically. This thesis reports novel and improved syntheses and solved the critical issues of early publications such as the color, some spectroscopic properties and the structure of this key compound. Single crystal analyses of alkali metal, ammonium and tetramethylammonium salts of hexafluoridotechnetate(IV) are presented. In aqueous alkaline solutions, the ammonium salt of hexafluoridotechnetate(IV) undergoes hydrolysis and forms an oxido-bridged dimeric complex. It is the first step hydrolysis product of hexafluoridotechnetate(IV) and was characterized by spectroscopic and crystallographic methods. Low-valent technetium fluorides with the metal in the oxidation states of ''+2'' or ''+1'' are almost unknown. A detailed description of the synthesis and characterization of pentafluoridonitrosyltechnetate(II) is presented. The complex was isolated as alkali metal salts, and spectroscopic as well as structural features of the complexes are presented. Different salts of the trans

  7. Single port Billroth I gastrectomy

    Directory of Open Access Journals (Sweden)

    Jeremy R Huddy

    2013-01-01

    Full Text Available Introduction: Experience has allowed increasingly complex procedures to be undertaken by single port surgery. We describe a technique for single port Billroth I gastrectomy with a hand-sewn intracorporeal anastomosis in the resection of a benign tumour diagnosed incidentally on a background of cholelithiasis. Materials and Methods: Single port Billroth I gastrectomy and cholecystectomy was performed using a transumbilical quadport. Flexible tipped camera and straight conventional instruments were used throughout the procedure. The stomach was mobilised including a limited lymph node dissection and resection margins in the proximal antrum and duodenum were divided with a flexible tipped laparoscopic stapler. The lesser curve was reconstructed and an intracorporal hand sewn two layer end-to-end anastomosis was performed using unidirectional barbed sutures. Intraoperative endoscopy confirmed the anastomosis to be patent without leak. Results: Enteral feed was started on the day of surgery, increasing to a full diet by day 6. Analgesic requirements were a patient-controlled analgesia morphine pump for 4 postoperative days and paracetamol for 6 days. There were no postoperative complications and the patient was discharged on the eighth day. Histology confirmed gastric submucosal lipoma. Discussion: As technology improves more complex procedures are possible by single port laparoscopic surgery. In this case, flexible tipped cameras and unidirectional barbed sutures have facilitated an intracorporal hand-sewn two layer end-to-end anastomosis. Experience will allow such techniques to become mainstream.

  8. Magnetic properties of 1 : 4 complexes of CoCl2 and pyridines carrying carbenes (S(0) = 4/2, 6/2, and 8/2) in diluted frozen solution; influence of carbene multiplicity on heterospin single-molecule magnets.

    Science.gov (United States)

    Karasawa, Satoru; Nakano, Kimihiro; Tanokashira, Jun-ichi; Yamamoto, Noriko; Yoshizaki, Takahito; Koga, Noboru

    2012-11-28

    The microcrystalline sample of a parent complex, [CoCl(2)(py)(4)], showed a single-molecule magnet (SMM) behavior with an effective activation barrier, U(eff)/k(B), of 16 K for reversal of the magnetism in the presence of a dc field of 3 kOe. Pyridine ligands having 2-4 diazo moieties, DYpy; Y = 2, 3l, 3b, and 4, were prepared and confirmed to be quintet, septet, septet, and nonet in the ground state, respectively, after irradiation. The 1 : 4 complexes, CoCl(2)(DYpy)(4); Y = 2, 3l, 3b, and 4 in frozen solutions after irradiation showed the magnetic behaviors of SMMs with total spin multiplicity, S(total) = 17/2, 25/2, 25/2, and 33/2, respectively. Hysteresis loops depending on the temperature were observed and the values of coercive force, H(c), at 1.9 K were 12, 8.4, 11, and 8.1 kOe for CoCl(2)(CYpy)(4); Y = 2, 3l, 3b, and 4, respectively. In dynamic magnetic susceptibility experiments, ac magnetic susceptibility data obeyed the Arrhenius law to give U(eff)/k(B) values of 94, 92, 93, and 87 K for CoCl(2)(CYpy)(4); Y = 2, 3l, 3b, and 4, respectively, while the relaxation times for CoCl(2)(CYpy)(4); Y = 2 and 3l, obtained by dc magnetization decay in the range of 3.5-1.9 K slightly deviated downward from Arrhenius plots on cooling. The dynamic magnetic behaviors for CoCl(2)(CYpy)(4) including [CoCl(2)(py)(4)] and CoCl(2)(C1py)(4) suggested that the generated carbenes interacted with the cobalt ion to increase the relaxation time, τ(q), due to the spin quantum tunneling magnetization, which became larger with increasing S(total) of the complex.

  9. Conformation driven complexation of two analogous benzimidazole ...

    Indian Academy of Sciences (India)

    metal-organic framework involving Ag(I) and a neutral, semirigid, tripodal ligand, 1 .... tion quality single crystals of the complex, suitable for single crystal diffraction ..... Mohanty J S, Baksi A, Leeb H and Pradeep T 2015 RSC. Adv. 5 48039. 14.

  10. Simple inorganic complexes but intricate hydrogen bonding ...

    Indian Academy of Sciences (India)

    Administrator

    We are interested in obtaining single crystals of metal-opda complexes because their crystal structures would show complex hydrogen bonding network due to the presence of. –NH2 groups in the opda ligand (hydrogen bonding donor sites) and inorganic anions having mostly oxo groups (hydrogen bonding acceptor sites) ...

  11. Strategies of complexity leadership in governance systems

    NARCIS (Netherlands)

    Nooteboom, S.G.; Termeer, C.J.A.M.

    2013-01-01

    In complex governance systems, innovations may emerge, not controlled by a single leader, but enabled by many. We discuss how these leaders are embedded in networks and which strategies they use. The theoretical framework is based on Complexity Leadership Theory. We conducted participatory

  12. Molecular Dynamics Simulations and Kinetic Measurements to Estimate and Predict Protein-Ligand Residence Times.

    Science.gov (United States)

    Mollica, Luca; Theret, Isabelle; Antoine, Mathias; Perron-Sierra, Françoise; Charton, Yves; Fourquez, Jean-Marie; Wierzbicki, Michel; Boutin, Jean A; Ferry, Gilles; Decherchi, Sergio; Bottegoni, Giovanni; Ducrot, Pierre; Cavalli, Andrea

    2016-08-11

    Ligand-target residence time is emerging as a key drug discovery parameter because it can reliably predict drug efficacy in vivo. Experimental approaches to binding and unbinding kinetics are nowadays available, but we still lack reliable computational tools for predicting kinetics and residence time. Most attempts have been based on brute-force molecular dynamics (MD) simulations, which are CPU-demanding and not yet particularly accurate. We recently reported a new scaled-MD-based protocol, which showed potential for residence time prediction in drug discovery. Here, we further challenged our procedure's predictive ability by applying our methodology to a series of glucokinase activators that could be useful for treating type 2 diabetes mellitus. We combined scaled MD with experimental kinetics measurements and X-ray crystallography, promptly checking the protocol's reliability by directly comparing computational predictions and experimental measures. The good agreement highlights the potential of our scaled-MD-based approach as an innovative method for computationally estimating and predicting drug residence times.

  13. Structural insights, protein-ligand interactions and spectroscopic characterization of isoformononetin

    Science.gov (United States)

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

    2017-04-01

    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.

  14. Calculation of absolute protein-ligand binding free energy using distributed replica sampling.

    Science.gov (United States)

    Rodinger, Tomas; Howell, P Lynne; Pomès, Régis

    2008-10-21

    Distributed replica sampling [T. Rodinger et al., J. Chem. Theory Comput. 2, 725 (2006)] is a simple and general scheme for Boltzmann sampling of conformational space by computer simulation in which multiple replicas of the system undergo a random walk in reaction coordinate or temperature space. Individual replicas are linked through a generalized Hamiltonian containing an extra potential energy term or bias which depends on the distribution of all replicas, thus enforcing the desired sampling distribution along the coordinate or parameter of interest regardless of free energy barriers. In contrast to replica exchange methods, efficient implementation of the algorithm does not require synchronicity of the individual simulations. The algorithm is inherently suited for large-scale simulations using shared or heterogeneous computing platforms such as a distributed network. In this work, we build on our original algorithm by introducing Boltzmann-weighted jumping, which allows moves of a larger magnitude and thus enhances sampling efficiency along the reaction coordinate. The approach is demonstrated using a realistic and biologically relevant application; we calculate the standard binding free energy of benzene to the L99A mutant of T4 lysozyme. Distributed replica sampling is used in conjunction with thermodynamic integration to compute the potential of mean force for extracting the ligand from protein and solvent along a nonphysical spatial coordinate. Dynamic treatment of the reaction coordinate leads to faster statistical convergence of the potential of mean force than a conventional static coordinate, which suffers from slow transitions on a rugged potential energy surface.

  15. G-LoSA for Prediction of Protein-Ligand Binding Sites and Structures.

    Science.gov (United States)

    Lee, Hui Sun; Im, Wonpil

    2017-01-01

    Recent advances in high-throughput structure determination and computational protein structure prediction have significantly enriched the universe of protein structure. However, there is still a large gap between the number of available protein structures and that of proteins with annotated function in high accuracy. Computational structure-based protein function prediction has emerged to reduce this knowledge gap. The identification of a ligand binding site and its structure is critical to the determination of a protein's molecular function. We present a computational methodology for predicting small molecule ligand binding site and ligand structure using G-LoSA, our protein local structure alignment and similarity measurement tool. All the computational procedures described here can be easily implemented using G-LoSA Toolkit, a package of standalone software programs and preprocessed PDB structure libraries. G-LoSA and G-LoSA Toolkit are freely available to academic users at http://compbio.lehigh.edu/GLoSA . We also illustrate a case study to show the potential of our template-based approach harnessing G-LoSA for protein function prediction.

  16. IChem: A Versatile Toolkit for Detecting, Comparing, and Predicting Protein-Ligand Interactions.

    Science.gov (United States)

    Da Silva, Franck; Desaphy, Jeremy; Rognan, Didier

    2018-03-20

    Structure-based ligand design requires an exact description of the topology of molecular entities under scrutiny. IChem is a software package that reflects the many contributions of our research group in this area over the last decade. It facilitates and automates many tasks (e.g., ligand/cofactor atom typing, identification of key water molecules) usually left to the modeler's choice. It therefore permits the detection of molecular interactions between two molecules in a very precise and flexible manner. Moreover, IChem enables the conversion of intricate three-dimensional (3D) molecular objects into simple representations (fingerprints, graphs) that facilitate knowledge acquisition at very high throughput. The toolkit is an ideal companion for setting up and performing many structure-based design computations. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  17. A chemical library to screen protein and protein-ligand crystallization using a versatile microfluidic platform

    OpenAIRE

    Gerard , Charline ,; Ferry , Gilles; Vuillard , Laurent ,; Boutin , Jean ,; Ferte , Nathalie ,; Grossier , Romain ,; Candoni , Nadine ,; Veesler , Stéphane ,

    2018-01-01

    Here, we describe a plug-and-play microfluidic platform, suitable for protein crystallization. The droplet factory is designed to generate hundreds of droplets as small as a few nanoliters (2 to 10nL) for screening and optimization of crystallization conditions. Commercially-available microfluidic junctions and tubing are combined to create the appropriate geometry. In addition, a " chemical library " is produced in tubing. The microfluidic geometry for a " crystallization agent-based chemica...

  18. Preclinical Testing of a Translocator Protein Ligand for the Treatment of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2017-03-01

    investigated the neuroprotective effect and therapeutic value of a drug : the translocator protein (TSPO) ligand PK11195 (PK), which we found to be...Translocator protein (TSPO) ligand Neuroprotective drugs In vitro models of neurodegeneration Axon preservation Neuromuscular junctions 5 3...pharmacokinetic data of the JNK study were showing that daily gavage (30 mg/kg/day) allowed an efficient delivery of the drugs in the brain and the spinal

  19. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  20. Discovering rules for protein-ligand specificity using support vector inductive logic programming.

    Science.gov (United States)

    Kelley, Lawrence A; Shrimpton, Paul J; Muggleton, Stephen H; Sternberg, Michael J E

    2009-09-01

    Structural genomics initiatives are rapidly generating vast numbers of protein structures. Comparative modelling is also capable of producing accurate structural models for many protein sequences. However, for many of the known structures, functions are not yet determined, and in many modelling tasks, an accurate structural model does not necessarily tell us about function. Thus, there is a pressing need for high-throughput methods for determining function from structure. The spatial arrangement of key amino acids in a folded protein, on the surface or buried in clefts, is often the determinants of its biological function. A central aim of molecular biology is to understand the relationship between such substructures or surfaces and biological function, leading both to function prediction and to function design. We present a new general method for discovering the features of binding pockets that confer specificity for particular ligands. Using a recently developed machine-learning technique which couples the rule-discovery approach of inductive logic programming with the statistical learning power of support vector machines, we are able to discriminate, with high precision (90%) and recall (86%) between pockets that bind FAD and those that bind NAD on a large benchmark set given only the geometry and composition of the backbone of the binding pocket without the use of docking. In addition, we learn rules governing this specificity which can feed into protein functional design protocols. An analysis of the rules found suggests that key features of the binding pocket may be tied to conformational freedom in the ligand. The representation is sufficiently general to be applicable to any discriminatory binding problem. All programs and data sets are freely available to non-commercial users at http://www.sbg.bio.ic.ac.uk/svilp_ligand/.

  1. Drosophila olfactory memory: single genes to complex neural circuits.

    Science.gov (United States)

    Keene, Alex C; Waddell, Scott

    2007-05-01

    A central goal of neuroscience is to understand how neural circuits encode memory and guide behaviour. Studying simple, genetically tractable organisms, such as Drosophila melanogaster, can illuminate principles of neural circuit organization and function. Early genetic dissection of D. melanogaster olfactory memory focused on individual genes and molecules. These molecular tags subsequently revealed key neural circuits for memory. Recent advances in genetic technology have allowed us to manipulate and observe activity in these circuits, and even individual neurons, in live animals. The studies have transformed D. melanogaster from a useful organism for gene discovery to an ideal model to understand neural circuit function in memory.

  2. Characteristic Ligand-Induced Crystal Forms of HIV-1 Protease Complexes: A Novel Discovery of X-Ray Crystallography

    International Nuclear Information System (INIS)

    Olajuyigbe, Folasade M.; Geremia, Silvano

    2009-10-01

    Mixtures of saquinavir (SQV) and ritonavir (RTV) were cocrystallized with HIV-1 protease (PR) in an attempt to compare their relative potencies using a crystallographic approach and factors responsible for the respective crystal forms obtained were examined. The mixture ratio of the SQV/RTV was in the range of 1:1 to 1:50 with increasing concentration of dimethyl sulphoxide (DMSO) used. Two crystal forms of PR complexes were obtained. At concentrations of 0.8 and 1.2 % DMSO using 1:1 and 1:15 ratios of SQV/RTV, the crystal form was monoclinic while increasing the concentration of DMSO to 3.2 and 5.0% using 1:15 and 1:50 ratios of SQV/RTV, the orthorhombic crystal form was obtained. The high resolution X-ray crystal structures of the PR/ inhibitor complexes reveal that crystal forms with respective space groups are dependent on the occupancy of either SQV or RTV in the active site of the PR. The occupancy of either of the PR inhibitors in the active site of PR has interestingly demonstrated unique cooperativity effects in crystallization of protein-ligand complexes. The crystal forms obtained were also related to the concentration of DMSO and ammonium sulphate in crystallization, and storage conditions of purified PR. Surprisingly, the relative occupancies of these inhibitors in the active site suggested a competition between the two inhibitors which were not inhibition constants related. Analysis of the structures in both crystal forms show no difference in DMSO content but at higher concentration of DMSO (3.2 - 5.0%) in the orthorhombic crystal forms, there were protein-sulphate interactions which were absent in the monoclinic forms with lower concentration (0.8 - 1.2%) of DMSO. This work has clearly demonstrated that there is cooperativity in crystallization and the conditions of crystallization influence specific intermolecular contacts in crystal packing (crystal form). (author)

  3. The DFT calculations of structures and EPR parameters for the dinuclear paddle-wheel copper(II) complex {Cu_2(μ_2-O_2CCH_3)_4}(OCNH{sub 2}CH{sub 3}) as powder or single crystal

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Chang-Chun; Wu, Shao-Yi; Xu, Yong-Qiang; Zhang, Li-Juan; Zhang, Zhi-Hong; Zhu, Qin-Sheng; Wu, Ming-He; Teng, Bao-Hua [Univ. of Electronic Science and Technology of China, Chengdu (China). School of Physical Electronics

    2017-07-01

    Density functional theory (DFT) calculations of the structures and the Cu{sup 2+} g factors (g{sub x}, g{sub y} and g{sub z}) and hyperfine coupling tensor A (A{sub x}, A{sub y} and A{sub z}) were performed for the paddle-wheel (PW)-type binuclear copper(II) complex {Cu_2(μ_2-O_2CCH_3)_4}(OCNH{sub 2}CH{sub 3}) powder and single crystal. Calculations were carried out with the ORCA software using the functionals BHandHlyp, B3P86 and B3LYP with five different basis sets: 6-311g, 6-311g(d,p), VTZ, def-2 and def2-TZVP. Results were tested by the MPAD analysis to find the most suitable functional and basis sets. The electronic structure and covalency between copper and oxygen were investigated by the electron localisation function and the localised orbital locator as well as the Mayer bond order for the [CuO{sub 5}] group. The optical spectra were theoretically calculated by the time-dependent DFT module and plotted by the Multiwfn program for the [CuO{sub 5}] group and reasonably associated with the local structure in the vicinity of the central ion copper. In addition, the interactions between the OCNH{sub 2}CH{sub 3}, NH{sub 3} and H{sub 2}O molecules and the uncoordinated PW copper(II) complex were studied, and the corresponding adsorption energies, the frequency shifts with respect to the free molecules and the changes of the Cu-Cu distances were calculated and compared with the relevant systems.

  4. A multistep single-crystal-to-single-crystal bromodiacetylene dimerization

    Science.gov (United States)

    Hoheisel, Tobias N.; Schrettl, Stephen; Marty, Roman; Todorova, Tanya K.; Corminboeuf, Clémence; Sienkiewicz, Andrzej; Scopelliti, Rosario; Schweizer, W. Bernd; Frauenrath, Holger

    2013-04-01

    Packing constraints and precise placement of functional groups are the reason that organic molecules in the crystalline state often display unusual physical or chemical properties not observed in solution. Here we report a single-crystal-to-single-crystal dimerization of a bromodiacetylene that involves unusually large atom displacements as well as the cleavage and formation of several bonds. Density functional theory computations support a mechanism in which the dimerization is initiated by a [2 + 1] photocycloaddition favoured by the nature of carbon-carbon short contacts in the crystal structure. The reaction proceeded up to the theoretical degree of conversion without loss of crystallinity, and it was also performed on a preparative scale with good yield. Moreover, it represents the first synthetic pathway to (E)-1,2-dibromo-1,2-diethynylethenes, which could serve as synthetic intermediates for the preparation of molecular carbon scaffolds. Our findings both extend the scope of single-crystal-to-single-crystal reactions and highlight their potential as a synthetic tool for complex transformations.

  5. Association theories for complex thermodynamics

    DEFF Research Database (Denmark)

    Kontogeorgis, Georgios; Rafiqul Gani

    2013-01-01

    of this review is two-fold: first to illustrate some of the significant capabilities of these association theories and why indeed they have already been extensively used and are expected to find even more applications in the future. The second and most important aspect of this review is to outline many...... applications. While specialized models can handle different cases, even complex ones, with the advent of powerful theories and computers there is the hope that a single or a few models could be suitable for a general modeling of complex thermodynamics. After more than 100 years with active use of thermodynamic...... models, we have now come to the understanding that simple one-fluid theories like the cubic equations of state or the various forms of local composition models will never be able to model a wide range of complex systems with sufficient accuracy. While various modern approaches have appeared, one very...

  6. Fluorido complexes of technetium

    Energy Technology Data Exchange (ETDEWEB)

    Mariappan Balasekaran, Samundeeswari

    2013-07-04

    Fluorine chemistry has received considerable interest during recent years due to its significant role in the life sciences, especially for drug development. Despite the great nuclear medicinal importance of the radioactive metal technetium in radiopharmaceuticals, its coordination chemistry with the fluorido ligand is by far less explored than that of other ligands. Up to now, only a few technetium fluorides are known. This thesis contains the synthesis, spectroscopic and structural characterization of novel technetium fluorides in the oxidation states ''+1'', ''+2'', ''+4'' and ''+6''. In the oxidation state ''+6'', the fluoridotechnetates were synthesized either from nitridotechnetic(VI) acid or from pertechnetate by using reducing agent and have been isolated as cesium or tetraethylammonium salts. The compounds were characterized spectroscopically and structurally. In the intermediate oxidation state ''+4'', hexafluoridotechnetate(IV) was known for long time and studied spectroscopically. This thesis reports novel and improved syntheses and solved the critical issues of early publications such as the color, some spectroscopic properties and the structure of this key compound. Single crystal analyses of alkali metal, ammonium and tetramethylammonium salts of hexafluoridotechnetate(IV) are presented. In aqueous alkaline solutions, the ammonium salt of hexafluoridotechnetate(IV) undergoes hydrolysis and forms an oxido-bridged dimeric complex. It is the first step hydrolysis product of hexafluoridotechnetate(IV) and was characterized by spectroscopic and crystallographic methods. Low-valent technetium fluorides with the metal in the oxidation states of ''+2'' or ''+1'' are almost unknown. A detailed description of the synthesis and characterization of pentafluoridonitrosyltechnetate(II) is presented. The

  7. Measurement methods on the complexity of network

    Institute of Scientific and Technical Information of China (English)

    LIN Lin; DING Gang; CHEN Guo-song

    2010-01-01

    Based on the size of network and the number of paths in the network,we proposed a model of topology complexity of a network to measure the topology complexity of the network.Based on the analyses of the effects of the number of the equipment,the types of equipment and the processing time of the node on the complexity of the network with the equipment-constrained,a complexity model of equipment-constrained network was constructed to measure the integrated complexity of the equipment-constrained network.The algorithms for the two models were also developed.An automatic generator of the random single label network was developed to test the models.The results show that the models can correctly evaluate the topology complexity and the integrated complexity of the networks.

  8. Single Audit: Single Audit Act Effectiveness Issues

    National Research Council Canada - National Science Library

    Thompson, Sally

    2002-01-01

    As discussed in the report we are releasing today, our work to review agency actions to ensure that recipients take timely and appropriate corrective actions to fix audit findings contained in single...

  9. Complex Dynamic Development of Poliovirus Membranous Replication Complexes

    Science.gov (United States)

    Nair, Vinod; Hansen, Bryan T.; Hoyt, Forrest H.; Fischer, Elizabeth R.; Ehrenfeld, Ellie

    2012-01-01

    Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as “vesicles” are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from cis-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single-membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive-strand RNA viruses. PMID:22072780

  10. Three perspectives on complexity: entropy, compression, subsymmetry

    Science.gov (United States)

    Nagaraj, Nithin; Balasubramanian, Karthi

    2017-12-01

    There is no single universally accepted definition of `Complexity'. There are several perspectives on complexity and what constitutes complex behaviour or complex systems, as opposed to regular, predictable behaviour and simple systems. In this paper, we explore the following perspectives on complexity: effort-to-describe (Shannon entropy H, Lempel-Ziv complexity LZ), effort-to-compress (ETC complexity) and degree-of-order (Subsymmetry or SubSym). While Shannon entropy and LZ are very popular and widely used, ETC is relatively a new complexity measure. In this paper, we also propose a novel normalized complexity measure SubSym based on the existing idea of counting the number of subsymmetries or palindromes within a sequence. We compare the performance of these complexity measures on the following tasks: (A) characterizing complexity of short binary sequences of lengths 4 to 16, (B) distinguishing periodic and chaotic time series from 1D logistic map and 2D Hénon map, (C) analyzing the complexity of stochastic time series generated from 2-state Markov chains, and (D) distinguishing between tonic and irregular spiking patterns generated from the `Adaptive exponential integrate-and-fire' neuron model. Our study reveals that each perspective has its own advantages and uniqueness while also having an overlap with each other.

  11. Complex analysis and geometry

    CERN Document Server

    Silva, Alessandro

    1993-01-01

    The papers in this wide-ranging collection report on the results of investigations from a number of linked disciplines, including complex algebraic geometry, complex analytic geometry of manifolds and spaces, and complex differential geometry.

  12. Complex Systems: An Introduction

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 9. Complex Systems: An Introduction - Anthropic Principle, Terrestrial Complexity, Complex Materials. V K Wadhawan. General Article Volume 14 Issue 9 September 2009 pp 894-906 ...

  13. Single-Sex Classrooms

    Science.gov (United States)

    Protheroe, Nancy

    2009-01-01

    Although single-sex education was once the norm in the U.S., the practice has largely been confined to private schools for more than a century. However, with the introduction of the final version of the U.S. Department of Education's so-called single-sex regulations in 2006, public schools were allowed greater flexibility to offer single-sex…

  14. Superconducting Single Photon Detectors

    NARCIS (Netherlands)

    Dorenbos, S.N.

    2011-01-01

    This thesis is about the development of a detector for single photons, particles of light. New techniques are being developed that require high performance single photon detection, such as quantum cryptography, single molecule detection, optical radar, ballistic imaging, circuit testing and

  15. Single frequency intracavity SRO

    DEFF Research Database (Denmark)

    Abitan, Haim; Buchhave, Preben

    2000-01-01

    Summary form only given. A single resonance optical parametric oscillator (SRO) is inserted intracavity to a CW high power, single frequency, and ring Nd:YVO4 laser. We obtain a stable single frequency CW SRO with output at 1.7-1.9 μm (idler) and a resonating signal at 2.3-2.6 μm. The behavior...

  16. Single-cell technologies in environmental omics

    KAUST Repository

    Kodzius, Rimantas; Gojobori, Takashi

    2015-01-01

    Environmental studies are primarily done by culturing isolated microorganisms or by amplifying and sequencing conserved genes. Difficulties understanding the complexity of large numbers of various microorganisms in an environment led to the development of techniques to enrich specific microorganisms for upstream analysis, ultimately leading to single-cell isolation and analyses. We discuss the significance of single-cell technologies in omics studies with focus on metagenomics and metatranscriptomics. We propose that by reducing sample heterogeneity using single-cell genomics, metaomic studies can be simplified.

  17. Single-cell technologies in environmental omics

    KAUST Repository

    Kodzius, Rimantas

    2015-10-22

    Environmental studies are primarily done by culturing isolated microorganisms or by amplifying and sequencing conserved genes. Difficulties understanding the complexity of large numbers of various microorganisms in an environment led to the development of techniques to enrich specific microorganisms for upstream analysis, ultimately leading to single-cell isolation and analyses. We discuss the significance of single-cell technologies in omics studies with focus on metagenomics and metatranscriptomics. We propose that by reducing sample heterogeneity using single-cell genomics, metaomic studies can be simplified.

  18. Single atom oscillations

    International Nuclear Information System (INIS)

    Wiorkowski, P.; Walther, H.

    1990-01-01

    Modern methods of laser spectroscopy allow the study of single atoms or ions in an unperturbed environment. This has opened up interesting new experiments, among them the detailed study of radiation-atom coupling. In this paper, the following two experiments dealing with this problem are reviewed: the single-atom maser and the study of the resonance fluorescence of a single stored ion. The simplest and most fundamental system for studying radiation-matter coupling is a single two-level atom interacting with a single mode of an electromagnetic field in a cavity. This problem received a great deal of attention shortly after the maser was invented

  19. Extracting Models in Single Molecule Experiments

    Science.gov (United States)

    Presse, Steve

    2013-03-01

    Single molecule experiments can now monitor the journey of a protein from its assembly near a ribosome to its proteolytic demise. Ideally all single molecule data should be self-explanatory. However data originating from single molecule experiments is particularly challenging to interpret on account of fluctuations and noise at such small scales. Realistically, basic understanding comes from models carefully extracted from the noisy data. Statistical mechanics, and maximum entropy in particular, provide a powerful framework for accomplishing this task in a principled fashion. Here I will discuss our work in extracting conformational memory from single molecule force spectroscopy experiments on large biomolecules. One clear advantage of this method is that we let the data tend towards the correct model, we do not fit the data. I will show that the dynamical model of the single molecule dynamics which emerges from this analysis is often more textured and complex than could otherwise come from fitting the data to a pre-conceived model.

  20. Single port VATS: recent developments in Asia.

    Science.gov (United States)

    Yu, Peter S Y; Capili, Freddie; Ng, Calvin S H

    2016-03-01

    Single port video-assisted thoracic surgery (VATS) is the most recent evolution in minimally invasive thoracic surgery. With increasing global popularity, the single port VATS approach has been adopted by experienced thoracic surgeons in many Asian countries. From initial experience of single port VATS lobectomy to the more complex sleeve resection procedures now forming part of daily practice in some Asia institutes, the region has been the proving ground for single port VATS approaches' feasibility and safety. In addition, certain technical refinements in single port VATS lung resection and lymph node dissection have also sprung from Asia. Novel equipment designed to facilitate single port VATS allowing further reduce access trauma are being realized by the partnership between surgeons and the industries. Advanced thoracoscopes and staplers that are narrower and more maneuverable are particularly important in the smaller habitus of patients from Asia. These and similar new generation equipment are being applied to single port VATS in novel ways. As dedicated thoracic surgeons in the region continue to striving for excellence, innovative ideas in single incision access including subxiphoid and embryonic natural-orifice transluminal endoscopic surgery (e-NOTES) have been explored. Adjunct techniques and technology used in association with single port VATS such as non-intubated surgery, hybrid operating room image guidance and electromagnetic navigational bronchoscopy are all in rapid development in Asia.

  1. Instruction sequences and non-uniform complexity theory

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2008-01-01

    We develop theory concerning non-uniform complexity in a setting in which the notion of single-pass instruction sequence considered in program algebra is the central notion. We define counterparts of the complexity classes P/poly and NP/poly and formulate a counterpart of the complexity theoretic

  2. Structure of Complex Verb Forms in Meiteilon

    Directory of Open Access Journals (Sweden)

    Lourembam Surjit Singh

    2016-12-01

    Full Text Available This piece of work proposes to descriptively investigate the structures of complex verbs in Meiteilon. The categorization of such verbs is based on the nature of semantic and syntactic functions of a lexeme or verbal lexeme. A lexeme or verbal lexeme in Meiteilon may have multifunctional properties in the nature of occurrence. Such lexical items can be co-occurred together in a phrase as single functional word. Specifically, in the co-occurrences of two lexical items, the first component of lexical items has different semantic and syntactic functions in comparison to semantic and syntactic functions of the second component of lexical items. Such co-occurrences of two lexical items are the forms of complex verb that are covered with the term complex predicate in this work. The investigation in constructing complex predicate is thoroughly presenting in this work. Keywords: Structures, complex verb, conjunct verb, compound verb, complex predicate

  3. Encyclopedia of Complexity and Systems Science

    CERN Document Server

    Meyers, Robert A

    2009-01-01

    Encyclopedia of Complexity and Systems Science provides an authoritative single source for understanding and applying the concepts of complexity theory together with the tools and measures for analyzing complex systems in all fields of science and engineering. The science and tools of complexity and systems science include theories of self-organization, complex systems, synergetics, dynamical systems, turbulence, catastrophes, instabilities, nonlinearity, stochastic processes, chaos, neural networks, cellular automata, adaptive systems, and genetic algorithms. Examples of near-term problems and major unknowns that can be approached through complexity and systems science include: The structure, history and future of the universe; the biological basis of consciousness; the integration of genomics, proteomics and bioinformatics as systems biology; human longevity limits; the limits of computing; sustainability of life on earth; predictability, dynamics and extent of earthquakes, hurricanes, tsunamis, and other n...

  4. Nano-soldering to single atomic layer

    Science.gov (United States)

    Girit, Caglar O [Berkeley, CA; Zettl, Alexander K [Kensington, CA

    2011-10-11

    A simple technique to solder submicron sized, ohmic contacts to nanostructures has been disclosed. The technique has several advantages over standard electron beam lithography methods, which are complex, costly, and can contaminate samples. To demonstrate the soldering technique graphene, a single atomic layer of carbon, has been contacted, and low- and high-field electronic transport properties have been measured.

  5. Mixed biexcitons in single quantum wells

    DEFF Research Database (Denmark)

    Wagner, Hans Peter; Langbein, Wolfgang Werner; Hvam, Jørn Märcher

    1999-01-01

    Biexcitonic complexes in a ZnSe single quantum well are investigated by spectrally resolved four-wave mixing (FWM). The formation of heavy-heavy-hole XXh and of mixed heavy-light-hole XXm biexcitons showing binding energies of Delta(h) = 4.8 meV and Delta(m)= 2.8 meV is identified by polarization...

  6. Robotic-assisted single-port donor nephrectomy using the da Vinci single-site platform.

    Science.gov (United States)

    LaMattina, John C; Alvarez-Casas, Josue; Lu, Irene; Powell, Jessica M; Sultan, Samuel; Phelan, Michael W; Barth, Rolf N

    2018-02-01

    Although single-port donor nephrectomy offers improved cosmetic outcomes, technical challenges have limited its application to selected centers. Our center has performed over 400 single-port donor nephrectomies. The da Vinci single-site robotic platform was utilized in an effort to overcome the steric, visualization, ergonomic, and other technical limitations associated with the single-port approach. Food and Drug Administration device exemption was obtained. Selection criteria for kidney donation included body mass index da Vinci single-site platform. Our experience supported the safety of this approach but found that the technology added cost and complexity without tangible benefit. Development of articulating instruments, energy, and stapling devices will be necessary for increased application of robotic single-site surgery for donor nephrectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Single-Phase PLLs

    DEFF Research Database (Denmark)

    Golestan, Saeed; Guerrero, Josep M.; Quintero, Juan Carlos Vasquez

    2017-01-01

    Single-phase phase-locked loops (PLLs) are popular for the synchronization and control of single-phase gridconnected converters. They are also widely used for monitoring and diagnostic purposes in the power and energy areas. In recent years, a large number of single-phase PLLs with different stru......-PLLs). The members of each category are then described and their pros and cons are discussed. This work provides a deep insight into characteristics of different single-phase PLLs and, therefore, can be considered as a reference for researchers and engineers....

  8. Single ventricle cardiac defect

    International Nuclear Information System (INIS)

    Eren, B.; Turkmen, N.; Fedakar, R.; Cetin, V.

    2010-01-01

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  9. Single photon emission tomography

    International Nuclear Information System (INIS)

    Buvat, Irene

    2011-09-01

    The objective of this lecture is to present the single photon emission computed tomography (SPECT) imaging technique. Content: 1 - Introduction: anatomic, functional and molecular imaging; Principle and role of functional or molecular imaging; 2 - Radiotracers: chemical and physical constraints, main emitters, radioisotopes production, emitters type and imaging techniques; 3 - Single photon emission computed tomography: gamma cameras and their components, gamma camera specifications, planar single photon imaging characteristics, gamma camera and tomography; 4 - Quantification in single photon emission tomography: attenuation, scattering, un-stationary spatial resolution, partial volume effect, movements, others; 5 - Synthesis and conclusion

  10. Complex differential geometry

    CERN Document Server

    Zheng, Fangyang

    2002-01-01

    The theory of complex manifolds overlaps with several branches of mathematics, including differential geometry, algebraic geometry, several complex variables, global analysis, topology, algebraic number theory, and mathematical physics. Complex manifolds provide a rich class of geometric objects, for example the (common) zero locus of any generic set of complex polynomials is always a complex manifold. Yet complex manifolds behave differently than generic smooth manifolds; they are more coherent and fragile. The rich yet restrictive character of complex manifolds makes them a special and interesting object of study. This book is a self-contained graduate textbook that discusses the differential geometric aspects of complex manifolds. The first part contains standard materials from general topology, differentiable manifolds, and basic Riemannian geometry. The second part discusses complex manifolds and analytic varieties, sheaves and holomorphic vector bundles, and gives a brief account of the surface classifi...

  11. Superspace de Rham complex and relative cohomology

    Energy Technology Data Exchange (ETDEWEB)

    III, William D. Linch; Randall, Stephen [Center for String and Particle Theory,Department of Physics, University of Maryland at College Park,College Park, MD 20742-4111 (United States)

    2015-09-28

    We investigate the super-de Rham complex of five-dimensional superforms with N=1 supersymmetry. By introducing a free supercommutative algebra of auxiliary variables, we show that this complex is equivalent to the Chevalley-Eilenberg complex of the translation supergroup with values in superfields. Each cocycle of this complex is defined by a Lorentz- and iso-spin-irreducible superfield subject to a set of constraints. Restricting to constant coefficients results in a subcomplex in which components of the cocycles are coboundaries while the constraints on the defining superfields span the cohomology. This reduces the computation of all of the superspace Bianchi identities to a single linear algebra problem the solution of which implies new features not present in the standard four-dimensional, N=1 complex. These include splitting/joining in the complex and the existence of cocycles that do not correspond to irreducible supermultiplets of closed differential forms. Interpreting the five-dimensional de Rham complex as arising from dimensional reduction from the six-dimensional complex, we find a second five-dimensional complex associated to the relative de Rham complex of the embedding of the latter in the former. This gives rise to a second source of closed differential forms previously attributed to the phenomenon called “Weyl triviality”.

  12. Sensing single electrons with single molecules

    International Nuclear Information System (INIS)

    Plakhotnik, Taras

    2007-01-01

    We propose a new methodology for probing transport of just one electron, a process of great importance both in nature and in artificial devices. Our idea for locating a single electron is analogues to the conventional GPS where signals from several satellites are used to locate a macro object. Using fluorescent molecules as tiny sensors, it is possible to determine 3D displacement vector of an electron

  13. Complex and symplectic geometry

    CERN Document Server

    Medori, Costantino; Tomassini, Adriano

    2017-01-01

    This book arises from the INdAM Meeting "Complex and Symplectic Geometry", which was held in Cortona in June 2016. Several leading specialists, including young researchers, in the field of complex and symplectic geometry, present the state of the art of their research on topics such as the cohomology of complex manifolds; analytic techniques in Kähler and non-Kähler geometry; almost-complex and symplectic structures; special structures on complex manifolds; and deformations of complex objects. The work is intended for researchers in these areas.

  14. Single-Molecule Interfacial Electron Transfer

    Energy Technology Data Exchange (ETDEWEB)

    Lu, H. Peter [Bowling Green State Univ., Bowling Green, OH (United States). Dept. of Chemistry and Center for Photochemical Sciences

    2017-11-28

    This project is focused on the use of single-molecule high spatial and temporal resolved techniques to study molecular dynamics in condensed phase and at interfaces, especially, the complex reaction dynamics associated with electron and energy transfer rate processes. The complexity and inhomogeneity of the interfacial ET dynamics often present a major challenge for a molecular level comprehension of the intrinsically complex systems, which calls for both higher spatial and temporal resolutions at ultimate single-molecule and single-particle sensitivities. Combined single-molecule spectroscopy and electrochemical atomic force microscopy approaches are unique for heterogeneous and complex interfacial electron transfer systems because the static and dynamic inhomogeneities can be identified and characterized by studying one molecule at a specific nanoscale surface site at a time. The goal of our project is to integrate and apply these spectroscopic imaging and topographic scanning techniques to measure the energy flow and electron flow between molecules and substrate surfaces as a function of surface site geometry and molecular structure. We have been primarily focusing on studying interfacial electron transfer under ambient condition and electrolyte solution involving both single crystal and colloidal TiO2 and related substrates. The resulting molecular level understanding of the fundamental interfacial electron transfer processes will be important for developing efficient light harvesting systems and broadly applicable to problems in fundamental chemistry and physics. We have made significant advancement on deciphering the underlying mechanism of the complex and inhomogeneous interfacial electron transfer dynamics in dyesensitized TiO2 nanoparticle systems that strongly involves with and regulated by molecule-surface interactions. We have studied interfacial electron transfer on TiO2 nanoparticle surfaces by using ultrafast single

  15. Single-sided NMR

    CERN Document Server

    Casanova, Federico; Blümich, Bernhard

    2011-01-01

    Single-Sided NMR describes the design of the first functioning single-sided tomograph, the related measurement methods, and a number of applications. One of the key advantages to this method is the speed at which the images are obtained.

  16. Understanding Single Adulthood.

    Science.gov (United States)

    Stein, Peter J.

    The life styles and life chances of the unmarried include elements of choices. Singles may be grouped and characterized according to whether their status may be considered stable or temporary. A life cycle, or continuum model of singlehood is reviewed, including its different factors, or phases. A new model for singles is proposed--a life spiral…

  17. Single gaze gestures

    DEFF Research Database (Denmark)

    Møllenbach, Emilie; Lilholm, Martin; Gail, Alastair

    2010-01-01

    This paper examines gaze gestures and their applicability as a generic selection method for gaze-only controlled interfaces. The method explored here is the Single Gaze Gesture (SGG), i.e. gestures consisting of a single point-to-point eye movement. Horizontal and vertical, long and short SGGs were...

  18. Single molecules and nanotechnology

    CERN Document Server

    Vogel, Horst

    2007-01-01

    This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

  19. Single-photon imaging

    CERN Document Server

    Seitz, Peter

    2011-01-01

    The acquisition and interpretation of images is a central capability in almost all scientific and technological domains. In particular, the acquisition of electromagnetic radiation, in the form of visible light, UV, infrared, X-ray, etc. is of enormous practical importance. The ultimate sensitivity in electronic imaging is the detection of individual photons. With this book, the first comprehensive review of all aspects of single-photon electronic imaging has been created. Topics include theoretical basics, semiconductor fabrication, single-photon detection principles, imager design and applications of different spectral domains. Today, the solid-state fabrication capabilities for several types of image sensors has advanced to a point, where uncoooled single-photon electronic imaging will soon become a consumer product. This book is giving a specialist´s view from different domains to the forthcoming “single-photon imaging” revolution. The various aspects of single-photon imaging are treated by internati...

  20. Single Nanoparticle Plasmonic Sensors

    Directory of Open Access Journals (Sweden)

    Manish Sriram

    2015-10-01

    Full Text Available The adoption of plasmonic nanomaterials in optical sensors, coupled with the advances in detection techniques, has opened the way for biosensing with single plasmonic particles. Single nanoparticle sensors offer the potential to analyse biochemical interactions at a single-molecule level, thereby allowing us to capture even more information than ensemble measurements. We introduce the concepts behind single nanoparticle sensing and how the localised surface plasmon resonances of these nanoparticles are dependent upon their materials, shape and size. Then we outline the different synthetic approaches, like citrate reduction, seed-mediated and seedless growth, that enable the synthesis of gold and silver nanospheres, nanorods, nanostars, nanoprisms and other nanostructures with tunable sizes. Further, we go into the aspects related to purification and functionalisation of nanoparticles, prior to the fabrication of sensing surfaces. Finally, the recent developments in single nanoparticle detection, spectroscopy and sensing applications are discussed.

  1. Single Policy Study

    DEFF Research Database (Denmark)

    Kronsell, Annica; Manners, Ian James

    2015-01-01

    Single policy studies are the most common form of European Union (EU) research. Single policy studies are widely used to understand the role of the EU in a wide variety of sectors, together with their development over time, and often offer public policy prescriptions. This chapter discusses...... the relevance of single policy studies in EU research and give examples of how such research can be designed and carried out. The chapter reviews three examples of single policy studies using different methods based on EU environmental policy, the EU biofuels directive, and the EU Common Security and Defence...... Policy (CSDP). The examples are illustrative of how single policy studies can be designed to use different approaches in the analysis: multiple streams approach to policy-making; a comparative hypothesis testing; and feminist institutional theory....

  2. Oligocyclopentadienyl transition metal complexes

    Energy Technology Data Exchange (ETDEWEB)

    de Azevedo, Cristina G.; Vollhardt, K. Peter C.

    2002-01-18

    Synthesis, characterization, and reactivity studies of oligocyclopentadienyl transition metal complexes, namely those of fulvalene, tercyclopentadienyl, quatercyclopentadienyl, and pentacyclopentadienyl(cyclopentadienyl) are the subject of this account. Thermal-, photo-, and redox chemistries of homo- and heteropolynuclear complexes are described.

  3. Photocytotoxic lanthanide complexes

    Indian Academy of Sciences (India)

    Among many applications of lanthanides, gadolinium complexes are used as magnetic resonance imaging (MRI) contrast agents in clinical radiology and luminescent lanthanides for bioanalysis, imaging and sensing. The chemistry of photoactive lanthanide complexes showing biological applications is of recent origin.

  4. Pinning Synchronization of Switched Complex Dynamical Networks

    Directory of Open Access Journals (Sweden)

    Liming Du

    2015-01-01

    Full Text Available Network topology and node dynamics play a key role in forming synchronization of complex networks. Unfortunately there is no effective synchronization criterion for pinning synchronization of complex dynamical networks with switching topology. In this paper, pinning synchronization of complex dynamical networks with switching topology is studied. Two basic problems are considered: one is pinning synchronization of switched complex networks under arbitrary switching; the other is pinning synchronization of switched complex networks by design of switching when synchronization cannot achieved by using any individual connection topology alone. For the two problems, common Lyapunov function method and single Lyapunov function method are used respectively, some global synchronization criteria are proposed and the designed switching law is given. Finally, simulation results verify the validity of the results.

  5. Single photon ECT

    International Nuclear Information System (INIS)

    Maeda, Toshio; Matsuda, Hiroshi; Tada, Akira; Bunko, Hisashi; Koizumi, Kiyoshi

    1982-01-01

    The detectability of lesions located deep in a body or overlapped with a physiologically increased activity improve with the help of single photon ECT. In some cases, the ECT is superior to the conventional gamma camera images and X-ray CT scans in the evaluation of the location and size of lesion. The single photon ECT of the brain compares favorably with the contrast enhansed X-ray CT scans. The most important adaptation of the single photon ECT are the detection of recurrent brain tumors after craniotomy and the evaluation of ischemic heart diseases. (author)

  6. Single Electron Tunneling

    International Nuclear Information System (INIS)

    Ruggiero, Steven T.

    2005-01-01

    Financial support for this project has led to advances in the science of single-electron phenomena. Our group reported the first observation of the so-called ''Coulomb Staircase'', which was produced by tunneling into ultra-small metal particles. This work showed well-defined tunneling voltage steps of width e/C and height e/RC, demonstrating tunneling quantized on the single-electron level. This work was published in a now well-cited Physical Review Letter. Single-electron physics is now a major sub-field of condensed-matter physics, and fundamental work in the area continues to be conducted by tunneling in ultra-small metal particles. In addition, there are now single-electron transistors that add a controlling gate to modulate the charge on ultra-small photolithographically defined capacitive elements. Single-electron transistors are now at the heart of at least one experimental quantum-computer element, and single-electron transistor pumps may soon be used to define fundamental quantities such as the farad (capacitance) and the ampere (current). Novel computer technology based on single-electron quantum dots is also being developed. In related work, our group played the leading role in the explanation of experimental results observed during the initial phases of tunneling experiments with the high-temperature superconductors. When so-called ''multiple-gap'' tunneling was reported, the phenomenon was correctly identified by our group as single-electron tunneling in small grains in the material. The main focus throughout this project has been to explore single electron phenomena both in traditional tunneling formats of the type metal/insulator/particles/insulator/metal and using scanning tunneling microscopy to probe few-particle systems. This has been done under varying conditions of temperature, applied magnetic field, and with different materials systems. These have included metals, semi-metals, and superconductors. Amongst a number of results, we have

  7. Single-molecule dynamics in nanofabricated traps

    Science.gov (United States)

    Cohen, Adam

    2009-03-01

    The Anti-Brownian Electrokinetic trap (ABEL trap) provides a means to immobilize a single fluorescent molecule in solution, without surface attachment chemistry. The ABEL trap works by tracking the Brownian motion of a single molecule, and applying feedback electric fields to induce an electrokinetic motion that approximately cancels the Brownian motion. We present a new design for the ABEL trap that allows smaller molecules to be trapped and more information to be extracted from the dynamics of a single molecule than was previously possible. In particular, we present strategies for extracting dynamically fluctuating mobilities and diffusion coefficients, as a means to probe dynamic changes in molecular charge and shape. If one trapped molecule is good, many trapped molecules are better. An array of single molecules in solution, each immobilized without surface attachment chemistry, provides an ideal test-bed for single-molecule analyses of intramolecular dynamics and intermolecular interactions. We present a technology for creating such an array, using a fused silica plate with nanofabricated dimples and a removable cover for sealing single molecules within the dimples. With this device one can watch the shape fluctuations of single molecules of DNA or study cooperative interactions in weakly associating protein complexes.

  8. Complex Correspondence Principle

    International Nuclear Information System (INIS)

    Bender, Carl M.; Meisinger, Peter N.; Hook, Daniel W.; Wang Qinghai

    2010-01-01

    Quantum mechanics and classical mechanics are distinctly different theories, but the correspondence principle states that quantum particles behave classically in the limit of high quantum number. In recent years much research has been done on extending both quantum and classical mechanics into the complex domain. These complex extensions continue to exhibit a correspondence, and this correspondence becomes more pronounced in the complex domain. The association between complex quantum mechanics and complex classical mechanics is subtle and demonstrating this relationship requires the use of asymptotics beyond all orders.

  9. Uranium thiolate complexes

    International Nuclear Information System (INIS)

    Leverd, Pascal C.

    1994-01-01

    This research thesis proposes a new approach to the chemistry of uranium thiolate complexes as these compounds are very promising for various uses (in bio-inorganic chemistry, in some industrial processes like oil desulphurization). It more particularly addresses the U-S bond or more generally bonds between polarizable materials and hard metals. The author thus reports the study of uranium organometallic thiolates (tricyclo-penta-dienic and mono-cyclo-octa-tetraenylic complexes), and of uranium homoleptic thiolates (tetra-thiolate complexes, hexa-thiolate complexes, reactivity of homoleptic thiolate complexes) [fr

  10. Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

    Directory of Open Access Journals (Sweden)

    Max Greenfeld

    Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

  11. In-silico single nucleotide polymorphisms (SNP) mining of Sorghum ...

    African Journals Online (AJOL)

    Single nucleotide polymorphisms (SNPs) may be considered the ultimate genetic markers as they represent the finest resolution of a DNA sequence (a single nucleotide), and are generally abundant in populations with a low mutation rate. SNPs are important tools in studying complex genetic traits and genome evolution.

  12. Single Beam Holography.

    Science.gov (United States)

    Chen, Hsuan; Ruterbusch, Paul H.

    1979-01-01

    Discusses how holography can be used as part of undergraduate physics laboratories. The authors propose a single beam technique of holography, which will reduce the recording scheme as well as relax the isolation requirements. (HM)

  13. Single-photon sources

    International Nuclear Information System (INIS)

    Lounis, Brahim; Orrit, Michel

    2005-01-01

    The concept of the photon, central to Einstein's explanation of the photoelectric effect, is exactly 100 years old. Yet, while photons have been detected individually for more than 50 years, devices producing individual photons on demand have only appeared in the last few years. New concepts for single-photon sources, or 'photon guns', have originated from recent progress in the optical detection, characterization and manipulation of single quantum objects. Single emitters usually deliver photons one at a time. This so-called antibunching of emitted photons can arise from various mechanisms, but ensures that the probability of obtaining two or more photons at the same time remains negligible. We briefly recall basic concepts in quantum optics and discuss potential applications of single-photon states to optical processing of quantum information: cryptography, computing and communication. A photon gun's properties are significantly improved by coupling it to a resonant cavity mode, either in the Purcell or strong-coupling regimes. We briefly recall early production of single photons with atomic beams, and the operation principles of macroscopic parametric sources, which are used in an overwhelming majority of quantum-optical experiments. We then review the photophysical and spectroscopic properties and compare the advantages and weaknesses of various single nanometre-scale objects used as single-photon sources: atoms or ions in the gas phase and, in condensed matter, organic molecules, defect centres, semiconductor nanocrystals and heterostructures. As new generations of sources are developed, coupling to cavities and nano-fabrication techniques lead to improved characteristics, delivery rates and spectral ranges. Judging from the brisk pace of recent progress, we expect single photons to soon proceed from demonstrations to applications and to bring with them the first practical uses of quantum information

  14. Single particle dynamics

    International Nuclear Information System (INIS)

    Siemens, P.J.; Jensen, A.S.

    1985-01-01

    It is shown that the opening of the 3-quasiparticle continuum at 3Δ sets the energy scale for the enhancement of the effective mass near the Fermi surface of nuclei. The authors argue that the spreading width of single-particle states due to coupling with low-lying collective modes is qualitatively different from the two-body collision mechanism, and contributes little to the single-particle lifetime in the sense of the optical model. (orig.)

  15. Physics of Complex Polymeric Molecules

    Science.gov (United States)

    Kelly, Joshua Walter

    The statistical physics of complex polymers with branches and circuits is the topic of this dissertation. An important motivation are large, single-stranded (ss) RNA molecules. Such molecules form complex ``secondary" and ``tertiary" structures that can be represented as branched polymers with circuits. Such structures are in part directly determined by the nucleotide sequence and in part subject to thermal fluctuations. The polymer physics literature on molecules in this class has mostly focused on randomly branched polymers without circuits while there has been minimal research on polymers with specific structures and on polymers that contain circuits. The dissertation is composed of three parts: Part I studies branched polymers with thermally fluctuating structure confined to a potential well as a simple model for the encapsidation of viral RNA. Excluded volume interactions were ignored. In Part II, I apply Flory theory to the study of the encapsidation of viral ss RNA molecules with specific branched structures, but without circuits, in the presence of excluded volume interaction. In Part III, I expand on Part II and consider complex polymers with specific structure including both branching and circuits. I introduce a method based on the mathematics of Laplacian matrices that allows me to calculate density profiles for such molecules, which was not possible within Flory theory.

  16. Structure of Coordination Complexes: The Synergy between NMR ...

    African Journals Online (AJOL)

    NICO

    determined by density functional theory (DFT) methods and the application of the Boltzmann equation, are in ... single crystals suitable for crystallography can be obtained, ...... NMR analysis of bonding in transition metal olefin complexes.

  17. Defect complexes in carbon and boron nitride nanotubes

    CSIR Research Space (South Africa)

    Mashapa, MG

    2012-05-01

    Full Text Available The effect of defect complexes on the stability, structural and electronic properties of single-walled carbon nanotubes and boron nitride nanotubes is investigated using the ab initio pseudopotential density functional method implemented...

  18. Simplicial complexes of graphs

    CERN Document Server

    Jonsson, Jakob

    2008-01-01

    A graph complex is a finite family of graphs closed under deletion of edges. Graph complexes show up naturally in many different areas of mathematics, including commutative algebra, geometry, and knot theory. Identifying each graph with its edge set, one may view a graph complex as a simplicial complex and hence interpret it as a geometric object. This volume examines topological properties of graph complexes, focusing on homotopy type and homology. Many of the proofs are based on Robin Forman's discrete version of Morse theory. As a byproduct, this volume also provides a loosely defined toolbox for attacking problems in topological combinatorics via discrete Morse theory. In terms of simplicity and power, arguably the most efficient tool is Forman's divide and conquer approach via decision trees; it is successfully applied to a large number of graph and digraph complexes.

  19. On Complex Random Variables

    Directory of Open Access Journals (Sweden)

    Anwer Khurshid

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE In this paper, it is shown that a complex multivariate random variable  is a complex multivariate normal random variable of dimensionality if and only if all nondegenerate complex linear combinations of  have a complex univariate normal distribution. The characteristic function of  has been derived, and simpler forms of some theorems have been given using this characterization theorem without assuming that the variance-covariance matrix of the vector  is Hermitian positive definite. Marginal distributions of  have been given. In addition, a complex multivariate t-distribution has been defined and the density derived. A characterization of the complex multivariate t-distribution is given. A few possible uses of this distribution have been suggested.

  20. Cobalt(III) complex

    Indian Academy of Sciences (India)

    Administrator

    e, 40 µM complex, 10 hrs after dissolution, f, 40 µM complex, after irradiation dose 15 Gy. and H-atoms result in reduction of Co(III) to Co. (II). 6. It is interesting to see in complex containing multiple ligands what is the fate of electron adduct species formed by electron addition. Reduction to. Co(II) and intramolecular transfer ...

  1. Complex Systems and Dependability

    CERN Document Server

    Zamojski, Wojciech; Sugier, Jaroslaw

    2012-01-01

    Typical contemporary complex system is a multifaceted amalgamation of technical, information, organization, software and human (users, administrators and management) resources. Complexity of such a system comes not only from its involved technical and organizational structure but mainly from complexity of information processes that must be implemented in the operational environment (data processing, monitoring, management, etc.). In such case traditional methods of reliability analysis focused mainly on technical level are usually insufficient in performance evaluation and more innovative meth

  2. Lanthanide complexes with pivaloylacetone

    International Nuclear Information System (INIS)

    Eliseeva, S.V.; Chugarov, N.V.; Kuz'mina, N.P.; Martynenko, L.I.; Nichiporuk, R.V.; Ivanov, S.A.

    2003-01-01

    Complexes Ln(pa) 3 ·2H 2 O (Ln=La, Gd, Lu, Hpa - pivaloylacetone) are synthesized and investigated by the methods of element, IR spectroscopic and thermal analyses. Behaviour of the complexes during heating in vacuum is compared with such one for acetylacetonates and dipivaloylmethanates. Structure of the complexes in solution is studied by 1 H NMR and MALDI-MS [ru

  3. Single-Mode VCSELs

    Science.gov (United States)

    Larsson, Anders; Gustavsson, Johan S.

    The only active transverse mode in a truly single-mode VCSEL is the fundamental mode with a near Gaussian field distribution. A single-mode VCSEL produces a light beam of higher spectral purity, higher degree of coherence and lower divergence than a multimode VCSEL and the beam can be more precisely shaped and focused to a smaller spot. Such beam properties are required in many applications. In this chapter, after discussing applications of single-mode VCSELs, we introduce the basics of fields and modes in VCSELs and review designs implemented for single-mode emission from VCSELs in different materials and at different wavelengths. This includes VCSELs that are inherently single-mode as well as inherently multimode VCSELs where higher-order modes are suppressed by mode selective gain or loss. In each case we present the current state-of-the-art and discuss pros and cons. At the end, a specific example with experimental results is provided and, as a summary, the most promising designs based on current technologies are identified.

  4. Single-photon imaging

    International Nuclear Information System (INIS)

    Seitz, Peter; Theuwissen, Albert J.P.

    2011-01-01

    The acquisition and interpretation of images is a central capability in almost all scientific and technological domains. In particular, the acquisition of electromagnetic radiation, in the form of visible light, UV, infrared, X-ray, etc. is of enormous practical importance. The ultimate sensitivity in electronic imaging is the detection of individual photons. With this book, the first comprehensive review of all aspects of single-photon electronic imaging has been created. Topics include theoretical basics, semiconductor fabrication, single-photon detection principles, imager design and applications of different spectral domains. Today, the solid-state fabrication capabilities for several types of image sensors has advanced to a point, where uncooled single-photon electronic imaging will soon become a consumer product. This book is giving a specialist's view from different domains to the forthcoming ''single-photon imaging'' revolution. The various aspects of single-photon imaging are treated by internationally renowned, leading scientists and technologists who have all pioneered their respective fields. (orig.)

  5. Phospholyl-uranium complexes

    International Nuclear Information System (INIS)

    Gradoz, Philippe

    1993-01-01

    After having reported a bibliographical study on penta-methylcyclopentadienyl uranium complexes, and a description of the synthesis and radioactivity of uranium (III) and (IV) boron hydrides compounds, this research thesis reports the study of mono and bis-tetramethyl-phospholyl uranium complexes comprising chloride, boron hydride, alkyl and alkoxide ligands. The third part reports the comparison of structures, stabilities and reactions of homologue complexes in penta-methylcyclopentadienyl and tetramethyl-phospholyl series. The last part addresses the synthesis of tris-phospholyl uranium (III) and (IV) complexes. [fr

  6. Nuclear weapons complex

    International Nuclear Information System (INIS)

    Rezendes, V.S.

    1991-03-01

    In this book, GAO characterizes DOE's January 1991 Nuclear Weapons Complex Reconfiguration Study as a starting point for reaching agreement on solutions to many of the complex's safety and environmental problems. Key decisions still need to be made about the size of the complex, where to relocate plutonium operations, what technologies to use for new tritium production, and what to do with excess plutonium. The total cost for reconfiguring and modernizing the complex is still uncertain, and some management issues remain unresolved. Congress faces a difficult task in making test decisions given the conflicting demands for scarce resources in a time of growing budget deficits and war in the Persian Gulf

  7. Conducting metal dithiolate complexes

    DEFF Research Database (Denmark)

    Underhill, A. E.; Ahmad, M. M.; Turner, D. J.

    1985-01-01

    Further work on the chemical composition of the one-dimensional metallic metal dithiolene complex Li-Pt(mnt) is reported. The electrical conduction and thermopower properties of the nickel and palladium complexes are reported and compared with those of the platinum compound......Further work on the chemical composition of the one-dimensional metallic metal dithiolene complex Li-Pt(mnt) is reported. The electrical conduction and thermopower properties of the nickel and palladium complexes are reported and compared with those of the platinum compound...

  8. Changes in signal transducer and activator of transcription 3 (STAT3) dynamics induced by complexation with pharmacological inhibitors of Src homology 2 (SH2) domain dimerization.

    Science.gov (United States)

    Resetca, Diana; Haftchenary, Sina; Gunning, Patrick T; Wilson, Derek J

    2014-11-21

    The activity of the transcription factor signal transducer and activator of transcription 3 (STAT3) is dysregulated in a number of hematological and solid malignancies. Development of pharmacological STAT3 Src homology 2 (SH2) domain interaction inhibitors holds great promise for cancer therapy, and a novel class of salicylic acid-based STAT3 dimerization inhibitors that includes orally bioavailable drug candidates has been recently developed. The compounds SF-1-066 and BP-1-102 are predicted to bind to the STAT3 SH2 domain. However, given the highly unstructured and dynamic nature of the SH2 domain, experimental confirmation of this prediction was elusive. We have interrogated the protein-ligand interaction of STAT3 with these small molecule inhibitors by means of time-resolved electrospray ionization hydrogen-deuterium exchange mass spectrometry. Analysis of site-specific evolution of deuterium uptake induced by the complexation of STAT3 with SF-1-066 or BP-1-102 under physiological conditions enabled the mapping of the in silico predicted inhibitor binding site to the STAT3 SH2 domain. The binding of both inhibitors to the SH2 domain resulted in significant local decreases in dynamics, consistent with solvent exclusion at the inhibitor binding site and increased rigidity of the inhibitor-complexed SH2 domain. Interestingly, inhibitor binding induced hot spots of allosteric perturbations outside of the SH2 domain, manifesting mainly as increased deuterium uptake, in regions of STAT3 important for DNA binding and nuclear localization. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Surface Induced Dissociation Coupled with High Resolution Mass Spectrometry Unveils Heterogeneity of a 211 kDa Multicopper Oxidase Protein Complex

    Science.gov (United States)

    Zhou, Mowei; Yan, Jing; Romano, Christine A.; Tebo, Bradley M.; Wysocki, Vicki H.; Paša-Tolić, Ljiljana

    2018-01-01

    Manganese oxidation is an important biogeochemical process that is largely regulated by bacteria through enzymatic reactions. However, the detailed mechanism is poorly understood due to challenges in isolating and characterizing these unknown enzymes. A manganese oxidase, Mnx, from Bacillus sp. PL-12 has been successfully overexpressed in active form as a protein complex with a molecular mass of 211 kDa. We have recently used surface induced dissociation (SID) and ion mobility-mass spectrometry (IM-MS) to release and detect folded subcomplexes for determining subunit connectivity and quaternary structure. The data from the native mass spectrometry experiments led to a plausible structural model of this multicopper oxidase, which has been difficult to study by conventional structural biology methods. It was also revealed that each Mnx subunit binds a variable number of copper ions. Becasue of the heterogeneity of the protein and limited mass resolution, ambiguities in assigning some of the observed peaks remained as a barrier to fully understanding the role of metals and potential unknown ligands in Mnx. In this study, we performed SID in a modified Fourier transform-ion cyclotron resonance (FTICR) mass spectrometer. The high mass accuracy and resolution offered by FTICR unveiled unexpected artificial modifications on the protein that had been previously thought to be iron bound species based on lower resolution spectra. Additionally, isotopically resolved spectra of the released subcomplexes revealed the metal binding stoichiometry at different structural levels. This method holds great potential for in-depth characterization of metalloproteins and protein-ligand complexes. [Figure not available: see fulltext.

  10. Study on synthesis, kit formulation and chemical kinetics of dissociation of 99mTc labeled PnAO biotin complex

    International Nuclear Information System (INIS)

    Afshan, A.; Jafri, S.R.A.; Maecke, H.

    2004-01-01

    Full text: A bifunctional ligand of PnAO-biotin has recently been synthesized, with a better percentage yield of 63% in the presence of newly developed coupling agent 0-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexaflorophos phate (HATU). Then lyophilized kit with 150μg of PnAObiotin has been developed and labeled with high specific activity of technetium-99m (2500-3000MBq) to get maximum radiochemical purity of 99mTc-PnAO-biotin complex i.e. > 97%. The association of avidin and streptavidin is among the strongest known non-covalent protein ligand interaction Ka 1015 M-1 and 1013 M-1 respectively. We measured the dissociation rate constant of PnAO-biotin from avidin and streptavidin challenged with excess of cold biotin. For the separation of bound and free-labeled biotin we employed ultrafilteration technique. The results of these experiments demonstrated that the non-covalent binding between 99mTc-PnAO-biotin with avidin and 99mTc-PnAO-biotin with streptavidin is more than 99%. Both biotin-binding proteins exhibited a faster initial phase and the rate of dissociation of 99mTc-PnAO-biotin with avidin is found to be 8.2x10-8 at 250C and 2.6x10-7 at 370C while the rate of dissociation 99mTc-PnAO-biotin from streptavidin is found to be 6x10-7 at 250C and 1.06x10-6 at 370C. The in-vitro study of the kinetics of dissociation exhibits the strong interaction of 99mTc-PnAO-biotin complex with both proteins, which suggests that this bifunctional PnAO-biotin ligand can be used for tumor localization with monoclonal antibodies to achieve high tumor to non-tumor ratio. (author)

  11. Single port laparoscopic surgery

    DEFF Research Database (Denmark)

    Springborg, Henrik; Istre, Olav

    2012-01-01

    LESS, or laparo-endoscopic single site surgery, is a promising new method in minimally invasive surgery. An increasing number of surgical procedures are being performed using this technique, however, its large-scale adoption awaits results of prospective randomized controlled studies confirming...... potential benefits. Theoretically, cosmetic outcomes, postoperative pain and complication rates could be improved with use of single site surgery. This study describes introduction of the method in a private hospital in Denmark, in which 40 patients have been treated for benign gynecologic conditions....... Although the operations described are the first of their kind reported in Denmark, favorable operating times and very low complication rates are seen. It is the authors' opinion that in addition to being feasible for hysterectomy, single port laparoscopy may become the preferred method for many simple...

  12. Nickel(II) complexes having Imidazol-2-ylidene-N′-phenylurea ...

    Indian Academy of Sciences (India)

    The nickel complex 2 was obtained by the reaction of [Ni(acac)2], mesityl derivative of ... Solid-state structures of both the new complexes were established by single crystal ..... ORTEP diagram of 2 with thermal displacement parameters drawn.

  13. Single Cell Oncogenesis

    Science.gov (United States)

    Lu, Xin

    It is believed that cancer originates from a single cell that has gone through generations of evolution of genetic and epigenetic changes that associate with the hallmarks of cancer. In some cancers such as various types of leukemia, cancer is clonal. Yet in other cancers like glioblastoma (GBM), there is tremendous tumor heterogeneity that is likely to be caused by simultaneous evolution of multiple subclones within the same tissue. It is obvious that understanding how a single cell develops into a clonal tumor upon genetic alterations, at molecular and cellular levels, holds the key to the real appreciation of tumor etiology and ultimate solution for therapeutics. Surprisingly very little is known about the process of spontaneous tumorigenesis from single cells in human or vertebrate animal models. The main reason is the lack of technology to track the natural process of single cell changes from a homeostatic state to a progressively cancerous state. Recently, we developed a patented compound, photoactivatable (''caged'') tamoxifen analogue 4-OHC and associated technique called optochemogenetic switch (OCG switch), which we believe opens the opportunity to address this urgent biological as well as clinical question about cancer. We propose to combine OCG switch with genetically engineered mouse models of head and neck squamous cell carcinoma and high grade astrocytoma (including GBM) to study how single cells, when transformed through acute loss of tumor suppressor genes PTEN and TP53 and gain of oncogenic KRAS, can develop into tumor colonies with cellular and molecular heterogeneity in these tissues. The abstract is for my invited talk in session ``Beyond Darwin: Evolution in Single Cells'' 3/18/2016 11:15 AM.

  14. Vibrations and stability of complex beam systems

    CERN Document Server

    Stojanović, Vladimir

    2015-01-01

     This book reports on solved problems concerning vibrations and stability of complex beam systems. The complexity of a system is considered from two points of view: the complexity originating from the nature of the structure, in the case of two or more elastically connected beams; and the complexity derived from the dynamic behavior of the system, in the case of a damaged single beam, resulting from the harm done to its simple structure. Furthermore, the book describes the analytical derivation of equations of two or more elastically connected beams, using four different theories (Euler, Rayleigh, Timoshenko and Reddy-Bickford). It also reports on a new, improved p-version of the finite element method for geometrically nonlinear vibrations. The new method provides more accurate approximations of solutions, while also allowing us to analyze geometrically nonlinear vibrations. The book describes the appearance of longitudinal vibrations of damaged clamped-clamped beams as a result of discontinuity (damage). It...

  15. Single well techniques

    International Nuclear Information System (INIS)

    Drost, W.

    1983-01-01

    The single well technique method includes measurement of parameters of groundwater flow in saturated rock. For determination of filtration velocity the dilution of radioactive tracer is measured, for direction logging the collimeter is rotated in the probe linked with the compass. The limiting factor for measurement of high filtration velocities is the occurrence of turbulent flow. The single well technique is used in civil engineering projects, water works and subsurface drainage of liquid waste from disposal sites. The radioactive tracer method for logging the vertical fluid movement in bore-holes is broadly used in groundwater survey and exploitation. (author)

  16. SINGLE HEATER TEST FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    J.B. Cho

    1999-05-01

    The Single Heater Test is the first of the in-situ thermal tests conducted by the U.S. Department of Energy as part of its program of characterizing Yucca Mountain in Nevada as the potential site for a proposed deep geologic repository for the disposal of spent nuclear fuel and high-level nuclear waste. The Site Characterization Plan (DOE 1988) contained an extensive plan of in-situ thermal tests aimed at understanding specific aspects of the response of the local rock-mass around the potential repository to the heat from the radioactive decay of the emplaced waste. With the refocusing of the Site Characterization Plan by the ''Civilian Radioactive Waste Management Program Plan'' (DOE 1994), a consolidated thermal testing program emerged by 1995 as documented in the reports ''In-Situ Thermal Testing Program Strategy'' (DOE 1995) and ''Updated In-Situ Thermal Testing Program Strategy'' (CRWMS M&O 1997a). The concept of the Single Heater Test took shape in the summer of 1995 and detailed planning and design of the test started with the beginning fiscal year 1996. The overall objective of the Single Heater Test was to gain an understanding of the coupled thermal, mechanical, hydrological, and chemical processes that are anticipated to occur in the local rock-mass in the potential repository as a result of heat from radioactive decay of the emplaced waste. This included making a priori predictions of the test results using existing models and subsequently refining or modifying the models, on the basis of comparative and interpretive analyses of the measurements and predictions. A second, no less important, objective was to try out, in a full-scale field setting, the various instruments and equipment to be employed in the future on a much larger, more complex, thermal test of longer duration, such as the Drift Scale Test. This ''shake down'' or trial aspect of the Single Heater Test applied

  17. SINGLE HEATER TEST FINAL REPORT

    International Nuclear Information System (INIS)

    J.B. Cho

    1999-01-01

    The Single Heater Test is the first of the in-situ thermal tests conducted by the U.S. Department of Energy as part of its program of characterizing Yucca Mountain in Nevada as the potential site for a proposed deep geologic repository for the disposal of spent nuclear fuel and high-level nuclear waste. The Site Characterization Plan (DOE 1988) contained an extensive plan of in-situ thermal tests aimed at understanding specific aspects of the response of the local rock-mass around the potential repository to the heat from the radioactive decay of the emplaced waste. With the refocusing of the Site Characterization Plan by the ''Civilian Radioactive Waste Management Program Plan'' (DOE 1994), a consolidated thermal testing program emerged by 1995 as documented in the reports ''In-Situ Thermal Testing Program Strategy'' (DOE 1995) and ''Updated In-Situ Thermal Testing Program Strategy'' (CRWMS M and O 1997a). The concept of the Single Heater Test took shape in the summer of 1995 and detailed planning and design of the test started with the beginning fiscal year 1996. The overall objective of the Single Heater Test was to gain an understanding of the coupled thermal, mechanical, hydrological, and chemical processes that are anticipated to occur in the local rock-mass in the potential repository as a result of heat from radioactive decay of the emplaced waste. This included making a priori predictions of the test results using existing models and subsequently refining or modifying the models, on the basis of comparative and interpretive analyses of the measurements and predictions. A second, no less important, objective was to try out, in a full-scale field setting, the various instruments and equipment to be employed in the future on a much larger, more complex, thermal test of longer duration, such as the Drift Scale Test. This ''shake down'' or trial aspect of the Single Heater Test applied not just to the hardware, but also to the teamwork and cooperation between

  18. Visual Complexity: A Review

    Science.gov (United States)

    Donderi, Don C.

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from…

  19. Complexity in Picture Books

    Science.gov (United States)

    Sierschynski, Jarek; Louie, Belinda; Pughe, Bronwyn

    2015-01-01

    One of the key requirements of Common Core State Standards (CCSS) in English Language Arts is that students are able to read and access complex texts across all grade levels. The CCSS authors emphasize both the limitations and lack of accuracy in the current CCSS model of text complexity, calling for the development of new frameworks. In response…

  20. Method of complex scaling

    International Nuclear Information System (INIS)

    Braendas, E.

    1986-01-01

    The method of complex scaling is taken to include bound states, resonances, remaining scattering background and interference. Particular points of the general complex coordinate formulation are presented. It is shown that care must be exercised to avoid paradoxical situations resulting from inadequate definitions of operator domains. A new resonance localization theorem is presented