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Sample records for backbone structure based

  1. Process-based network decomposition reveals backbone motif structure.

    Science.gov (United States)

    Wang, Guanyu; Du, Chenghang; Chen, Hao; Simha, Rahul; Rong, Yongwu; Xiao, Yi; Zeng, Chen

    2010-06-08

    A central challenge in systems biology today is to understand the network of interactions among biomolecules and, especially, the organizing principles underlying such networks. Recent analysis of known networks has identified small motifs that occur ubiquitously, suggesting that larger networks might be constructed in the manner of electronic circuits by assembling groups of these smaller modules. Using a unique process-based approach to analyzing such networks, we show for two cell-cycle networks that each of these networks contains a giant backbone motif spanning all the network nodes that provides the main functional response. The backbone is in fact the smallest network capable of providing the desired functionality. Furthermore, the remaining edges in the network form smaller motifs whose role is to confer stability properties rather than provide function. The process-based approach used in the above analysis has additional benefits: It is scalable, analytic (resulting in a single analyzable expression that describes the behavior), and computationally efficient (all possible minimal networks for a biological process can be identified and enumerated).

  2. Inferential protein structure determination and refinement using fast, electronic structure based backbone amide chemical shift predictions

    CERN Document Server

    Christensen, Anders S

    2015-01-01

    This report covers the development of a new, fast method for calculating the backbone amide proton chemical shifts in proteins. Through quantum chemical calculations, structure-based forudsiglese the chemical shift for amidprotonen in protein has been parameterized. The parameters are then implemented in a computer program called Padawan. The program has since been implemented in protein folding program Phaistos, wherein the method andvendes to de novo folding of the protein structures and to refine the existing protein structures.

  3. A Multi-Objective Approach for Protein Structure Prediction Based on an Energy Model and Backbone Angle Preferences.

    Science.gov (United States)

    Tsay, Jyh-Jong; Su, Shih-Chieh; Yu, Chin-Sheng

    2015-07-03

    Protein structure prediction (PSP) is concerned with the prediction of protein tertiary structure from primary structure and is a challenging calculation problem. After decades of research effort, numerous solutions have been proposed for optimisation methods based on energy models. However, further investigation and improvement is still needed to increase the accuracy and similarity of structures. This study presents a novel backbone angle preference factor, which is one of the factors inducing protein folding. The proposed multiobjective optimisation approach simultaneously considers energy models and backbone angle preferences to solve the ab initio PSP. To prove the effectiveness of the multiobjective optimisation approach based on the energy models and backbone angle preferences, 75 amino acid sequences with lengths ranging from 22 to 88 amino acids were selected from the CB513 data set to be the benchmarks. The data sets were highly dissimilar, therefore indicating that they are meaningful. The experimental results showed that the root-mean-square deviation (RMSD) of the multiobjective optimization approach based on energy model and backbone angle preferences was superior to those of typical energy models, indicating that the proposed approach can facilitate the ab initio PSP.

  4. A Multi-Objective Approach for Protein Structure Prediction Based on an Energy Model and Backbone Angle Preferences

    Directory of Open Access Journals (Sweden)

    Jyh-Jong Tsay

    2015-07-01

    Full Text Available Protein structure prediction (PSP is concerned with the prediction of protein tertiary structure from primary structure and is a challenging calculation problem. After decades of research effort, numerous solutions have been proposed for optimisation methods based on energy models. However, further investigation and improvement is still needed to increase the accuracy and similarity of structures. This study presents a novel backbone angle preference factor, which is one of the factors inducing protein folding. The proposed multiobjective optimisation approach simultaneously considers energy models and backbone angle preferences to solve the ab initio PSP. To prove the effectiveness of the multiobjective optimisation approach based on the energy models and backbone angle preferences, 75 amino acid sequences with lengths ranging from 22 to 88 amino acids were selected from the CB513 data set to be the benchmarks. The data sets were highly dissimilar, therefore indicating that they are meaningful. The experimental results showed that the root-mean-square deviation (RMSD of the multiobjective optimization approach based on energy model and backbone angle preferences was superior to those of typical energy models, indicating that the proposed approach can facilitate the ab initio PSP.

  5. Backbone cup – a structure design competition based on topology optimization and 3D printing

    Directory of Open Access Journals (Sweden)

    Zhu Ji-Hong

    2016-01-01

    Full Text Available This paper addresses a structure design competition based on topology optimization and 3D Printing, and proposes an experimental approach to efficiently and quickly measure the mechanical performance of the structures designed using topology optimization. Since the topology optimized structure designs are prone to be geometrically complex, it is extremely inconvenient to fabricate these designs with traditional machining. In this study, we not only fabricated the topology optimized structure designs using one kind of 3D Printing technology known as stereolithography (SLA, but also tested the mechanical performance of the produced prototype parts. The finite element method is used to analyze the structure responses, and the consistent results of the numerical simulations and structure experiments prove the validity of this new structure testing approach. This new approach will not only provide a rapid access to topology optimized structure designs verifying, but also cut the turnaround time of structure design significantly.

  6. Combining automated peak tracking in SAR by NMR with structure-based backbone assignment from 15N-NOESY

    KAUST Repository

    Jang, Richard

    2012-03-21

    Background: Chemical shift mapping is an important technique in NMR-based drug screening for identifying the atoms of a target protein that potentially bind to a drug molecule upon the molecule\\'s introduction in increasing concentrations. The goal is to obtain a mapping of peaks with known residue assignment from the reference spectrum of the unbound protein to peaks with unknown assignment in the target spectrum of the bound protein. Although a series of perturbed spectra help to trace a path from reference peaks to target peaks, a one-to-one mapping generally is not possible, especially for large proteins, due to errors, such as noise peaks, missing peaks, missing but then reappearing, overlapped, and new peaks not associated with any peaks in the reference. Due to these difficulties, the mapping is typically done manually or semi-automatically, which is not efficient for high-throughput drug screening.Results: We present PeakWalker, a novel peak walking algorithm for fast-exchange systems that models the errors explicitly and performs many-to-one mapping. On the proteins: hBclXL, UbcH5B, and histone H1, it achieves an average accuracy of over 95% with less than 1.5 residues predicted per target peak. Given these mappings as input, we present PeakAssigner, a novel combined structure-based backbone resonance and NOE assignment algorithm that uses just 15N-NOESY, while avoiding TOCSY experiments and 13C-labeling, to resolve the ambiguities for a one-to-one mapping. On the three proteins, it achieves an average accuracy of 94% or better.Conclusions: Our mathematical programming approach for modeling chemical shift mapping as a graph problem, while modeling the errors directly, is potentially a time- and cost-effective first step for high-throughput drug screening based on limited NMR data and homologous 3D structures. 2012 Jang et al.; licensee BioMed Central Ltd.

  7. Combining ambiguous chemical shift mapping with structure-based backbone and NOE assignment from 15N-NOESY

    KAUST Repository

    Jang, Richard

    2011-01-01

    Chemical shift mapping is an important technique in NMRbased drug screening for identifying the atoms of a target protein that potentially bind to a drug molecule upon the molecule\\'s introduction in increasing concentrations. The goal is to obtain a mapping of peaks with known residue assignment from the reference spectrum of the unbound protein to peaks with unknown assignment in the target spectrum of the bound protein. Although a series of perturbed spectra help to trace a path from reference peaks to target peaks, a one-to-one mapping generally is not possible, especially for large proteins, due to errors, such as noise peaks, missing peaks, missing but then reappearing, overlapped, and new peaks not associated with any peaks in the reference. Due to these difficulties, the mapping is typically done manually or semi-automatically. However, automated methods are necessary for high-throughput drug screening. We present PeakWalker, a novel peak walking algorithm for fast-exchange systems that models the errors explicitly and performs many-to-one mapping. On the proteins: hBclXL, UbcH5B, and histone H1, it achieves an average accuracy of over 95% with less than 1.5 residues predicted per target peak. Given these mappings as input, we present PeakAssigner, a novel combined structure-based backbone resonance and NOE assignment algorithm that uses just 15N-NOESY, while avoiding TOCSY experiments and 13C- labeling, to resolve the ambiguities for a one-toone mapping. On the three proteins, it achieves an average accuracy of 94% or better. Copyright © 2011 ACM.

  8. Triazine-Based Sequence-Defined Polymers with Side-Chain Diversity and Backbone-Backbone Interaction Motifs.

    Science.gov (United States)

    Grate, Jay W; Mo, Kai-For; Daily, Michael D

    2016-03-14

    Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone-backbone interactions, including H-bonding motifs and pi-pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone-backbone hydrogen-bonding motifs, and will thus enable new macromolecules and materials with useful functions.

  9. MCBT: Multi-Hop Cluster Based Stable Backbone Trees for Data Collection and Dissemination in WSNs.

    Science.gov (United States)

    Shin, Inyoung; Kim, Moonseong; Mutka, Matt W; Choo, Hyunseung; Lee, Tae-Jin

    2009-01-01

    We propose a stable backbone tree construction algorithm using multi-hop clusters for wireless sensor networks (WSNs). The hierarchical cluster structure has advantages in data fusion and aggregation. Energy consumption can be decreased by managing nodes with cluster heads. Backbone nodes, which are responsible for performing and managing multi-hop communication, can reduce the communication overhead such as control traffic and minimize the number of active nodes. Previous backbone construction algorithms, such as Hierarchical Cluster-based Data Dissemination (HCDD) and Multicluster, Mobile, Multimedia radio network (MMM), consume energy quickly. They are designed without regard to appropriate factors such as residual energy and degree (the number of connections or edges to other nodes) of a node for WSNs. Thus, the network is quickly disconnected or has to reconstruct a backbone. We propose a distributed algorithm to create a stable backbone by selecting the nodes with higher energy or degree as the cluster heads. This increases the overall network lifetime. Moreover, the proposed method balances energy consumption by distributing the traffic load among nodes around the cluster head. In the simulation, the proposed scheme outperforms previous clustering schemes in terms of the average and the standard deviation of residual energy or degree of backbone nodes, the average residual energy of backbone nodes after disseminating the sensed data, and the network lifetime.

  10. Application of Multicast-based Video Conference on CERNET Backbone

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Multicast-based video conference is a representative application in advanced network. In multi-point video conference using multicast can get better efficiency facilitated by inner-group broadcast mechanism. In the application, the multicast-based network resources assignment, management and security should be considered together. This paper presents a framework model of multicast-based video conferencing application with three layers. And a practical multicast-based video conferencing is implemented in CERNET(China Education and Research Network) backbone. The practice is valuable for the development of multicast-based video conferencing application in China.

  11. On Backbone Structure for a Future Multipurpose Network

    DEFF Research Database (Denmark)

    Gutierrez Lopez, Jose Manuel; Cuevas, Ruben; Riaz, M. Tahir

    2008-01-01

    Telecommunications are evolving towards the unification of services and infrastructures. This unification must be achieved at the highest hierarchical level for a complete synergy of services. Therefore, one of the requirements is a multipurpose backbone network capable of supporting all the curr......Telecommunications are evolving towards the unification of services and infrastructures. This unification must be achieved at the highest hierarchical level for a complete synergy of services. Therefore, one of the requirements is a multipurpose backbone network capable of supporting all...

  12. Protein structure quality assessment based on the distance profiles of consecutive backbone Cα atoms [v3; ref status: indexed, http://f1000r.es/2kg

    Directory of Open Access Journals (Sweden)

    Sandeep Chakraborty

    2013-12-01

    Full Text Available Predicting the three dimensional native state structure of a protein from its primary sequence is an unsolved grand challenge in molecular biology. Two main computational approaches have evolved to obtain the structure from the protein sequence - ab initio/de novo methods and template-based modeling - both of which typically generate multiple possible native state structures. Model quality assessment programs (MQAP validate these predicted structures in order to identify the correct native state structure. Here, we propose a MQAP for assessing the quality of protein structures based on the distances of consecutive Cα atoms. We hypothesize that the root-mean-square deviation of the distance of consecutive Cα (RDCC atoms from the ideal value of 3.8 Å, derived from a statistical analysis of high quality protein structures (top100H database, is minimized in native structures. Based on tests with the top100H set, we propose a RDCC cutoff value of 0.012 Å, above which a structure can be filtered out as a non-native structure. We applied the RDCC discriminator on decoy sets from the Decoys 'R' Us database to show that the native structures in all decoy sets tested have RDCC below the 0.012 Å cutoff. While most decoy sets were either indistinguishable using this discriminator or had very few violations, all the decoy structures in the fisa decoy set were discriminated by applying the RDCC criterion. This highlights the physical non-viability of the fisa decoy set, and possible issues in benchmarking other methods using this set. The source code and manual is made available at https://github.com/sanchak/mqap and permanently available on 10.5281/zenodo.7134.

  13. Systematic determination of the mosaic structure of bacterial genomes: species backbone versus strain-specific loops

    Directory of Open Access Journals (Sweden)

    Gendrault-Jacquemard A

    2005-07-01

    Full Text Available Abstract Background Public databases now contain multitude of complete bacterial genomes, including several genomes of the same species. The available data offers new opportunities to address questions about bacterial genome evolution, a task that requires reliable fine comparison data of closely related genomes. Recent analyses have shown, using pairwise whole genome alignments, that it is possible to segment bacterial genomes into a common conserved backbone and strain-specific sequences called loops. Results Here, we generalize this approach and propose a strategy that allows systematic and non-biased genome segmentation based on multiple genome alignments. Segmentation analyses, as applied to 13 different bacterial species, confirmed the feasibility of our approach to discern the 'mosaic' organization of bacterial genomes. Segmentation results are available through a Web interface permitting functional analysis, extraction and visualization of the backbone/loops structure of documented genomes. To illustrate the potential of this approach, we performed a precise analysis of the mosaic organization of three E. coli strains and functional characterization of the loops. Conclusion The segmentation results including the backbone/loops structure of 13 bacterial species genomes are new and available for use by the scientific community at the URL: http://genome.jouy.inra.fr/mosaic.

  14. Changing the topology of protein backbone: the effect of backbone cyclization on the structure and dynamics of a SH3 domain

    Directory of Open Access Journals (Sweden)

    Frank H Schumann

    2015-04-01

    Full Text Available Understanding of the effects of the backbone cyclization on the structure and dynamics of a protein is essential for using protein topology engineering to alter protein stability and function. Here we have determined, for the first time, the structure and dynamics of the linear and various circular constructs of the N-SH3 domain from protein c-Crk. These constructs differ in the length and amino acid composition of the cyclization region. The backbone cyclization was carried out using intein-mediated intramolecular chemical ligation between the juxtaposed N- and the C-termini. The structure and backbone dynamics studies were performed using solution NMR. Our data suggest that the backbone cyclization has little effect on the overall three-dimensional structure of the SH3 domain: besides the termini, only minor structural changes were found in the proximity of the cyclization region. In contrast to the structure, backbone dynamics are significantly affected by the cyclization. On the subnanosecond time scale, the backbone of all circular constructs on average appears more rigid than that of the linear SH3 domain; this effect is observed over the entire backbone and is not limited to the cyclization site. The backbone mobility of the circular constructs becomes less restricted with increasing length of the circularization loop. In addition, significant conformational exchange motions (on the sub-millisecond time scale were found in the N-Src loop and in the adjacent β-strands in all circular constructs studied in this work. These effects of backbone cyclization on protein dynamics have potential implications for the stability of the protein fold and for ligand binding.

  15. Effect of Liquid-Crystalline Epoxy Backbone Structure on Thermal Conductivity of Epoxy-Alumina Composites

    Science.gov (United States)

    Giang, Thanhkieu; Kim, Jinhwan

    2017-01-01

    In a series of papers published recently, we clearly demonstrated that the most important factor governing the thermal conductivity of epoxy-Al2O3 composites is the backbone structure of the epoxy. In this study, three more epoxies based on diglycidyl ester-terminated liquid-crystalline epoxy (LCE) have been synthesized to draw conclusions regarding the effect of the epoxy backbone structure on the thermal conductivity of epoxy-alumina composites. The synthesized structures were characterized by proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared (FT-IR) spectroscopy. Differential scanning calorimetry, thermogravimetric analysis, and optical microscopy were also employed to examine the thermal and optical properties of the synthesized LCEs and the cured composites. All three LCE resins exhibited typical liquid-crystalline behaviors: clear solid crystalline state below the melting temperature ( T m), sharp crystalline melting at T m, and transition to nematic phase above T m with consequent isotropic phase above the isotropic temperature ( T i). The LCE resins displayed distinct nematic liquid-crystalline phase over a wide temperature range and retained liquid-crystalline phase after curing, with high thermal conductivity of the resulting composite. The thermal conductivity values ranged from 3.09 W/m-K to 3.89 W/m-K for LCE-Al2O3 composites with 50 vol.% filler loading. The steric effect played a governing role in the difference. The neat epoxy resin thermal conductivity was obtained as 0.35 W/m-K to 0.49 W/m-K based on analysis using the Agari-Uno model. The results clearly support the objective of this study in that the thermal conductivity of the LCE-containing networks strongly depended on the epoxy backbone structure and the degree of ordering in the cured network.

  16. APPECT: An Approximate Backbone-Based Clustering Algorithm for Tags

    DEFF Research Database (Denmark)

    Zong, Yu; Xu, Guandong; Jin, Pin

    2011-01-01

    algorithm for Tags (APPECT). The main steps of APPECT are: (1) we execute the K-means algorithm on a tag similarity matrix for M times and collect a set of tag clustering results Z={C1,C2,…,Cm}; (2) we form the approximate backbone of Z by executing a greedy search; (3) we fix the approximate backbone...... resulting from the severe difficulty of ambiguity, redundancy and less semantic nature of tags. Clustering method is a useful tool to address the aforementioned difficulties. Most of the researches on tag clustering are directly using traditional clustering algorithms such as K-means or Hierarchical...

  17. Improving prediction of secondary structure, local backbone angles, and solvent accessible surface area of proteins by iterative deep learning.

    Science.gov (United States)

    Heffernan, Rhys; Paliwal, Kuldip; Lyons, James; Dehzangi, Abdollah; Sharma, Alok; Wang, Jihua; Sattar, Abdul; Yang, Yuedong; Zhou, Yaoqi

    2015-01-01

    Direct prediction of protein structure from sequence is a challenging problem. An effective approach is to break it up into independent sub-problems. These sub-problems such as prediction of protein secondary structure can then be solved independently. In a previous study, we found that an iterative use of predicted secondary structure and backbone torsion angles can further improve secondary structure and torsion angle prediction. In this study, we expand the iterative features to include solvent accessible surface area and backbone angles and dihedrals based on Cα atoms. By using a deep learning neural network in three iterations, we achieved 82% accuracy for secondary structure prediction, 0.76 for the correlation coefficient between predicted and actual solvent accessible surface area, 19° and 30° for mean absolute errors of backbone φ and ψ angles, respectively, and 8° and 32° for mean absolute errors of Cα-based θ and τ angles, respectively, for an independent test dataset of 1199 proteins. The accuracy of the method is slightly lower for 72 CASP 11 targets but much higher than those of model structures from current state-of-the-art techniques. This suggests the potentially beneficial use of these predicted properties for model assessment and ranking.

  18. Influence of structures of polymer backbones on cooperative photoreorientation behavior of p-cyanoazobenzene side chains

    DEFF Research Database (Denmark)

    Han, Mina; Kidowaki, Masatoshi; Ichimura, Kunihiro;

    2001-01-01

    Photoinduced orientational behavior of a polymethacrylate (CN6) and a polyester (p6a12) with p-cyanoazobenzene side chains was studied to reveal the structural effect of the liquid crystalline polymer backbones. Irradiation with linearly polarized W light resulted in the reorientation of the azob...

  19. Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR.

    Science.gov (United States)

    Knight, Michael J; Pell, Andrew J; Bertini, Ivano; Felli, Isabella C; Gonnelli, Leonardo; Pierattelli, Roberta; Herrmann, Torsten; Emsley, Lyndon; Pintacuda, Guido

    2012-07-10

    We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with (1)H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of (15)N and (13)C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu(+) (diamagnetic) or Cu(2+) (paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to (1)H-(1)H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable.

  20. East vergent structure of Backbone Range: Insights from A-Lan-Yi area and sandbox modeling

    Science.gov (United States)

    Lee, C. A.; Lu, C. Y.

    2015-12-01

    Southern Taiwan, including Pingtung peninsula and Taitung, is the incipient oblique collision zone of Eurasian plate and Philippine Sea plate. The Luzon volcanic arc converged toward Taiwan Island and formed Hengchun Ridge south offshore Taiwan. Thus, Taiwan mountain belt developed from north to south as the Backbone Range, so that we can infer the incipient feature structure from the topography and outcrop study of southern Taiwan. Our field survey of this study concentrated at the southeast coastline of Taiwan, also known as A-Lan-Yi Trail. According to previous study, the deformational structures such as faults and folds are consistent with regional kinematic processes, and the preserved transpression structure is the most important evidence of incipient collision. In this study, we use the sedimentary sequences of study area to trace the regional tectonics from north to south. Discovered structures in this area show the similar kinematic history as the eastern flank of Backbone Range, so that we suggest they are at the same series of a tectonic event. To complete the regional structure mapping in this accessible area, besides the field geological data, we also applied the LiDAR-derived DTM which is a 3D visualization technology to improve our topography information. In addition, we use the sandbox modeling to demonstrate the development of structures in the eastern flank of Backbone Range. After combining the results of field observation and regional structure mapping, this study provides a strong evidence of backthrusting and backfolding deformation during the incipient oblique collision stage.

  1. Synthesis, Characterization and Structure of Chiral Amino Acids and Their Corresponding Amino Alcohols with Camphoric Backbone

    Institute of Scientific and Technical Information of China (English)

    QIAN Hui-Fen; HUANG Wei; LI Hui-Hui; YAO Cheng

    2006-01-01

    Chiral amino acids and their corresponding amino alcohols bearing camphoric backbone were prepared from D-(+)-camphoric imide and characterized by infrared, elemental analysis, ESI-MS, and NMR measurements. Among them, one intermediate (lS,3R)-3-amino-2,2,3-trimethyl cyclopentane-1-carboxylic acid hydrochloride 3 was structurally elucidated by X-ray diffraction techniques. Versatile intermolecular hydrogen bonding interactions observed in its packing structure result in a two-dimensional framework.

  2. Sequential backbone assignment based on dipolar amide-to-amide correlation experiments.

    Science.gov (United States)

    Xiang, ShengQi; Grohe, Kristof; Rovó, Petra; Vasa, Suresh Kumar; Giller, Karin; Becker, Stefan; Linser, Rasmus

    2015-07-01

    Proton detection in solid-state NMR has seen a tremendous increase in popularity in the last years. New experimental techniques allow to exploit protons as an additional source of information on structure, dynamics, and protein interactions with their surroundings. In addition, sensitivity is mostly improved and ambiguity in assignment experiments reduced. We show here that, in the solid state, sequential amide-to-amide correlations turn out to be an excellent, complementary way to exploit amide shifts for unambiguous backbone assignment. For a general assessment, we compare amide-to-amide experiments with the more common (13)C-shift-based methods. Exploiting efficient CP magnetization transfers rather than less efficient INEPT periods, our results suggest that the approach is very feasible for solid-state NMR.

  3. Sequential backbone assignment based on dipolar amide-to-amide correlation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, ShengQi; Grohe, Kristof; Rovó, Petra; Vasa, Suresh Kumar; Giller, Karin; Becker, Stefan; Linser, Rasmus, E-mail: rali@nmr.mpibpc.mpg.de [Max Planck Institute for Biophysical Chemistry, Department for NMR-Based Structural Biology (Germany)

    2015-07-15

    Proton detection in solid-state NMR has seen a tremendous increase in popularity in the last years. New experimental techniques allow to exploit protons as an additional source of information on structure, dynamics, and protein interactions with their surroundings. In addition, sensitivity is mostly improved and ambiguity in assignment experiments reduced. We show here that, in the solid state, sequential amide-to-amide correlations turn out to be an excellent, complementary way to exploit amide shifts for unambiguous backbone assignment. For a general assessment, we compare amide-to-amide experiments with the more common {sup 13}C-shift-based methods. Exploiting efficient CP magnetization transfers rather than less efficient INEPT periods, our results suggest that the approach is very feasible for solid-state NMR.

  4. Preparation of stable spherical micelles with rigid backbones based on polyaryletherketone copolymers containing lateral pyridyl groups

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shuling; Liu, Lingzhi; Guo, Yunliang; Jiang, Zhenhua; Wang, Guibin, E-mail: wgb@jlu.edu.cn

    2013-07-15

    A new bisphenol monomer, 3-(3,4-dihydroxyphenylimine) pyridine (PYPH), was synthesized via a deoxidization reaction of an amine. A series of novel polyaryletherketone copolymers containing lateral pyridyl groups (PY-PAEKs) based on PYPH, 2,2-di(4-hydroxyphenyl)propane and 4,4′-difluorobenzophenone were prepared by nucleophilic aromatic substitution polycondensation reactions. Furthermore, spherical micelles with rigid PY-PAEKs as the inner cores and flexible polyacrylic acid (PAA) as the outer shells were obtained in a selective solvent (H{sub 2}O) successfully. The formation of the spherical micelles was confirmed by scanning electron and transmission electron microscopy as well as by surface tension measurements. The formation and size of the spherical micelles depended on the weight ratio of PAA/PY-PAEK, the concentration and pH value of the mixed solution containing the PY-PAEK and PAA, and the number of pyridyl groups in the PY-PAEK. The structure of the spherical micelles could be stabilized by a cross-linking reaction between the pyridyl groups of the PY-PAEKs and 1,4-dibromobutane. The diameter of the spherical micelles decreased because of the removal of the PAA shell from the PY-PAEK core after the cross-linking reaction. The resulting stable spherical micelles with rigid backbones did not dissolve in a number of polar solvents and remained unaffected by changes in the pH values. - Graphical abstract: Display Omitted - Highlights: • Polyaryletherketone copolymers containing lateral pyridyl groups were synthesized. • Spherical micelles were prepared using these copolymers and polyacrylic acid. • The copolymers and polyacrylic acid formed the core and the shell of the micelles, respectively. • The obtained micelles were stabilized by a cross-linking reaction. • The cross-linked micelles had rigid backbones, independent of solvents and pH values.

  5. The structure of the carbohydrate backbone of the lipopolysaccharide of Pectinatus frisingensis strain VTT E-79104.

    Science.gov (United States)

    Vinogradov, Evgeny; Li, Jianjun; Sadovskaya, Irina; Jabbouri, Said; Helander, Ilkka M

    2004-06-22

    The structure of the carbohydrate backbone of the lipopolysaccharide from Pectinatus frisingensis strain VTT E-79104 was analyzed using chemical degradations, NMR spectroscopy, mass spectrometry, and chemical methods. The LPS contains two major structural variants, differing in the presence or absence of an octasaccharide fragment. The largest structure of the carbohydrate backbone of the LPS, that could be deduced from experimental results, consists of 20 monosaccharides arranged in a nonrepetitive sequence: [carbohydrate structure: see text] where R is H or 4-O-Me-alpha-L-Fuc-(1-2)-4-O-Me-beta-Hep-(1-3)-alpha-GlcNAc-(1-2)-beta-Man-(1-3)-beta-ManNAc-(1-4)-alpha-Gal-(1-4)-beta-Hep-(1-3)-beta-GalNAc-(1- where Hep is a residue of D-glycero-D-galacto-heptose; all monosaccharides have the D-configuration except for 4-O-Me-L-Fuc and L-Ara4N. This structure is architecturally similar to the oligosaccharide system reported previously in P. frisingensis VTT E-82164 LPS, but differs from the latter in composition and also in the size of the outer region.

  6. On correlation between protein secondary structure, backbone bond angles, and side-chain orientations

    CERN Document Server

    Lundgren, Martin

    2012-01-01

    We investigate the fine structure of the sp3 hybridized covalent bond geometry that governs the tetrahedral architecture around the central C$_\\alpha$ carbon of a protein backbone, and for this we develop new visualization techniques to analyze high resolution X-ray structures in Protein Data Bank. We observe that there is a correlation between the deformations of the ideal tetrahedral symmetry and the local secondary structure of the protein. We propose a universal coarse grained energy function to describe the ensuing side-chain geometry in terms of the C$_\\beta$ carbon orientations. The energy function can model the side-chain geometry with a sub-atomic precision. As an example we construct the C$_\\alpha$-C$_\\beta$ structure of HP35 chicken villin headpiece. We obtain a configuration that deviates less than 0.4 \\.A in root-mean-square distance from the experimental X-ray structure.

  7. Structure and assembly of group B streptococcus pilus 2b backbone protein.

    Science.gov (United States)

    Cozzi, Roberta; Malito, Enrico; Lazzarin, Maddalena; Nuccitelli, Annalisa; Castagnetti, Andrea; Bottomley, Matthew J; Margarit, Immaculada; Maione, Domenico; Rinaudo, C Daniela

    2015-01-01

    Group B Streptococcus (GBS) is a major cause of invasive disease in infants. Like other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation mechanism to generate cell surface pili from backbone and ancillary pilin precursor substrates. The three pilus types identified in GBS contain structural subunits that are highly immunogenic and are promising candidates for the development of a broadly-protective vaccine. Here we report the X-ray crystal structure of the backbone protein of pilus 2b (BP-2b) at 1.06Å resolution. The structure reveals a classical IgG-like fold typical of the pilin subunits of other Gram-positive bacteria. The crystallized portion of the protein (residues 185-468) encompasses domains D2 and D3 that together confer high stability to the protein due to the presence of an internal isopeptide bond within each domain. The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire protein in conferring protection against GBS challenge in a well-established mouse model. By site-directed mutagenesis and complementation studies in GBS knock-out strains we identified the residues and motives essential for assembly of the BP-2b monomers into high-molecular weight complexes, thus providing new insights into pilus 2b polymerization.

  8. Structure and assembly of group B streptococcus pilus 2b backbone protein.

    Directory of Open Access Journals (Sweden)

    Roberta Cozzi

    Full Text Available Group B Streptococcus (GBS is a major cause of invasive disease in infants. Like other Gram-positive bacteria, GBS uses a sortase C-catalyzed transpeptidation mechanism to generate cell surface pili from backbone and ancillary pilin precursor substrates. The three pilus types identified in GBS contain structural subunits that are highly immunogenic and are promising candidates for the development of a broadly-protective vaccine. Here we report the X-ray crystal structure of the backbone protein of pilus 2b (BP-2b at 1.06Å resolution. The structure reveals a classical IgG-like fold typical of the pilin subunits of other Gram-positive bacteria. The crystallized portion of the protein (residues 185-468 encompasses domains D2 and D3 that together confer high stability to the protein due to the presence of an internal isopeptide bond within each domain. The D2+D3 region, lacking the N-terminal D1 domain, was as potent as the entire protein in conferring protection against GBS challenge in a well-established mouse model. By site-directed mutagenesis and complementation studies in GBS knock-out strains we identified the residues and motives essential for assembly of the BP-2b monomers into high-molecular weight complexes, thus providing new insights into pilus 2b polymerization.

  9. Backbone structures in human milk oligosaccharides: trans-glycosylation by metagenomic β-N-acetylhexosaminidases.

    Science.gov (United States)

    Nyffenegger, Christian; Nordvang, Rune Thorbjørn; Zeuner, Birgitte; Łężyk, Mateusz; Difilippo, Elisabetta; Logtenberg, Madelon J; Schols, Henk A; Meyer, Anne S; Mikkelsen, Jørn Dalgaard

    2015-10-01

    This paper describes the discovery and characterization of two novel β-N-acetylhexosaminidases HEX1 and HEX2, capable of catalyzing the synthesis of human milk oligosaccharides (HMO) backbone structures with fair yields using chitin oligomers as β-N-acetylglucosamine (GlcNAc) donor. The enzyme-encoding genes were identified by functional screening of a soil-derived metagenomic library. The β-N-acetylhexosaminidases were expressed in Escherichia coli with an N-terminal His6-tag and were purified by nickel affinity chromatography. The sequence similarities of the enzymes with their respective closest homologues are 59 % for HEX1 and 51 % for HEX2 on the protein level. Both β-N-acetylhexosaminidases are classified into glycosyl hydrolase family 20 (GH 20) are able to hydrolyze para-nitrophenyl-β-N-acetylglucosamine (pNP-GlcNAc) as well as para-nitrophenyl-β-N-acetylgalactosamine (pNP-GalNAc) and exhibit pH optima of 8 and 6 for HEX1 and HEX2, respectively. The enzymes are able to hydrolyze N-acetylchitooligosaccharides with a degree of polymerization of two, three, and four. The major findings were, that HEX1 and HEX2 catalyze trans-glycosylation reactions with lactose as acceptor, giving rise to the human milk oligosaccharide precursor lacto-N-triose II (LNT2) with yields of 2 and 8 % based on the donor substrate. In total, trans-glycosylation reactions were tested with the disaccharide acceptors β-lactose, sucrose, and maltose, as well as with the monosaccharides galactose and glucose resulting in the successful attachment of GlcNAc to the acceptor in all cases.

  10. Influence of backbone rigidness on single chain conformation of thiophene-based conjugated polymers.

    Science.gov (United States)

    Hu, Zhongjian; Liu, Jianhua; Simón-Bower, Lauren; Zhai, Lei; Gesquiere, Andre J

    2013-04-25

    Structural order of conjugated polymers at different length scales directs the optoelectronic properties of the corresponding materials; thus it is of critical importance to understand and control conjugated polymer morphology for successful application of these materials in organic optoelectronics. Herein, with the aim of probing the dependence of single chain folding properties on the chemical structure and rigidness of the polymer backbones, single molecule fluorescence spectroscopy was applied to four thiophene-based conjugated polymers. These include regioregular poly(3-hexylthiophene) (RR-P3HT), poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT-14), poly(2,5-bis(3-tetradecylthiophen-2-yl)thiophene-2-yl)thiophen-2-ylthiazolo[5,4-d]thiazole) (PTzQT-12), and poly(3,3-didodecylquaterthiophene)] (PQT-12). Our previous work has shown that RR-P3HT and PBTTT-14 polymer chains fold in their nanostructures, whereas PQT-12 and PTzQT-12 do not fold in their nanostructures. At the single molecule level, it was found that RR-P3HT single chains almost exclusively fold into loosely and strongly aggregated conformations, analogous to the folding properties in nanostructures. PQT-12 displays significant chain folding as well, but only into loosely aggregated conformations, showing an absence of strongly aggregated polymer chains. PBTTT-14 exhibits a significant fraction of rigid polymer chain. The findings made for single molecules of PQT-12 and PBTTT-14 are thus in contrast with the observations made in their corresponding nanostructures. PTzQT-12 appears to be the most rigid and planar conjugated polymer of these four polymers. However, although the presumably nonfolding polymers PQT-12 and PTzQT-12 exhibit less folding than RR-P3HT, there is still a significant occurrence of chain folding for these polymers at the single molecule level. These results suggest that the folding properties of conjugated polymers can be influenced by the architecture of the

  11. Formation of Hierarchical Structure Composed of (Co/Ni)Mn-LDH Nanosheets on MWCNT Backbones for Efficient Electrocatalytic Water Oxidation.

    Science.gov (United States)

    Jia, Gan; Hu, Yingfei; Qian, Qinfeng; Yao, Yingfang; Zhang, Shiying; Li, Zhaosheng; Zou, Zhigang

    2016-06-15

    Active, stable, and cost-effective electrocatalysts are attractive alternatives to the noble metal oxides that have been used in water splitting. The direct nucleation and growth of electrochemically active LDH materials on chemically modified MWCNTs exhibit considerable electrocatalytic activity toward oxygen evolution from water oxidation. CoMn-based and NiMn-based hybrids were synthesized using a facile chemical bath deposition method and the as-synthesized materials exhibited three-dimensional hierarchical configurations with tunable Co/Mn and Ni/Mn ratio. Benefiting from enhanced electrical conductivity with MWCNT backbones and LDH lamellar structure, the Co5Mn-LDH/MWCNT and Ni5Mn-LDH/MWCNT could generated a current density of 10 mA cm(-2) at overpotentials of ∼300 and ∼350 mV, respectively, in 1 M KOH. In addition, the materials also exhibited outstanding long-term electrocatalytic stability.

  12. APSY-NMR for protein backbone assignment in high-throughput structural biology

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Samit Kumar; Serrano, Pedro; Proudfoot, Andrew; Geralt, Michael [The Scripps Research Institute, Department of Integrative Structural and Computational Biology (United States); Pedrini, Bill [Paul Scherrer Institute (PSI), SwissFEL Project (Switzerland); Herrmann, Torsten [Université de Lyon, Institut des Sciences Analytiques, Centre de RMN à Très Hauts Champs, UMR 5280 CNRS, ENS Lyon, UCB Lyon 1 (France); Wüthrich, Kurt, E-mail: wuthrich@scripps.edu [The Scripps Research Institute, Department of Integrative Structural and Computational Biology (United States)

    2015-01-15

    A standard set of three APSY-NMR experiments has been used in daily practice to obtain polypeptide backbone NMR assignments in globular proteins with sizes up to about 150 residues, which had been identified as targets for structure determination by the Joint Center for Structural Genomics (JCSG) under the auspices of the Protein Structure Initiative (PSI). In a representative sample of 30 proteins, initial fully automated data analysis with the software UNIO-MATCH-2014 yielded complete or partial assignments for over 90 % of the residues. For most proteins the APSY data acquisition was completed in less than 30 h. The results of the automated procedure provided a basis for efficient interactive validation and extension to near-completion of the assignments by reference to the same 3D heteronuclear-resolved [{sup 1}H,{sup 1}H]-NOESY spectra that were subsequently used for the collection of conformational constraints. High-quality structures were obtained for all 30 proteins, using the J-UNIO protocol, which includes extensive automation of NMR structure determination.

  13. Structural dynamics of protein backbone {phi} angles: extended molecular dynamics simulations versus experimental {sup 3}J scalar couplings

    Energy Technology Data Exchange (ETDEWEB)

    Markwick, Phineus R. L. [CNRS/CEA/UJF, Protein Dynamics and Flexibility, Institut de Biologie Structurale Jean-Pierre Ebel UMR 5075 (France); Showalter, Scott A. [Florida State University, Department of Chemistry and Biochemistry, NHMFL (United States); Bouvignies, Guillaume [CNRS/CEA/UJF, Protein Dynamics and Flexibility, Institut de Biologie Structurale Jean-Pierre Ebel UMR 5075 (France); Brueschweiler, Rafael [Florida State University, Department of Chemistry and Biochemistry, NHMFL (United States)], E-mail: bruschweiler@magnet.fsu.edu; Blackledge, Martin [CNRS/CEA/UJF, Protein Dynamics and Flexibility, Institut de Biologie Structurale Jean-Pierre Ebel UMR 5075 (France)], E-mail: martin.blackledge@ibs.fr

    2009-09-15

    {sup 3}J scalar couplings report on the conformational averaging of backbone {phi} angles in peptides and proteins, and therefore represent a potentially powerful tool for studying the details of both structure and dynamics in solution. We have compared an extensive experimental dataset with J-couplings predicted from unrestrained molecular dynamics simulation using enhanced sampling available from accelerated molecular dynamics or using long timescale trajectories (200 ns). The dynamic fluctuations predicted to be present along the backbone, in agreement with residual dipolar coupling analysis, are compatible with the experimental {sup 3}J scalar couplings providing a slightly better reproduction of these experimental parameters than a high-resolution static structure.

  14. Unconventional N-H…N Hydrogen Bonds Involving Proline Backbone Nitrogen in Protein Structures.

    Science.gov (United States)

    Deepak, R N V Krishna; Sankararamakrishnan, Ramasubbu

    2016-05-10

    Contrary to DNA double-helical structures, hydrogen bonds (H-bonds) involving nitrogen as the acceptor are not common in protein structures. We systematically searched N-H…N H-bonds in two different sets of protein structures. Data set I consists of neutron diffraction and ultrahigh-resolution x-ray structures (0.9 Å resolution or better) and the hydrogen atom positions in these structures were determined experimentally. Data set II contains structures determined using x-ray diffraction (resolution ≤ 1.8 Å) and the positions of hydrogen atoms were generated using a computational method. We identified 114 and 14,347 potential N-H…N H-bonds from these two data sets, respectively, and 56-66% of these were of the Ni+1-Hi+1…Ni type, with Ni being the proline backbone nitrogen. To further understand the nature of such unusual contacts, we performed quantum chemical calculations on the model compound N-acetyl-L-proline-N-methylamide (Ace-Pro-NMe) with coordinates taken from the experimentally determined structures. A potential energy profile generated by varying the ψ dihedral angle in Ace-Pro-NMe indicates that the conformation with the N-H…N H-bond is the most stable. An analysis of H-bond-forming proline residues reveals that more than 30% of the proline carbonyl groups are also involved in n → π(∗) interactions with the carbonyl carbon of the preceding residue. Natural bond orbital analyses demonstrate that the strength of N-H…N H-bonds is less than half of that observed for a conventional H-bond. This study clearly establishes the H-bonding capability of proline nitrogen and its prevalence in protein structures. We found many proteins with multiple instances of H-bond-forming prolines. With more than 15% of all proline residues participating in N-H…N H-bonds, we suggest a new, to our knowledge, structural role for proline in providing stability to loops and capping regions of secondary structures in proteins.

  15. STARD6 on steroids: solution structure, multiple timescale backbone dynamics and ligand binding mechanism

    Science.gov (United States)

    Létourneau, Danny; Bédard, Mikaël; Cabana, Jérôme; Lefebvre, Andrée; Lehoux, Jean-Guy; Lavigne, Pierre

    2016-06-01

    START domain proteins are conserved α/β helix-grip fold that play a role in the non-vesicular and intracellular transport of lipids and sterols. The mechanism and conformational changes permitting the entry of the ligand into their buried binding sites is not well understood. Moreover, their functions and the identification of cognate ligands is still an active area of research. Here, we report the solution structure of STARD6 and the characterization of its backbone dynamics on multiple time-scales through 15N spin-relaxation and amide exchange studies. We reveal for the first time the presence of concerted fluctuations in the Ω1 loop and the C-terminal helix on the microsecond-millisecond time-scale that allows for the opening of the binding site and ligand entry. We also report that STARD6 binds specifically testosterone. Our work represents a milestone for the study of ligand binding mechanism by other START domains and the elucidation of the biological function of STARD6.

  16. The extension of a DNA double helix by an additional Watson-Crick base pair on the same backbone

    DEFF Research Database (Denmark)

    Kumar, P.; Sharma, P. K.; Madsen, Charlotte S.

    2013-01-01

    Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand.......Additional base pair: The DNA duplex can be extended with an additional Watson-Crick base pair on the same backbone by the use of double-headed nucleotides. These also work as compressed dinucleotides and form two base pairs with cognate nucleobases on the opposite strand....

  17. Interaction of Al-induced peptide backbone ring structure with the sidechains of His, Phe, Trp and Tyr

    Institute of Scientific and Technical Information of China (English)

    吴清雷; 宋波

    2015-01-01

    Aluminium is widely used as an antimicrobial coagulant, food additive, and cookware. However, many reports indicate that aluminium may be a critical factor in many amyloid diseases, such as Alzheimer’s disease and Parkinson’s disease. Unfortunately, the underlying mechanism is still poorly understood, which limits efforts to prevent and treat these diseases. In this paper, using an ab initio method, we studied the interaction of Al-backbone ring structure with theπ-electron-rich sidechains of His, Phe, Trp, and Tyr. We found that in the absence of water, the Al-backbone ring can stably bind with those sidechains. In the presence of water, the Al-backbone ring can bind to the His sidechain and cannot bind to the other sidechains. As revealed by further investigations, this could be attributed to the fact that there was a coordinate bond of the Al-backbone ring with the His sidechain, while there were theπ-πstacking and cation-π-like interactions with the other sidechains. These findings potentially provide a molecular understanding of Al-related toxicity, and may be helpful in designing drugs for those aforementioned aluminum-linked diseases and encourage treatment of Al-polluted water.

  18. CORBA and MPI-based 'backbone' for coupling advanced simulation tools

    Energy Technology Data Exchange (ETDEWEB)

    Seydaliev, M.; Caswell, D., E-mail: marat.seydaliev@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada)

    2014-12-01

    There is a growing international interest in using coupled, multidisciplinary computer simulations for a variety of purposes, including nuclear reactor safety analysis. Reactor behaviour can be modeled using a suite of computer programs simulating phenomena or predicting parameters that can be categorized into disciplines such as Thermalhydraulics, Neutronics, Fuel, Fuel Channels, Fission Product Release and Transport, Containment and Atmospheric Dispersion, and Severe Accident Analysis. Traditionally, simulations used for safety analysis individually addressed only the behaviour within a single discipline, based upon static input data from other simulation programs. The limitation of using a suite of stand-alone simulations is that phenomenological interdependencies or temporal feedback between the parameters calculated within individual simulations cannot be adequately captured. To remove this shortcoming, multiple computer simulations for different disciplines must exchange data during runtime to address these interdependencies. This article describes the concept of a new framework, which we refer to as the 'Backbone', to provide the necessary runtime exchange of data. The Backbone, currently under development at AECL for a preliminary feasibility study, is a hybrid design using features taken from the Common Object Request Broker Architecture (CORBA), a standard defined by the Object Management Group, and the Message Passing Interface (MPI), a standard developed by a group of researchers from academia and industry. Both have well-tested and efficient implementations, including some that are freely available under the GNU public licenses. The CORBA component enables individual programs written in different languages and running on different platforms within a network to exchange data with each other, thus behaving like a single application. MPI provides the process-to-process intercommunication between these programs. This paper outlines the different

  19. Rapid analysis of protein backbone resonance assignments using cryogenic probes, a distributed Linux-based computing architecture, and an integrated set of spectral analysis tools.

    Science.gov (United States)

    Monleón, Daniel; Colson, Kimberly; Moseley, Hunter N B; Anklin, Clemens; Oswald, Robert; Szyperski, Thomas; Montelione, Gaetano T

    2002-01-01

    Rapid data collection, spectral referencing, processing by time domain deconvolution, peak picking and editing, and assignment of NMR spectra are necessary components of any efficient integrated system for protein NMR structure analysis. We have developed a set of software tools designated AutoProc, AutoPeak, and AutoAssign, which function together with the data processing and peak-picking programs NMRPipe and Sparky, to provide an integrated software system for rapid analysis of protein backbone resonance assignments. In this paper we demonstrate that these tools, together with high-sensitivity triple resonance NMR cryoprobes for data collection and a Linux-based computer cluster architecture, can be combined to provide nearly complete backbone resonance assignments and secondary structures (based on chemical shift data) for a 59-residue protein in less than 30 hours of data collection and processing time. In this optimum case of a small protein providing excellent spectra, extensive backbone resonance assignments could also be obtained using less than 6 hours of data collection and processing time. These results demonstrate the feasibility of high throughput triple resonance NMR for determining resonance assignments and secondary structures of small proteins, and the potential for applying NMR in large scale structural proteomics projects.

  20. Role of monomer sequence and backbone structure in polypeptoid and polypeptide polymers for anti-fouling applications

    Science.gov (United States)

    Patterson, Anastasia; Rizis, Georgios; Wenning, Brandon; Finlay, John; Ober, Christopher; Segalman, Rachel

    Polymeric coatings rely on a fine balance of surface properties to achieve biofouling resistance. Bioinsipired polymers and oligomers provide a modular strategy for the inclusion of multiple functionalities with controlled architecture, sequence and surface properties. In this work, polypeptoid and polypeptide functionalized coatings based on PEO and PDMS block copolymers were compared with respect to surface presentation and fouling by Ulva linza. While polypeptoids and polypeptides are simple isomers of each other, the lack of backbone chirality and hydrogen bonding in polypeptoids leads to surprisingly different surface behavior. Specifically, the polypeptoids surface segregate much more strongly than analogous polypeptide functionalized polymers, which in turn affects the performance of the coating. Indeed, polypeptoid functionalized surfaces were significantly better both in terms of anti-fouling and fouling release than the corresponding polypeptide-bearing polymers. The role of specific monomer sequence and backbone chemistry will be further discussed in this poster.

  1. Structural basis for the enhanced stability of protein model compounds and peptide backbone unit in ammonium ionic liquids.

    Science.gov (United States)

    Vasantha, T; Attri, Pankaj; Venkatesu, Pannuru; Devi, R S Rama

    2012-10-04

    Protein folding/unfolding is a fascinating study in the presence of cosolvents, which protect/disrupt the native structure of protein, respectively. The structure and stability of proteins and their functional groups may be modulated by the addition of cosolvents. Ionic liquids (ILs) are finding a vast array of applications as novel cosolvents for a wide variety of biochemical processes that include protein folding. Here, the systematic and quantitative apparent transfer free energies (ΔG'(tr)) of protein model compounds from water to ILs through solubility measurements as a function of IL concentration at 25 °C have been exploited to quantify and interpret biomolecular interactions between model compounds of glycine peptides (GPs) with ammonium based ILs. The investigated aqueous systems consist of zwitterionic glycine peptides: glycine (Gly), diglycine (Gly(2)), triglycine (Gly(3)), tetraglycine (Gly(4)), and cyclic glycylglycine (c(GG)) in the presence of six ILs such as diethylammonium acetate (DEAA), diethylammonium hydrogen sulfate (DEAS), triethylammonium acetate (TEAA), triethylammonium hydrogen sulfate (TEAS), triethylammonium dihydrogen phosphate (TEAP), and trimethylammonium acetate (TMAA). We have observed positive values of ΔG'(tr) for GPs from water to ILs, indicating that interactions between ILs and GPs are unfavorable, which leads to stabilization of the structure of model protein compounds. Moreover, our experimental data ΔG'(tr) is used to obtain transfer free energies (Δg'(tr)) of the peptide backbone unit (or glycyl unit) (-CH(2)C═ONH-), which is the most numerous group in globular proteins, from water to IL solutions. To obtain the mechanism events of the ILs' role in enhancing the stability of the model compounds, we have further obtained m-values for GPs from solubility limits. These results explicitly elucidate that all alkyl ammonium ILs act as stabilizers for model compounds through the exclusion of ILs from model compounds of

  2. Trappist: european project dedicated to an open backbone structure for NDT expertise; Trappist: un projet europeen pour realiser une structure de gestion des donnees de CND

    Energy Technology Data Exchange (ETDEWEB)

    Nouailhas, B.; Vailhen, O.

    1993-12-31

    Non Destructive Testing (NDT) on critical components such as the reactor vessel, primary coolant pipes and steam generators have already been, and are still the subject of many development concerning the improvement of measuring techniques, data processing and on site operation. The tools developed for these tests are generally closed, difficult to extend and of proprietary type. Productivity could be increased if an open backbone structure common to several types of test were available. Moreover, these components are generally submitted to a test involving a single method. In certain cases, the produced information is an insufficient basis for drawing up a satisfactory diagnosis: the test operator or expert often faces problems in extracting more information from signals that are generally noisy. It may prove necessary to complete the inspection with another NDT method based on different principles in order to obtain better performances. It is then by combining the information obtained by two complementary methods that it will be possible to draw up a more reliable diagnosis. These components have also a complex shape. In the case of ultrasonic testing, the accurate following of probe paths requires 3D representation of the geometry, as it is built, to position and display the data obtained from the inspection. To take these geometric constraints into account, it is imperative to use computer tools allowing the three-dimensional representation of the reconstructed information on the components` actual geometry. This specific difficulty, which has long been appreciated, is the subject of developments resulting to industrial products that are more or less satisfactory. The aim of the European Project TRAPPIST (Race Program) is to study an open backbone structure. A mock-up of an analysis station dedicated to NDT expertise will be built and evaluated with specific examples. (authors). 6 figs., 1 ref.

  3. Backbone structures in human milk oligosaccharides: trans-glycosylation by metagenomic β-N-acetylhexosaminidases

    DEFF Research Database (Denmark)

    Nyffenegger, Christian; Nordvang, Rune Thorbjørn; Zeuner, Birgitte

    2015-01-01

    This paper describes the discovery and characterization of two novel β-N-acetylhexosaminidases HEX1 and HEX2, capable of catalyzing the synthesis of human milk oligosaccharides (HMO) backbone structures with fair yields using chitin oligomers as β-N-acetylglucosamine (GlcNAc) donor. The enzyme......-encoding genes were identified by functional screening of a soil-derived metagenomic library. The β-N-acetylhexosaminidases were expressed in Escherichia coli with an N-terminal His6-tag and were purified by nickel affinity chromatography. The sequence similarities of the enzymes with their respective closest...

  4. Backbone structure of Yersinia pestis Ail determined in micelles by NMR-restrained simulated annealing with implicit membrane solvation

    Energy Technology Data Exchange (ETDEWEB)

    Marassi, Francesca M., E-mail: fmarassi@sbmri.org; Ding, Yi [Sanford-Burnham Medical Research Institute (United States); Schwieters, Charles D. [National Institutes of Health, Division of Computational Bioscience, Center for Information Technology (United States); Tian, Ye; Yao, Yong [Sanford-Burnham Medical Research Institute (United States)

    2015-09-15

    The outer membrane protein Ail (attachment invasion locus) is a virulence factor of Yersinia pestis that mediates cell invasion, cell attachment and complement resistance. Here we describe its three-dimensional backbone structure determined in decyl-phosphocholine (DePC) micelles by NMR spectroscopy. The NMR structure was calculated using the membrane function of the implicit solvation potential, eefxPot, which we have developed to facilitate NMR structure calculations in a physically realistic environment. We show that the eefxPot force field guides the protein towards its native fold. The resulting structures provide information about the membrane-embedded global position of Ail, and have higher accuracy, higher precision and improved conformational properties, compared to the structures calculated with the standard repulsive potential.

  5. Analytical Model based on Green Criteria for Optical Backbone Network Interconnection

    DEFF Research Database (Denmark)

    Gutierrez Lopez, Jose Manuel; Riaz, M. Tahir; Pedersen, Jens Myrup

    2011-01-01

    to the evaluation of the environmental impact of networks from physical interconnection point of view. Networks deployment, usage, and disposal are analyzed as contributing elements to ICT’s (Information and Communications Technology) CO2 emissions. This paper presents an analytical model for evaluating...... and quantifying the CO2 emissions of optical backbone networks during their lifetime. The main goal of this work is to present the model and illustrate how to evaluate the physical interconnection of backbones from an environmental perspective. This model can be applied as a new type of decision support criteria...... for backbone’s interconnection, since minimization of CO2 emissions is becoming an important factor. In addition, two case studies are presented to illustrate the use and application of this model, and the need for de facto and international standards to reduce CO2 emissions through good network planning....

  6. Poly(meta-phenylene) Derivative with Rigid Twisted Biphenyl Units in Backbone: Synthesis, Structural Characterization,Photophysical Properties and Electroluminescence

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yan; YANG Bing; ZHANG Hai-quan; LU Ping; SHEN Fang-zhong; LIU Lin-lin; XU Hai; YANG Guang-di; MA Yu-guang

    2007-01-01

    A soluble poly(meta-phenylene) derivative with rigid twisted biphenyl unit was synthesized by the Yamamoto coupling reaction. The polymer is soluble in common organic solvents, and the number-average molecular weight is about 6500. The UV-Vis and quantum chemical calculation indicate that the different conformation segments named "conformers" exist in the polymer backbones; it was also further confirmed by the single crystal X-ray diffraction study of the dimeric model compound. The π-π* transition of biphenyl segments of twisted and planar conformations made the polymer exhibit a strong absorption around 256 nm and a weak absorption at about 300 nm. Furthermore,the polymer exhibits a strong UV photoluminescence at 372 nm when the excitation wavelengths are longer than 300 nm. The ultraviolet-emitting electroluminescence(EL) device with the single layer structure shows EL λmax of the derivative at 370 nm.

  7. A fusion networking model for smart grid power distribution backbone communication network based on PTN

    Directory of Open Access Journals (Sweden)

    Wang Hao

    2016-01-01

    Full Text Available In current communication network for distribution in Chinese power grid systems, the fiber communication backbone network for distribution and TD-LTE power private wireless backhaul network of power grid are both bearing by the SDH optical transmission network, which also carries the communication network of transformer substation and main electric. As the data traffic of the distribution communication and TD-LTE power private wireless network grow rapidly in recent years, it will have a big impact with the SDH network’s bearing capacity which is mainly used for main electric communication in high security level. This paper presents a fusion networking model which use a multiple-layer PTN network as the unified bearing of the TD-LTE power private wireless backhaul network and fiber communication backbone network for distribution. Network dataflow analysis shows that this model can greatly reduce the capacity pressure of the traditional SDH network as well as ensure the reliability of the transmission of the communication network for distribution and TD-LTE power private wireless network.

  8. Structure of the exceptionally large nonrepetitive carbohydrate backbone of the lipopolysaccharide of Pectinatus frisingensis strain VTT E-82164.

    Science.gov (United States)

    Vinogradov, Evgeny; Petersen, Bent O; Sadovskaya, Irina; Jabbouri, Said; Duus, Jens Ø; Helander, Ilkka M

    2003-07-01

    The structures of the oligosaccharides obtained after acetic acid hydrolysis and alkaline deacylation of the rough-type lipopolysaccharide (LPS) from Pectinatus frisingensis strain VTT E-82164 were analysed using NMR spectroscopy, MS and chemical methods. The LPS contains two major structural variants, differing by a decasaccharide fragment, and some minor variants lacking the terminal glucose residue. The largest structure of the carbohydrate backbone of the LPS that could be deduced from experimental results consists of 25 monosaccharides (including the previously found Ara4NP residue in lipid A) arranged in a well-defined nonrepetitive structure: We presume that the shorter variant with R1 = H represents the core-lipid A part of the LPS, and the additional fragment is present instead of the O-specific polysaccharide. Structures of this type have not been previously described. Analysis of the deacylation products obtained from the LPS of the smooth strain, VTT E-79100T, showed that it contains a very similar core but with one different glycosidic linkage.

  9. An improved algorithm for finding community structure in networks with an application to IPv6 backbone network

    Institute of Scientific and Technical Information of China (English)

    GUO Yingxin; XU Ke

    2007-01-01

    The discovery of community structure in a large number of complex networks has attracted lots of interest in recent years.One category of algorithms for detecting community structure,the divisive algorithms,has been proposed and improved impressively.In this paper,we propose an improved divisive algorithm,the basic idea of which is to take more than one parameters into consideration to describe the networks from different points of view.Although its basic idea appears to be a little simple,it is shown experimentally that it outperforms some other algorithms when it is applied to the networks with a relatively obscure community structure.We also demonstrate its effectiveness by applying it to IPv6 backbone network.The communities detected by our algorithm indicate that although underdeveloped compared with IPv4 network,IPv6 network has already exhibited a preliminary community structure.Moreover,our algorithm can be further extended and adapted in the future.In fact,it suggests a simple yet possibly efficient way to improve algorithms.

  10. The Effects of NHC-Backbone Substitution on Efficiency in Ruthenium-based Olefin Metathesis

    Science.gov (United States)

    Kuhn, Kevin M.; Bourg, Jean-Baptiste; Chung, Cheol K.; Virgil, Scott C.; Grubbs, Robert H.

    2009-01-01

    A series of ruthenium olefin metathesis catalysts bearing N-heterocyclic carbene (NHC) ligands with varying degrees of backbone and N-aryl substitution have been prepared. These complexes show greater resistance to decomposition through C–H activation of the N-aryl group, resulting in increased catalyst lifetimes. This work has utilized robotic technology to examine the activity and stability of each catalyst in metathesis, providing insights into the relationship between ligand architecture and enhanced efficiency. The development of this robotic methodology has also shown that, under optimized conditions, catalyst loadings as low as 25 ppm can lead to 100% conversion in the ring-closing metathesis of diethyl diallylmalonate. PMID:19351207

  11. A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone.

    Science.gov (United States)

    Osorio, Jorge E; Wallace, Derek; Stinchcomb, Dan T

    2016-01-01

    Dengue fever is caused by infection with one of four dengue virus (DENV) serotypes (DENV-1-4), necessitating tetravalent dengue vaccines that can induce protection against all four DENV. Takeda's live attenuated tetravalent dengue vaccine candidate (TDV) comprises an attenuated DENV-2 strain plus chimeric viruses containing the prM and E genes of DENV-1, -3 and -4 cloned into the attenuated DENV-2 'backbone'. In Phase 1 and 2 studies, TDV was well tolerated by children and adults aged 1.5-45 years, irrespective of prior dengue exposure; mild injection-site symptoms were the most common adverse events. TDV induced neutralizing antibody responses and seroconversion to all four DENV as well as cross-reactive T cell-mediated responses that may be necessary for broad protection against dengue fever.

  12. Quality of service estimation based on maximum bottleneck algorithm for domain aggregation in backbone networks

    Institute of Scientific and Technical Information of China (English)

    WANG Yang; ZHAN Yi-chun; YU Shao-hua

    2007-01-01

    This paper investigates the routing among autonomous systems (ASs) with quality of service (QoS) requirements. To avoid the intractability of the problem, abstract QoS capability must be informed among ASs, because the routhing which constrained QoS has been proved to be nondeterministic polynomial-time (NP) hard even inside an AS. This paper employs the modified Dijkstra algorithm to compute the maximum bottleneck bandwidth inside an AS. This approach lays a basis for the AS-level switching capability on which interdomain advertisement can be performed. Furthermore, the paper models the aggregated traffic in backbone network with fractional Brownian motion (FBM), and by integrating along the time axis in short intervals, a good estimation of the distribution of queue length in the next short intervals can be obtained. The proposed advertisement mechanism can be easily implemented with the current interdomain routing protocols. Numerical study indicates that the presented scheme is effective and feasible.

  13. Folding of RNA tertiary structure: Linkages between backbone phosphates, ions, and water.

    Science.gov (United States)

    Draper, David E

    2013-12-01

    The functional forms of many RNAs have compact architectures. The placement of phosphates within such structures must be influenced not only by the strong electrostatic repulsion between phosphates, but also by networks of interactions between phosphates, water, and mobile ions. This review first explores what has been learned of the basic thermodynamic constraints on these arrangements from studies of hydration and ions in simple DNA molecules, and then gives an overview of what is known about ion and water interactions with RNA structures. A brief survey of RNA crystal structures identifies several interesting architectures in which closely spaced phosphates share hydration shells or phosphates are buried in environments that provide intramolecular hydrogen bonds or site-bound cations. Formation of these structures must require strong coupling between the uptake of ions and release of water.

  14. Nucleic Acid Backbone Structure Variations: Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    Nielsen, Peter E.

    2010-01-01

    )RNA and in the future also antigene applications targeting the double-stranded DNA of the genes themselves leading to gene silencing or guiding specific gene repair. Finally, the special chemical and structural properties of PNA suggest that these or similar molecules might have played a role in the prebiotic origin...

  15. Tridentate Lewis Acids Based on 1,3,5-Trisilacyclohexane Backbones and an Example of Their Host-Guest Chemistry.

    Science.gov (United States)

    Weisheim, Eugen; Reuter, Christian G; Heinrichs, Peter; Vishnevskiy, Yury V; Mix, Andreas; Neumann, Beate; Stammler, Hans-Georg; Mitzel, Norbert W

    2015-08-24

    Directed tridentate Lewis acids based on the 1,3,5-trisilacyclohexane skeleton with three ethynyl groups [CH2Si(Me)(C2H)]3 were synthesised and functionalised by hydroboration with HB(C6F5)2, yielding the ethenylborane {CH2Si(Me)[C2H2B(C6F5)2]}3, and by metalation with gallium and indium organyls affording {CH2Si(Me)[C2M(R)2]}3 (M = Ga, In, R = Me, Et). In the synthesis of the backbone the influence of substituents (MeO, EtO and iPrO groups at Si) on the orientation of the methyl group was studied with the aim to increase the abundance of the all-cis isomer. New compounds were identified by elemental analyses, multi-nuclear NMR spectroscopy and in some cases by IR spectroscopy. Crystal structures were obtained for cis-trans-[CH2Si(Me)(Cl)]3, all-cis-[CH2Si(Me)(H)]3, all-cis-[CH2Si(Me)(C2H)]3, cis-trans-[CH2Si(Me)(C2H)]3 and all-cis-[CH2Si(Me)(C2SiMe3)]3. A gas-phase electron diffraction experiment for all-cis-[CH2Si(Me)(C2H)]3 provides information on the relative stabilities of the all-equatorial and all-axial form; the first is preferred in both solid and gas phase. The gallium-based Lewis acid {CH2Si(Me)[C2Ga(Et)2]}3 was reacted with a tridentate Lewis base (1,3,5-trimethyl-1,3,5-triazacyclohexane) in an NMR titration experiment. The generated host-guest complexes involved in the equilibria during this reaction were identified by DOSY NMR spectroscopy by comparing measured diffusion coefficients with those of the suitable reference compounds of same size and shape.

  16. a Proposal for a General Method for Determining Semi-Experimental Equilibrium Structures of Carbon Atom Backbones

    Science.gov (United States)

    Craig, Norman C.

    2010-06-01

    Semi-experimental equilibrium structures are determined from ground state rotational constants derived from the analysis of rotational transitions in high-resolution spectra and from the quantum chemical calculation of spectroscopic alphas. In the full application of this method, spectra of numerous isotopic species must be investigated. Most of these isotopic species require specialized synthesis. We now propose focusing on the carbon atoms, for which microwave spectroscopy routinely yields spectra for polar molecules with 13C substitution in natural abundance. Needed spectroscopic alphas can be computed with Gaussian software. Application of the Kraitchman substitution relationships gives Cartesian coordinates for the carbon atoms and thence bond parameters for the carbon backbone. This method will be evaluated with ethylene, 1,1-difluoroethylene, 1,1-difluorocyclopropane, propene, and butadiene. The method will then be applied to cis-hexatriene and the two conformers of glycidol. R. D. Suenram, B. H. Pate, A. Lessari, J. L. Neill, S. Shipman, R. A. Holmes, M. C. Leyden, and N. C. Craig, J. Phys. Chem. A 113, 1864-1868 (2009). A. R. Conrad, N. H. Teumelsan, P. E. Wang, and M. J. Tubergen, J. Phys. Chem. A 114, 336-342 (2010).

  17. Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

    KAUST Repository

    Maadooliat, Mehdi

    2012-08-27

    Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence-structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu. edu/~madoliat/LagSVD) that can be used to produce informative animations. © The Author 2012. Published by Oxford University Press.

  18. TACN-based cationic lipids with amino acid backbone and double tails: materials for non-viral gene delivery.

    Science.gov (United States)

    Wang, Bing; Yi, Wen-Jing; Zhang, Ji; Zhang, Qin-Fang; Xun, Miao-Miao; Yu, Xiao-Qi

    2014-04-01

    Cationic lipids have become an efficient type of non-viral vectors for gene delivery. In this Letter, four cationic lipids containing 1,4,7-triazacyclononane (TACN) headgroup, glutamic/aspartic acid backbone and dioleyl tails were designed and synthesized. The TACN headgroup gives these lipids excellent pH buffering capacities, which were higher than branched 25 kDa PEI. Cationic liposomes prepared from these lipids and DOPE showed good DNA affinity, and full DNA condensation was found at N/P ratio of 3 via agarose gel electrophoresis. The lipoplexes were characterized by dynamic light scattering (DLS) assay, which gave proper particle sizes and zeta-potentials for transfection. In vitro gene transfection results in two cell lines reveal that TAN (with aspartic acid and amide bond in the structure) shows the best transfection efficiency, which is close to commercially available transfection agent Lipofectamine 2000.

  19. Proton-detected MAS NMR experiments based on dipolar transfers for backbone assignment of highly deuterated proteins

    Science.gov (United States)

    Chevelkov, Veniamin; Habenstein, Birgit; Loquet, Antoine; Giller, Karin; Becker, Stefan; Lange, Adam

    2014-05-01

    Proton-detected solid-state NMR was applied to a highly deuterated insoluble, non-crystalline biological assembly, the Salmonella typhimurium type iii secretion system (T3SS) needle. Spectra of very high resolution and sensitivity were obtained at a low protonation level of 10-20% at exchangeable amide positions. We developed efficient experimental protocols for resonance assignment tailored for this system and the employed experimental conditions. Using exclusively dipolar-based interspin magnetization transfers, we recorded two sets of 3D spectra allowing for an almost complete backbone resonance assignment of the needle subunit PrgI. The additional information provided by the well-resolved proton dimension revealed the presence of two sets of resonances in the N-terminal helix of PrgI, while in previous studies employing 13C detection only a single set of resonances was observed.

  20. Solid State Nuclear Magnetic Resonance Investigation of Polymer Backbone Dynamics in Poly(Ethylene Oxide) Based Lithium and Sodium Polyether-ester-sulfonate Ionomers

    Energy Technology Data Exchange (ETDEWEB)

    Roach, David J.; Dou, Shichen; Colby, Ralph H.; Mueller, Karl T.

    2013-01-01

    Polymer backbone dynamics of single ion conducting poly(ethylene oxide) (PEO)-based ionomer samples with low glass transition temperatures (Tg) have been investigated using solid-state nuclear magnetic resonance (NMR). Experiments detecting 13C with 1H decoupling under magic angle spinning (MAS) conditions identified the different components of the polymer backbone (PEO spacer and isophthalate groups) and their relative mobilities for a suite of lithium- and sodium-containing ionomer samples with varying cation contents. Variable temperature (203-373 K) 1H-13C cross-polarization MAS (CP-MAS) experiments also provided qualitative assessment of the differences in the motions of the polymer backbone components as a function of cation content and identity. Each of the main backbone components exhibit distinct motions, following the trends expected for motional characteristics based on earlier Quasi Elastic Neutron Scattering and 1H spin-lattice relaxation rate measurements. Previous 1H and 7Li spin-lattice relaxation measurements focused on both the polymer backbone and cation motion on the nanosecond timescale. The studies presented here assess the slower timescale motion of the polymer backbone allowing for a more comprehensive understanding of the polymer dynamics. The temperature dependences of 13C linewidths were used to both qualitatively and quantitatively examine the effects of cation content and identity on PEO spacer mobility. Variable contact time 1H-13C CP-MAS experiments were used to further assess the motions of the polymer backbone on the microsecond timescale. The motion of the PEO spacer, reported via the rate of magnetization transfer from 1H to 13C nuclei, becomes similar for T ≳ 1.1 Tg in all ionic samples, indicating that at similar elevated reduced temperatures the motions of the polymer backbones on the microsecond timescale become insensitive to ion interactions. These results present an improved picture, beyond those of previous findings, for

  1. Testing Backbone.js

    CERN Document Server

    Roemer, Ryan

    2013-01-01

    This book is packed with the step by step tutorial and instructions in recipe format helping you setup test infrastructure and gradually advance your skills to plan, develop, and test your backbone applications.If you are a JavaScript developer looking for recipes to create and implement test support for your backbone application, then this book is ideal for you.

  2. Predicting disease-related proteins based on clique backbone in protein-protein interaction network.

    Science.gov (United States)

    Yang, Lei; Zhao, Xudong; Tang, Xianglong

    2014-01-01

    Network biology integrates different kinds of data, including physical or functional networks and disease gene sets, to interpret human disease. A clique (maximal complete subgraph) in a protein-protein interaction network is a topological module and possesses inherently biological significance. A disease-related clique possibly associates with complex diseases. Fully identifying disease components in a clique is conductive to uncovering disease mechanisms. This paper proposes an approach of predicting disease proteins based on cliques in a protein-protein interaction network. To tolerate false positive and negative interactions in protein networks, extending cliques and scoring predicted disease proteins with gene ontology terms are introduced to the clique-based method. Precisions of predicted disease proteins are verified by disease phenotypes and steadily keep to more than 95%. The predicted disease proteins associated with cliques can partly complement mapping between genotype and phenotype, and provide clues for understanding the pathogenesis of serious diseases.

  3. A lysosome-targeted drug delivery system based on sorbitol backbone towards efficient cancer therapy.

    Science.gov (United States)

    Maniganda, Santhi; Sankar, Vandana; Nair, Jyothi B; Raghu, K G; Maiti, Kaustabh K

    2014-09-14

    A straightforward synthetic approach was adopted for the construction of a lysosome-targeted drug delivery system (TDDS) using sorbitol scaffold (Sor) linked to octa-guanidine and tetrapeptide GLPG, a peptide substrate of lysosomal cysteine protease, cathepsin B. The main objective was to efficiently deliver the potential anticancer drug, doxorubicin to the target sites, thereby minimizing dose-limiting toxicity. Three TDDS vectors were synthesized viz., DDS1: Sor-GLPG-Fl, DDS2: Sor-Fl (control) and DDS3: Sor-GLPGC-SMCC-Dox. Dox release from DDS3 in the presence of cathepsin B was studied by kinetics measurement based on the fluorescent property of Dox. The cytotoxicity of DDS1 was assessed and found to be non-toxic. Cellular internalization and colocalization studies of all the 3 systems were carried out by flow cytometry and confocal microscopy utilizing cathepsin B-expressing HeLa cells. DDS1 and DDS3 revealed significant localization within the lysosomes, in contrast to DDS2 (control). The doxorubicin-conjugated carrier, DDS3, demonstrated significant cytotoxic effect when compared to free Dox by MTT assay and also by flow cytometric analysis. The targeted approach with DDS3 is expected to be promising, because it is indicated to be advantageous over free Dox, which possesses dose-limiting toxicity, posing risk of injury to normal tissues.

  4. Root-mean-square-deviation-based rapid backbone resonance assignments in proteins.

    Science.gov (United States)

    Rout, Ashok K; Barnwal, Ravi P; Agarwal, Geetika; Chary, Kandala V R

    2010-10-01

    We have shown that the methodology based on the estimation of root-mean-square deviation (RMSD) between two sets of chemical shifts is very useful to rapidly assign the spectral signatures of (1)H(N), (13)C(α), (13)C(β), (13)C', (1)H(α) and (15)N spins of a given protein in one state from the knowledge of its resonance assignments in a different state, without resorting to routine established procedures (manual and automated). We demonstrate the utility of this methodology to rapidly assign the 3D spectra of a metal-binding protein in its holo-state from the knowledge of its assignments in apo-state, the spectra of a protein in its paramagnetic state from the knowledge of its assignments in diamagnetic state and, finally, the spectra of a mutant protein from the knowledge of the chemical shifts of the corresponding wild-type protein. The underlying assumption of this methodology is that, it is impossible for any two amino acid residues in a given protein to have all the six chemical shifts degenerate and that the protein under consideration does not undergo large conformational changes in going from one conformational state to another. The methodology has been tested using experimental data on three proteins, M-crystallin (8.5 kDa, predominantly β-sheet, for apo- to holo-state), Calbindin (7.5 kDa, predominantly α-helical, for diamagnetic to paramagnetic state and apo to holo) and EhCaBP1 (14.3 kDa, α-helical, the wild-type protein with one of its mutant). In all the cases, the extent of assignment is found to be greater than 85%.

  5. Residual dipolar couplings in short peptidic foldamers: combined analyses of backbone and side-chain conformations and evaluation of structure coordinates of rigid unnatural amino acids.

    Science.gov (United States)

    Schmid, Markus B; Fleischmann, Matthias; D'Elia, Valerio; Reiser, Oliver; Gronwald, Wolfram; Gschwind, Ruth M

    2009-02-13

    A flexible tool for rigid systems. Residual dipolar couplings (RDCs) have proven to be valuable NMR structural parameters that provide insights into the backbone conformations of short linear peptidic foldamers, as illustrated here. This study demonstrates that RDCs at natural abundance can provide essential structural information even in the case of short linear peptides with unnatural amino acids. In addition, they allow for the detection of proline side-chain conformations and are used as a quality check for the parameterizations of rigid unnatural amino acids.

  6. Future High Capacity Backbone Networks

    DEFF Research Database (Denmark)

    Wang, Jiayuan

    This thesis - Future High Capacity Backbone Networks - deals with the energy efficiency problems associated with the development of future optical networks. In the first half of the thesis, novel approaches for using multiple/single alternative energy sources for improving energy efficiency...... the context of the integrated control plane structure. Results show improvements of energy efficiency over three types of traffic, while still keeping acceptable QoS levels for high priority traffic....

  7. Progress in palladium-based catalytic systems for the sustainable synthesis of annulated heterocycles: a focus on indole backbones.

    Science.gov (United States)

    Platon, Mélanie; Amardeil, Régine; Djakovitch, Laurent; Hierso, Jean-Cyrille

    2012-05-21

    A survey highlighting the most recent palladium catalytic systems produced and their performances for progress in direct synthesis of indole backbones by heterocarbocyclization of reactive substrates is provided. The discussion is developed in relation with the principles of sustainable chemistry concerning atom and mass economy. In this respect, the general convergent character of the syntheses is of particular interest (one-pot, domino, cascade or tandem reactions), and the substrates accessibility and reactivity, together with the final waste production, are also important. This critical review clearly indicates that the development of ligand chemistry, mainly phosphines and carbenes, in the last few decades gave a significant impetus to powerful functionalization of indoles at virtually all positions of this ubiquitous backbone (118 references).

  8. NMR solution structure and backbone dynamics of domain III of the E protein of tick-borne Langat flavivirus suggests a potential site for molecular recognition.

    Science.gov (United States)

    Mukherjee, Munia; Dutta, Kaushik; White, Mark A; Cowburn, David; Fox, Robert O

    2006-06-01

    Flaviviruses cause many human diseases, including dengue fever, yellow fever, West Nile viral encephalitis, and hemorrhagic fevers, and are transmitted to their vertebrate hosts by infected mosquitoes and ticks. Domain III of the envelope protein (E-D3) is considered to be the primary viral determinant involved in the virus-host-cell receptor interaction, and thus represents an excellent target for antiviral drug development. Langat (LGT) virus is a naturally attenuated BSL-2 TBE virus and is a model for the pathogenic BSL-3 and BSL-4 viruses in the serogroup. We have determined the solution structure of LGT-E-D3 using heteronuclear NMR spectroscopy. The backbone dynamics of LGT-E-D3 have been investigated using 15N relaxation measurements. A detailed analysis of the solution structure and dynamics of LGT-E-D3 suggests potential residues that could form a surface for molecular recognition, and thereby represent a target site for antiviral therapeutics design.

  9. 2D IR spectroscopy of histidine: probing side-chain structure and dynamics via backbone amide vibrations.

    Science.gov (United States)

    Ghosh, Ayanjeet; Tucker, Matthew J; Gai, Feng

    2014-07-17

    It is well known that histidine is involved in many biological functions due to the structural versatility of its side chain. However, probing the conformational transitions of histidine in proteins, especially those occurring on an ultrafast time scale, is difficult. Herein we show, using a histidine dipeptide as a model, that it is possible to probe the tautomer and protonation status of a histidine residue by measuring the two-dimensional infrared (2D IR) spectrum of its amide I vibrational transition. Specifically, for the histidine dipeptide studied, the amide unit of the histidine gives rise to three spectrally resolvable amide I features at approximately 1630, 1644, and 1656 cm(-1), respectively, which, based on measurements at different pH values and frequency calculations, are assigned to a τ tautomer (1630 cm(-1) component) and a π tautomer with a hydrated (1644 cm(-1) component) or dehydrated (1656 cm(-1) component) amide. Because of the intrinsic ultrafast time resolution of 2D IR spectroscopy, we believe that the current approach, when combined with the isotope editing techniques, will be useful in revealing the structural dynamics of key histidine residues in proteins that are important for function.

  10. Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells

    Science.gov (United States)

    Yu, Yuan; Tong, Qi; Li, Zhongxia; Tian, Jinhai; Wang, Yizhi; Su, Feng; Wang, Yongsheng; Liu, Jun; Zhang, Yong

    2014-02-01

    PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.

  11. General order parameter based correlation analysis of protein backbone motions between experimental NMR relaxation measurements and molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qing; Shi, Chaowei [Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026 (China); Yu, Lu [Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui, 230031 (China); Zhang, Longhua [Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026 (China); Xiong, Ying, E-mail: yxiong73@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026 (China); Tian, Changlin, E-mail: cltian@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui, 230031 (China)

    2015-02-13

    Internal backbone dynamic motions are essential for different protein functions and occur on a wide range of time scales, from femtoseconds to seconds. Molecular dynamic (MD) simulations and nuclear magnetic resonance (NMR) spin relaxation measurements are valuable tools to gain access to fast (nanosecond) internal motions. However, there exist few reports on correlation analysis between MD and NMR relaxation data. Here, backbone relaxation measurements of {sup 15}N-labeled SH3 (Src homology 3) domain proteins in aqueous buffer were used to generate general order parameters (S{sup 2}) using a model-free approach. Simultaneously, 80 ns MD simulations of SH3 domain proteins in a defined hydrated box at neutral pH were conducted and the general order parameters (S{sup 2}) were derived from the MD trajectory. Correlation analysis using the Gromos force field indicated that S{sup 2} values from NMR relaxation measurements and MD simulations were significantly different. MD simulations were performed on models with different charge states for three histidine residues, and with different water models, which were SPC (simple point charge) water model and SPC/E (extended simple point charge) water model. S{sup 2} parameters from MD simulations with charges for all three histidines and with the SPC/E water model correlated well with S{sup 2} calculated from the experimental NMR relaxation measurements, in a site-specific manner. - Highlights: • Correlation analysis between NMR relaxation measurements and MD simulations. • General order parameter (S{sup 2}) as common reference between the two methods. • Different protein dynamics with different Histidine charge states in neutral pH. • Different protein dynamics with different water models.

  12. ``Pinning strategy": a novel approach for predicting the backbone structure in terms of protein blocks from sequence

    Indian Academy of Sciences (India)

    A G De Brevern; C Etchebest; C Benros; S Hazout

    2007-01-01

    The description of protein 3D structures can be performed through a library of 3D fragments, named a structural alphabet. Our structural alphabet is composed of 16 small protein fragments of 5 C in length, called protein blocks (PBs). It allows an efficient approximation of the 3D protein structures and a correct prediction of the local structure. The 72 most frequent series of 5 consecutive PBs, called structural words (SWs) are able to cover more than 90% of the 3D structures. PBs are highly conditioned by the presence of a limited number of transitions between them. In this study, we propose a new method called “pinning strategy” that used this specific feature to predict long protein fragments. Its goal is to define highly probable successions of PBs. It starts from the most probable SW and is then extended with overlapping SWs. Starting from an initial prediction rate of 34.4%, the use of the SWs instead of the PBs allows a gain of 4.5%. The pinning strategy simply applied to the SWs increases the prediction accuracy to 39.9%. In a second step, the sequence-structure relationship is optimized, the prediction accuracy reaches 43.6%.

  13. Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.

    Directory of Open Access Journals (Sweden)

    Damien B Wilburn

    Full Text Available In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s without the immediate need for complementary mutations. Consequently

  14. Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.

    Science.gov (United States)

    Wilburn, Damien B; Bowen, Kathleen E; Doty, Kari A; Arumugam, Sengodagounder; Lane, Andrew N; Feldhoff, Pamela W; Feldhoff, Richard C

    2014-01-01

    In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP) superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF) is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s) without the immediate need for complementary mutations. Consequently, this unique

  15. Molecular Data for a Biochemical Model of DNA Radiation Damage: Electron Impact Ionization and Dissociative Ionization of DNA Bases and Sugar-Phosphate Backbone

    Science.gov (United States)

    Dateo, Christopher E.; Fletcher, Graham D.

    2004-01-01

    As part of the database for building up a biochemical model of DNA radiation damage, electron impact ionization cross sections of sugar-phosphate backbone and DNA bases have been calculated using the improved binary-encounter dipole (iBED) model. It is found that the total ionization cross sections of C3'- and C5'-deoxyribose-phospate, two conformers of the sugar-phosphate backbone, are close to each other. Furthermore, the sum of the ionization cross sections of the separate deoxyribose and phosphate fragments is in close agreement with the C3'- and C5'-deoxyribose-phospate cross sections, differing by less than 10%. Of the four DNA bases, the ionization cross section of guanine is the largest, then in decreasing order, adenine, thymine, and cytosine. The order is in accordance with the known propensity of oxidation of the bases by ionizing radiation. Dissociative ionization (DI), a process that both ionizes and dissociates a molecule, is investigated for cytosine. The DI cross section for the formation of H and (cytosine-Hl)(+), with the cytosine ion losing H at the 1 position, is also reported. The threshold of this process is calculated to be 17.1 eV. Detailed analysis of ionization products such as in DI is important to trace the sequential steps in the biochemical process of DNA damage.

  16. Orientation-dependent backbone-only residue pair scoring functions for fixed backbone protein design

    Directory of Open Access Journals (Sweden)

    Bordner Andrew J

    2010-04-01

    Full Text Available Abstract Background Empirical scoring functions have proven useful in protein structure modeling. Most such scoring functions depend on protein side chain conformations. However, backbone-only scoring functions do not require computationally intensive structure optimization and so are well suited to protein design, which requires fast score evaluation. Furthermore, scoring functions that account for the distinctive relative position and orientation preferences of residue pairs are expected to be more accurate than those that depend only on the separation distance. Results Residue pair scoring functions for fixed backbone protein design were derived using only backbone geometry. Unlike previous studies that used spherical harmonics to fit 2D angular distributions, Gaussian Mixture Models were used to fit the full 3D (position only and 6D (position and orientation distributions of residue pairs. The performance of the 1D (residue separation only, 3D, and 6D scoring functions were compared by their ability to identify correct threading solutions for a non-redundant benchmark set of protein backbone structures. The threading accuracy was found to steadily increase with increasing dimension, with the 6D scoring function achieving the highest accuracy. Furthermore, the 3D and 6D scoring functions were shown to outperform side chain-dependent empirical potentials from three other studies. Next, two computational methods that take advantage of the speed and pairwise form of these new backbone-only scoring functions were investigated. The first is a procedure that exploits available sequence data by averaging scores over threading solutions for homologs. This was evaluated by applying it to the challenging problem of identifying interacting transmembrane alpha-helices and found to further improve prediction accuracy. The second is a protein design method for determining the optimal sequence for a backbone structure by applying Belief Propagation

  17. (nBuCp)2ZrCl2-catalyzed Ethylene-4M1P Copolymerization: Copolymer Backbone Structure, Melt Behavior, and Crystallization

    KAUST Repository

    Atiqullah, Muhammad

    2016-01-08

    The judicious design of methylaluminoxane (MAO) anions expands the scope for developing industrial metallocene catalysts. Therefore, the effects of MAO anion design on the backbone structure, melt behavior, and crystallization of ethylene−4-methyl-1-pentene (E−4M1P) copolymer were investigated. Ethylene was homopolymerized, as well as copolymerized with 4M1P, using (i) MAO anion A (unsupported [MAOCl2]−) premixed with dehydroxylated silica, (nBuCp)2ZrCl2, and Me2SiCl2; and (ii) MAO anion B (Si−O−Me2Si−[MAOCl2]−) supported with (nBuCp)2ZrCl2 on Me2SiCl2-functionalized silica. Unsupported Me2SiCl2, opposite to the supported analogue, acted as a co-chain transfer agent with 4M1P. The modeling of polyethylene melting and crystallization kinetics, including critical crystallite stability, produced insightful results. This study especially illustrates how branched polyethylene can be prepared from ethylene alone using particularly one metallocene-MAO ion pair, and how a compound, that functionalizes silica as well as terminates the chain, can synthesize ethylene−α-olefin copolymers with novel structures. Hence, it unfolds prospective future research niches in polyethyne systhesis. This article is protected by copyright. All rights reserved.

  18. Prenylation and Backbone Structure of Flavonoids and Isoflavonoids from Licorice and Hop Influence Their Phase i and II Metabolism

    NARCIS (Netherlands)

    De Schans, Van Milou G.M.; Bovee, Toine F.H.; Stoopen, Geert M.; Lorist, Marlies; Gruppen, Harry; Vincken, Jean Paul

    2015-01-01

    In vitro liver metabolism of 11 prenylated flavonoids and isoflavonoids was investigated by determining their phase I glucuronyl and sulfate metabolites using pork liver preparations. One hundred metabolites were annotated using RP-UHPLC-ESI-MSn. A mass spectrometry-based data interpre

  19. Influence of Backbone Structure on Properties of Directly Polymerized Phenoxy Resins from Epichlorohydrin and Various Aromatic Dihydric Phenols Monomers

    Institute of Scientific and Technical Information of China (English)

    CAI Hong-li; BI Da-wu; SHAO Ke; ZHONG Shuang-ling; NA Hui

    2007-01-01

    A series of phenoxy resins was directly prepared through the polymerization of each of the various aromatic dihydric phenols and epichlorohydrin. FTIR and 1H NMR spectra were recorded to characterize the structures of the resins. The GPC curves were used to determine the molecular weight distribution. In addition, the thermal properties of the resins were studied with differential scanning calorimetry ( DSC ) and thermal gravimetric analysis (TGA). The thermal stabilities of the polymers increased with the content of the benzene ring, pendant group increasing or biphe nyl groups emerging. The adhesive properties of the polymers were evaluated in terms of the lap shear strength with Fe-Fe adherends. The fracture mechanisms were determined by SEM observation and it was found that there was an important participation of cohesive fracture mechanisms. Also, it has been demonstrated that the extension of these micro-cohesive mechanisms is directly correlated with the adhesive strength. According to these results, the phenoxy resin containing biphenyl groups presented a higher adhesive strength and could improve the adhesive property of the epoxy/phenoxy system to a certain extent.

  20. Refined solution structure and backbone dynamics of 15N-labeled C12A-p8MTCP studied by NMR relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Barthe, Philippe; Chiche, Laurent; Declerck, Nathalie; Delsuc, Marc-Andre [Universite de Montpellier I, Faculte de Pharmacie, Centre de Biochimie Structurale, CNRS-UMR 9955, INSERM-U414 (France); Lefevre, Jean-Francois [Universite Louis Pasteur, CNRS UPR-9003, ESBS (France); Malliavin, Therese [Universite de Montpellier I, Faculte de Pharmacie, Centre de Biochimie Structurale, CNRS-UMR 9955, INSERM-U414 (France); Mispelter, Joel [Centre Universitaire Bat 112, INSERM-U350, Institut Curie, Biologie (France); Stern, Marc-Henri [Hopital Saint-Louis, Unite INSERM-U462 (France); Lhoste, Jean-Marc; Roumestand, Christian [Universite de Montpellier I, Faculte de Pharmacie, Centre de Biochimie Structurale, CNRS-UMR 9955, INSERM-U414 (France)

    1999-12-15

    MTCP1 (for Mature-T-Cell Proliferation) was the first gene unequivocally identified in the group of uncommon leukemias with a mature phenotype. The three-dimensional solution structure of the human p8{sup MTCP} protein encoded by the MTCP1 oncogene has been previously determined by homonuclear proton two-dimensional NMR methods at 600 MHz: it consists of an original scaffold comprising three {alpha}-helices, associated with a new cysteine motif. Two of the helices are covalently paired by two disulfide bridges, forming an {alpha}-hairpin which resembles an antiparallel coiled-coil. The third helix is orientated roughly parallel to the plane defined by the {alpha}-antiparallel motif and appears less well defined. In order to gain more insight into the details of this new scaffold, we uniformly labeled with nitrogen-15 a mutant of this protein (C12A-p8{sup MTCP1}) in which the unbound cysteine at position 12 has been replaced by an alanine residue, thus allowing reproducibly high yields of recombinant protein. The refined structure benefits from 211 additional NOEs, extracted from {sup 15}N-edited 3D experiments, and from a nearly complete set of {phi} angular restraints allowing the estimation of the helical content of the structured part of the protein. Moreover, measurements of {sup 15} N spin relaxation times and heteronuclear {sup 15} N{sup 1}HNOEs provided additional insights into the dynamics of the protein backbone. The analysis of the linear correlation between J(0) and J({omega}) was used to interpret relaxation parameters. It appears that the apparent relative disorder seen in helix III is not simply due to a lack of experimental constraints, but associated with substantial contributions of sub-nanosecond motions in this segment.

  1. A new ligand system based on a bipyridine-functionalized calix[4]arene backbone leading to mono- and bimetallic complexes.

    Science.gov (United States)

    Dorta, Reto; Shimon, Linda J W; Rozenberg, Haim; Ben-David, Yehoshoa; Milstein, David

    2003-05-19

    The synthesis of a new ligand system for mono- and bimetallic complexes based on a calixarene is described. Ligand BBPC (3, bis(bipyridine)-calix[4]arene) is obtained in three steps in 40% overall yield by first brominating one of the methyl groups of the 4,4'-dimethyl-2,2'-bipyridine in two steps and subsequently reacting it with p-tert-butylcalix[4]arene under basic conditions. Reaction of BBPC (3) with 2 equiv of [Rh(NBD)(2)]BF(4) or [Rh(NBD)(CH(3)CN)(2)]BF(4) (NBD = norbornadiene) produces the bimetallic compound BBPC[Rh(NBD)BF(4)](2) (4). Treatment of the ligand with PdCl(2)(CH(3)CN)(2) leads to the isolation of the bimetallic complex BBPC[PdCl(2)](2) (5). When the nickel precursor NiBr(2)(DME) (DME = dimethoxyethane) is reacted with BBPC, the bimetallic complex BBPC[NiBr(2)](2) (6) is isolated which, upon crystallization from methanol, gives the mononuclear bis(bipyridine) complex BBPC[NiBr(OMe)] (7). Full characterization includes X-ray structural studies of complexes 4, 5, and 7. The bimetallic compounds 4 and 5 show metal to metal distances of 4.334 A (for 4) and 3.224 A (for 5). For all three complexes, unique molecular packing arrangements were found, based on hydrophobic/hydrophilic interactions.

  2. Molecular data for a biochemical model of DNA damage: Electron impact ionization and dissociative ionization cross sections of DNA bases and sugar-phosphate backbone

    Energy Technology Data Exchange (ETDEWEB)

    Huo, Winifred M. [NASA Ames Research Center, Mail Stop T27B-1, Moffett Field, CA 94035-1000 (United States)]. E-mail: whuo@mail.arc.nasa.gov; Dateo, Christopher E. [ELORET Corporation, Sunnyvale, CA (United States); Fletcher, Graham D. [ELORET Corporation, Sunnyvale, CA (United States)

    2006-10-15

    As part of the database for building up a biochemical model of DNA radiation damage, electron impact ionization cross sections of sugar-phosphate backbone and DNA bases have been calculated using the improved binary-encounter dipole (iBED) model. It is found that the total ionization cross sections of C{sub 3}{sup '}- and C{sub 5}{sup '}-deoxyribose-phosphate, two conformers of the sugar-phosphate backbone, are close to each other. Furthermore, the sum of the ionization cross sections of the separate deoxyribose and phosphate fragments is in close agreement with the C{sub 3}{sup '}- and C{sub 5}{sup '}-deoxyribose-phosphate cross sections, differing by less than 10%, an indication that a building-up principle may be applicable. Of the four DNA bases, the ionization cross section of guanine is the largest, then in decreasing order, adenine, thymine, and cytosine. The order is in accordance with the known propensity of oxidation of the bases by ionizing radiation. Dissociative ionization (DI), a process that both ionizes and dissociates a molecule, is investigated for cytosine. The DI cross section for the formation of H and (cytosine-H1){sup +}, with the cytosine ion losing H at the 1 position, is also reported. The threshold of this process is calculated to be 16.9eV. Detailed analysis of ionization products such as in DI is important to trace the sequential steps in the biochemical process of DNA damage.

  3. Investigation of novel solid oxide fuel cell cathodes based on impregnation of SrTixFe1-xO3-δ into ceria-based backbones

    DEFF Research Database (Denmark)

    Brinch-Larsen, Mathias; Søgaard, Martin; Hjelm, Johan;

    2013-01-01

    and electrochemical stability as a thin film electrode have been reported for these materials. XRD measurements showed a high degree of secondary phase formation in the infiltrate as well as reaction with the CGO backbone. Microstructural analysis showed that the STF infiltrate had formed a coating on the CGO...

  4. Peptaibol antiamoebin I: spatial structure, backbone dynamics, interaction with bicelles and lipid-protein nanodiscs, and pore formation in context of barrel-stave model.

    Science.gov (United States)

    Shenkarev, Zakhar O; Paramonov, Alexander S; Lyukmanova, Ekaterina N; Gizatullina, Albina K; Zhuravleva, Anastasia V; Tagaev, Andrey A; Yakimenko, Zoya A; Telezhinskaya, Irina N; Kirpichnikov, Mikhail P; Ovchinnikova, Tatiana V; Arseniev, Alexander S

    2013-05-01

    Antiamoebin I (Aam-I) is a membrane-active peptaibol antibiotic isolated from fungal species belonging to the genera Cephalosporium, Emericellopsis, Gliocladium, and Stilbella. In comparison with other 16-amino acid-residue peptaibols, e.g., zervamicin IIB (Zrv-IIB), Aam-I possesses relatively weak biological and channel-forming activities. In MeOH solution, Aam-I demonstrates fast cooperative transitions between right-handed and left-handed helical conformation of the N-terminal (1-8) region. We studied Aam-I spatial structure and backbone dynamics in the membrane-mimicking environment (DMPC/DHPC bicelles)(1) ) by heteronuclear (1) H,(13) C,(15) N-NMR spectroscopy. Interaction with the bicelles stabilizes the Aam-I right-handed helical conformation retaining significant intramolecular mobility on the ms-μs time scale. Extensive ms-μs dynamics were also detected in the DPC and DHPC micelles and DOPG nanodiscs. In contrast, Zrv-IIB in the DPC micelles demonstrates appreciably lesser mobility on the μs-ms time scale. Titration with Mn(2+) and 16-doxylstearate paramagnetic probes revealed Aam-I binding to the bicelle surface with the N-terminus slightly immersed into hydrocarbon region. Fluctuations of the Aam-I helix between surface-bound and transmembrane (TM) state were observed in the nanodisc membranes formed from the short-chain (diC12 : 0) DLPC/DLPG lipids. All the obtained experimental data are in agreement with the barrel-stave model of TM pore formation, similarly to the mechanism proposed for Zrv-IIB and other peptaibols. The observed extensive intramolecular dynamics explains the relatively low activity of Aam-I.

  5. Backbone analysis and algorithm design for the quadratic assignment problem

    Institute of Scientific and Technical Information of China (English)

    JIANG He; ZHANG XianChao; CHEN GuoLiang; LI MingChu

    2008-01-01

    As the hot line in NP-hard problems research in recent years, backbone analysis is crucial for phase transition, hardness, and algorithm design. Whereas theoretical analysis of backbone and its applications in algorithm design are still at a begin-ning state yet, this paper took the quadratic assignment problem (QAP) as a case study and proved by theoretical analysis that it is NP-hard to find the backbone, l.e., no algorithm exists to obtain the backbone of a QAP in polynomial time. Results of this paper showed that it is reasonable to acquire approximate backbone by inter-section of local optimal solutions. Furthermore, with the method of constructing biased instances, this paper proposed a new meta-heuristic - biased instance based approximate backbone (BI-AB), whose basic idea is as follows: firstly, con-struct a new biased instance for every QAP instance (the optimal solution of the new instance is also optimal for the original one); secondly, the approximate backbone is obtained by intersection of multiple local optimal solutions computed by some existing algorithm; finally, search for the optimal solutions in the reduced space by fixing the approximate backbone. Work of the paper enhanced the re-search area of theoretical analysis of backbone. The meta-heuristic proposed in this paper provided a new way for general algorithm design of NP-hard problems as well.

  6. SYNTHESIS AND CHARACTERIZATION OF A NEW COMBLIKE POLYMER BASED ON POLY (VINYL METHYL ETHER-ALT-MALEIC ANHYDRIDE) BACKBONE

    Institute of Scientific and Technical Information of China (English)

    DING Liming; LIN Yunqing; ZHOU Zinan; NI Jianlong; CHEN Donglin

    1995-01-01

    A new comblike polymer host for polymer electrolyte was synthesized by reacting monomethyl ether of poly(ethylene glycol) with poly(vinyl methyl ether-alt-maleic anhydride) and endcapping the residual carboxylic acid with methanol. Butanone was selected as a solvent for the esterification in order to obtain a completely soluble product. The synthesis process was traced through by IR. Compared with the model compounds, the presumed structure of this comblike polymer has been proved to be valid by 13C NMR. The comb polymer is a white rubbery solid. It can be dissolved in butanone and THF, and manifests good film forming ability.

  7. Diketene-based neat four-component synthesis of the dihydropyrimidinones and dihydropyridine backbones using silica sulfuric acid (SSA)

    Institute of Scientific and Technical Information of China (English)

    Sadegh Rostamnia; Kamran Lamei

    2012-01-01

    Heterocyclic skeleton building blocks to afford dihydropyrimidinones and dihydropyridines based on neat adducts of diketene,alcohols and aldehydes via silica sulfuric acid (SSA) catalyzed ring opening of diketene in four-c6mponent Biginelli-type and Hantzsch-type reactions are presented.

  8. Negative-ion Electrospray Tandem Mass Spectrometry and Microarray Analyses of Developmentally-regulated Antigens Based on Type 1 and Type 2 Backbone Sequences

    Science.gov (United States)

    Gao, Chao; Zhang, Yibing; Liu, Yan; Feizi, Ten; Chai, Wengang

    2016-01-01

    Type 1 (Galβ1-3GlcNAc) and type 2 (Galβ1-4GlcNAc) sequences are constituents of the backbones of a large family of glycans of glycoproteins and glycolipids whose branching and peripheral substitutions are developmentally-regulated. It is highly desirable to have micro-sequencing methods that can be used to precisely identify and monitor these oligosaccharide sequences with high sensitivity. Negative-ion electrospray tandem mass spectrometry with collision-induced dissociation has been used for characterization of branching points, peripheral substitutions and partial assignment of linkages in reducing oligosaccharides. We now extend this method to characterizing entire sequences of linear type 1 and type 2 chain-based glycans, focusing on the type 1 and -2 units in the internal regions including the linkages connecting type 1 and type 2 disaccharide units. We apply the principles to sequence analysis of closely related isomeric oligosaccharides and demonstrate by microarray analyses distinct binding activities of antibodies and a lectin toward various combinations of type 1 and 2 units joined by 1,3- and 1,6-linkages. These sequence-specific carbohydrate-binding proteins are in turn valuable tools for detecting and distinguishing the type 1 and type 2-based developmentally-regulated glycan sequences. PMID:26530895

  9. Negative-Ion Electrospray Tandem Mass Spectrometry and Microarray Analyses of Developmentally Regulated Antigens Based on Type 1 and Type 2 Backbone Sequences.

    Science.gov (United States)

    Gao, Chao; Zhang, Yibing; Liu, Yan; Feizi, Ten; Chai, Wengang

    2015-12-01

    Type 1 (Galβ1-3GlcNAc) and type 2 (Galβ1-4GlcNAc) sequences are constituents of the backbones of a large family of glycans of glycoproteins and glycolipids whose branching and peripheral substitutions are developmentally regulated. It is highly desirable to have microsequencing methods that can be used to precisely identify and monitor these oligosaccharide sequences with high sensitivity. Negative-ion electrospray tandem mass spectrometry with collision-induced dissociation has been used for characterization of branching points, peripheral substitutions, and partial assignment of linkages in reducing oligosaccharides. We now extend this method to characterizing entire sequences of linear type 1 and type 2 chain-based glycans, focusing on the type 1 and type 2 units in the internal regions including the linkages connecting type 1 and type 2 disaccharide units. We apply the principles to sequence analysis of closely related isomeric oligosaccharides and demonstrate by microarray analyses distinct binding activities of antibodies and a lectin toward various combinations of type 1 and 2 units joined by 1,3- and 1,6-linkages. These sequence-specific carbohydrate-binding proteins are in turn valuable tools for detecting and distinguishing the type 1 and type 2-based developmentally regulated glycan sequences.

  10. EFFICIENT WHITE EMITTING COPOLYMERS BASED ON BIPOLAR FLUORENE-co-DIBENZOTHIOPHENE-S,S-DIOXIDE-co-CARBAZOLE BACKBONE

    Institute of Scientific and Technical Information of China (English)

    Lei Ying; Yan-hu Li; Cai-hong Wei; Min-quan Wang; Wei Yang; Hong-bin Wu; Yong Cao

    2013-01-01

    Efficient white light emitting polymers were synthesized based on poly(9,9-dioctylfluorene-co-dibenzothiopheneS,S-dioxide) as blue emitter and a bisphenylamine functionalized 2,1,3-benzothiadiazole (DPABT) as red emitter.It was found that the incorporation of hole-transporting carbazole moiety into polymer main chain could effectively reduce the hole injection barriers,which can lead to distinctly improved charge balance in the emissive layer.Additionally,the holetransporting carbazole units may form efficient bipolar host with electron-transporting dibenzothiophene-S,S-dioxide units.The white light emitting diodes based on single polymer PFSOCzDPABT showed the maximum luminous efficiency of 3.3 cd/A with the maximum luminance of 10282 cd/m2,and the luminous efficiency showed only 24% roll off at current density of 400 mA/cm2.These Commission Intemationale d'Enclairage (CIE) coordinates of the devices changed slightly with the driving voltages increasing from 8 V to 12 V,and were very close to National Television System Committee (NTSC) standard white light emission of (0.33,0.33).The results indicated that the incorporating bipolar host and low band gap DPABT unit was a promising way to achieve efficient single white light emitting copolymers.

  11. Constructing backbone network by using tinker algorithm

    Science.gov (United States)

    He, Zhiwei; Zhan, Meng; Wang, Jianxiong; Yao, Chenggui

    2017-01-01

    Revealing how a biological network is organized to realize its function is one of the main topics in systems biology. The functional backbone network, defined as the primary structure of the biological network, is of great importance in maintaining the main function of the biological network. We propose a new algorithm, the tinker algorithm, to determine this core structure and apply it in the cell-cycle system. With this algorithm, the backbone network of the cell-cycle network can be determined accurately and efficiently in various models such as the Boolean model, stochastic model, and ordinary differential equation model. Results show that our algorithm is more efficient than that used in the previous research. We hope this method can be put into practical use in relevant future studies.

  12. High Performance Infiltrated Backbones for Cathode-Supported SOFC's

    DEFF Research Database (Denmark)

    Gil, Vanesa; Kammer Hansen, Kent

    2014-01-01

    A four-step infiltration method has been developed to infiltrate La0.75Sr0.25MnO3+δ (LSM25) nanoparticles into porous structures (YSZ or LSM-YSZ backbones). The pore size distribution in the backbones is obtained either by using PMMA and/or graphites as pore formers or by leaching treatment of sa...... of samples with Ni remained in the YSZ structure at high temperatures. All impregnated backbones, presented Rs comparable to a standard screen printed cathode, which proves that LSM nanoparticles forms a pathway for electron conduction....

  13. High Performance Infiltrated Backbones for Cathode-Supported SOFC's

    DEFF Research Database (Denmark)

    Gil, Vanesa; Kammer Hansen, Kent

    2014-01-01

    The concept of using highly ionic conducting backbones with subsequent infiltration of electronically conducting particles has widely been used to develop alternative anode-supported SOFC's. In this work, the idea was to develop infiltrated backbones as an alternative design based on cathode......-supported SOFC. The cathodes are obtained by infiltrating LSM into a sintered either thick (300 μm) yttria stabilized zirconia (YSZ) backbone or a thin YSZ backbone (10-15 μm) integrated onto a thick (300 μm) porous strontium substituted lanthanum manganite (LSM) and YSZ composite. Fabrication challenges...... printed symmetrical cells. Samples with LSM/YSZ composite and YSZ backbones made with graphite+PMMA as pore formers exhibited comparable Rp values to the screen printed LSM/YSZ cathode. This route was chosen as the best to fabricate the cathode supported cells. SEM micrograph of a cathode supported cell...

  14. Mechanical reliability of porous low-k dielectrics for advanced interconnect: Study of the instability mechanisms in porous low-k dielectrics and their mediation through inert plasma induced re-polymerization of the backbone structure

    Science.gov (United States)

    Sa, Yoonki

    siloxane backbone structure under 300˜400°C by reaction with -OH, and simultaneously creating a new Si-O-Si crosslink. As an alternative way of increasing the thermo-mechanical reliability, PLK dielectric film with an intrinsically robust structure by controlling pore morphology is fabricated. Since pore surface is susceptible to be damaged by BEOL integration damage, pore morphology in terms of size, distribution, and connectivity should be controlled in order to increase the robustness of PLK dielectrics. Generally, pores in PLK matrix are created by depositing organic fragment (called 'porogen') into the film and removed later by thermal and electron beam cure to form porous PLK layer (; Subtractive deposition). However, during the curing Si-O-Si backbone crosslink is broken and pores are easily interconnected, leading to vulnerable structure to the extrinsic damage. Constitutive deposition approach is feasible for the introduction of smaller nano-pores with little or no interconnectivity by steric hindrance. Due to the closed pore system, thermally-induced stress and plasma-induced damage is restricted merely to the surface of the dielectric film. This is attributed to the stable siloxane (Si-O-Si) backbone and the terminally bonded methyl group attached to silicon (Si-CH3), inducing steric hindrance that lowers the density of the films. The low dielectric constant and mechanical stability are closely involved with the formation of the Si-O-Si cage-like structure and an appropriate combination of stable Si-O-Si, Si-CH3 groups. Based on the FTIR and XPS spectra, it is concluded that the formation of the Si-O-Si cage-like structure was enhanced by structural method. It is believed that all these changes are beneficial for improving PLK stability as will be detailed in this dissertation. Especially, the originality and particular advantage of this study regarding plasma-induced damage repair will be highlighted.

  15. Backbone amide linker strategy

    DEFF Research Database (Denmark)

    Shelton, Anne Pernille Tofteng; Jensen, Knud Jørgen

    2013-01-01

    amino acid residue by reductive amination. This can be used as a general approach for the introduction of other C-terminal modifications as well as functionalities, such as fluorophors. The second step is an acylation of a secondary amine, followed by standard Fmoc-based solid-phase synthesis...

  16. Semiexperimental equilibrium structure for the C6 backbone of cis-1,3,5-hexatriene; structural evidence for greater pi-electron delocalization with increasing chain length in polyenes.

    Science.gov (United States)

    Suenram, Richard D; Pate, Brooks H; Lesarri, Alberto; Neill, Justin L; Shipman, Steven; Holmes, Robin A; Leyden, Matthew C; Craig, Norman C

    2009-03-05

    Twenty-five microwave lines were observed for cis-1,3,5-hexatriene (0.05 D dipole moment) and a smaller number for its three (13)C isotopomers in natural abundance. Ground-state rotational constants were fitted for all four species to a Watson-type rotational Hamiltonian for an asymmetric top (kappa = -0.9768). Vibration-rotation (alpha) constants were predicted with a B3LYP/cc-pVTZ model and used to adjust the ground-state rotational constants to equilibrium rotational constants. The small inertial defect for cis-hexatriene shows that the molecule is planar, despite significant H-H repulsion. The substitution method was applied to the equilibrium rotational constants to give a semiexperimental equilibrium structure for the C(6) backbone. This structure and one predicted with the B3LYP/cc-pVTZ model show structural evidence for increased pi-electron delocalization in comparison with butadiene, the first member of the polyene series.

  17. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    Science.gov (United States)

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  18. Peptoid-Peptide hybrid backbone architectures

    DEFF Research Database (Denmark)

    Olsen, Christian Adam

    2010-01-01

    -amino acids (alpha/beta-peptides) have been investigated in some detail as well. The present Minireview is a survey of the literature concerning hybrid structures of alpha-amino acids and peptoids, including beta-peptoids (N-alkyl-beta-alanine oligomers), and is intended to give an overview of this area......Peptidomimetic oligomers and foldamers have received considerable attention for over a decade, with beta-peptides and the so-called peptoids (N-alkylglycine oligomers) representing prominent examples of such architectures. Lately, hybrid or mixed backbones consisting of both alpha- and beta...

  19. Construction of a novel coarse grain model for simulations of HIV capsid assembly to capture the backbone structure and inter-domain motions in solution

    Directory of Open Access Journals (Sweden)

    Xin Qiao

    2015-12-01

    Full Text Available We show the construction of a novel coarse grain model for simulations of HIV capsid assembly based on four structural models of HIV capsid proteins: isolated hexamer 3H47.pdb, tubular assembly 3J34.pdb, isolated pentamer 3P05.pdb and C-terminus dimer 2KOD.pdb. The data demonstrates the derivation of inter-domain motions from all atom Molecular Dynamics simulations and comparison with the motions derived from the analysis of solution NMR results defined in 2M8L.pdb. Snapshots from a representative Monte Carlo simulation with 128 dimeric subunit proteins based on 3J34.pdb are shown in addition to the quantitative analysis of its assembly pathway. Movies of the assembly process are compiled with snapshots of representative simulations of four structural models. The methods and data in this article were utilized in Qiao et al. (in press [1] to probe the mechanism of polymorphism and curvature control of HIV capsid assembly.

  20. Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures.

    Science.gov (United States)

    Nowotarski, Shannon L; Pachaiyappan, Boobalan; Holshouser, Steven L; Kutz, Craig J; Li, Youxuan; Huang, Yi; Sharma, Shiv K; Casero, Robert A; Woster, Patrick M

    2015-04-01

    Methylation at specific histone lysine residues is a critical post-translational modification that alters chromatin architecture, and dysregulated lysine methylation/demethylation is associated with the silencing of tumor suppressor genes. The enzyme lysine-specific demethylase 1 (LSD1) complexed to specific transcription factors catalyzes the oxidative demethylation of mono- and dimethyllysine 4 of histone H3 (H3K4me and H3K4me2, respectively). We have previously reported potent (bis)urea and (bis)thiourea LSD1 inhibitors that increase cellular levels of H3K4me and H3K4me2, promote the re-expression of silenced tumor suppressor genes and suppress tumor growth in vitro. Here we report the design additional (bis)urea and (bis)thiourea LSD1 inhibitors that feature 3-5-3 or 3-6-3 carbon backbone architectures. Three of these compounds displayed single-digit IC50 values in a recombinant LSD1 assay. In addition, compound 6d exhibited an IC50 of 4.2μM against the Calu-6 human lung adenocarcinoma line, and 4.8μM against the MCF7 breast tumor cell line, in an MTS cell viability assay. Following treatment with 6b-6d, Calu-6 cells exhibited a significant increase in the mRNA expression for the silenced tumor suppressor genes SFRP2, HCAD and p16, and modest increases in GATA4 message. The compounds described in this paper represent the most potent epigenetic modulators in this series, and have potential for use as antitumor agents.

  1. Tuning backbones and side-chains of cationic conjugated polymers for optical signal amplification of fluorescent DNA detection.

    Science.gov (United States)

    Huang, Yan-Qin; Liu, Xing-Fen; Fan, Qu-Li; Wang, Lihua; Song, Shiping; Wang, Lian-Hui; Fan, Chunhai; Huang, Wei

    2009-06-15

    Three cationic conjugated polymers (CCPs) exhibiting different backbone geometries and charge densities were used to investigate how their conjugated backbone and side chain properties, together with the transitions of DNA amphiphilic properties, interplay in the CCP/DNA-C* (DNA-C*: fluorophore-labeled DNA) complexes to influence the optical signal amplification of fluorescent DNA detection based on Förster resonance energy transfer (FRET). By examining the FRET efficiencies to dsDNA-C* (dsDNA: double-stranded DNA) and ssDNA-C* (ssDNA: single-stranded DNA) for each CCP, twisted conjugated backbones and higher charge densities were proved to facilitate electrostatic attraction in CCP/dsDNA-C* complexes, and induced improved sensitivity to DNA hybridization. Especially, by using the CCP with twisted conjugated backbone and the highest charge density, a more than 7-fold higher efficiency of FRET to dsDNA-C* was found than to ssDNA-C*, indicating a high signal amplification for discriminating between dsDNA and ssDNA. By contrast, linear conjugated backbones and lower charge density were demonstrated to favor hydrophobic interactions in CCP/ssDNA-C* complexes. These findings provided guidelines for the design of novel sensitive CCP, which can be useful to recognize many other important DNA activities involving transitions of DNA amphiphilic properties like DNA hybridization, such as specific DNA binding with ions, some secondary or tertiary structural changes of DNA, and so forth.

  2. Reconstruction of Protein Backbones from the BriX Collection of Canonical Protein Fragments

    OpenAIRE

    Lies Baeten; Joke Reumers; Vicente Tur; François Stricher; Tom Lenaerts; Luis Serrano; Frederic Rousseau; Joost Schymkowitz

    2008-01-01

    As modeling of changes in backbone conformation still lacks a computationally efficient solution, we developed a discretisation of the conformational states accessible to the protein backbone similar to the successful rotamer approach in side chains. The BriX fragment database, consisting of fragments from 4 to 14 residues long, was realized through identification of recurrent backbone fragments from a non-redundant set of high-resolution protein structures. BriX contains an alphabet of more ...

  3. Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones.

    Science.gov (United States)

    Voortman, Thomas P; Chiechi, Ryan C

    2015-12-30

    This paper compares the morphologies of films of conjugated polymers in which the backbone (main chain) and pendant groups are varied between ionic/hydrophilic and aliphatic/hydrophobic. We observe that conjugated polymers in which the pendant groups and backbone are matched, either ionic-ionic or hydrophobic-hydrophobic, form smooth, structured, homogeneous films from water (ionic) or tetrahydrofuran (hydrophobic). Mismatched conjugated polymers, by contrast, form inhomogeneous films with rough topologies. The polymers with ionic backbone chains are conjugated polyions (conjugated polymers with closed-shell charges in the backbone), which are semiconducting materials with tunable bad-gaps, not unlike uncharged conjugated polymers.

  4. Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design.

    Directory of Open Access Journals (Sweden)

    Kevin Drew

    Full Text Available Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones, oligooxopiperazines, oligo-peptoids, [Formula: see text]-peptides, hydrogen bond surrogate helices and oligosaccharides. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols (http://rosie.rosettacommons.org. This work helps address the peptidomimetic community's need for an automated and expandable

  5. A novel dengue virus serotype 1 vaccine candidate based on Japanese encephalitis virus vaccine strain SA14-14-2 as the backbone.

    Science.gov (United States)

    Yang, Huiqiang; Li, Zhushi; Lin, Hua; Wang, Wei; Yang, Jian; Liu, Lina; Zeng, Xianwu; Wu, Yonglin; Yu, Yongxin; Li, Yuhua

    2016-06-01

    To develop a potential dengue vaccine candidate, a full-length cDNA clone of a novel chimeric virus was constructed using recombinant DNA technology, with Japanese encephalitis virus (JEV) vaccine strain SA14-14-2 as the backbone, with its premembrane (prM) and envelope (E) genes substituted by their counterparts from dengue virus type 1 (DENV1). The chimeric virus (JEV/DENV1) was successfully recovered from primary hamster kidney (PHK) cells by transfection with the in vitro transcription products of JEV/DENV1 cDNA and was identified by complete genome sequencing and immunofluorescent staining. No neuroinvasiveness of this chimeric virus was observed in mice inoculated by the subcutaneous route (s.c.) or by the intraperitoneal route (i.p.), while some neurovirulence was displayed in mice that were inoculated directly by the intracerebral route (i.c.). The chimeric virus was able to stimulate high-titer production of antibodies against DENV1 and provided protection against lethal challenge with neuroadapted dengue virus in mice. These results suggest that the chimeric virus is a promising dengue vaccine candidate.

  6. A hierarchical virtual backbone construction protocol for mobile ad hoc networks

    Directory of Open Access Journals (Sweden)

    Bharti Sharma

    2016-07-01

    Full Text Available We propose a hierarchical backbone construction protocol for mobile ad hoc networks. Our protocol is based on the idea of using an efficient extrema finding method to create clusters comprising the nodes that are within certain prespecified wireless hop distance. Afterward, we apply our ‘diameter’ algorithm among clusters to identify the dominating nodes that are, finally, connected via multi-hop virtual links to construct the backbone. We present the analytic as well as simulation study of our algorithm and also a method for the dynamic maintenance of constructed backbone. In the end, we illustrate the use of the virtual backbone with the help of an interesting application.

  7. Structure and backbone dynamics of vanadate-bound PRL-3: comparison of 15N nuclear magnetic resonance relaxation profiles of free and vanadate-bound PRL-3.

    Science.gov (United States)

    Jeong, Ki-Woong; Kang, Dong-Il; Lee, Eunjung; Shin, Areum; Jin, Bonghwan; Park, Young-Guen; Lee, Chung-Kyoung; Kim, Eun-Hee; Jeon, Young Ho; Kim, Eunice Eunkyeong; Kim, Yangmee

    2014-07-29

    Phosphatases of regenerating liver (PRLs) constitute a novel class of small, prenylated phosphatases with oncogenic activity. PRL-3 is particularly important in cancer metastasis and represents a potential therapeutic target. The flexibility of the WPD loop as well as the P-loop of protein tyrosine phosphatases is closely related to their catalytic activity. Using nuclear magnetic resonance spectroscopy, we studied the structure of vanadate-bound PRL-3, which was generated by addition of sodium orthovanadate to PRL-3. The WPD loop of free PRL-3 extended outside of the active site, forming an open conformation, whereas that of vanadate-bound PRL-3 was directed into the active site by a large movement, resulting in a closed conformation. We suggest that vanadate binding induced structural changes in the WPD loop, P-loop, helices α4-α6, and the polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer α4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by helices α4-α6 with a depth of 14-15 Å can accommodate a farnesyl chain at the truncated prenylation motif of PRL-3, i.e., from R169 to M173. Conformational exchange data suggested that the WPD loop moves between open and closed conformations with a closing rate constant k(close) of 7 s(-1). This intrinsic loop flexibility of PRL-3 may be related to their catalytic rate and may play a role in substrate recognition.

  8. Variation of protein backbone amide resonance by electrostatic field

    OpenAIRE

    Sharley, John N.

    2015-01-01

    Amide resonance is found to be sensitive to electrostatic field with component parallel or antiparallel the amide C-N bond. This effect is linear and without threshold in the biologically plausible electrostatic field range -0.005 to 0.005 au. Variation of amide resonance varies Resonance-Assisted Hydrogen Bonding such as occurs in the hydrogen bonded chains of backbone amides of protein secondary structures such as beta sheet and alpha helix, varying the stability of the secondary structure....

  9. 基于改进BBO优化算法和电网生存性的核心骨干网架构建%A Method of Constructing Core Backbone Grid Based on Improved BBO Optimization Algorithm and Survivability of Power Grid

    Institute of Scientific and Technical Information of China (English)

    董飞飞; 刘涤尘; 吴军; 潘旭东; 王浩磊; 赵一婕; 宋春丽

    2014-01-01

    Constructing core backbone grid has instruction function for strengthening the construction of the grid structure, improving the ability of withstanding natural disasters, as well as realizing power grid’s differentiation planning reasonably and scientifically. A method of constructing core backbone grid with the target of the smallest total line length and the largest integrated survivability index based on survivability index system was put forward with constraint conditions of network connectivity and power grid safe operation. The cosine migration model, the premature judgment mechanism, and the mutative scale of chaos and Cauchy mutation strategy were introduced into the improved biogeography-based optimization algorithm (BBO) to search for the optimal core backbone grid. Simulation results show that the proposed method is accurate and effective. Its convergence speed is faster and its convergence precision is higher than that of traditional BBO, particle swarm optimization (PSO), binary ant colony algorithm (BACA) and genetic algorithm (GA).%构建核心骨干网架,对于有针对性地加强电网结构建设、提高电网抵御自然灾害能力、合理科学地进行差异化电网规划具有重要的指导作用。基于生存性指标体系,提出一种线路总长度最小、生存性综合指标最大的核心骨干网架构建方法,以网络连通性和电网安全运行为约束条件,采用引入余弦迁移模型、早熟判断机制以及变尺度混沌和柯西变异策略的改进生物地理学优化算法(improved biogeography-based optimization algorithm,IBBO)搜索最优骨干网架方案,并与传统的生物地理学优化算法(biogeography-based optimization algorithm, BBO)、粒子群算法(particle swarm optimization,PSO)、蚁群算法(binary ant colony algorithm, BACA)、遗传算法(genetic algorithm,GA)的搜索结果进行对比分析。仿真算例表明,所提方法准确有效,且具有收敛速

  10. Optimal sink placement in backbone assisted wireless sensor networks

    Directory of Open Access Journals (Sweden)

    I. Snigdh

    2016-07-01

    Full Text Available This article proposes a scheme for selecting the best site for sink placement in WSN applications employing backbone assisted communications. By placing the sink at a specific position, energy scavenging and delay constraints can effectively be controlled. In contrast to the conventional scheme for base station placement at the geographical centre or random placement at the end of the region of interest, the proposed scheme places the base station at either the graph theoretical centre or centroid of the backbone connecting nodes in the region of interest. This strategy shows a considerable reduction in the total number of hops that each packet needs to travel to reach the sink. The proposed scheme is applied on all the families of graphs prevalent in backbone assisted sensor networks to confirm the performance consistency and improvement in network parameters of the communication backbone measured in terms of delay, the carried load and the total energy consumption, eventually affected by the average number of hops for the message to reach the sink.

  11. Efficient protocol for backbone and side-chain assignments of large, intrinsically disordered proteins: transient secondary structure analysis of 49.2 kDa microtubule associated protein 2c

    Energy Technology Data Exchange (ETDEWEB)

    Novacek, Jiri; Janda, Lubomir; Dopitova, Radka; Zidek, Lukas, E-mail: lzidek@chemi.muni.cz; Sklenar, Vladimir [Masaryk University, Faculty of Science, NCBR, and CEITEC (Czech Republic)

    2013-08-15

    Microtubule-associated proteins (MAPs) are abundantly present in axons and dendrites, and have been shown to play crucial role during the neuronal morphogenesis. The period of main dendritic outgrowth and synaptogenesis coincides with high expression levels of one of MAPs, the MAP2c, in rats. The MAP2c is a 49.2 kDa intrinsically disordered protein. To achieve an atomic resolution characterization of such a large protein, we have developed a protocol based on the acquisition of two five-dimensional {sup 13}C-directly detected NMR experiments. Our previously published 5D CACONCACO experiment (Novacek et al. in J Biomol NMR 50(1):1-11, 2011) provides the sequential assignment of the backbone resonances, which is not interrupted by the presence of the proline residues in the amino acid sequence. A novel 5D HC(CC-TOCSY)CACON experiment facilitates the assignment of the aliphatic side chain resonances. To streamline the data analysis, we have developed a semi-automated procedure for signal assignments. The obtained data provides the first atomic resolution insight into the conformational state of MAP2c and constitutes a model for further functional studies of MAPs.

  12. Identification of systems containing nonlinear stiffnesses using backbone curves

    Science.gov (United States)

    Londoño, Julián M.; Cooper, Jonathan E.; Neild, Simon A.

    2017-02-01

    This paper presents a method for the dynamic identification of structures containing discrete nonlinear stiffnesses. The approach requires the structure to be excited at a single resonant frequency, enabling measurements to be made in regimes of large displacements where nonlinearities are more likely to be significant. Measured resonant decay data is used to estimate the system backbone curves. Linear natural frequencies and nonlinear parameters are identified using these backbone curves assuming a form for the nonlinear behaviour. Numerical and experimental examples, inspired by an aerospace industry test case study, are considered to illustrate how the method can be applied. Results from these models demonstrate that the method can successfully deliver nonlinear models able to predict the response of the test structure nonlinear dynamics.

  13. NMR backbone dynamics of VEK-30 bound to the human plasminogen kringle 2 domain.

    Science.gov (United States)

    Wang, Min; Prorok, Mary; Castellino, Francis J

    2010-07-07

    To gain insights into the mechanisms for the tight and highly specific interaction of the kringle 2 domain of human plasminogen (K2(Pg)) with a 30-residue internal peptide (VEK-30) from a group A streptococcal M-like protein, the dynamic properties of free and bound K2(Pg) and VEK-30 were investigated using backbone amide (15)N-NMR relaxation measurements. Dynamic parameters, namely the generalized order parameter, S(2), the local correlation time, tau(e), and the conformational exchange contribution, R(ex), were obtained for this complex by Lipari-Szabo model-free analysis. The results show that VEK-30 displays distinctly different dynamic behavior as a consequence of binding to K2(Pg), manifest by decreased backbone flexibility, particularly at the binding region of the peptide. In contrast, the backbone dynamics parameters of K2(Pg) displayed similar patterns in the free and bound forms, but, nonetheless, showed interesting differences. Based on our previous structure-function studies of this interaction, we also made comparisons of the VEK-30/K2(Pg) dynamics results from different kringle modules complexed with small lysine analogs. The differences in dynamics observed for kringles with different ligands provide what we believe to be new insights into the interactions responsible for protein-ligand recognition and a better understanding of the differences in binding affinity and binding specificity of kringle domains with various ligands.

  14. The Backbone of the Climate Networks

    Science.gov (United States)

    Zou, Y.; Donges, J. F.; Marwan, N.; Kurths, J.

    2009-12-01

    We propose a method to reconstruct and analyze a complex network from data generated by a spatio-temporal dynamical system, relying on the nonlinear mutual information of time series analysis and betweenness centrality of complex network theory. We show, that this approach reveals a rich internal structure in complex climate networks constructed from reanalysis and model surface air temperature data. Our novel method uncovers peculiar wave-like structures of high energy flow, that we relate to global surface ocean currents. This points to a major role of the oceanic surface circulation in coupling and stabilizing the global temperature field in the long term mean (140 years for the model run and 60 years for reanalysis data). We find that these results cannot be obtained using classical linear methods of multivariate data analysis. Furthermore, we introduce significance tests to quantify the robustness of measured network properties to uncertainties. References: [1] J.F. Donges, Y. Zou, N. Marwan, and J. Kurths. Complex networks in climate dynamics -- -- Comparing linear and nonlinear network construction methods. European Physical Journal -- Special Topics, 174, 157-179, 2009. [2] J.F. Donges, Y. Zou, N. Marwan, and J. Kurths. Backbone of the climate network. Europhysics Letters, in press, 2009.

  15. Exercise: The Backbone of Spine Treatment

    Medline Plus

    Full Text Available Exercise: The Backbone of Spine Treatment | View Video Back About Video Struggling with Low Back Pain? Many people are surprised to learn that carefully selected exercise can actually reduce back pain. Some exercises can ...

  16. Structure-based druggability assessment of the mammalian structural proteome with inclusion of light protein flexibility.

    Directory of Open Access Journals (Sweden)

    Kathryn A Loving

    2014-07-01

    Full Text Available Advances reported over the last few years and the increasing availability of protein crystal structure data have greatly improved structure-based druggability approaches. However, in practice, nearly all druggability estimation methods are applied to protein crystal structures as rigid proteins, with protein flexibility often not directly addressed. The inclusion of protein flexibility is important in correctly identifying the druggability of pockets that would be missed by methods based solely on the rigid crystal structure. These include cryptic pockets and flexible pockets often found at protein-protein interaction interfaces. Here, we apply an approach that uses protein modeling in concert with druggability estimation to account for light protein backbone movement and protein side-chain flexibility in protein binding sites. We assess the advantages and limitations of this approach on widely-used protein druggability sets. Applying the approach to all mammalian protein crystal structures in the PDB results in identification of 69 proteins with potential druggable cryptic pockets.

  17. NET amyloidogenic backbone in human activated neutrophils.

    Science.gov (United States)

    Pulze, L; Bassani, B; Gini, E; D'Antona, P; Grimaldi, A; Luini, A; Marino, F; Noonan, D M; Tettamanti, G; Valvassori, R; de Eguileor, M

    2016-03-01

    Activated human neutrophils produce a fibrillar DNA network [neutrophil extracellular traps (NETs)] for entrapping and killing bacteria, fungi, protozoa and viruses. Our results suggest that the neutrophil extracellular traps show a resistant amyloidogenic backbone utilized for addressing reputed proteins and DNA against the non-self. The formation of amyloid fibrils in neutrophils is regulated by the imbalance of reactive oxygen species (ROS) in the cytoplasm. The intensity and source of the ROS signal is determinant for promoting stress-associated responses such as amyloidogenesis and closely related events: autophagy, exosome release, activation of the adrenocorticotrophin hormone/α-melanocyte-stimulating hormone (ACTH/α-MSH) loop and synthesis of specific cytokines. These interconnected responses in human activated neutrophils, that have been evaluated from a morphofunctional and quantitative viewpoint, represent primitive, but potent, innate defence mechanisms. In invertebrates, circulating phagocytic immune cells, when activated, show responses similar to those described previously for activated human neutrophils. Invertebrate cells within endoplasmic reticulum cisternae produce a fibrillar material which is then assembled into an amyloidogenic scaffold utilized to convey melanin close to the invader. These findings, in consideration to the critical role played by NET in the development of several pathologies, could explain the structural resistance of these scaffolds and could provide the basis for developing new diagnostic and therapeutic approaches in immunomediated diseases in which the innate branch of the immune system has a pivotal role.

  18. Properties of polyimide liquid crystal alignment layer with different backbone structure%聚酰亚胺主链结构对液晶取向膜性能的影响

    Institute of Scientific and Technical Information of China (English)

    刘露露; 刘明; 龚世铭; 汪映寒

    2015-01-01

    A series polyimides (PIs)were prepared by one-step method.These PIs were comprised of a functional diamine N,N-bis (4-aminophenyl )-4-(dodecylo-xy-biphenyl )-4′-amino-phenylether (C1 2 -BAAPE),one of two commercially available diamines 2,2′-Bis(trifluoromethy-l)-4,4′-diaminobiphe-nyl (TFDB),4,4′-Oxydianiline (ODA)and one of two dianhydride 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA)and 4,4′-Oxydiphthalic anhydride (ODPA)in order to get different backbone structures.The structures and thermo properties of these PIs were characterized by NMR, FT-IR,DSC and TGA.Pretilt angles and alignment abilities were carried out by pretilt angle tester and polarization microscope.Solubility of PIs was tested by dissolving PIs in various organic solvents. DSC and TGA curves showed that PI-2 had higher glass transition temperature (T g )and decomposi-tion temperature (T d )than PI-1 and PI-3.Three PI films presented vertical alignment before mechan-ical rubbing and only PI-2 maintained it after rubbing process.Conformations of these PIs were simu-lated by Material Studio (MS).The vertical conformation existed in PI-2 ’s backbones improved rubbing resistance and showed vertical alignment ability after rubbing.%采用一步法,以 N,N-二(4-氨基苯基)-4-(十二烷氧基联苯基)-4’-氨基苯醚(C12-BAAPE)为控制预倾角的功能性二胺,2,2’-双三氟甲基-4,4’-联苯二胺(TFDB)或4,4’-二氨基二苯醚(ODA)为辅助二胺,分别与2,2’-双(3,4-二羧苯基)六氟丙烷四羧酸二酐(6FDA)和4,4’-联苯醚二酐(ODPA)聚合,得到三种主链结构不同的聚酰亚胺(PI-1、PI-2和PI-3)。利用 NMR、FT-IR、DSC、TGA、偏光显微镜和预倾角测试仪对聚合物的结构、热性能以及制备的液晶盒的取向性进行了表征,同时测试了3种 PI 的溶解性能。结果表明,PI-2液晶取向膜的耐摩擦性能明显优于 PI-1和 PI-3,且具有更高的玻璃化转变温度(T g )和分解温度(T d ),更好

  19. Post-translational heterocyclic backbone modifications in the 43-peptide antibiotic microcin B17. Structure elucidation and NMR study of a 13C,15N-labelled gyrase inhibitor.

    Science.gov (United States)

    Bayer, A; Freund, S; Jung, G

    1995-12-01

    Microcin B17 (McB17), the first known gyrase inhibitor of peptidic nature, is produced by ribosomal synthesis and post-translational modification of the 69-residue precursor protein by an Escherichia coli strain. To elucidate the chemical structure of the mature 43-residue peptide antibiotic, fermentation and purification protocols were established and optimized which allowed the isolation and purification of substantial amounts of highly pure McB17 (non-labelled, 15N-labelled and 13C/15N-labelled peptide. By ultraviolet-absorption spectroscopy. HPLC-electrospray mass spectrometry and GC-mass spectrometry, amino acid analysis, protein sequencing, and, in particular, multidimensional NMR, we could demonstrate and unequivocally prove that the enzymic modification of the precursor backbone at Gly-Cys and Gly-Ser segments leads to the formation of 2-aminomethylthiazole-4-carboxylic acid and 2-aminomethyloxazole-4-carboxylic acid, respectively. In addition, two bicyclic modifications 2-(2-aminomethyloxazolyl)thiazole-4-carboxylic acid and 2-(2-aminomethylthiazolyl)oxazole-4-carboxylic acid were found that consist of directly linked thiazole and oxazole rings derived from one Gly-Ser-Cys and one Gly-Cys-Ser segment. Analogous to the thiazole and oxazole rings found in antitumor peptides of microbial and marine origin, these heteroaromatic ring systems of McB17 presumably play an important role in its gyrase-inhibiting activity, e.g. interacting with the DNA to trap the covalent protein-DNA intermediate of the breakage-reunion reaction of the gyrase.

  20. High Speed Fibre Optic Backbone LAN

    Science.gov (United States)

    Tanimoto, Masaaki; Hara, Shingo; Kajita, Yuji; Kashu, Fumitoshi; Ikeuchi, Masaru; Hagihara, Satoshi; Tsuzuki, Shinji

    1987-09-01

    Our firm has developed the SUMINET-4100 series, a fibre optic local area network (LAN), to serve the communications system trunk line needs for facilities, such as steel refineries, automobile plants and university campuses, that require large transmission capacity, and for the backbone networks used in intelligent building systems. The SUMINET-4100 series is already in service in various fields of application. Of the networks available in this series, the SUMINET-4150 has a trunk line speed of 128 Mbps and the multiplexer used for time division multiplexing (TDM) was enabled by designing an ECL-TTL gate array (3000 gates) based custom LSI. The synchronous, full-duplex V.24 and V.3.5 interfaces (SUMINET-2100) are provided for use with general purpose lines. And the IBM token ring network, the SUMINET-3200, designed for heterogeneous PCs and the Ethernet can all be connected to sub loops. Further, the IBM 3270 TCA and 5080 CADAM can be connected in the local mode. Interfaces are also provided for the NTT high-speed digital service, the digital PBX systems, and the Video CODEC system. The built-in loop monitor (LM) and network supervisory processor (NSP) provide management of loop utilization and send loop status signals to the host CPU's network configuration and control facility (NCCF). These built-in functions allow both the computer system and LAN to be managed from a single source at the host. This paper outlines features of the SUMINET-4150 and provides an example of its installation.

  1. Limits on variations in protein backbone dynamics from precise measurements of scalar couplings.

    Science.gov (United States)

    Vögeli, Beat; Ying, Jinfa; Grishaev, Alexander; Bax, Ad

    2007-08-01

    3JHN,Halpha, 3JHN,Cbeta, and 3JHN,C' couplings, all related to the backbone torsion angle phi, were measured for the third immunoglobulin binding domain of protein G, or GB3. Measurements were carried out using both previously published methods and novel sequences based on the multiple-quantum principle, which limit attenuation of experimental couplings caused by finite lifetimes of the spin states of passive spins. High reproducibility between the multiple-quantum and conventional approaches confirms the accuracy of the measurements. With few exceptions, close agreement between 3JHN,Halpha, 3JHN,Cbeta, and 3JHN,C' and values predicted by their respective Karplus equations is observed. For the three types of couplings, up to 20% better agreement is obtained when fitting the experimental couplings to a dynamic ensemble NMR structure, which has a phi angle root-mean-square spread of 9 +/- 4 degrees and was previously calculated on the basis of a very extensive set of residual dipolar couplings, than for any single static NMR structure. Fits of 3J couplings to a 1.1-A X-ray structure, with hydrogens added in idealized positions, are 40-90% worse. Approximately half of the improvement when fitting to the NMR structures relates to the amide proton deviating from its idealized, in-peptide-plane position, indicating that the positioning of hydrogens relative to the backbone atoms is one of the factors limiting the accuracy at which the backbone torsion angle phi can be extracted from 3J couplings. Introducing an additional, residue-specific variable for the amplitude of phi angle fluctuations does not yield a statistically significant improvement when fitting to a set of dynamic Karplus curves, pointing to a homogeneous behavior of these amplitudes.

  2. Controlled Conjugated Backbone Twisting for an Increased Open-Circuit Voltage while Having a High Short-Circuit Current in Poly(hexylthiophene) Derivatives

    KAUST Repository

    Ko, Sangwon

    2012-03-21

    Conjugated polymers with nearly planar backbones have been the most commonly investigated materials for organic-based electronic devices. More twisted polymer backbones have been shown to achieve larger open-circuit voltages in solar cells, though with decreased short-circuit current densities. We systematically impose twists within a family of poly(hexylthiophene)s and examine their influence on the performance of polymer:fullerene bulk heterojunction (BHJ) solar cells. A simple chemical modification concerning the number and placement of alkyl side chains along the conjugated backbone is used to control the degree of backbone twisting. Density functional theory calculations were carried out on a series of oligothiophene structures to provide insights on how the sterically induced twisting influences the geometric, electronic, and optical properties. Grazing incidence X-ray scattering measurements were performed to investigate how the thin-film packing structure was affected. The open-circuit voltage and charge-transfer state energy of the polymer:fullerene BHJ solar cells increased substantially with the degree of twist induced within the conjugated backbone-due to an increase in the polymer ionization potential-while the short-circuit current decreased as a result of a larger optical gap and lower hole mobility. A controlled, moderate degree of twist along the poly(3,4-dihexyl-2,2′:5′,2′′- terthiophene) (PDHTT) conjugated backbone led to a 19% enhancement in the open-circuit voltage (0.735 V) vs poly(3-hexylthiophene)-based devices, while similar short-circuit current densities, fill factors, and hole-carrier mobilities were maintained. These factors resulted in a power conversion efficiency of 4.2% for a PDHTT:[6,6]-phenyl-C 71-butyric acid methyl ester (PC 71BM) blend solar cell without thermal annealing. This simple approach reveals a molecular design avenue to increase open-circuit voltage while retaining the short-circuit current. © 2012 American

  3. Backbone of complex networks of corporations: The flow of control

    Science.gov (United States)

    Glattfelder, J. B.; Battiston, S.

    2009-09-01

    We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

  4. Backbone of complex networks of corporations: the flow of control.

    Science.gov (United States)

    Glattfelder, J B; Battiston, S

    2009-09-01

    We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

  5. Green Network Planning Model for Optical Backbones

    DEFF Research Database (Denmark)

    Gutierrez Lopez, Jose Manuel; Riaz, M. Tahir; Jensen, Michael

    2010-01-01

    Communication networks are becoming more essential for our daily lives and critically important for industry and governments. The intense growth in the backbone traffic implies an increment of the power demands of the transmission systems. This power usage might have a significant negative effect...... on the environment in general. In network planning there are existing planning models focused on QoS provisioning, investment minimization or combinations of both and other parameters. But there is a lack of a model for designing green optical backbones. This paper presents novel ideas to be able to define...

  6. Efficient White Light Emission Using a Single Copolymer with Red and Green Chromophores on a Conjugated Polyfluorene Backbone Hybridized with InGaN-Based Light-Emitting Diodes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yong; HOU Qiong; NIU Qiao-Li; ZHENG Shu-Wen; LI Shu-Ti; HE Miao; FAN Guang-Han

    2009-01-01

    We report an efficient white-light emission based on a single copolymer/InGaN hybrid light-emitting diode.The single copolymer consists of a conjugated polyfluorene backbone by incorporating 2,1,3-benzothiadiazole (BT) and 4, 7-bis(2-thienyl)-2,1,3-benzothiadiazole (DBT) as green and red light-emitting units, respectively. For the single eopolymer/lnGaN hybrid device, the Commission Internationale de l'Eclairage (CIE) coordinates,color temperature Tc and color rendering index Ra at 20mA are (0.323,0.329), 5960K and 86, respectively.In comparison with the performance of red copolymer PFO-DBT15 (DOF:DBT=85:15 with DOF being 9'9-dioctylfluorene) and green copolymer PFO-BT35 (DOF:BT=65:35) blend/InGaN hybrid white devices, it is concluded that the chemically doped copolymer hybridized device shows a higher emission intensity and spectral stability at a high driving current than the polymer blend.

  7. Structural Analysis of Plate Based Tensegrity Structures

    DEFF Research Database (Denmark)

    Hald, Frederik; Kirkegaard, Poul Henning; Damkilde, Lars

    2013-01-01

    Plate tensegrity structures combine tension cables with a cross laminated timber plate and can then form e.g. a roof structure. The topology of plate tensegrity structures is investigated through a parametric investigation. Plate tensegrity structures are investigated, and a method...... for determination of the structures pre-stresses is used. A parametric investigation is performed to determine a more optimized form of the plate based tensegrity structure. Conclusions of the use of plate based tensegrity in civil engineering and further research areas are discussed....

  8. Microsoft Operations Framework implementation for The Backbone

    NARCIS (Netherlands)

    Kienhuis, G.H.

    2007-01-01

    Doel The Backbone ontwerpt, implementeert en beheert IT infrastructuren voor bedrijven en instellingen. Beheer wordt proactief uitgevoerd met behulp van Microsoft Operation Manager (MOM) 2005. MOM is een applicatie die de status en gebeurtenissen van systemen zichtbaar maakt vanuit één locatie. Om

  9. mulPBA: an efficient multiple protein structure alignment method based on a structural alphabet.

    Science.gov (United States)

    Léonard, Sylvain; Joseph, Agnel Praveen; Srinivasan, Narayanaswamy; Gelly, Jean-Christophe; de Brevern, Alexandre G

    2014-04-01

    The increasing number of available protein structures requires efficient tools for multiple structure comparison. Indeed, multiple structural alignments are essential for the analysis of function, evolution and architecture of protein structures. For this purpose, we proposed a new web server called multiple Protein Block Alignment (mulPBA). This server implements a method based on a structural alphabet to describe the backbone conformation of a protein chain in terms of dihedral angles. This 'sequence-like' representation enables the use of powerful sequence alignment methods for primary structure comparison, followed by an iterative refinement of the structural superposition. This approach yields alignments superior to most of the rigid-body alignment methods and highly comparable with the flexible structure comparison approaches. We implement this method in a web server designed to do multiple structure superimpositions from a set of structures given by the user. Outputs are given as both sequence alignment and superposed 3D structures visualized directly by static images generated by PyMol or through a Jmol applet allowing dynamic interaction. Multiple global quality measures are given. Relatedness between structures is indicated by a distance dendogram. Superimposed structures in PDB format can be also downloaded, and the results are quickly obtained. mulPBA server can be accessed at www.dsimb.inserm.fr/dsimb_tools/mulpba/ .

  10. Polystyrene Backbone Polymers Consisting of Alkyl-Substituted Triazine Side Groups for Phosphorescent OLEDs

    Directory of Open Access Journals (Sweden)

    Beatrice Ch. D. Salert

    2012-01-01

    Full Text Available This paper describes the synthesis of new electron-transporting styrene monomers and their corresponding polystyrenes all with a 2,4,6-triphenyl-1,3,5-triazine basic structure in the side group. The monomers differ in the alkyl substitution and in the meta-/paralinkage of the triazine to the polymer backbone. The thermal and spectroscopic properties of the new electron-transporting polymers are discussed in regard to their chemical structures. Phosphorescent OLEDs were prepared using the obtained electron-transporting polymers as the emissive layer material in blend systems together with a green iridium-based emitter 13 and a small molecule as an additional cohost with wideband gap characteristics (CoH-001. The performance of the OLEDs was characterized and discussed in regard to the chemical structure of the new electron-transporting polymers.

  11. RNA-Redesign: a web server for fixed-backbone 3D design of RNA.

    Science.gov (United States)

    Yesselman, Joseph D; Das, Rhiju

    2015-07-01

    RNA is rising in importance as a design medium for interrogating fundamental biology and for developing therapeutic and bioengineering applications. While there are several online servers for design of RNA secondary structure, there are no tools available for the rational design of 3D RNA structure. Here we present RNA-Redesign (http://rnaredesign.stanford.edu), an online 3D design tool for RNA. This resource utilizes fixed-backbone design to optimize the sequence identity and nucleobase conformations of an RNA to match a desired backbone, analogous to fundamental tools that underlie rational protein engineering. The resulting sequences suggest thermostabilizing mutations that can be experimentally verified. Further, sequence preferences that differ between natural and computationally designed sequences can suggest whether natural sequences possess functional constraints besides folding stability, such as cofactor binding or conformational switching. Finally, for biochemical studies, the designed sequences can suggest experimental tests of 3D models, including concomitant mutation of base triples. In addition to the designs generated, detailed graphical analysis is presented through an integrated and user-friendly environment.

  12. A Cooperative Game Based Data Center Backbone Network Bandwidth Allocation Policy%基于合作博弈的数据中心骨干网带宽分配策略

    Institute of Scientific and Technical Information of China (English)

    孟飞; 兰巨龙; 胡宇翔

    2016-01-01

    数据中心(data center ,DC)之间通过部署流量工程来提高连接各个数据中心骨干网的利用率,虽然效率提升显著,但对不同类型汇聚流的带宽分配的公平性没有考虑。将多个汇聚流对带宽分配的竞争行为建模为一个合作博弈,通过寻求此博弈的纳什谈判解(Nash bargaining solution ,NBS)来确定优化的带宽分配策略 CGBA(cooperation game based bandwidth allocation ),权衡各汇聚流的最小带宽保证与带宽分配的公平性。在 Mininet 平台上进行实验仿真并和典型的带宽分配策略对比,结果表明CGBA 不但可保证各汇聚流的最小带宽需求,还确保了各类流对带宽资源竞争的公平性。%Currently ,traffic engineering is typically deployed to improve the utilization of data centers (DC) backbone networks ,which usually belongs to the same online service providers .Although the efficiency is remarkable ,the bandwidth allocation fairness of different aggregate flow isn’t considered . Hence ,the QoS guarantee is restricted .Because the bandwidth resource is expensive and packet loss is typically thought unacceptable ,the bandwidth utilization should be maximized ,at the same time , the QoS guarantee of different flow should be improved .In this paper ,the problem of contending the share bandwidth is modeled as a cooperative game ,and different aggregate flow compets the share bandwidth and maximizes the overall bandwidth resource utilization simultaneously ,and the optimal bandwidth allocation policy ,called cooperation game based bandwidth allocation (CGBA) ,is obtained through searching the Nash bargaining solution (NBS) of the game and balancing the tradeoff between minimum bandwidth guarantee and bandwidth allocation fairness .Simulation on a Mininet testbed shows that the proposed policy can effectively guarantee minimum bandwidth of each aggregate flow while ensuring the allocation fairness , compared with three

  13. Control of polymer-packing orientation in thin films through synthetic tailoring of backbone coplanarity

    KAUST Repository

    Chen, Mark S.

    2013-10-22

    Controlling solid-state order of π-conjugated polymers through macromolecular design is essential for achieving high electronic device performance; yet, it remains a challenge, especially with respect to polymer-packing orientation. Our work investigates the influence of backbone coplanarity on a polymer\\'s preference to pack face-on or edge-on relative to the substrate. Isoindigo-based polymers were synthesized with increasing planarity by systematically substituting thiophenes for phenyl rings in the acceptor comonomer. This increasing backbone coplanarity, supported by density functional theory (DFT) calculations of representative trimers, leads to the narrowing of polymer band gaps as characterized by ultraviolet-visible-near infrared (UV-vis-NIR) spectroscopy and cyclic voltammetry. Among the polymers studied, regiosymmetric II and TII polymers exhibited the highest hole mobilities in organic field-effect transistors (OFETs), while in organic photovoltaics (OPVs), TBII polymers that display intermediate levels of planarity provided the highest power conversion efficiencies. Upon thin-film analysis by atomic force microscropy (AFM) and grazing-incidence X-ray diffraction (GIXD), we discovered that polymer-packing orientation could be controlled by tuning polymer planarity and solubility. Highly soluble, planar polymers favor face-on orientation in thin films while the less soluble, nonplanar polymers favor an edge-on orientation. This study advances our fundamental understanding of how polymer structure influences nanostructural order and reveals a new synthetic strategy for the design of semiconducting materials with rationally engineered solid-state properties. © 2013 American Chemical Society.

  14. Protonation–deprotonation of the glycine backbone as followed by Raman scattering and multiconformational analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hernández, Belén; Pflüger, Fernando [Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny cedex (France); Kruglik, Sergei G. [Laboratoire Jean Perrin, FRE 3231, Université Pierre et Marie Curie (Paris 6), Case courrier 138, 75252 Paris Cedex 05 (France); Ghomi, Mahmoud, E-mail: mahmoud.ghomi@univ-paris13.fr [Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, Université Paris 13, Sorbonne Paris Cité, 74 rue Marcel Cachin, 93017 Bobigny cedex (France)

    2013-11-08

    Highlights: • New pH-dependent Raman spectra in the middle wavenumber region (1800-300 cm{sup −1}). • New quantum mechanical calculations for exploring the Gly conformational landscape. • Construction of muticonformation based theoretical Raman spectra. - Abstract: Because of the absence of the side chain in its chemical structure and its well defined Raman spectra, glycine was selected here to follow its backbone protonation–deprotonation. The scan of the recorded spectra in the 1800–300 cm{sup −1} region led us to assign those obtained at pH 1, 6 and 12 to the cationic, zwitterionic and anionic species, respectively. These data complete well those previously published by Bykov et al. (2008) [16] devoted to the high wavenumber Raman spectra (>2500 cm{sup −1}). To reinforce our discussion, DFT calculations were carried out on the clusters of glycine + 5H{sub 2}O, mimicking reasonably the first hydration shell of the amino acid. Geometry optimization of 141 initial clusters, reflecting plausible combinations of the backbone torsion angles, allowed exploration of the conformational features, as well as construction of the theoretical Raman spectra by considering the most stable clusters containing each glycine species.

  15. Optimization of Protein Backbone Dihedral Angles by Means of Hamiltonian Reweighting.

    Science.gov (United States)

    Margreitter, Christian; Oostenbrink, Chris

    2016-09-26

    Molecular dynamics simulations depend critically on the accuracy of the underlying force fields in properly representing biomolecules. Hence, it is crucial to validate the force-field parameter sets in this respect. In the context of the GROMOS force field, this is usually achieved by comparing simulation data to experimental observables for small molecules. In this study, we develop new amino acid backbone dihedral angle potential energy parameters based on the widely used 54A7 parameter set by matching to experimental J values and secondary structure propensity scales. In order to find the most appropriate backbone parameters, close to 100 000 different combinations of parameters have been screened. However, since the sheer number of combinations considered prohibits actual molecular dynamics simulations for each of them, we instead predicted the values for every combination using Hamiltonian reweighting. While the original 54A7 parameter set fails to reproduce the experimental data, we are able to provide parameters that match significantly better. However, to ensure applicability in the context of larger peptides and full proteins, further studies have to be undertaken.

  16. Porous solid backbone impregnation for electrochemical energy conversion systems

    KAUST Repository

    Boulfrad, Samir

    2013-09-19

    An apparatus and method for impregnating a porous solid backbone. The apparatus may include a platform for holding a porous solid backbone, an ink jet nozzle configured to dispense a liquid solution onto the porous solid backbone, a positioning mechanism configured to position the ink jet nozzle proximate to a plurality of locations of the porous solid backbone, and a control unit configured to control the positioning mechanism to position the ink jet nozzle proximate to the plurality of locations and cause the ink jet nozzle to dispense the liquid solution onto the porous solid backbone.

  17. RNABC: forward kinematics to reduce all-atom steric clashes in RNA backbone.

    Science.gov (United States)

    Wang, Xueyi; Kapral, Gary; Murray, Laura; Richardson, David; Richardson, Jane; Snoeyink, Jack

    2008-01-01

    Although accurate details in RNA structure are of great importance for understanding RNA function, the backbone conformation is difficult to determine, and most existing RNA structures show serious steric clashes (>or= 0.4 A overlap) when hydrogen atoms are taken into account. We have developed a program called RNABC (RNA Backbone Correction) that performs local perturbations to search for alternative conformations that avoid those steric clashes or other local geometry problems. Its input is an all-atom coordinate file for an RNA crystal structure (usually from the MolProbity web service), with problem areas specified. RNABC rebuilds a suite (the unit from sugar to sugar) by anchoring the phosphorus and base positions, which are clearest in crystallographic electron density, and reconstructing the other atoms using forward kinematics. Geometric parameters are constrained within user-specified tolerance of canonical or original values, and torsion angles are constrained to ranges defined through empirical database analyses. Several optimizations reduce the time required to search the many possible conformations. The output results are clustered and presented to the user, who can choose whether to accept one of the alternative conformations. Two test evaluations show the effectiveness of RNABC, first on the S-motifs from 42 RNA structures, and second on the worst problem suites (clusters of bad clashes, or serious sugar pucker outliers) in 25 unrelated RNA structures. Among the 101 S-motifs, 88 had diagnosed problems, and RNABC produced clash-free conformations with acceptable geometry for 71 of those (about 80%). For the 154 worst problem suites, RNABC proposed alternative conformations for 72. All but 8 of those were judged acceptable after examining electron density (where available) and local conformation. Thus, even for these worst cases, nearly half the time RNABC suggested corrections suitable to initiate further crystallographic refinement. The program is

  18. A comparison of the structures of some 2- and 3-substituted chromone derivatives: a structural study on the importance of the secondary carboxamide backbone for the inhibitory activity of MAO-B

    Directory of Open Access Journals (Sweden)

    Ligia R. Gomes

    2015-11-01

    Full Text Available The crystal structures of the 3-substituted tertiary chromone carboxamide derivative, C17H13NO3, N-methyl-4-oxo-N-phenyl-4H-chromene-3-carboxamide (1, and the chromone carbonyl pyrrolidine derivatives, C14H13NO3, 3-(pyrrolidine-1-carbonyl-4H-chromen-4-one (3 and 2-(pyrrolidine-1-carbonyl-4H-chromen-4-one (4 have been determined. Their structural features are discussed and compared with similar compounds namely with respect to their MAO-B inhibitory activities. The chromone carboxamide presents a –syn conformation with the aromatic rings twisted with respect to each other [the dihedral angle between the mean planes of the chromone system and the exocyclic phenyl ring is 58.48 (8°]. The pyrrolidine derivatives also display a significant twist: the dihedral angles between the chromone system and the best plane formed by the pyrrolidine atoms are 48.9 (2 and 23.97 (12° in (3 and (4, respectively. Compound (3 shows a short C—H...O intramolecular contact forming an S(7 ring. The supramolecular structures for each compound are defined by weak C—H...O hydrogen bonds, which link the molecules into chains and sheets. The Cambridge Structural Database gave 45 hits for compounds with a pyrrolidinecarbonyl group. A simple statistical analysis of their geometric parameters is made in order to compare them with those of the molecules determined in the present work.

  19. Instant Backbone.js application development

    CERN Document Server

    Hunter, Thomas

    2013-01-01

    Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. This book is a practical, step-by-step tutorial that will teach you to build Backbone.js applications quickly and efficiently.This book is targeted towards developers. It is assumed that you have at least a basic understanding of JavaScript and jQuery selectors. If you are interested in building dynamic Single Page Applications that interact heavily with a backend server, then this is the book for you.

  20. Backbone building from quadrilaterals: a fast and accurate algorithm for protein backbone reconstruction from alpha carbon coordinates.

    Science.gov (United States)

    Gront, Dominik; Kmiecik, Sebastian; Kolinski, Andrzej

    2007-07-15

    In this contribution, we present an algorithm for protein backbone reconstruction that comprises very high computational efficiency with high accuracy. Reconstruction of the main chain atomic coordinates from the alpha carbon trace is a common task in protein modeling, including de novo structure prediction, comparative modeling, and processing experimental data. The method employed in this work follows the main idea of some earlier approaches to the problem. The details and careful design of the present approach are new and lead to the algorithm that outperforms all commonly used earlier applications. BBQ (Backbone Building from Quadrilaterals) program has been extensively tested both on native structures as well as on near-native decoy models and compared with the different available existing methods. Obtained results provide a comprehensive benchmark of existing tools and evaluate their applicability to a large scale modeling using a reduced representation of protein conformational space. The BBQ package is available for downloading from our website at http://biocomp.chem.uw.edu.pl/services/BBQ/. This webpage also provides a user manual that describes BBQ functions in detail.

  1. Peptide-functionalized semiconductor surfaces: strong surface electronic effects from minor alterations to backbone composition.

    Science.gov (United States)

    Matmor, Maayan; Lengyel, George A; Horne, W Seth; Ashkenasy, Nurit

    2017-02-22

    The use of non-canonical amino acids is a powerful way to control protein structure. Here, we show that subtle changes to backbone composition affect the ability of a dipeptide to modify solid surface electronic properties. The extreme sensitivity of the interactions to the peptide structure suggests potential applications in improving the performance of electronic devices.

  2. Sulfolobus acidocaldarius UDG Can Remove dU from the RNA Backbone: Insight into the Specific Recognition of Uracil Linked with Deoxyribose

    Directory of Open Access Journals (Sweden)

    Gang-Shun Yi

    2017-01-01

    Full Text Available Sulfolobus acidocaldarius encodes family 4 and 5 uracil-DNA glycosylase (UDG. Two recombinant S. acidocaldarius UDGs (SacUDG were prepared and biochemically characterized using oligonucleotides carrying a deaminated base. Both SacUDGs can remove deoxyuracil (dU base from both double-stranded DNA and single-stranded DNA. Interestingly, they can remove U linked with deoxyribose from single-stranded RNA backbone, suggesting that the riboses on the backbone have less effect on the recognition of dU and hydrolysis of the C-N glycosidic bond. However, the removal of rU from DNA backbone is inefficient, suggesting strong steric hindrance comes from the 2′ hydroxyl of ribose linked to uracil. Both SacUDGs cannot remove 2,2′-anhydro uridine, hypoxanthine, and 7-deazaxanthine from single-stranded DNA and single-stranded DNA. Compared with the family 2 MUG, other family UDGs have an extra N-terminal structure consisting of about 50 residues. Removal of the 46 N-terminal residues of family 5 SacUDG resulted in only a 40% decrease in activity, indicating that the [4Fe-4S] cluster and truncated secondary structure are not the key elements in hydrolyzing the glycosidic bond. Combining our biochemical and structural results with those of other groups, we discussed the UDGs’ catalytic mechanism and the possible repair reactions of deaminated bases in prokaryotes.

  3. Sulfolobus acidocaldarius UDG Can Remove dU from the RNA Backbone: Insight into the Specific Recognition of Uracil Linked with Deoxyribose.

    Science.gov (United States)

    Yi, Gang-Shun; Wang, Wei-Wei; Cao, Wei-Guo; Wang, Feng-Ping; Liu, Xi-Peng

    2017-01-18

    Sulfolobus acidocaldarius encodes family 4 and 5 uracil-DNA glycosylase (UDG). Two recombinant S. acidocaldarius UDGs (SacUDG) were prepared and biochemically characterized using oligonucleotides carrying a deaminated base. Both SacUDGs can remove deoxyuracil (dU) base from both double-stranded DNA and single-stranded DNA. Interestingly, they can remove U linked with deoxyribose from single-stranded RNA backbone, suggesting that the riboses on the backbone have less effect on the recognition of dU and hydrolysis of the C-N glycosidic bond. However, the removal of rU from DNA backbone is inefficient, suggesting strong steric hindrance comes from the 2' hydroxyl of ribose linked to uracil. Both SacUDGs cannot remove 2,2'-anhydro uridine, hypoxanthine, and 7-deazaxanthine from single-stranded DNA and single-stranded DNA. Compared with the family 2 MUG, other family UDGs have an extra N-terminal structure consisting of about 50 residues. Removal of the 46 N-terminal residues of family 5 SacUDG resulted in only a 40% decrease in activity, indicating that the [4Fe-4S] cluster and truncated secondary structure are not the key elements in hydrolyzing the glycosidic bond. Combining our biochemical and structural results with those of other groups, we discussed the UDGs' catalytic mechanism and the possible repair reactions of deaminated bases in prokaryotes.

  4. Synthesis and Molecular Recognition of Novel Cyclic Pseudopeptides Containing L-Glutamic Acid or L-Aspartic Acid Backbones

    Institute of Scientific and Technical Information of China (English)

    WANG Tao王涛; HUANG Xiao-Yi黄小毅; XIA Chuan-Qin夏传琴; YU Xiao-Qi余孝其; XIE Ru-Gang谢如刚

    2004-01-01

    Novel cyclic pseudopeptides containing L-glutamic acid or L-aspartic acid backbone structures were efficiently synthesized and characterized. Their chiral recognition properties for L- and D-amino acid methyl ester hydrochloride were discussed also.

  5. Variation of protein backbone amide resonance by electrostatic field

    CERN Document Server

    Sharley, John N

    2015-01-01

    Amide resonance is found to be sensitive to electrostatic field with component parallel or antiparallel the amide C-N bond. This effect is linear and without threshold in the biologically plausible electrostatic field range -0.005 to 0.005 au. Variation of amide resonance varies Resonance Assisted Hydrogen Bonding such as occurs in the hydrogen bonded chains of backbone amides of protein secondary structures such as beta sheet and non-polyproline helix such as alpha helix, varying the stability of the secondary structure. The electrostatic properties including permittivity of amino acid residue sidegroups influence the electrostatic field component parallel or antiparallel the C-N bond of each amide. The significance of this factor relative to other factors in protein folding depends on the magnitude of electrostatic field component parallel or antiparallel the C-N bond of each amide, and preliminary protein-scale calculations of the magnitude of these components suggest this factor warrants investigation in ...

  6. Reliability based structural design

    NARCIS (Netherlands)

    Vrouwenvelder, A.C.W.M.

    2014-01-01

    According to ISO 2394, structures shall be designed, constructed and maintained in such a way that they are suited for their use during the design working life in an economic way. To fulfil this requirement one needs insight into the risk and reliability under expected and non-expected actions. A ke

  7. Reliability based structural design

    NARCIS (Netherlands)

    Vrouwenvelder, A.C.W.M.

    2013-01-01

    According to ISO 2394, structures shall be designed, constructed and maintained in such a way that they are suited for their use during the design working life in an economic way. To fulfil this requirement one needs insight into the risk and reliability under expected and non-expected actions. A ke

  8. Characterizing Aciniform Silk Repetitive Domain Backbone Dynamics and Hydrodynamic Modularity

    Directory of Open Access Journals (Sweden)

    Marie-Laurence Tremblay

    2016-08-01

    Full Text Available Spider aciniform (wrapping silk is a remarkable fibrillar biomaterial with outstanding mechanical properties. It is a modular protein consisting, in Argiope trifasciata, of a core repetitive domain of 200 amino acid units (W units. In solution, the W units comprise a globular folded core, with five α-helices, and disordered tails that are linked to form a ~63-residue intrinsically disordered linker in concatemers. Herein, we present nuclear magnetic resonance (NMR spectroscopy-based 15N spin relaxation analysis, allowing characterization of backbone dynamics as a function of residue on the ps–ns timescale in the context of the single W unit (W1 and the two unit concatemer (W2. Unambiguous mapping of backbone dynamics throughout W2 was made possible by segmental NMR active isotope-enrichment through split intein-mediated trans-splicing. Spectral density mapping for W1 and W2 reveals a striking disparity in dynamics between the folded core and the disordered linker and tail regions. These data are also consistent with rotational diffusion behaviour where each globular domain tumbles almost independently of its neighbour. At a localized level, helix 5 exhibits elevated high frequency dynamics relative to the proximal helix 4, supporting a model of fibrillogenesis where this helix unfolds as part of the transition to a mixed α-helix/β-sheet fibre.

  9. The orientational preferences of backbones of proteins

    Institute of Scientific and Technical Information of China (English)

    CHEN Ying; WANG Jun; XUE Bin; WANG Wei

    2006-01-01

    The orientation between the backboneresidues of proteins is defined based on the local configurations and the corresponding preferences are analyzed by statistics. It is found that all the residue pairs have some specific preferences of orientations. The statistical analysis is mainly concentrated in the orientational distributions for two kinds of groupings of residues based on the hydrophobicity and secondary structural features. The statistics for such two types of groupings shows different orientational preferences. It is found that for the former grouping the orientational preference is rather weak,while for the later a kind of strong orientational preferences. This suggests that the formation of local structures and of secondary structures are highly related to the orientational preferences.

  10. Extracting the information backbone in online system

    CERN Document Server

    Zhang, Qian-Ming; Shang, Ming-Sheng

    2013-01-01

    Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers mainly dedicated to improve the recommendation performance (accuracy and diversity) of the algorithms while overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improve both of...

  11. Sofosbuvir as backbone of interferon free treatments.

    Science.gov (United States)

    Bourlière, Marc; Oules, Valèrie; Ansaldi, Christelle; Adhoute, Xavier; Castellani, Paul

    2014-12-15

    Sofosbuvir is the first-in-class NS5B nucleotide analogues to be launched for hepatitis C virus (HCV) treatment. Its viral potency, pangenotypic activity and high barrier to resistance make it the ideal candidate to become a backbone for several IFN-free regimens. Recent data demonstrated that sofosbuvir either with ribavirin alone or in combination with other direct-acting antivirals (DAAs) as daclatasvir, ledipasvir or simeprevir are able to cure HCV in at least 90% or over of patients. Treatment experienced genotype 3 population may remain the most difficult to treat population, but ongoing DAA combination studies will help to fill this gap. Safety profile of sofosbuvir or combination with other DAAs is good. Resistance to sofosbuvir did not appear as a significant issue. The rationale for using this class of drug and the available clinical data are reviewed.

  12. Extracting the information backbone in online system.

    Science.gov (United States)

    Zhang, Qian-Ming; Zeng, An; Shang, Ming-Sheng

    2013-01-01

    Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity) of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency.

  13. Stretched and overwound DNA forms a Pauling-like structure with exposed bases.

    Science.gov (United States)

    Allemand, J F; Bensimon, D; Lavery, R; Croquette, V

    1998-11-24

    We investigate structural transitions within a single stretched and supercoiled DNA molecule. With negative supercoiling, for a stretching force >0.3 pN, we observe the coexistence of B-DNA and denatured DNA from sigma approximately -0.015 down to sigma = -1. Surprisingly, for positively supercoiled DNA (sigma > +0.037) stretched by 3 pN, we observe a similar coexistence of B-DNA and a new, highly twisted structure. Experimental data and molecular modeling suggest that this structure has approximately 2.62 bases per turn and an extension 75% larger than B-DNA. This structure has tightly interwound phosphate backbones and exposed bases in common with Pauling's early DNA structure [Pauling, L. & Corey, R. B. (1953), Proc. Natl. Acad. Sci. USA 39, 84-97] and an unusual structure proposed for the Pf1 bacteriophage [Liu, D. J. & Day, L. A. (1994) Science 265, 671-674].

  14. Impact of Backbone Fluorination on π-Conjugated Polymers in Organic Photovoltaic Devices: A Review

    Directory of Open Access Journals (Sweden)

    Nicolas Leclerc

    2016-01-01

    Full Text Available Solution-processed bulk heterojunction solar cells have experienced a remarkable acceleration in performances in the last two decades, reaching power conversion efficiencies above 10%. This impressive progress is the outcome of a simultaneous development of more advanced device architectures and of optimized semiconducting polymers. Several chemical approaches have been developed to fine-tune the optoelectronics and structural polymer parameters required to reach high efficiencies. Fluorination of the conjugated polymer backbone has appeared recently to be an especially promising approach for the development of efficient semiconducting polymers. As a matter of fact, most currently best-performing semiconducting polymers are using fluorine atoms in their conjugated backbone. In this review, we attempt to give an up-to-date overview of the latest results achieved on fluorinated polymers for solar cells and to highlight general polymer properties’ evolution trends related to the fluorination of their conjugated backbone.

  15. Contribution of Peptide Backbone to Anti-Citrullinated Peptide Antibody Reactivity.

    Directory of Open Access Journals (Sweden)

    Nicole Hartwig Trier

    Full Text Available Rheumatoid arthritis (RA is one of the most common autoimmune diseases, affecting approximately 1-2% of the world population. One of the characteristic features of RA is the presence of autoantibodies. Especially the highly specific anti-citrullinated peptide antibodies (ACPAs, which have been found in up to 70% of RA patients' sera, have received much attention. Several citrullinated proteins are associated with RA, suggesting that ACPAs may react with different sequence patterns, separating them from traditional antibodies, whose reactivity usually is specific towards a single target. As ACPAs have been suggested to be involved in the development of RA, knowledge about these antibodies may be crucial. In this study, we examined the influence of peptide backbone for ACPA reactivity in immunoassays. The antibodies were found to be reactive with a central Cit-Gly motif being essential for ACPA reactivity and to be cross-reactive between the selected citrullinated peptides. The remaining amino acids within the citrullinated peptides were found to be of less importance for antibody reactivity. Moreover, these findings indicated that the Cit-Gly motif in combination with peptide backbone is essential for antibody reactivity. Based on these findings it was speculated that any amino acid sequence, which brings the peptide into a properly folded structure for antibody recognition is sufficient for antibody reactivity. These findings are in accordance with the current hypothesis that structural homology rather than sequence homology are favored between citrullinated epitopes. These findings are important in relation to clarifying the etiology of RA and to determine the nature of ACPAs, e.g., why some Cit-Gly-containing sequences are not targeted by ACPAs.

  16. INFLUENCE OF BACKBONE RIGIDITY ON THE LIQUID CRYSTALLINITY OF MESOGEN-CONTAINING POLYACETYLENES

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    Two acetylene polymers containing cyanobiphenyl-based mesogens,poly{10-[((4'-cyano-4-biphenylyl)oxy)carbonyl]-1-decyne} (PA8CN), which has a relatively flexible polyalkyne backbone, and poly {[4-(((12-((4'-cyano-4-biphenylyl)oxy)dodecyl)oxy)carbonyl) phenyl]-acetylene} (PB12CN), which has a fairly rigid poly(phenylacetylene)backbone, were synthesized using respectively WCl6 and [Rh(nbd)Cl]2 as the catalysts.PA8CN exhibits enantiotropic interdigitated smectic A phase (SAd) over a temperature range as wide as ca. 100℃, whereas PB12CN is non-mesomorphic, demonstrating that the backbone rigidity plays an important role in determining the liquid crystallinity of the polyacetylenes.

  17. Side-Chain-Induced Rigid Backbone Organization of Polymer Semiconductors through Semifluoroalkyl Side Chains.

    Science.gov (United States)

    Kang, Boseok; Kim, Ran; Lee, Seon Baek; Kwon, Soon-Ki; Kim, Yun-Hi; Cho, Kilwon

    2016-03-23

    While high-mobility p-type conjugated polymers have been widely reported, high-mobility n-type conjugated polymers are still rare. In the present work, we designed semifluorinated alkyl side chains and introduced them into naphthalene diimide-based polymers (PNDIF-T2 and PNDIF-TVT). We found that the strong self-organization of these side chains induced a high degree of order in the attached polymer backbones by forming a superstructure composed of "backbone crystals" and "side-chain crystals". This phenomenon was shown to greatly enhance the ordering along the backbone direction, and the resulting polymers thus exhibited unipolar n-channel transport in field-effect transistors with remarkably high electron mobility values of up to 6.50 cm(2) V(-1) s(-1) and with a high on-off current ratio of 10(5).

  18. Transforming plastic surfaces with electrophilic backbones from hydrophobic to hydrophilic.

    Science.gov (United States)

    Kim, Samuel; Bowen, Raffick A R; Zare, Richard N

    2015-01-28

    We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone.

  19. NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis

    Directory of Open Access Journals (Sweden)

    Veronica Paradiso

    2016-01-01

    Full Text Available The catalytic properties of olefin metathesis ruthenium complexes bearing N-heterocyclic carbene ligands with stereogenic centers on the backbone are described. Differences in catalytic behavior depending on the backbone configurations of symmetrical and unsymmetrical NHCs are discussed. In addition, an overview on asymmetric olefin metathesis promoted by chiral catalysts bearing C2-symmetric and C1-symmetric NHCs is provided.

  20. NHC Backbone Configuration in Ruthenium-Catalyzed Olefin Metathesis.

    Science.gov (United States)

    Paradiso, Veronica; Costabile, Chiara; Grisi, Fabia

    2016-01-20

    The catalytic properties of olefin metathesis ruthenium complexes bearing N-heterocyclic carbene ligands with stereogenic centers on the backbone are described. Differences in catalytic behavior depending on the backbone configurations of symmetrical and unsymmetrical NHCs are discussed. In addition, an overview on asymmetric olefin metathesis promoted by chiral catalysts bearing C₂-symmetric and C₁-symmetric NHCs is provided.

  1. Extracting the information backbone in online system.

    Directory of Open Access Journals (Sweden)

    Qian-Ming Zhang

    Full Text Available Information overload is a serious problem in modern society and many solutions such as recommender system have been proposed to filter out irrelevant information. In the literature, researchers have been mainly dedicated to improving the recommendation performance (accuracy and diversity of the algorithms while they have overlooked the influence of topology of the online user-object bipartite networks. In this paper, we find that some information provided by the bipartite networks is not only redundant but also misleading. With such "less can be more" feature, we design some algorithms to improve the recommendation performance by eliminating some links from the original networks. Moreover, we propose a hybrid method combining the time-aware and topology-aware link removal algorithms to extract the backbone which contains the essential information for the recommender systems. From the practical point of view, our method can improve the performance and reduce the computational time of the recommendation system, thus improving both of their effectiveness and efficiency.

  2. Plasma-based accelerator structures

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Carl B. [Univ. of California, Berkeley, CA (United States)

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  3. A model for the [C+-GxC]n triple helix derived from observation of the C+-GxC base triplet in a crystal structure.

    Science.gov (United States)

    Nunn, C M; Trent, J O; Neidle, S

    1997-10-13

    A molecular modelling study on the [C+-GxC]n triple helix is reported. We have observed the C+-GxC base triplet in the crystal structure of an oligonucleotide-drug complex, between the minor-groove drug netropsin and the decanucleotide d(CGCAATTGCG)2. The complex was crystallised at pH 7.0, but the crystal structure, at a resolution of 2.4 A, shows that a terminal cytosine has become protonated and participates in a parallel C+-GxC base triplet. The structure of this triplet and its associated sugar-phosphate backbones have been energy-refined and then used to generate a triple helix. This has characteristics of the B-type family of DNA structures for two strands, with the third, the C+ strand, having backbone conformations closer to the A family.

  4. Energies and 2'-Hydroxyl Group Orientations of RNA Backbone Conformations. Benchmark CCSD(T)/CBS Database, Electronic Analysis, and Assessment of DFT Methods and MD Simulations.

    Science.gov (United States)

    Mládek, Arnošt; Banáš, Pavel; Jurečka, Petr; Otyepka, Michal; Zgarbová, Marie; Šponer, Jiří

    2014-01-14

    Sugar-phosphate backbone is an electronically complex molecular segment imparting RNA molecules high flexibility and architectonic heterogeneity necessary for their biological functions. The structural variability of RNA molecules is amplified by the presence of the 2'-hydroxyl group, capable of forming multitude of intra- and intermolecular interactions. Bioinformatics studies based on X-ray structure database revealed that RNA backbone samples at least 46 substates known as rotameric families. The present study provides a comprehensive analysis of RNA backbone conformational preferences and 2'-hydroxyl group orientations. First, we create a benchmark database of estimated CCSD(T)/CBS relative energies of all rotameric families and test performance of dispersion-corrected DFT-D3 methods and molecular mechanics in vacuum and in continuum solvent. The performance of the DFT-D3 methods is in general quite satisfactory. The B-LYP-D3 method provides the best trade-off between accuracy and computational demands. B3-LYP-D3 slightly outperforms the new PW6B95-D3 and MPW1B95-D3 and is the second most accurate density functional of the study. The best agreement with CCSD(T)/CBS is provided by DSD-B-LYP-D3 double-hybrid functional, although its large-scale applications may be limited by high computational costs. Molecular mechanics does not reproduce the fine energy differences between the RNA backbone substates. We also demonstrate that the differences in the magnitude of the hyperconjugation effect do not correlate with the energy ranking of the backbone conformations. Further, we investigated the 2'-hydroxyl group orientation preferences. For all families, we conducted a QM and MM hydroxyl group rigid scan in gas phase and solvent. We then carried out set of explicit solvent MD simulations of folded RNAs and analyze 2'-hydroxyl group orientations of different backbone families in MD. The solvent energy profiles determined primarily by the sugar pucker match well with the

  5. Solvent-induced differentiation of protein backbone hydrogen bonds in calmodulin.

    Science.gov (United States)

    Juranić, Nenad; Atanasova, Elena; Streiff, John H; Macura, Slobodan; Prendergast, Franklyn G

    2007-07-01

    In apo and holoCaM, almost half of the hydrogen bonds (H-bonds) at the protein backbone expected from the corresponding NMR or X-ray structures were not detected by h3JNC' couplings. The paucity of the h3JNC' couplings was considered in terms of dynamic features of these structures. We examined a set of seven proteins and found that protein-backbone H-bonds form two groups according to the h3JNC' couplings measured in solution. H-bonds that have h3JNC' couplings above the threshold of 0.2 Hz show distance/angle correlation among the H-bond geometrical parameters, and appear to be supported by the backbone dynamics in solution. The other H-bonds have no such correlation; they populate the water-exposed and flexible regions of proteins, including many of the CaM helices. The observed differentiation in a dynamical behavior of backbone H-bonds in apo and holoCaM appears to be related to protein functions.

  6. Animals without Backbones: The Invertebrate Story. Grade Level 5-9.

    Science.gov (United States)

    Jerome, Brian; Fuqua, Paul

    This guide, when used in tandem with the videotape "Animals Without Backbones," helps students learn about invertebrates. These materials promote hands-on discovery and learning. The guide is composed of six curriculum-based teaching units: (1) "Getting Started"; (2) "Porifera"; (3) "Cnidarians"; (4) "Worms"; (5) "Mollusks"; (6) "Arthropods"; and…

  7. Reliability Based Ship Structural Design

    DEFF Research Database (Denmark)

    Dogliani, M.; Østergaard, C.; Parmentier, G.;

    1996-01-01

    with developments of models of load effects and of structural collapse adopted in reliability formulations which aim at calibrating partial safety factors for ship structural design. New probabilistic models of still-water load effects are developed both for tankers and for containerships. New results are presented......This paper deals with the development of different methods that allow the reliability-based design of ship structures to be transferred from the area of research to the systematic application in current design. It summarises the achievements of a three-year collaborative research project dealing...... structure of several tankers and containerships. The results of the reliability analysis were the basis for the definition of a target safety level which was used to asses the partial safety factors suitable for in a new design rules format to be adopted in modern ship structural design. Finally...

  8. Prediction of nonregular secondary structures of proteins based on wavelet analysis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The secondary structures of proteins fall into two classes: regular structure and nonregular structure. Helices and sheets are termed "regular" structures because their residues have repeating main-chain torsion angles, and their backbone N-H and C-O groups are arranged in a periodic pattern of hydrogen bonding. In contrast, the remaining structures with nonrepeating backbone torsion angles are called nonregular secondary structures. In this note, we performed an extensive sequence analysis of nonregular secondary structures and showed that these nonregular parts could be effectively predicted by continuous wavelet transform.

  9. NMR study of non-structural proteins--part I: (1)H, (13)C, (15)N backbone and side-chain resonance assignment of macro domain from Mayaro virus (MAYV).

    Science.gov (United States)

    Melekis, Efstathios; Tsika, Aikaterini C; Lichière, Julie; Chasapis, Christos T; Margiolaki, Irene; Papageorgiou, Nicolas; Coutard, Bruno; Bentrop, Detlef; Spyroulias, Georgios A

    2015-04-01

    Macro domains are ADP-ribose-binding modules present in all eukaryotic organisms, bacteria and archaea. They are also found in non-structural proteins of several positive strand RNA viruses such as alphaviruses. Here, we report the high yield expression and preliminary structural analysis through solution NMR spectroscopy of the macro domain from New World Mayaro Alphavirus. The recombinant protein was well-folded and in a monomeric state. An almost complete sequence-specific assignment of its (1)H, (15)N and (13)C resonances was obtained and its secondary structure determined by TALOS+.

  10. A backbone lever-arm effect enhances polymer mechanochemistry

    Science.gov (United States)

    Klukovich, Hope M.; Kouznetsova, Tatiana B.; Kean, Zachary S.; Lenhardt, Jeremy M.; Craig, Stephen L.

    2013-02-01

    Mechanical forces along a polymer backbone can be used to bring about remarkable reactivity in embedded mechanically active functional groups, but little attention has been paid to how a given polymer backbone delivers that force to the reactant. Here, single-molecule force spectroscopy was used to directly quantify and compare the forces associated with the ring opening of gem-dibromo and gem-dichlorocyclopropanes affixed along the backbone of cis-polynorbornene and cis-polybutadiene. The critical force for isomerization drops by about one-third in the polynorbornene scaffold relative to polybutadiene. The root of the effect lies in more efficient chemomechanical coupling through the polynorbornene backbone, which acts as a phenomenological lever with greater mechanical advantage than polybutadiene. The experimental results are supported computationally and provide the foundation for a new strategy by which to engineer mechanochemical reactivity.

  11. LOAD AWARE ADAPTIVE BACKBONE SYNTHESIS IN WIRELESS MESH NETWORKS

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan; Zheng Baoyu

    2009-01-01

    Wireless Mesh Networks (WMNs) are envisioned to support the wired backbone with a wireless Backbone Networks (BNet) for providing internet connectivity to large-scale areas.With a wide range of internet-oriented applications with different Quality of Service (QoS) requirement,the large-scale WMNs should have good scalability and large bandwidth.In this paper,a Load Aware Adaptive Backbone Synthesis (LAABS) algorithm is proposed to automatically balance the traffic flow in the WMNs.The BNet will dynamically split into smaller size or merge into bigger one according to statistic load information of Backbone Nodes (BNs).Simulation results show LAABS generates moderate BNet size and converges quickly,thus providing scalable and stable BNet to facilitate traffic flow.

  12. Thermodynamic contribution of backbone conformational entropy in the binding between SH3 domain and proline-rich motif.

    Science.gov (United States)

    Zeng, Danyun; Shen, Qingliang; Cho, Jae-Hyun

    2017-02-26

    Biological functions of intrinsically disordered proteins (IDPs), and proteins containing intrinsically disordered regions (IDRs) are often mediated by short linear motifs, like proline-rich motifs (PRMs). Upon binding to their target proteins, IDPs undergo a disorder-to-order transition which is accompanied by a large conformational entropy penalty. Hence, the molecular mechanisms underlying control of conformational entropy are critical for understanding the binding affinity and selectivity of IDPs-mediated protein-protein interactions (PPIs). Here, we investigated the backbone conformational entropy change accompanied by binding of the N-terminal SH3 domain (nSH3) of CrkII and PRM derived from guanine nucleotide exchange factor 1 (C3G). In particular, we focused on the estimation of conformational entropy change of disordered PRM upon binding to the nSH3 domain. Quantitative characterization of conformational dynamics of disordered peptides like PRMs is limited. Hence, we combined various methods, including NMR model-free analysis, δ2D, DynaMine, and structure-based calculation of entropy loss. This study demonstrates that the contribution of backbone conformational entropy change is significant in the PPIs mediated by IDPs/IDRs.

  13. Backbone topology, access, and the commercial Internet, 1997 - 2000

    OpenAIRE

    Morton E O'Kelly; Grubesic, Tony H.

    2002-01-01

    As the Internet grows in popularity, telecommunications infrastructure in the United States continues to increase in capacity and geographic reach to meet market demand. Important components of this infrastructure include the commercial fiber-optic backbones used to transport digital information between locations. The spatial organization of commercial Internet backbones reflects an increasingly competitive privatized market for service provision, in which certain locations are more accessibl...

  14. n Silico Analysis of Envelope Dengue Virus-2 and Envelope Dengue Virus-3 Protein as the Backbone of Dengue Virus Tetravalent Vaccine by Using Homology Modeling Method

    Directory of Open Access Journals (Sweden)

    Rizky I. Taufik

    2009-01-01

    Full Text Available Problem statement: Dengue fever, which was caused by Dengue virus infection, had became a major public health problem in the tropic and subtropical countries. Dengue virus (DENV had four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4, based on their immunogenic in the human body. Preventive measure will be necessary to decrease the prevalence of dengue fever, by developing modern vaccine. Approach: This research was focused on in silico study of dengue virus vaccines, by using envelope (E protein of DENV-2 and DENV-3 as their backbones. T cell epitope prediction was determined by using MULTIPRED server and B cell epitope prediction was determined by using Conformational Epitope Prediction server (CEP. Homology modeling study of E DENV-3 protein as the vaccine backbone had produced six dengue vaccine peptides (HMM Vaccine 1-6. Moreover, homology modeling study of E DENV-2 protein as vaccine backbone had produced six dengue vaccine peptides (ANN vaccine 1-6. Results: The BLAST analysis of HMM and ANN vaccines had produced 93% and 91% identity, respectively. The Ramachandran Plot of both vaccines had shown less than 15% non glycine residue in the disallowed region, therefore it showed the solid stability of the proteins. The VAST analysis of E DENV-3 backbone vaccines had determined, that HMM4 and HMM6 had the highest structure similarity with native E DENV-3. HMM4 and HMM6 had the highest VAST score of 64.5. Moreover, the VAST analysis of E DENV-2 backbone vaccines had determined, that ANN1, ANN3, ANN4, ANN5 and ANN6 had the highest structure similarity with native E DENV-2. ANN1, ANN3, ANN4, ANN5 and ANN6 have the highest VAST score of 64.7. Conclusion/Recommendation: It could be inferred from this research that HMM4; HMM6; ANN1; ANN3; ANN4; ANN5; and ANN6 were the best in silico vaccine design, based on their similarity with native E DENV Proteins. This research could be applied for the wet

  15. Is there a Climate Network - A Backbone of the Climate System? (Invited)

    Science.gov (United States)

    Kurths, J.

    2010-12-01

    We consider an inverse problem: Is there a backbone-like structure underlying the climate system? For this we propose a method to reconstruct and analyze a complex network from data generated by a spatio-temporal dynamical system. This technique is then applied to reanalysis and model surface air temperature data. Parameters of this network, as betweenness centrality, uncover relations to global circulation patterns in oceans and atmosphere. We especially study the role of hubs and of long range connections, called teleconnections, in the flows of energy and matter in the climate system. The global scale view on climate networks offers promising new perspectives for detecting dynamical structures based on nonlinear physical processes in the climate system. References Arenas, A., A. Diaz-Guilera, J. Kurths, Y. Moreno, and C. Zhou, Phys. Reports 2008, 469, 93. Donges, J., Y. Zou, N. Marwan, and J. Kurths, Europ. Phys. J. ST 2009, 174, 157-179. Donges, J., Y. Zou, N. Marwan, and J. Kurths, Europhys. Lett. 2009, 87, 48007. Nawrath, J. et al., Phys. Rev. Lett. 2010, 104, 038701. Donner, R., Y. Zou, J. Donges, N. Marwan, and J. Kurths, Phys. Rev. E 2010, 81, 015101(R ).

  16. Displacement based multilevel structural optimization

    Science.gov (United States)

    Striz, Alfred G.

    1995-01-01

    Multidisciplinary design optimization (MDO) is expected to play a major role in the competitive transportation industries of tomorrow, i.e., in the design of aircraft and spacecraft, of high speed trains, boats, and automobiles. All of these vehicles require maximum performance at minimum weight to keep fuel consumption low and conserve resources. Here, MDO can deliver mathematically based design tools to create systems with optimum performance subject to the constraints of disciplines such as structures, aerodynamics, controls, etc. Although some applications of MDO are beginning to surface, the key to a widespread use of this technology lies in the improvement of its efficiency. This aspect is investigated here for the MDO subset of structural optimization, i.e., for the weight minimization of a given structure under size, strength, and displacement constraints. Specifically, finite element based multilevel optimization of structures (here, statically indeterminate trusses and beams for proof of concept) is performed. In the system level optimization, the design variables are the coefficients of assumed displacement functions, and the load unbalance resulting from the solution of the stiffness equations is minimized. Constraints are placed on the deflection amplitudes and the weight of the structure. In the subsystems level optimizations, the weight of each element is minimized under the action of stress constraints, with the cross sectional dimensions as design variables. This approach is expected to prove very efficient, especially for complex structures, since the design task is broken down into a large number of small and efficiently handled subtasks, each with only a small number of variables. This partitioning will also allow for the use of parallel computing, first, by sending the system and subsystems level computations to two different processors, ultimately, by performing all subsystems level optimizations in a massively parallel manner on separate

  17. Reliability-based optimization of engineering structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2008-01-01

    The theoretical basis for reliability-based structural optimization within the framework of Bayesian statistical decision theory is briefly described. Reliability-based cost benefit problems are formulated and exemplitied with structural optimization. The basic reliability-based optimization prob...

  18. Backbone Assignment of the MALT1 Paracaspase by Solution NMR.

    Science.gov (United States)

    Unnerståle, Sofia; Nowakowski, Michal; Baraznenok, Vera; Stenberg, Gun; Lindberg, Jimmy; Mayzel, Maxim; Orekhov, Vladislav; Agback, Tatiana

    2016-01-01

    Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a unique paracaspase protein whose protease activity mediates oncogenic NF-κB signalling in activated B cell-like diffuse large B cell lymphomas (ABC-DLBCLs). ABC-DLBCLs are aggressive lymphomas with high resistance to current chemotherapies. Low survival rate among patients emphasizes the urgent need for alternative treatment options. The characterization of the MALT1 will be an essential tool for developing new target-directed drugs against MALT1 dependent disorders. As the first step in the atomic-level NMR studies of the system, here we report, the (15)N/(13)C/(1)H backbone assignment of the apo form of the MALT1 paracaspase region together with the third immunoglobulin-like (Ig3) domain, 44 kDa, by high resolution NMR. In addition, the non-uniform sampling (NUS) based targeted acquisition procedure is evaluated as a mean of decreasing acquisition and analysis time for larger proteins.

  19. Backbone Assignment of the MALT1 Paracaspase by Solution NMR.

    Directory of Open Access Journals (Sweden)

    Sofia Unnerståle

    Full Text Available Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1 is a unique paracaspase protein whose protease activity mediates oncogenic NF-κB signalling in activated B cell-like diffuse large B cell lymphomas (ABC-DLBCLs. ABC-DLBCLs are aggressive lymphomas with high resistance to current chemotherapies. Low survival rate among patients emphasizes the urgent need for alternative treatment options. The characterization of the MALT1 will be an essential tool for developing new target-directed drugs against MALT1 dependent disorders. As the first step in the atomic-level NMR studies of the system, here we report, the (15N/(13C/(1H backbone assignment of the apo form of the MALT1 paracaspase region together with the third immunoglobulin-like (Ig3 domain, 44 kDa, by high resolution NMR. In addition, the non-uniform sampling (NUS based targeted acquisition procedure is evaluated as a mean of decreasing acquisition and analysis time for larger proteins.

  20. Tren-based analogues of bacillibactin: structure and stability.

    Science.gov (United States)

    Dertz, Emily A; Xu, Jide; Raymond, Kenneth N

    2006-07-10

    Synthetic analogues were designed to highlight the effect of the glycine moiety of bacillibactin on the overall stability of the ferric complex as compared to synthetic analogues of enterobactin. Insertion of a variety of amino acids to catecholamide analogues based on a Tren (tris(2-aminoethyl)amine) backbone increased the overall acidity of the ligands, causing an enhancement of the stability of the resulting ferric complex as compared to TRENCAM. Solution thermodynamic behavior of these siderophores and their synthetic analogues was investigated through potentiometric and spectrophotometric titrations. X-ray crystallography, circular dichroism, and molecular modeling were used to determine the chirality and geometry of the ferric complexes of bacillibactin and its analogues. In contrast to the Tren scaffold, addition of a glycine to the catechol chelating arms causes an inversion of the trilactone backbone, resulting in opposite chiralities of the two siderophores and a destabilization of the ferric complex of bacillibactin compared to ferric enterobactin.

  1. The backbone of the climate network

    Energy Technology Data Exchange (ETDEWEB)

    Donges, Jonathan Friedemann; Kurths, Juergen [Potsdam Institute for Climate Impact Research, P.O. Box 601203, 14412 Potsdam (Germany); Department of Physics, Humboldt University Berlin, Newtonstr. 15, 12489 Berlin (Germany); Zou, Yong; Marwan, Norbert [Potsdam Institute for Climate Impact Research, P.O. Box 601203, 14412 Potsdam (Germany)

    2010-07-01

    We propose a method to reconstruct and analyze a complex network from data generated by a spatio-temporal dynamical system, relying on the nonlinear mutual information of time series analysis and betweenness centrality of complex network theory. We show, that this approach reveals a rich internal structure in complex climate networks constructed from reanalysis and model surface air temperature data. Our novel method uncovers peculiar wave-like structures of high energy flow, that we relate to global surface ocean currents. This points to a major role of the oceanic surface circulation in coupling and stabilizing the global temperature field in the long term mean (140 years for the model run and 60 years for reanalysis data). We find that these results cannot be obtained using classical linear methods of multivariate data analysis, and have ensured their robustness by intensive significance testing.

  2. The backbone of the climate network

    CERN Document Server

    Donges, Jonathan F; Marwan, Norbert; Kurths, Juergen; 10.1209/0295-5075/87/48007

    2010-01-01

    We propose a method to reconstruct and analyze a complex network from data generated by a spatio-temporal dynamical system, relying on the nonlinear mutual information of time series analysis and betweenness centrality of complex network theory. We show, that this approach reveals a rich internal structure in complex climate networks constructed from reanalysis and model surface air temperature data. Our novel method uncovers peculiar wave-like structures of high energy flow, that we relate to global surface ocean currents. This points to a major role of the oceanic surface circulation in coupling and stabilizing the global temperature field in the long term mean (140 years for the model run and 60 years for reanalysis data). We find that these results cannot be obtained using classical linear methods of multivariate data analysis, and have ensured their robustness by intensive significance testing.

  3. Smart-Grid Backbone Network Real-Time Delay Reduction via Integer Programming.

    Science.gov (United States)

    Pagadrai, Sasikanth; Yilmaz, Muhittin; Valluri, Pratyush

    2016-08-01

    This research investigates an optimal delay-based virtual topology design using integer linear programming (ILP), which is applied to the current backbone networks such as smart-grid real-time communication systems. A network traffic matrix is applied and the corresponding virtual topology problem is solved using the ILP formulations that include a network delay-dependent objective function and lightpath routing, wavelength assignment, wavelength continuity, flow routing, and traffic loss constraints. The proposed optimization approach provides an efficient deterministic integration of intelligent sensing and decision making, and network learning features for superior smart grid operations by adaptively responding the time-varying network traffic data as well as operational constraints to maintain optimal virtual topologies. A representative optical backbone network has been utilized to demonstrate the proposed optimization framework whose simulation results indicate that superior smart-grid network performance can be achieved using commercial networks and integer programming.

  4. Energy Efficient Low-Cost Virtual Backbone Construction for Optimal Routing in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    K. Mohaideen Pitchai

    2014-01-01

    Full Text Available Many prominent applications in wireless sensor networks which require collected information have to be routed to end nodes in an efficient manner. In general, weighted connected dominating Sets (WCDS based routing is a promising approach for enhancing the routing efficiency in sensor networks. Backbone has been used extensively in routing. Here an efficient WCDS algorithm for constructing a virtual backbone with low total cost, hop spanning ratio, and minimum number of dominators is proposed. We report a systematic approach, which has three phases. Initial phase considers the issues of revoking a partial CDS tree from a complete CDS tree. Secondary and final phases make the design of the complete algorithm by considering the determination of dominators using an iteration process. Our findings reveal better performance than the existing algorithms in terms of total cost, hop spanning ratio, and number of dominators.

  5. Automating unambiguous NOE data usage in NVR for NMR protein structure-based assignments.

    Science.gov (United States)

    Akhmedov, Murodzhon; Çatay, Bülent; Apaydın, Mehmet Serkan

    2015-12-01

    Nuclear Magnetic Resonance (NMR) Spectroscopy is an important technique that allows determining protein structure in solution. An important problem in protein structure determination using NMR spectroscopy is the mapping of peaks to corresponding amino acids, also known as the assignment problem. Structure-Based Assignment (SBA) is an approach to solve this problem using a template structure that is homologous to the target. Our previously developed approach Nuclear Vector Replacement-Binary Integer Programming (NVR-BIP) computed the optimal solution for small proteins, but was unable to solve the assignments of large proteins. NVR-Ant Colony Optimization (ACO) extended the applicability of the NVR approach for such proteins. One of the input data utilized in these approaches is the Nuclear Overhauser Effect (NOE) data. NOE is an interaction observed between two protons if the protons are located close in space. These protons could be amide protons, protons attached to the alpha-carbon atom in the backbone of the protein, or side chain protons. NVR only uses backbone protons. In this paper, we reformulate the NVR-BIP model to distinguish the type of proton in NOE data and use the corresponding proton coordinates in the extended formulation. In addition, the threshold value over interproton distances is set in a standard manner for all proteins by extracting the NOE upper bound distance information from the data. We also convert NOE intensities into distance thresholds. Our new approach thus handles the NOE data correctly and without manually determined parameters. We accordingly adapt NVR-ACO solution methodology to these changes. Computational results show that our approaches obtain optimal solutions for small proteins. For the large proteins our ant colony optimization-based approach obtains promising results.

  6. Alkali metal salts of formazanate ligands : diverse coordination modes as a result of the nitrogen-rich [NNCNN] ligand backbone

    NARCIS (Netherlands)

    Travieso-Puente, Raquel; Chang, Mu-Chieh; Otten, Edwin

    2014-01-01

    Alkali metal salts of redox-active formazanate ligands were prepared, and their structures in the solid-state and in solution are determined. The nitrogen-rich [NNCNN] backbone of formazanates results in a varied coordination chemistry, with both the internal and terminal nitrogen atoms available fo

  7. Tailor-made synthesis of various backbone-substituted imidazolinium salts by triflic anhydride mediated intramolecular cyclisation.

    Science.gov (United States)

    Zhang, Jun; Su, Xiaolong; Fu, Jun; Qin, Xinke; Zhao, Meixin; Shi, Min

    2012-09-21

    We have found a Tf(2)O-mediated intramolecular cyclization reaction and have revealed an intriguing stereoselectivity and a regioselectivity during the preparation of intermediate alcohols, which allow for the tailor-made synthesis of various backbone-substituted imidazolinium salts, and structurally specific syn-4,5-disubstituted imidazolinium salts.

  8. Protein backbone dynamics revealed by quasi spectral density function analysis of amide N-15 nuclei.

    Science.gov (United States)

    Ishima, R; Nagayama, K

    1995-03-14

    Spectral density functions J(0), J(omega N), and J(omega H + omega N) of individual amide N-15 nuclei in proteins were approximated by a quasi spectral density function (QSDF). Using this function, the backbone dynamics were analyzed for seven protein systems on which data have been published. We defined J(0; omega N) as the difference between the J(0) and the J(omega N) values, which describes motions slower than 50 (or 60) MHz, and J(omega N; omega H+N) as the difference between the J(omega N) and the J(omega H + omega N) values, which describes motions slower than 450 (or 540) MHz. The QSDF analysis can easily extract the J(0; omega N) of protein backbones, which have often some relation to biologically relevant reactions. Flexible N-terminal regions in eglin c and glucose permease IIA and a loop region in eglin c showed smaller values of both the J(0; omega N) and the J(omega N; omega H+N) as compared with the other regions, indicating increases in motions faster than nanosecond. The values of the J(0; omega N) for the backbone of the FK506 binding protein showed a large variation in the apoprotein but fell in a very narrow range after the binding of FK506. Characteristic increase or decrease in the values of J(0) and J(omega N) was observed in two or three residues located between secondary structures.

  9. Effect of backbone chemistry on hybridization thermodynamics of oligonucleic acids: a coarse-grained molecular dynamics simulation study.

    Science.gov (United States)

    Ghobadi, Ahmadreza F; Jayaraman, Arthi

    2016-02-28

    In this paper we study how varying oligonucleic acid backbone chemistry affects the hybridization/melting thermodynamics of oligonucleic acids. We first describe the coarse-grained (CG) model with tunable parameters that we developed to enable the study of both naturally occurring oligonucleic acids, such as DNA, and their chemically-modified analogues, such as peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). The DNA melting curves obtained using such a CG model and molecular dynamics simulations in an implicit solvent and with explicit ions match with the melting curves obtained using the empirical nearest-neighbor models. We use these CG simulations to then elucidate the effect of backbone flexibility, charge, and nucleobase spacing along the backbone on the melting curves, potential energy and conformational entropy change upon hybridization and base-pair hydrogen bond residence time. We find that increasing backbone flexibility decreases duplex thermal stability and melting temperature mainly due to increased conformational entropy loss upon hybridization. Removing charges from the backbone enhances duplex thermal stability due to the elimination of electrostatic repulsion and as a result a larger energetic gain upon hybridization. Lastly, increasing nucleobase spacing decreases duplex thermal stability due to decreasing stacking interactions that are important for duplex stability.

  10. The Graphical Representation of the Digital Astronaut Physiology Backbone

    Science.gov (United States)

    Briers, Demarcus

    2010-01-01

    This report summarizes my internship project with the NASA Digital Astronaut Project to analyze the Digital Astronaut (DA) physiology backbone model. The Digital Astronaut Project (DAP) applies integrated physiology models to support space biomedical operations, and to assist NASA researchers in closing knowledge gaps related to human physiologic responses to space flight. The DA physiology backbone is a set of integrated physiological equations and functions that model the interacting systems of the human body. The current release of the model is HumMod (Human Model) version 1.5 and was developed over forty years at the University of Mississippi Medical Center (UMMC). The physiology equations and functions are scripted in an XML schema specifically designed for physiology modeling by Dr. Thomas G. Coleman at UMMC. Currently it is difficult to examine the physiology backbone without being knowledgeable of the XML schema. While investigating and documenting the tags and algorithms used in the XML schema, I proposed a standard methodology for a graphical representation. This standard methodology may be used to transcribe graphical representations from the DA physiology backbone. In turn, the graphical representations can allow examination of the physiological functions and equations without the need to be familiar with the computer programming languages or markup languages used by DA modeling software.

  11. Solution-based growth and structural characterization of homo- and heterobranched semiconductor nanowires.

    Science.gov (United States)

    Dong, Angang; Tang, Rui; Buhro, William E

    2007-10-10

    Colloidal homobranched ZnSe nanowires (NWs) and heterobranched CdSe-ZnSe NWs are successfully synthesized by combining a sequential seeding strategy with the solution-liquid-solid (SLS) growth process. We have developed an efficient approach to deposit secondary bismuth nanoparticles onto the NW backbone to induce the subsequent SLS branch growth. The density, length, and diameter of branches are rationally controlled by varying reaction conditions. Structural characterization reveals that crystalline branches grow epitaxially from the backbone in both homo- and heterobranched NWs. Two different branching structures are observed in the CdSe-ZnSe heterobranched NWs, owing to the phase admixture, i.e., cubic and hexagonal crystal structures, coexisting in the CdSe NW backbones. These branched NWs with well-designed architectures are expected to have potential as three-dimensional building blocks in the fabrication of nanoscale electronics and photonics.

  12. HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone.

    Directory of Open Access Journals (Sweden)

    Michelle Bronze

    Full Text Available To date, the majority of HIV-1 phenotypic resistance testing has been performed with subtype B virus backbones (e.g. HXB2. However, the relevance of using this backbone to determine resistance in non-subtype B HIV-1 viruses still needs to be assessed. From 114 HIV-1 subtype C clinical samples (36 ARV-naïve, 78 ARV-exposed, pol amplicons were produced and analyzed for phenotypic resistance using both a subtype B- and C-backbone in which the pol fragment was deleted. Phenotypic resistance was assessed in resulting recombinant virus stocks (RVS for a series of antiretroviral drugs (ARV's and expressed as fold change (FC, yielding 1660 FC comparisons. These Antivirogram® derived FC values were categorized as having resistant or sensitive susceptibility based on biological cut-off values (BCOs. The concordance between resistance calls obtained for the same clinical sample but derived from two different backbones (i.e. B and C accounted for 86.1% (1429/1660 of the FC comparisons. However, when taking the assay variability into account, 95.8% (1590/1660 of the phenotypic data could be considered as being concordant with respect to their resistance call. No difference in the capacity to detect resistance associated with M184V, K103N and V106M mutations was noted between the two backbones. The following was concluded: (i A high level of concordance was shown between the two backbone phenotypic resistance profiles; (ii Assay variability is largely responsible for discordant results (i.e. for FC values close to BCO; (iii Confidence intervals should be given around the BCO's, when assessing resistance in HIV-1 subtype C; (iv No systematic resistance under- or overcalling of subtype C amplicons in the B-backbone was observed; (v Virus backbone subtype sequence variability outside the pol region does not contribute to phenotypic FC values. In conclusion the HXB2 virus backbone remains an acceptable vector for phenotyping HIV-1 subtype C pol amplicons.

  13. The Legal Ethical Backbone of Conscientious Refusal

    DEFF Research Database (Denmark)

    Munthe, Christian; Nielsen, Morten Ebbe Juul

    2017-01-01

    This article analyzes the idea of a legal right to conscientious refusal for healthcare professionals from a basic legal ethical standpoint, using refusal to perform tasks related to legal abortion (in cases of voluntary employment) as a case in point. The idea of a legal right to conscientious...... refusal is distinguished from ideas regarding moral rights or reasons related to conscientious refusal, and none of the latter are found to support the notion of a legal right. Reasons for allowing some sort of room for conscientious refusal for healthcare professionals based on the importance of cultural...... identity and the fostering of a critical atmosphere might provide some support, if no countervailing factors apply. One such factor is that a legal right to healthcare professionals’ conscientious refusal must comply with basic legal ethical tenets regarding the rule of law and equal treatment...

  14. Predicting the tolerated sequences for proteins and protein interfaces using RosettaBackrub flexible backbone design.

    Directory of Open Access Journals (Sweden)

    Colin A Smith

    Full Text Available Predicting the set of sequences that are tolerated by a protein or protein interface, while maintaining a desired function, is useful for characterizing protein interaction specificity and for computationally designing sequence libraries to engineer proteins with new functions. Here we provide a general method, a detailed set of protocols, and several benchmarks and analyses for estimating tolerated sequences using flexible backbone protein design implemented in the Rosetta molecular modeling software suite. The input to the method is at least one experimentally determined three-dimensional protein structure or high-quality model. The starting structure(s are expanded or refined into a conformational ensemble using Monte Carlo simulations consisting of backrub backbone and side chain moves in Rosetta. The method then uses a combination of simulated annealing and genetic algorithm optimization methods to enrich for low-energy sequences for the individual members of the ensemble. To emphasize certain functional requirements (e.g. forming a binding interface, interactions between and within parts of the structure (e.g. domains can be reweighted in the scoring function. Results from each backbone structure are merged together to create a single estimate for the tolerated sequence space. We provide an extensive description of the protocol and its parameters, all source code, example analysis scripts and three tests applying this method to finding sequences predicted to stabilize proteins or protein interfaces. The generality of this method makes many other applications possible, for example stabilizing interactions with small molecules, DNA, or RNA. Through the use of within-domain reweighting and/or multistate design, it may also be possible to use this method to find sequences that stabilize particular protein conformations or binding interactions over others.

  15. The Legal Ethical Backbone of Conscientious Refusal.

    Science.gov (United States)

    Munthe, Christian; Nielsen, Morten Ebbe Juul

    2017-01-01

    This article analyzes the idea of a legal right to conscientious refusal for healthcare professionals from a basic legal ethical standpoint, using refusal to perform tasks related to legal abortion (in cases of voluntary employment) as a case in point. The idea of a legal right to conscientious refusal is distinguished from ideas regarding moral rights or reasons related to conscientious refusal, and none of the latter are found to support the notion of a legal right. Reasons for allowing some sort of room for conscientious refusal for healthcare professionals based on the importance of cultural identity and the fostering of a critical atmosphere might provide some support, if no countervailing factors apply. One such factor is that a legal right to healthcare professionals' conscientious refusal must comply with basic legal ethical tenets regarding the rule of law and equal treatment, and this requirement is found to create serious problems for those wishing to defend the idea under consideration. We conclude that the notion of a legal right to conscientious refusal for any profession is either fundamentally incompatible with elementary legal ethical requirements, or implausible because it undermines the functioning of a related professional sector (healthcare) or even of society as a whole.

  16. Laccase-assisted grafting of poly(3-hydroxybutyrate) onto the bacterial cellulose as backbone polymer: development and characterisation.

    Science.gov (United States)

    Iqbal, Hafiz M N; Kyazze, Godfrey; Tron, Thierry; Keshavarz, Tajalli

    2014-11-26

    Bacterial cellulose (BC) exhibits high purity, mechanical strength and an ultra-fine fibrous 3-D network structure with bio-compatible and bio-degradable characteristics, while P(3 HB) are a bio-degradable matrix material derived from natural resources. Herein, we report a mild and eco-friendly fabrication of indigenously isolated P(3 HB) based novel composites consisting of BC (a straight-chain polysaccharide) as a backbone polymer and laccase was used as a grafting tool. The resulting composites were characterised by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), dynamic mechanical analyser (DMA) and water contact angle analyser (WCA). The FTIR spectra of the pure P(3 HB) and P(3 HB) containing graft composites [P(3 HB)-g-BC] showed their strong characteristic bands at 3358 cm(-1), 1721 cm(-1) and 1651 cm(-1), respectively. A homogenous dispersion of P(3 HB) in the backbone polymer of BC was achieved as evident by the SEM micrographs. XRD pattern for P(3 HB) showed distinct peaks at 2θ values that represent the crystalline nature of P(3 HB). While, in comparison with those of neat P(3 HB), the degree of crystallinity for P(3 HB)-g-BC decreased and this reduction is mainly because of the new cross-linking of P(3 HB) within the backbone polymer that changes the morphology and destroys the crystallites. Laccase-assisted graft composite prepared from P(3 HB) and BC was fairly flexible and strong, judged by the tensile strength (64.5 MPa), elongations at break (15.7%), and Young's modulus (0.98 GPa) because inherently high strength of BC allowed the mechanical properties of P(3 HB) to improve in the P(3 HB)-g-BC composite. The hydrophilic property of the P(3 HB)-g-BC was much better than that of the individual counterparts which is also a desired characteristic to enhance the biocompatibility of the materials for proper cell adhesion and proliferation.

  17. Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.; Sheri, Venkat Reddy; Kassekert, Luke A.; Chen, Shujing; Agniswamy, Johnson; Wang, Yuan-Fang; Hayashi, Hironori; Aoki, Manabu; Weber, Irene T.; Mitsuya, Hiroaki (GSU); (Kumamoto); (Purdue)

    2015-10-30

    Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand–binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolution X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligand–binding site interactions are possibly responsible for their potent activity.

  18. Backbone amide linker strategy for the synthesis of 1,4-triazole-containing cyclic tetra- and pentapeptides

    NARCIS (Netherlands)

    Springer, J.; de Cuba, K.R.; Calvet-Vitale, S.; Geenevasen, J.A.J.; Hermkens, P.H.H.; Hiemstra, H.; van Maarseveen, J.H.

    2008-01-01

    A backbone amide linker strategy was chosen for the solid-phase synthesis of triazole-containing Cyclic tetra- and pentapeptides. An alkyne-substituted linker derived from 4-hydroxy-2-methoxybenzaldehyde was elongated by using standard "Fmoc-based" solid phase chemistry and terminated by coupling of

  19. PPM-One: a static protein structure based chemical shift predictor

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dawei; Brüschweiler, Rafael, E-mail: bruschweiler.1@osu.edu [The Ohio State University, Campus Chemical Instrument Center (United States)

    2015-07-15

    We mined the most recent editions of the BioMagResDataBank and the protein data bank to parametrize a new empirical knowledge-based chemical shift predictor of protein backbone atoms using either a linear or an artificial neural network model. The resulting chemical shift predictor PPM-One accepts a single static 3D structure as input and emulates the effect of local protein dynamics via interatomic steric contacts. Furthermore, the chemical shift prediction was extended to most side-chain protons and it is found that the prediction accuracy is at a level allowing an independent assessment of stereospecific assignments. For a previously established set of test proteins some overall improvement was achieved over current top-performing chemical shift prediction programs.

  20. Assessment of template-based protein structure predictions in CASP10.

    Science.gov (United States)

    Huang, Yuanpeng J; Mao, Binchen; Aramini, James M; Montelione, Gaetano T

    2014-02-01

    Template-based modeling (TBM) is a major component of the critical assessment of protein structure prediction (CASP). In CASP10, some 41,740 predicted models submitted by 150 predictor groups were assessed as TBM predictions. The accuracy of protein structure prediction was assessed by geometric comparison with experimental X-ray crystal and NMR structures using a composite score that included both global alignment metrics and distance-matrix-based metrics. These included GDT-HA and GDC-all global alignment scores, and the superimposition-independent LDDT distance-matrix-based score. In addition, a superimposition-independent RPF metric, similar to that described previously for comparing protein models against experimental NMR data, was used for comparing predicted protein structure models against experimental protein structures. To score well on all four of these metrics, models must feature accurate predictions of both backbone and side-chain conformations. Performance rankings were determined independently for server and the combined server plus human-curated predictor groups. Final rankings were made using paired head-to-head Student's t-test analysis of raw metric scores among the top 25 performing groups in each category.

  1. RosettaRemodel: a generalized framework for flexible backbone protein design.

    Directory of Open Access Journals (Sweden)

    Po-Ssu Huang

    Full Text Available We describe RosettaRemodel, a generalized framework for flexible protein design that provides a versatile and convenient interface to the Rosetta modeling suite. RosettaRemodel employs a unified interface, called a blueprint, which allows detailed control over many aspects of flexible backbone protein design calculations. RosettaRemodel allows the construction and elaboration of customized protocols for a wide range of design problems ranging from loop insertion and deletion, disulfide engineering, domain assembly, loop remodeling, motif grafting, symmetrical units, to de novo structure modeling.

  2. Backbone resonance assignments of the micro-RNA precursor binding region of human TRBP.

    Science.gov (United States)

    Benoit, Matthieu P M H; Plevin, Michael J

    2013-10-01

    TAR-RNA binding protein (TRBP) is a multidomain human protein involved in micro-RNA (miRNA) biogenesis. TRBP is a component of both the Dicer complex, which processes precursor miRNAs, and the RNA-induced silencing complex-loading complex. In addition, TRBP is implicated in the human immunodeficiency virus replication cycle and interferon-protein kinase R activity. TRBP contains 3 double-stranded RNA binding domains the first two of which have been shown to interact with miRNA precursors. Here we present the backbone resonance assignments and secondary structure of residues 19-228 of human TRBP2.

  3. Backbone decomposition for continuous-state branching processes with immigration

    CERN Document Server

    Ren, A E Kyprianou Y-X

    2011-01-01

    In the spirit of Duqesne and Winkel (2007) and Berestycki et al. (2011) we show that supercritical continuous-state branching process with a general branching mechanism and general immigration mechanism is equal in law to a continuous-time Galton Watson process with immigration with Poissonian dressing. The result also characterises the limiting backbone decomposition which is predictable from the work on consistent growth of Galton-Watson trees with immigration in Cao and Winkel (2010).

  4. On the influence of hydrated imidazolium-based ionic liquid on protein structure stability: A molecular dynamics simulation study

    Science.gov (United States)

    Shao, Qiang

    2013-09-01

    The structure stability of three α-helix bundle (the B domain of protein A) in an imidazolium-based ionic liquid (1-butyl-3-methylimidazolium chloride (BMIM-Cl)) is studied by molecular dynamics simulations. Consistent with previous experiments, the present simulation results show that the native structure of the protein is consistently stabilized in BMIM-Cl solutions with different concentrations. It is observed that BMIM+ cations have a strong tendency to accumulate on protein surface whereas Cl- anions are expelled from protein. BMIM+ cations cannot only have electrostatic interactions with the carbonyl groups on backbone and the carboxylate groups on negatively charged side chains, but also have hydrophobic interactions with the side chains of non-polar residues. In the meanwhile, the accumulation of large-size BMIM+ cations on protein surface could remove the surrounding water molecules, reduce the hydrogen bonding from water to protein, and thus stabilize the backbone hydrogen bonds. In summary, the present study could improve our understanding of the molecular mechanism of the impact of water-miscible ionic liquid on protein structure.

  5. Extracting the multiscale backbone of complex weighted networks

    Science.gov (United States)

    Serrano, M. Ángeles; Boguñá, Marián; Vespignani, Alessandro

    2009-01-01

    A large number of complex systems find a natural abstraction in the form of weighted networks whose nodes represent the elements of the system and the weighted edges identify the presence of an interaction and its relative strength. In recent years, the study of an increasing number of large-scale networks has highlighted the statistical heterogeneity of their interaction pattern, with degree and weight distributions that vary over many orders of magnitude. These features, along with the large number of elements and links, make the extraction of the truly relevant connections forming the network's backbone a very challenging problem. More specifically, coarse-graining approaches and filtering techniques come into conflict with the multiscale nature of large-scale systems. Here, we define a filtering method that offers a practical procedure to extract the relevant connection backbone in complex multiscale networks, preserving the edges that represent statistically significant deviations with respect to a null model for the local assignment of weights to edges. An important aspect of the method is that it does not belittle small-scale interactions and operates at all scales defined by the weight distribution. We apply our method to real-world network instances and compare the obtained results with alternative backbone extraction techniques. PMID:19357301

  6. Common and distinctive features of GNRA tetraloops based on a GUAA tetraloop structure at 1.4 A resolution.

    Science.gov (United States)

    Correll, Carl C; Swinger, Kerren

    2003-03-01

    GNRA tetraloops (N is A, C, G, or U; R is A or G) are basic building blocks of RNA structure that often interact with proteins or other RNA structural elements. Understanding sequence-dependent structural variation among different GNRA tetraloops is an important step toward elucidating the molecular basis of specific GNRA tetraloop recognition by proteins and RNAs. Details of the geometry and hydration of this motif have been based on high-resolution crystallographic structures of the GRRA subset of tetraloops; less is known about the GYRA subset (Y is C or U). We report here the structure of a GUAA tetraloop determined to 1.4 A resolution to better define these details and any distinctive features of GYRA tetraloops. The tetraloop is part of a 27-nt structure that mimics the universal sarcin/ricin loop from Escherichia coli 23S ribosomal RNA in which a GUAA tetraloop replaces the conserved GAGA tetraloop. The adenosines of the GUAA tetraloop form an intermolecular contact that is a commonplace RNA tertiary interaction called an A-minor motif. This is the first structure to reveal in great detail the geometry and hydration of a GUAA tetraloop and an A-minor motif. Comparison of tetraloop structures shows a common backbone geometry for each of the eight possible tetraloop sequences and suggests a common hydration. After backbone atom superposition, equivalent bases from different tetraloops unexpectedly depart from coplanarity by as much as 48 degrees. This variation displaces the functional groups of tetraloops implicated in protein and RNA binding, providing a recognition feature.

  7. Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit.

    Directory of Open Access Journals (Sweden)

    Daniel A Keedy

    2015-10-01

    Full Text Available Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP to evaluate an extremely large number of combinations of sidechain conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the "flap" regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Overall, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems.

  8. Exposing Hidden Alternative Backbone Conformations in X-ray Crystallography Using qFit.

    Science.gov (United States)

    Keedy, Daniel A; Fraser, James S; van den Bedem, Henry

    2015-10-01

    Proteins must move between different conformations of their native ensemble to perform their functions. Crystal structures obtained from high-resolution X-ray diffraction data reflect this heterogeneity as a spatial and temporal conformational average. Although movement between natively populated alternative conformations can be critical for characterizing molecular mechanisms, it is challenging to identify these conformations within electron density maps. Alternative side chain conformations are generally well separated into distinct rotameric conformations, but alternative backbone conformations can overlap at several atomic positions. Our model building program qFit uses mixed integer quadratic programming (MIQP) to evaluate an extremely large number of combinations of sidechain conformers and backbone fragments to locally explain the electron density. Here, we describe two major modeling enhancements to qFit: peptide flips and alternative glycine conformations. We find that peptide flips fall into four stereotypical clusters and are enriched in glycine residues at the n+1 position. The potential for insights uncovered by new peptide flips and glycine conformations is exemplified by HIV protease, where different inhibitors are associated with peptide flips in the "flap" regions adjacent to the inhibitor binding site. Our results paint a picture of peptide flips as conformational switches, often enabled by glycine flexibility, that result in dramatic local rearrangements. Our results furthermore demonstrate the power of large-scale computational analysis to provide new insights into conformational heterogeneity. Overall, improved modeling of backbone heterogeneity with high-resolution X-ray data will connect dynamics to the structure-function relationship and help drive new design strategies for inhibitors of biomedically important systems.

  9. Reduced Dimensionality (4,3)D-hnCOCANH Experiment: An Efficient Backbone Assignment tool for NMR studies of Proteins

    CERN Document Server

    Kumar, Dinesh

    2013-01-01

    Sequence specific resonance assignment and secondary structure determination of proteins form the basis for variety of structural and functional proteomics studies by NMR. In this context, an efficient standalone method for rapid assignment of backbone (1H, 15N, 13Ca and 13C') resonances and secondary structure determination of proteins has been presented here. Compared to currently available strategies used for the purpose, the method employs only a single reduced dimensionality (RD) experiment -(4,3)D-hnCOCANH and exploits the linear combinations of backbone (13Ca and 13C') chemical shifts to achieve a dispersion relatively better compared to those of individual chemical shifts (see the text) for efficient and rapid data analysis. Further, the experiment leads to the spectrum with direct distinction of self (intra-residue) and sequential (inter-residue) carbon correlation peaks; these appear opposite in signs and therefore can easily be discriminated without using an additional complementary experiment. On ...

  10. An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields.

    Science.gov (United States)

    Whitford, Paul C; Noel, Jeffrey K; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y; Onuchic, José N

    2009-05-01

    Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase, and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a C(alpha) structure-based model and an all-atom empirical forcefield. Key findings include: (1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature, (2) folding mechanisms are robust to variations of the energetic parameters, (3) protein folding free-energy barriers can be manipulated through parametric modifications, (4) the global folding mechanisms in a C(alpha) model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model, and (5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Because this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function.

  11. Icosahedral medium-range orders and backbone formation in an amorphous alloy

    Science.gov (United States)

    Lee, Mirim; Kim, Hong-Kyu; Lee, Jae-Chul

    2010-12-01

    Analyses of metallic amorphous solids constructed using molecular dynamics (MD) simulations have demonstrated that individual short-range orders (SROs) are linked with neighboring SROs and form various medium-range orders (MROs). These MROs have been observed to have different structural stability depending on their linking patterns. On the basis of the assessment of the structural stability of various MROs, we propose new types of structural organization, namely, icosahedral medium-range orders (I-MROs) and their extended-range order that forms the backbone of amorphous solids. We also discuss why the atomic-scale structure of an amorphous alloy can be more appropriately described in terms of I-MROs, rather than by the degree of short-range ordering as characterized by the fractions of SROs.

  12. Backbone tuning in indenylidene–ruthenium complexes bearing an unsaturated N-heterocyclic carbene

    Directory of Open Access Journals (Sweden)

    César A. Urbina-Blanco

    2010-11-01

    Full Text Available The steric and electronic influence of backbone substitution in IMes-based (IMes = 1,3-bis(2,4,6-trimethylphenylimidazol-2-ylidene N-heterocyclic carbenes (NHC was probed by synthesizing the [RhCl(CO2(NHC] series of complexes to quantify experimentally the Tolman electronic parameter (electronic and the percent buried volume (%Vbur, steric parameters. The corresponding ruthenium–indenylidene complexes were also synthesized and tested in benchmark metathesis transformations to establish possible correlations between reactivity and NHC electronic and steric parameters.

  13. The determinants of bond angle variability in protein/peptide backbones: A comprehensive statistical/quantum mechanics analysis.

    Science.gov (United States)

    Improta, Roberto; Vitagliano, Luigi; Esposito, Luciana

    2015-11-01

    The elucidation of the mutual influence between peptide bond geometry and local conformation has important implications for protein structure refinement, validation, and prediction. To gain insights into the structural determinants and the energetic contributions associated with protein/peptide backbone plasticity, we here report an extensive analysis of the variability of the peptide bond angles by combining statistical analyses of protein structures and quantum mechanics calculations on small model peptide systems. Our analyses demonstrate that all the backbone bond angles strongly depend on the peptide conformation and unveil the existence of regular trends as function of ψ and/or φ. The excellent agreement of the quantum mechanics calculations with the statistical surveys of protein structures validates the computational scheme here employed and demonstrates that the valence geometry of protein/peptide backbone is primarily dictated by local interactions. Notably, for the first time we show that the position of the H(α) hydrogen atom, which is an important parameter in NMR structural studies, is also dependent on the local conformation. Most of the trends observed may be satisfactorily explained by invoking steric repulsive interactions; in some specific cases the valence bond variability is also influenced by hydrogen-bond like interactions. Moreover, we can provide a reliable estimate of the energies involved in the interplay between geometry and conformations.

  14. Quantification of the curvature of the spine by a method based on the projection harmful structured light; Cuantificacion de la curvatura de la columna vertebral mediante un metodo no lesivo basado en la proyeccion de luz estructurada

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de la O, F. J.; Cibrian, R.; Salvador, R.; Gonzalez-Pena, R.; Minguez, M. F.; Pino, L.; Jover, A.; Guillen, J.; Reinado, D.; Cortina, T.; Chinillach, N.; Dalmases, F.; Romero, M. C.; Martinez-Celerio, R.; Diez, R.; Rosello, J.

    2011-07-01

    This paper shows the application of a method for determining harmful surface topography based on structured light, to find back the topography of the variables that create a characteristic pattern and differentiating between different groups. Once the topography has calculated three angles along the backbone that characterize its curvature. This pattern has been determined for two study groups, one of athletes and other patients with scoliosis.

  15. Importance of backbone angles versus amino acid configurations in peptide vibrational Raman optical activity spectra

    Science.gov (United States)

    Herrmann, Carmen; Ruud, Kenneth; Reiher, Markus

    2008-01-01

    In this work, we investigate whether the differential scattering of right- and left-circularly polarized light in peptide Raman optical activity spectra are uniquely dominated by the backbone conformation, or whether the configurations of the individual amino acid also play a significant role. This is achieved by calculating Raman optical activity spectra using density functional theory for four structurally related peptides with a common backbone conformation, but with different sequences of amino acid configurations. Furthermore, the ROA signals of the amide normal modes are decomposed into contributions from groups of individual atoms. It is found that the amino acid configuration has a considerable influence on the ROA peaks in the amide I, II, and III regions, although the local decomposition reveals that the side-chain atoms only contribute to those peaks directly in the case of the amide II vibrations. Furthermore, small changes in the amide normal modes may lead to large and irregular modifications in the ROA intensity differences, making it difficult to establish transferable ROA intensity differences even for structurally similar vibrations.

  16. Towards fully automated structure-based NMR resonance assignment of 15N-labeled proteins from automatically picked peaks

    KAUST Repository

    Jang, Richard

    2011-03-01

    In NMR resonance assignment, an indispensable step in NMR protein studies, manually processed peaks from both N-labeled and C-labeled spectra are typically used as inputs. However, the use of homologous structures can allow one to use only N-labeled NMR data and avoid the added expense of using C-labeled data. We propose a novel integer programming framework for structure-based backbone resonance assignment using N-labeled data. The core consists of a pair of integer programming models: one for spin system forming and amino acid typing, and the other for backbone resonance assignment. The goal is to perform the assignment directly from spectra without any manual intervention via automatically picked peaks, which are much noisier than manually picked peaks, so methods must be error-tolerant. In the case of semi-automated/manually processed peak data, we compare our system with the Xiong-Pandurangan-Bailey- Kellogg\\'s contact replacement (CR) method, which is the most error-tolerant method for structure-based resonance assignment. Our system, on average, reduces the error rate of the CR method by five folds on their data set. In addition, by using an iterative algorithm, our system has the added capability of using the NOESY data to correct assignment errors due to errors in predicting the amino acid and secondary structure type of each spin system. On a publicly available data set for human ubiquitin, where the typing accuracy is 83%, we achieve 91% accuracy, compared to the 59% accuracy obtained without correcting for such errors. In the case of automatically picked peaks, using assignment information from yeast ubiquitin, we achieve a fully automatic assignment with 97% accuracy. To our knowledge, this is the first system that can achieve fully automatic structure-based assignment directly from spectra. This has implications in NMR protein mutant studies, where the assignment step is repeated for each mutant. © Copyright 2011, Mary Ann Liebert, Inc.

  17. Design of an IPTV Multicast System for Internet Backbone Networks

    OpenAIRE

    T. H. Szymanski; Gilbert, D

    2010-01-01

    The design of an IPTV multicast system for the Internet backbone network is presented and explored through extensive simulations. In the proposed system, a resource reservation algorithm such as RSVP, IntServ, or DiffServ is used to reserve resources (i.e., bandwidth and buffer space) in each router in an IP multicast tree. Each router uses an Input-Queued, Output-Queued, or Crosspoint-Queued switch architecture with unity speedup. A recently proposed Recursive Fair Stochastic Matrix Decompos...

  18. Resistance of Feynman diagrams and the percolation backbone dimension.

    Science.gov (United States)

    Janssen, H K; Stenull, O; Oerding, K

    1999-06-01

    We present an alternative view of Feynman diagrams for the field theory of random resistor networks, in which the diagrams are interpreted as being resistor networks themselves. This simplifies the field theory considerably as we demonstrate by calculating the fractal dimension D(B) of the percolation backbone to three loop order. Using renormalization group methods we obtain D(B)=2+epsilon/21-172epsilon(2)/9261+2epsilon(3)[-74 639+22 680zeta(3)]/4 084 101, where epsilon=6-d with d being the spatial dimension and zeta(3)=1.202 057... .

  19. Unique optimal solution instance and computational complexity of backbone in the graph bi-partitioning problem

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    As an important tool for heuristic design of NP-hard problems, backbone analysis has become a hot spot in theoretical computer science in recent years. Due to the difficulty in the research on computational complexity of the backbone, many researchers analyzed the backbone by statistic ways. Aiming to increase the backbone size which is usually very small by the existing methods, the unique optimal solution instance construction (UOSIC) is proposed for the graph bi-partitioning problem (GBP). Also, we prove by using the UOSIC that it is NP-hard to obtain the backbone, i.e. no algorithm exists to obtain the backbone of a GBP in polynomial time under the assumption that P ( NP. Our work expands the research area of computational complexity of the backbone. And the UOSIC provides a new way for heuristic design of NP-hard problems.

  20. Sulfation and Cation Effects on the Conformational Properties of the Glycan Backbone of Chondroitin Sulfate Disaccharides

    Science.gov (United States)

    Faller, Christina E.; Guvench, Olgun

    2015-01-01

    Chondroitin sulfate (CS) is one of several glycosaminoglycans that are major components of proteoglycans. A linear polymer consisting of repeats of the disaccharide -4GlcAβ1-3GalNAcβ1-, CS undergoes differential sulfation resulting in five unique sulfation patterns. Because of the dimer repeat, the CS glycosidic “backbone” has two distinct sets of conformational degrees of freedom defined by pairs of dihedral angles: (ϕ1, ψ1) about the β1-3 glycosidic linkage and (ϕ2, ψ2) about the β1-4 glycosidic linkage. Differential sulfation and the possibility of cation binding, combined with the conformational flexibility and biological diversity of CS, complicate experimental efforts to understand CS three-dimensional structures at atomic resolution. Therefore, all-atom explicit-solvent molecular dynamics simulations with Adaptive Biasing Force sampling of the CS backbone were applied to obtain high resolution, high precision free energies of CS disaccharides as a function of all possible backbone geometries. All ten disaccharides (β1-3 vs. β1-4 linkage x five different sulfation patterns) were studied; additionally, ion effects were investigated by considering each disaccharide in the presence of either neutralizing sodium or calcium cations. GlcAβ1-3GalNAc disaccharides have a single, broad, thermodynamically important free-energy minimum whereas GalNAcβ1-4GlcA disaccharides have two such minima. Calcium cations but not sodium cations bind to the disaccharides, and binding is primarily to the GlcA –COO− moiety as opposed to sulfate groups. This binding alters the glycan backbone thermodynamics in instances where a calcium cation bound to –COO− can act to bridge and stabilize an interaction with an adjacent sulfate group, whereas, in the absence of this cation, the proximity of a sulfate group to –COO− results in two like charges being both desolvated and placed adjacent to each other and is found to be destabilizing. In addition to providing

  1. Motion Structural Optimization Strategy for Rhombic Element Based Foldable Structure

    Directory of Open Access Journals (Sweden)

    Seung Hyun Jeong

    2015-02-01

    Full Text Available This research presents a new systematical design approach of foldable structure composed of several rhombic elements by applying genetic algorithm. As structural shapes represented by a foldable structure can be easily and dramatically morphed by manipulating rotational directions and angle of joints, the foldable structure has been used for various elementary structural members and engineering mechanisms. However a systematic design approach determining detail rotational angle and directions of unit cells for arbitrary shaped target areas has not been proposed yet. This research contributes to it by developing a new structural optimization method determining optimal angle and rotation directions to cover arbitrary shaped target areas of interest with aggregated rhombic elements. To achieve this purpose, we present an optimization formulation minimizing the sum of distances between each reference joint of an arbitrary shaped target area and its closest outer joints of foldable structure. To find out the outer joint set of a given foldable structure, an efficient geometric analysis method based on Delaunay triangulation is also developed and implemented. To show the validity and limitations of the present approach, several foldable structure design problems for two-dimensional arbitrary shaped target areas are solved with the present optimization procedure.

  2. Higher order structural effects stabilizing the reverse watson-crick guanine-cytosine base pair in functional RNAs

    KAUST Repository

    Chawla, Mohit

    2013-10-10

    The G:C reverse Watson-Crick (W:W trans) base pair, also known as Levitt base pair in the context of tRNAs, is a structurally and functionally important base pair that contributes to tertiary interactions joining distant domains in functional RNA molecules and also participates in metabolite binding in riboswitches. We previously indicated that the isolated G:C W:W trans base pair is a rather unstable geometry, and that dicationic metal binding to the Guanine base or posttranscriptional modification of the Guanine can increase its stability. Herein, we extend our survey and report on other H-bonding interactions that can increase the stability of this base pair. To this aim, we performed a bioinformatics search of the PDB to locate all the occurencies of G:C trans base pairs. Interestingly, 66% of the G:C trans base pairs in the PDB are engaged in additional H-bonding interactions with other bases, the RNA backbone or structured water molecules. High level quantum mechanical calculations on a data set of representative crystal structures were performed to shed light on the structural stability and energetics of the various crystallographic motifs. This analysis was extended to the binding of the preQ1 metabolite to a preQ1-II riboswitch. 2013 The Author(s).

  3. On the role of thermal backbone fluctuations in myoglobin ligand gate dynamics

    CERN Document Server

    Krokhotin, Andrey; Peng, Xubiao

    2012-01-01

    We construct an energy function that describes the crystallographic structure of spermwhale myoglobin backbone. As a model in our construction, we use the Protein Data Bank entry 1ABS that has been measured at liquid helium temperature. Consequently the thermal B-factor fluctuations are very small, which is an advantage in our construction. The energy function that we utilize resembles that of the discrete non-linear Schrodinger equation. Likewise, ours supports solitons as local minimum energy configurations. We describe the 1ABS backbone in terms of solitons with a precision that deviates from 1ABS by an average root-mean-square distance, which is less than the experimentally observed Debye-Waller B-factor fluctuation distance. We then subject the multisoliton solution to extensive numerical heating and cooling experiments, over a very wide range of temperatures. We concentrate in particular to temperatures above 300K and below the theta-point unfolding temperature, which is around 348K. We confirm that the...

  4. Towards structure-based protein drug design.

    Science.gov (United States)

    Zhang, Changsheng; Lai, Luhua

    2011-10-01

    Structure-based drug design for chemical molecules has been widely used in drug discovery in the last 30 years. Many successful applications have been reported, especially in the field of virtual screening based on molecular docking. Recently, there has been much progress in fragment-based as well as de novo drug discovery. As many protein-protein interactions can be used as key targets for drug design, one of the solutions is to design protein drugs based directly on the protein complexes or the target structure. Compared with protein-ligand interactions, protein-protein interactions are more complicated and present more challenges for design. Over the last decade, both sampling efficiency and scoring accuracy of protein-protein docking have increased significantly. We have developed several strategies for structure-based protein drug design. A grafting strategy for key interaction residues has been developed and successfully applied in designing erythropoietin receptor-binding proteins. Similarly to small-molecule design, we also tested de novo protein-binder design and a virtual screen of protein binders using protein-protein docking calculations. In comparison with the development of structure-based small-molecule drug design, we believe that structure-based protein drug design has come of age.

  5. Structural choice based on knowledge discovery system

    Institute of Scientific and Technical Information of China (English)

    邢方亮; 王光远

    2002-01-01

    Structural choice is a significant decision having an important influence on structural function, socialeconomics, structural reliability and construction cost. A Case Based Reasoning system with its retrieval partconstructed with a KDD subsystem, is put forward to make a decision for a large scale engineering project. Atypical CBR system consists of four parts: case representation, case retriever, evaluation, and adaptation. Acase library is a set of parameterized excellent and successful structures. For a structural choice, the key pointis that the system must be able to detect the pattern classes hidden in the case library and classify the input pa-rameters into classes properly. That is done by using the KDD Data Mining algorithm based on Self-OrganizingFeature Maps ( SOFM), which makes the whole system more adaptive, self-organizing, self-learning and open.

  6. Di-Isocyanate Crosslinked Aerogels with 1, 6-Bis (Trimethoxysilyl) Hexane Incorporated in Silica Backbone

    Science.gov (United States)

    Vivod, Stephanie L.; Meador, Mary Ann B.; Nguyen, Baochau N.; Quade, Derek; Randall, Jason; Perry, Renee

    2008-01-01

    Silica aerogels are desirable materials for many applications that take advantage of their light weight and low thermal conductivity. Addition of a conformal polymer coating which bonds with the amine decorated surface of the silica network improves the strength of the aerogels by as much as 200 times. Even with vast improvement in strength they still tend to undergo brittle failure due to the rigid silica backbone. We hope to increase the flexibility and elastic recovery of the silica based aerogel by altering the silica back-bone by incorporation of more flexible hexane links. To this end, we investigated the use of 1,6-bis(trimethoxysilyl)hexane (BTMSH), a polysilsesquioxane precursor3, as an additional co-reactant to prepare silica gels which were subsequently cross-linked with di-isocyanate. Previously, this approach of adding flexibility by BTMSH incorporation was demonstrated with styrene cross-linked aerogels. In our study, we varied silane concentration, mol % of silicon from BTMSH and di-isocyanate concentration by weight percent to attempt to optimize both the flexibility and the strength of the aerogels.

  7. Structurally Diverse Polyamines: Solid-Phase Synthesis and Interaction with DNA.

    Science.gov (United States)

    Umezawa, Naoki; Horai, Yuhei; Imamura, Yuki; Kawakubo, Makoto; Nakahira, Mariko; Kato, Nobuki; Muramatsu, Akira; Yoshikawa, Yuko; Yoshikawa, Kenichi; Higuchi, Tsunehiko

    2015-08-17

    A versatile solid-phase approach based on peptide chemistry was used to construct four classes of structurally diverse polyamines with modified backbones: linear, partially constrained, branched, and cyclic. Their effects on DNA duplex stability and structure were examined. The polyamines showed distinct activities, thus highlighting the importance of polyamine backbone structure. Interestingly, the rank order of polyamine ability for DNA compaction was different to that for their effects on circular dichroism and melting temperature, thus indicating that these polyamines have distinct effects on secondary and higher-order structures of DNA.

  8. Backbones of evolutionary history test biodiversity theory for microbes.

    Science.gov (United States)

    O'Dwyer, James P; Kembel, Steven W; Sharpton, Thomas J

    2015-07-07

    Identifying the ecological and evolutionary mechanisms that determine biological diversity is a central question in ecology. In microbial ecology, phylogenetic diversity is an increasingly common and relevant means of quantifying community diversity, particularly given the challenges in defining unambiguous species units from environmental sequence data. We explore patterns of phylogenetic diversity across multiple bacterial communities drawn from different habitats and compare these data to evolutionary trees generated using theoretical models of biodiversity. We have two central findings. First, although on finer scales the empirical trees are highly idiosyncratic, on coarse scales the backbone of these trees is simple and robust, consistent across habitats, and displays bursts of diversification dotted throughout. Second, we find that these data demonstrate a clear departure from the predictions of standard neutral theories of biodiversity and that an alternative family of generalized models provides a qualitatively better description. Together, these results lay the groundwork for a theoretical framework to connect ecological mechanisms to observed phylogenetic patterns in microbial communities.

  9. Phase Transitions and Backbones of the Asymmetric Traveling Salesman Problem

    CERN Document Server

    Zhang, W

    2011-01-01

    In recent years, there has been much interest in phase transitions of combinatorial problems. Phase transitions have been successfully used to analyze combinatorial optimization problems, characterize their typical-case features and locate the hardest problem instances. In this paper, we study phase transitions of the asymmetric Traveling Salesman Problem (ATSP), an NP-hard combinatorial optimization problem that has many real-world applications. Using random instances of up to 1,500 cities in which intercity distances are uniformly distributed, we empirically show that many properties of the problem, including the optimal tour cost and backbone size, experience sharp transitions as the precision of intercity distances increases across a critical value. Our experimental results on the costs of the ATSP tours and assignment problem agree with the theoretical result that the asymptotic cost of assignment problem is pi ^2 /6 the number of cities goes to infinity. In addition, we show that the average computation...

  10. Bioactivities of fish protein hydrolysates from defatted salmon backbones

    Directory of Open Access Journals (Sweden)

    Rasa Slizyte

    2016-09-01

    Full Text Available Bioactivities of bulk fish protein hydrolysates (FPH from defatted salmon backbones obtained with eight different commercial enzymes and their combinations were tested. All FPH showed antioxidative activity in vitro. DPPH scavenging activity increased, while iron chelating ability decreased with increasing time of hydrolysis. All FPH showed ACE inhibiting effect which depended on type of enzyme and increased with time of hydrolysis. The highest effect was found for FPH produced with Trypsin. Bromelain + Papain hydrolysates reduced the uptake of radiolabelled glucose into CaCo-2 cells, a model of human enterocytes, indicating a potential antidiabetic effect of FPH. FPH obtained by Trypsin, Bromelain + Papain and Protamex showed the highest ACE inhibitory, cellular glucose transporter (GLUT/SGLT inhibitory and in vitro antioxidative activities, respectively. Correlation was observed between the measured bioactivities, degree of hydrolysis and molecular weight profiles, supporting prolonged hydrolysis to obtain high bioactivities.

  11. Dolutegravir treatment response by baseline viral load and NRTI backbone in treatment-naïve HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    C Small

    2012-11-01

    Full Text Available Background: In two 48-week studies in naïve subjects, dolutegravir with NRTI of choice has shown non-inferiority to raltegravir and, with ABC/3TC, superiority to Atripla. Factors that influenced choice of NRTIs included viral load, resistance and safety. Methods: We analysed response rates and time to virologic failure by NRTI backbone and baseline viral load in the pivotal DTG-naïve studies. SPRING-2 randomized participants to DTG 50 mg QD or RAL 400 mg BID, each in combination with investigator-selected NRTIs (TDF/FTC or ABC/3TC. SINGLE randomised participants to DTG 50 mg+ABC/3TC QD or TDF/FTC/EFV (Atripla QD. In SPRING-2, changes in serum creatinine were examined by INI and NRTI backbone. Results: The two studies randomized and treated 1655 subjects, of whom 249 (15% were female, 388 (23% non-white, 495 (30% had HIV-1 RNA >100,000 c/ml, and 224 (14% had CD4+ count <200 cells/mm3. Primary analyses demonstrated non-inferiority of DTG to RAL in SPRING-2 (Δ=2.5%; 95% CI:−2.2% to +7.1%, excluding −10%, and superiority of the DTG regimen in SINGLE (7.4%; +2.5% to +12.3%. In SPRING-2, response rates by NRTI backbone were comparable in each viral load stratum. In SINGLE, a 7% difference in response (favoring DTG+ABC/3TC was observed in each viral load stratum. Exploratory analyses examining time-to-virologic failure showed no difference in response rates between the NRTIs irrespective of baseline viral load or study. Resistance to INIs or NRTIs was not demonstrated in any subject on DTG-based therapy through 48 weeks. Withdrawals due to AEs on DTG-based regimen were few (2% in both studies. In SPRING-2, no significant differences were observed in serum creatinine change from baseline to Week 48 by NRTI backbones. Conclusions: In SPRING-2 and SINGLE, DTG was effective with both ABC/3TC and TDF/FTC, and in subjects with high and low viral load. DTG was well tolerated in both studies. Renal safety also was similar by NRTI backbone. DTG is a once

  12. Design of an IPTV Multicast System for Internet Backbone Networks

    Directory of Open Access Journals (Sweden)

    T. H. Szymanski

    2010-01-01

    Full Text Available The design of an IPTV multicast system for the Internet backbone network is presented and explored through extensive simulations. In the proposed system, a resource reservation algorithm such as RSVP, IntServ, or DiffServ is used to reserve resources (i.e., bandwidth and buffer space in each router in an IP multicast tree. Each router uses an Input-Queued, Output-Queued, or Crosspoint-Queued switch architecture with unity speedup. A recently proposed Recursive Fair Stochastic Matrix Decomposition algorithm used to compute near-perfect transmission schedules for each IP router. The IPTV traffic is shaped at the sources using Application-Specific Token Bucker Traffic Shapers, to limit the burstiness of incoming network traffic. The IPTV traffic is shaped at the destinations using Application-Specific Playback Queues, to remove residual network jitter and reconstruct the original bursty IPTV video streams at each destination. All IPTV traffic flows are regenerated at the destinations with essentially zero delay jitter and essentially-perfect QoS. The destination nodes deliver the IPTV streams to the ultimate end users using the same IPTV multicast system over a regional Metropolitan Area Network. It is shown that all IPTV traffic is delivered with essentially-perfect end-to-end QoS, with deterministic bounds on the maximum delay and jitter on each video frame. Detailed simulations of an IPTV distribution system, multicasting several hundred high-definition IPTV video streams over several essentially saturated IP backbone networks are presented.

  13. Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism.

    Directory of Open Access Journals (Sweden)

    Shridhar Bale

    2012-09-01

    Full Text Available Filoviruses, including Marburg virus (MARV and Ebola virus (EBOV, cause fatal hemorrhagic fever in humans and non-human primates. All filoviruses encode a unique multi-functional protein termed VP35. The C-terminal double-stranded (dsRNA-binding domain (RBD of VP35 has been implicated in interferon antagonism and immune evasion. Crystal structures of the VP35 RBD from two ebolaviruses have previously demonstrated that the viral protein caps the ends of dsRNA. However, it is not yet understood how the expanses of dsRNA backbone, between the ends, are masked from immune surveillance during filovirus infection. Here, we report the crystal structure of MARV VP35 RBD bound to dsRNA. In the crystal structure, molecules of dsRNA stack end-to-end to form a pseudo-continuous oligonucleotide. This oligonucleotide is continuously and completely coated along its sugar-phosphate backbone by the MARV VP35 RBD. Analysis of dsRNA binding by dot-blot and isothermal titration calorimetry reveals that multiple copies of MARV VP35 RBD can indeed bind the dsRNA sugar-phosphate backbone in a cooperative manner in solution. Further, MARV VP35 RBD can also cap the ends of the dsRNA in solution, although this arrangement was not captured in crystals. Together, these studies suggest that MARV VP35 can both coat the backbone and cap the ends, and that for MARV, coating of the dsRNA backbone may be an essential mechanism by which dsRNA is masked from backbone-sensing immune surveillance molecules.

  14. High performance and highly durable infiltrated cathodes using Pr-modified Ce0.9Gd0.1O1.95 backbone

    DEFF Research Database (Denmark)

    Samson, Alfred Junio; Søgaard, Martin; Bonanos, Nikolaos;

    2014-01-01

    the CGO backbone with Pr through infiltration into the structure followed by firing. The Pr – modified CGO backbone is then infiltrated with LSC. The electrochemical performance of the infiltrated cathodes with and without Pr modification in the backbone was studied by impedance spectroscopy on symmetric...... °C (without Pr: Rp from 0.094 to 0.45 Ω cm2, Rs from 0.74 to 0.79 Ω cm2; with Pr: Rp from 0.051 to 0.32 Ω cm2, Rs from 0.74 to 0.71 Ω cm2). The improved performance and heat treatment tolerance is thought to originate from the imparted electronic conductivity into the CGO backbone by introducing Pr.......Infiltration of electrocatalysts into ionic conducting backbones (e.g. Sr – doped LaCoO3 (LSC) into Ce0.9Gd0.1O1.95 (CGO)) is becoming a widely popular means of preparing composite cathodes for SOFCs. The high surface area nanoparticle grains of the electrocatalyst obtained using the method...

  15. A Framework for Preliminary Design of Aircraft Structures Based on Process Information. Part 1

    Science.gov (United States)

    Rais-Rohani, Masoud

    1998-01-01

    This report discusses the general framework and development of a computational tool for preliminary design of aircraft structures based on process information. The described methodology is suitable for multidisciplinary design optimization (MDO) activities associated with integrated product and process development (IPPD). The framework consists of three parts: (1) product and process definitions; (2) engineering synthesis, and (3) optimization. The product and process definitions are part of input information provided by the design team. The backbone of the system is its ability to analyze a given structural design for performance as well as manufacturability and cost assessment. The system uses a database on material systems and manufacturing processes. Based on the identified set of design variables and an objective function, the system is capable of performing optimization subject to manufacturability, cost, and performance constraints. The accuracy of the manufacturability measures and cost models discussed here depend largely on the available data on specific methods of manufacture and assembly and associated labor requirements. As such, our focus in this research has been on the methodology itself and not so much on its accurate implementation in an industrial setting. A three-tier approach is presented for an IPPD-MDO based design of aircraft structures. The variable-complexity cost estimation methodology and an approach for integrating manufacturing cost assessment into design process are also discussed. This report is presented in two parts. In the first part, the design methodology is presented, and the computational design tool is described. In the second part, a prototype model of the preliminary design Tool for Aircraft Structures based on Process Information (TASPI) is described. Part two also contains an example problem that applies the methodology described here for evaluation of six different design concepts for a wing spar.

  16. A renormalization approach to describe charge transport in quasiperiodic dangling backbone ladder (DBL)-DNA molecules

    Energy Technology Data Exchange (ETDEWEB)

    Sarmento, R.G. [Departamento de Fisica, Universidade Federal do Rio Grande do Norte, 59072-970 Natal, RN (Brazil); Fulco, U.L. [Departamento de Biofisica e Farmacologia, Universidade Federal do Rio Grande do Norte, 59072-970 Natal, RN (Brazil); Albuquerque, E.L., E-mail: eudenilson@gmail.com [Departamento de Biofisica e Farmacologia, Universidade Federal do Rio Grande do Norte, 59072-970 Natal, RN (Brazil); Caetano, E.W.S. [Instituto Federal de Educacao, Ciencia e Tecnologia do Ceara, 60040-531 Fortaleza, CE (Brazil); Freire, V.N. [Departamento de Fisica, Universidade Federal do Ceara, 60455-760 Fortaleza, CE (Brazil)

    2011-10-31

    Highlights: → One-step renormalization approach to describe the DBL-DNA molecule. → Electronic tight-binding Hamiltonian model. → A quasiperiodic sequence to mimic the DNA nucleotides arrangement. → Electronic transmission spectra. → I-V characteristics. -- Abstract: We study the charge transport properties of a dangling backbone ladder (DBL)-DNA molecule focusing on a quasiperiodic arrangement of its constituent nucleotides forming a Rudin-Shapiro (RS) and Fibonacci (FB) Poly (CG) sequences, as well as a natural DNA sequence (Ch22) for the sake of comparison. Making use of a one-step renormalization process, the DBL-DNA molecule is modeled in terms of a one-dimensional tight-binding Hamiltonian to investigate its transmissivity and current-voltage (I-V) profiles. Beyond the semiconductor I-V characteristics, a striking similarity between the electronic transport properties of the RS quasiperiodic structure and the natural DNA sequence was found.

  17. A renormalization approach to describe charge transport in quasiperiodic dangling backbone ladder (DBL)-DNA molecules

    Science.gov (United States)

    Sarmento, R. G.; Fulco, U. L.; Albuquerque, E. L.; Caetano, E. W. S.; Freire, V. N.

    2011-10-01

    We study the charge transport properties of a dangling backbone ladder (DBL)-DNA molecule focusing on a quasiperiodic arrangement of its constituent nucleotides forming a Rudin-Shapiro (RS) and Fibonacci (FB) Poly (CG) sequences, as well as a natural DNA sequence (Ch22) for the sake of comparison. Making use of a one-step renormalization process, the DBL-DNA molecule is modeled in terms of a one-dimensional tight-binding Hamiltonian to investigate its transmissivity and current-voltage (I-V) profiles. Beyond the semiconductor I-V characteristics, a striking similarity between the electronic transport properties of the RS quasiperiodic structure and the natural DNA sequence was found.

  18. Hamiltonian replica-exchange simulations with adaptive biasing of peptide backbone and side chain dihedral angles.

    Science.gov (United States)

    Ostermeir, Katja; Zacharias, Martin

    2014-01-15

    A Hamiltonian Replica-Exchange Molecular Dynamics (REMD) simulation method has been developed that employs a two-dimensional backbone and one-dimensional side chain biasing potential specifically to promote conformational transitions in peptides. To exploit the replica framework optimally, the level of the biasing potential in each replica was appropriately adapted during the simulations. This resulted in both high exchange rates between neighboring replicas and improved occupancy/flow of all conformers in each replica. The performance of the approach was tested on several peptide and protein systems and compared with regular MD simulations and previous REMD studies. Improved sampling of relevant conformational states was observed for unrestrained protein and peptide folding simulations as well as for refinement of a loop structure with restricted mobility of loop flanking protein regions.

  19. Modification of rifamycin polyketide backbone leads to improved drug activity against rifampicin-resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Nigam, Aeshna; Almabruk, Khaled H; Saxena, Anjali; Yang, Jongtae; Mukherjee, Udita; Kaur, Hardeep; Kohli, Puneet; Kumari, Rashmi; Singh, Priya; Zakharov, Lev N; Singh, Yogendra; Mahmud, Taifo; Lal, Rup

    2014-07-25

    Rifamycin B, a product of Amycolatopsis mediterranei S699, is the precursor of clinically used antibiotics that are effective against tuberculosis, leprosy, and AIDS-related mycobacterial infections. However, prolonged usage of these antibiotics has resulted in the emergence of rifamycin-resistant strains of Mycobacterium tuberculosis. As part of our effort to generate better analogs of rifamycin, we substituted the acyltransferase domain of module 6 of rifamycin polyketide synthase with that of module 2 of rapamycin polyketide synthase. The resulting mutants (rifAT6::rapAT2) of A. mediterranei S699 produced new rifamycin analogs, 24-desmethylrifamycin B and 24-desmethylrifamycin SV, which contained modification in the polyketide backbone. 24-Desmethylrifamycin B was then converted to 24-desmethylrifamycin S, whose structure was confirmed by MS, NMR, and X-ray crystallography. Subsequently, 24-desmethylrifamycin S was converted to 24-desmethylrifampicin, which showed excellent antibacterial activity against several rifampicin-resistant M. tuberculosis strains.

  20. Side chain and backbone contributions of Phe508 to CFTR folding

    Energy Technology Data Exchange (ETDEWEB)

    Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

    2010-12-07

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

  1. The Construction of Metal-Organic Framework with Active Backbones by the Utilization of Reticular Chemistry

    Science.gov (United States)

    Choi, Eunwoo

    With the principles of reticular chemistry, metal-organic frameworks with ultra-high porosity, chiral-recognition unit as a chiral stationary phase, metalloporhyrins for enhanced hydrogen adsorption and an intrinsic conductivity to form porous conductors, have been prepared. This dissertation presents how the principles of reticular chemistry were utilized to achieve in the preparations of metal-organic frameworks with a large surface area and active backbones. Through the simple isoreticular (having the same framework topology) expansion from MOF-177 composed with 1,3,5-tris(4'-carboxyphenyl-)benzene (BTB3-) as the strut; MOF-200 was prepared with 4,4',4"-(benzene-1,3,5-triyl-tris(benzene-4,1-diy1))tribenzoic acid an extension from BTB3- by a phenylene unit to yield one of the most porous MOFs with a Langmuir surface area of 10,400 m2. and the lowest density of 0.22 cm3.g-1. A successful thermal polymerization reaction at 325 °C inside of the pores of highly porous MOF, MOF-177, was performed and verified the integrity of the MOF structure even after the thermal reaction. 1,4-Diphenylbutadiyne that is known to polymerize upon heating to form a conjugated backbone was impregnated via solution-diffusion into MOF-177 and then subsequently polymerized by heat to form polymer impregnated MOF-177. Characterization was carried out using powder X-ray diffraction and volumetric sorption analyzer. MOF-1020 with a linear quaterphenyl dicarboxylate-based strut was designed to contain a chiral bisbinaphthyl crown-ether moiety for alkyl ammonium resolution was precisely placed into a Zn4O(CO2)6-based cubic MOF structure. Unfortunately, the chiral resolution was not achieved due to the sensitivity and the pore environment of MOF-1020. However, an interesting phenomenon was observed, where the loss of crystallinity occurs upon solvent removal while the crystallites remain shiny and crystalline, but it readily is restored upon re-solvation of the crystallites. This rare

  2. Reliability-Based Optimization in Structural Engineering

    DEFF Research Database (Denmark)

    Enevoldsen, I.; Sørensen, John Dalsgaard

    1994-01-01

    -based optimal inspection planning and reliability-based experiment planning. It is explained how these optimization problems can be solved by application of similar techniques. The reliability estimation is limited to first order reliability methods (FORM) for both component and systems reliability evaluation......, inclusion of the finite element method as the response evaluation tool and how the size of the problem can be made practicable. Finally, the important task of model evaluation and sensitivity analysis of the optimal solution is treated including a strategy for model-making with both pre and post-analysis.......In this paper reliability-based optimization problems in structural engineering are formulated on the basis of the classical decision theory. Several formulations are presented: Reliability-based optimal design of structural systems with component or systems reliability constraints, reliability...

  3. Subpicosecond protein backbone changes detected during the green-absorbing proteorhodopsin primary photoreaction.

    Science.gov (United States)

    Amsden, Jason J; Kralj, Joel M; Chieffo, Logan R; Wang, Xihua; Erramilli, Shyamsunder; Spudich, Elena N; Spudich, John L; Ziegler, Lawrence D; Rothschild, Kenneth J

    2007-10-11

    Recent studies demonstrate that photoactive proteins can react within several picoseconds to photon absorption by their chromophores. Faster subpicosecond protein responses have been suggested to occur in rhodopsin-like proteins where retinal photoisomerization may impulsively drive structural changes in nearby protein groups. Here, we test this possibility by investigating the earliest protein structural changes occurring in proteorhodopsin (PR) using ultrafast transient infrared (TIR) spectroscopy with approximately 200 fs time resolution combined with nonperturbing isotope labeling. PR is a recently discovered microbial rhodopsin similar to bacteriorhodopsin (BR) found in marine proteobacteria and functions as a proton pump. Vibrational bands in the retinal fingerprint (1175-1215 cm(-1)) and ethylenic stretching (1500-1570 cm(-1)) regions characteristic of all-trans to 13-cis chromophore isomerization and formation of a red-shifted photointermediate appear with a 500-700 fs time constant after photoexcitation. Bands characteristic of partial return to the ground state evolve with a 2.0-3.5 ps time constant. In addition, a negative band appears at 1548 cm(-1) with a time constant of 500-700 fs, which on the basis of total-15N and retinal C15D (retinal with a deuterium on carbon 15) isotope labeling is assigned to an amide II peptide backbone mode that shifts to near 1538 cm(-1) concomitantly with chromophore isomerization. Our results demonstrate that one or more peptide backbone groups in PR respond with a time constant of 500-700 fs, almost coincident with the light-driven retinylidene chromophore isomerization. The protein changes we observe on a subpicosecond time scale may be involved in storage of the absorbed photon energy subsequently utilized for proton transport.

  4. The Role of Backbone Hydrogen Bonds in the Transition State for Protein Folding of a PDZ Domain.

    Directory of Open Access Journals (Sweden)

    Søren W. Pedersen

    Full Text Available Backbone hydrogen bonds are important for the structure and stability of proteins. However, since conventional site-directed mutagenesis cannot be applied to perturb the backbone, the contribution of these hydrogen bonds in protein folding and stability has been assessed only for a very limited set of small proteins. We have here investigated effects of five amide-to-ester mutations in the backbone of a PDZ domain, a 90-residue globular protein domain, to probe the influence of hydrogen bonds in a β-sheet for folding and stability. The amide-to-ester mutation removes NH-mediated hydrogen bonds and destabilizes hydrogen bonds formed by the carbonyl oxygen. The overall stability of the PDZ domain generally decreased for all amide-to-ester mutants due to an increase in the unfolding rate constant. For this particular region of the PDZ domain, it is therefore clear that native hydrogen bonds are formed after crossing of the rate-limiting barrier for folding. Moreover, three of the five amide-to-ester mutants displayed an increase in the folding rate constant suggesting that the hydrogen bonds are involved in non-native interactions in the transition state for folding.

  5. The Prediction of Botulinum Toxin Structure Based on in Silico and in Vitro Analysis

    Science.gov (United States)

    Suzuki, Tomonori; Miyazaki, Satoru

    2011-01-01

    Many of biological system mediated through protein-protein interactions. Knowledge of protein-protein complex structure is required for understanding the function. The determination of huge size and flexible protein-protein complex structure by experimental studies remains difficult, costly and five-consuming, therefore computational prediction of protein structures by homolog modeling and docking studies is valuable method. In addition, MD simulation is also one of the most powerful methods allowing to see the real dynamics of proteins. Here, we predict protein-protein complex structure of botulinum toxin to analyze its property. These bioinformatics methods are useful to report the relation between the flexibility of backbone structure and the activity.

  6. Bamboo-based Panels for Structural Applications

    Institute of Scientific and Technical Information of China (English)

    CHENXuhe; WANGZheng

    2005-01-01

    With technical assistance from INBAR and the Research Institute of Wood Industry of the Chinese Academy of Forestry, the construction of the Pingbian Primary School was completed in 2004,where bamboo plywood panels and laminated beams were used for the roof trusses, sheathing boards and wall panels. This is the first time that bamboo-based panels are used for structural applications.

  7. (1)H, (13)C, and (15)N backbone resonance assignments of the full-length 40 kDa S. acidocaldarius Y-family DNA polymerase, dinB homolog.

    Science.gov (United States)

    Moro, Sean L; Cocco, Melanie J

    2015-10-01

    The dinB homolog (Dbh) is a member of the Y-family of translesion DNA polymerases, which are specialized to accurately replicate DNA across from a wide variety of lesions in living cells. Lesioned bases block the progression of high-fidelity polymerases and cause detrimental replication fork stalling; Y-family polymerases can bypass these lesions. The active site of the translesion synthesis polymerase is more open than that of a replicative polymerase; consequently Dbh polymerizes with low fidelity. Bypass polymerases also have low processivity. Short extension past the lesion allows the high-fidelity polymerase to switch back onto the site of replication. Dbh and the other Y-family polymerases have been used as structural models to investigate the mechanisms of DNA polymerization and lesion bypass. Many high-resolution crystal structures of Y-family polymerases have been reported. NMR dynamics studies can complement these structures by providing a measure of protein motions. Here we report the (15)N, (1)H, and (13)C backbone resonance assignments at two temperatures (35 and 50 °C) for Sulfolobus acidocaldarius Dbh polymerase. Backbone resonance assignments have been obtained for 86 % of the residues. The polymerase active site is assigned as well as the majority of residues in each of the four domains.

  8. Vibrational Based Inspection of Civil Engineering Structures

    DEFF Research Database (Denmark)

    Rytter, Anders

    at the University of Aalborg from 1988 to 1991. Secondly, a research project, In-Field Vibration Based Inspection of Civil Engineering Structures, which has been performed as a pilot project by the Consulting Engineers Rambøll, Hannemann and Højlund in cooperation with the department of Building Technology......The thesis has been written in relation to two different research projects. Firstly, an offshore test programme, Integrated Experimental/Numerical Analysis of the Dynamic behavior of offshore structures, which was performed at the department of Building Technology and Structural Engineering...... and Structural Engineering at the University of Aalborg since the beginning of 1992. Both projects have been supported by the Danish Technical Research Council. Further, the first mentioned project was supported by the Danish Energy Agency. Their financial support is gratefully acknowledged....

  9. STRUCTURAL EVOLUTION IN BIORENEWABLE SOY BASED POLYURETHANES

    Institute of Scientific and Technical Information of China (English)

    Deepa Puthanparambil; Casey Kimball; Shaw Ling Hsu; Zhiyong Ren

    2009-01-01

    Spectroscopic studies have revealed that the amount of polyureas formed and the kinetics of their formation in soy based polyurethane systems are considerably different from traditional systems employing ethylene oxide-propylene oxide (EO-PO) based polyols. The aggregation of polyureas was characterized by the hydrogen bonds formed utilizing FTIR spectroscopy. This study offered the opportunity to assign the previously undefined infrared features. The structural transformation is reflected in the segmental relaxation kinetics characterized by spin-spin diffusion most conveniently measured using low field NMR. The reaction kinetics and the products formed are directly related to the hydrophobic nature of the soy based polyols and its inability to disperse water.

  10. Efficiency of paramagnetism-based constraints to determine the spatial arrangement of {alpha}-helical secondary structure elements

    Energy Technology Data Exchange (ETDEWEB)

    Bertini, Ivano [University of Florence, CERM and Department of Chemistry (Italy)], E-mail: bertini@cerm.unifi.it; Longinetti, Marco [Dipartimento di Ingegneria Agraria e Forestale (Italy); Luchinat, Claudio; Parigi, Giacomo [University of Florence, CERM and Department of Agricultural Biotechnology (Italy); Sgheri, Luca [Istituto di Analisi Globale ed Applicazioni (CNR) (Italy)

    2002-02-15

    A computational approach has been developed to assess the power of paramagnetism-based backbone constraints with respect to the determination of the tertiary structure, once the secondary structure elements are known. This is part of the general assessment of paramagnetism-based constraints which are known to be relevant when used in conjunction with all classical constraints. The paramagnetism-based constraints here investigated are the pseudocontact shifts, the residual dipolar couplings due to self-orientation of the metalloprotein in high magnetic fields, and the cross correlation between dipolar relaxation and Curie relaxation. The relative constraints are generated by back-calculation from a known structure. The elements of secondary structure are supposed to be obtained from chemical shift index. The problem of the reciprocal orientation of the helices is addressed. It is shown that the correct fold can be obtained depending on the length of the {alpha}-helical stretches with respect to the length of the non helical segments connecting the {alpha}-helices. For example, the correct fold is straightforwardly obtained for the four-helix bundle protein cytochrome b{sub 562}, while the double EF-hand motif of calbindin D{sub 9k} is hardly obtained without ambiguity. In cases like calbindin D{sub 9k}, the availability of datasets from different metal ions is helpful, whereas less important is the location of the metal ion with respect to the secondary structure elements.

  11. A one-dimensional chain structure based on unusual tetranuclear manganese(II) clusters.

    Science.gov (United States)

    Che, Guang Bo; Wang, Jian; Liu, Chun Bo; Li, Xiu Ying; Liu, Bo

    2008-11-01

    The title coordination polymer, poly[bis(mu(4)-biphenyl-2,2'-dicarboxylato)(dipyrido[3,2-a:2',3'-c]phenazine)manganese(II)], [Mn(2)(C(14)H(8)O(4))(2)(C(18)H(10)N(4))](n), was obtained through the reaction of MnCl(2).4H(2)O, biphenyl-2,2'-dicarboxylic acid (H(2)dpdc) and dipyrido[3,2-a:2',3'-c]phenazine (L) under hydrothermal conditions. The asymmetric unit contains two crystallographically unique Mn(II) ions, one unique L ligand and two unique dpdc ligands. One Mn ion is six-coordinated by four O atoms from three different dpdc ligands and two N atoms from one L ligand, adopting a distorted octahedral coordination geometry. The distortions from ideal octahedral geometry are largely due to the presence of chelating ligands and the resulting acute N-Mn-N and O-Mn-O angles. The second Mn ion is coordinated in a distorted trigonal bipyramidal fashion by five O atoms from four distinct dpdc ligands. Four Mn(II) ions are bridged by the carboxylate groups of the dpdc ligands to form an unusual tetranuclear Mn(II) cluster. Clusters are further connected by the aromatic backbone of the dicarboxylate ligands, forming a one-dimensional chain structure along the b axis. The title compound is the first example of a chain structure based on a tetranuclear Mn(II) cluster.

  12. Geography-based structural analysis of the Internet

    Energy Technology Data Exchange (ETDEWEB)

    Kasiviswanathan, Shiva [Los Alamos National Laboratory; Eidenbenz, Stephan [Los Alamos National Laboratory; Yan, Guanhua [Los Alamos National Laboratory

    2010-01-01

    In this paper, we study some geographic aspects of the Internet. We base our analysis on a large set of geolocated IP hop-level session data (including about 300,000 backbone routers, 150 million end hosts, and 1 billion sessions) that we synthesized from a variety of different input sources such as US census data, computer usage statistics, Internet market share data, IP geolocation data sets, CAJDA's Skitter data set for backbone connectivity, and BGP routing tables. We use this model to perform a nationwide and statewide geographic analysis of the Internet. Our main observations are: (1) There is a dominant coast-to-coast pattern in the US Internet traffic. In fact, in many instances even if the end-devices are not near either coast, still the traffic between them takes a long detour through the coasts. (2) More than half of the Internet paths are inflated by 100% or more compared to their corresponding geometric straight-line distance. This circuitousness makes the average ratio between the routing distance and geometric distance big (around 10). (3) The weighted mean hop count is around 5, but the hop counts are very loosely correlated with the distances. The weighted mean AS count (number of ASes traversed) is around 3. (4) The AS size and the AS location number distributions are heavy-tailed and strongly correlated. Most of the ASes are medium sized and there is a wide variability in the geographic dispersion size (measured in terms of the convex hull area) of these ASes.

  13. Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones

    NARCIS (Netherlands)

    Voortman, Thomas P; Chiechi, Ryan C

    2015-01-01

    This paper compares the morphologies of films of conjugated polymers in which the backbone (main chain) and pendant groups are varied between ionic/hydrophilic and aliphatic/hydrophobic. We observe that conjugated polymers in which the pendant groups and backbone are matched, either ionic-ionic or h

  14. Generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation

    Directory of Open Access Journals (Sweden)

    Wang Genping

    2016-09-01

    Full Text Available Horizontal transfer of antibiotic resistance genes to animals and vertical transfer of herbicide resistance genes to the weedy relatives are perceived as major biosafety concerns in genetically modified (GM crops. In this study, five novel vectors which used gusA and bar as a reporter gene and a selection marker gene, respectively, were constructed based on the pCLEAN dual binary vector system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and 5TGTB154 carried two T-DNAs in the target plasmid with either one or double right borders, and 5BTG154 carried the selectable marker gene on the backbone outside of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154 and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to facilitate transformation. These five dual binary vector combinations were transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of marker-free transgenic plants and integration of backbone sequences in the obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154 were more efficient in generating marker-free transgenic wheat plants with no or minimal integration of backbone sequences in the wheat genome. The vector series developed in this study for generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation will be useful to facilitate the creation of ‘clean’ GM wheat containing only the foreign genes of agronomic importance.

  15. Generation of Marker- and/or Backbone-Free Transgenic Wheat Plants via Agrobacterium-Mediated Transformation

    Science.gov (United States)

    Wang, Gen-Ping; Yu, Xiu-Dao; Sun, Yong-Wei; Jones, Huw D.; Xia, Lan-Qin

    2016-01-01

    Horizontal transfer of antibiotic resistance genes to animals and vertical transfer of herbicide resistance genes to the weedy relatives are perceived as major biosafety concerns in genetically modified (GM) crops. In this study, five novel vectors which used gusA and bar as a reporter gene and a selection marker gene, respectively, were constructed based on the pCLEAN dual binary vector system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and 5TGTB154 carried two T-DNAs in the target plasmid with either one or double right borders, and 5BTG154 carried the selectable marker gene on the backbone outside of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154, and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to facilitate transformation. These five dual binary vector combinations were transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of marker-free transgenic plants, and integration of backbone sequences in the obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154) were more efficient in generating marker-free transgenic wheat plants with no or minimal integration of backbone sequences in the wheat genome. The vector series developed in this study for generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium-mediated transformation will be useful to facilitate the creation of “clean” GM wheat containing only the foreign genes of agronomic importance. PMID:27708648

  16. Hyperbolic metamaterials based on Bragg polariton structures

    Science.gov (United States)

    Sedov, E. S.; Charukhchyan, M. V.; Arakelyan, S. M.; Alodzhants, A. P.; Lee, R.-K.; Kavokin, A. V.

    2016-07-01

    A new hyperbolic metamaterial based on a modified semiconductor Bragg mirror structure with embedded periodically arranged quantum wells is proposed. It is shown that exciton polaritons in this material feature hyperbolic dispersion in the vicinity of the second photonic band gap. Exciton-photon interaction brings about resonant nonlinearity leading to the emergence of nontrivial topological polaritonic states. The formation of spatially localized breather-type structures (oscillons) representing kink-shaped solutions of the effective Ginzburg-Landau-Higgs equation slightly oscillating along one spatial direction is predicted.

  17. Structure determination of a flexible cyclic peptide based on NMR and MD simulation 3J-coupling.

    Science.gov (United States)

    Gattin, Zrinka; Zaugg, Judith; van Gunsteren, Wilfred F

    2010-03-15

    Molecular dynamics (MD) simulations, in which experimental values such as nuclear Overhauser effects (NOEs), dipolar couplings, (3)J-coupling constants or crystallographic structure factors are used to bias the values of specific molecular properties towards experimental ones, are often carried out to study the structure refinement of peptides and proteins. However, (3)J-coupling constants are usually not employed because of the multiplicity of torsional angle values (phi) corresponding to each (3)J-coupling constant value. Here, we apply the method of adaptively enforced restraining using a local-elevation (LE) biasing potential energy function in which a memory function penalizes conformations in case both the average and the current (3)J-values deviate from the experimental target value. Then, the molecule is forced to sample other parts of the conformational space, thereby being able to cross high energy barriers and to bring the simulated average close to the measured value. Herein, we show the applicability of this method in structure refinement of a cyclo-beta-tetrapeptide by enforcing the (3)J-value restraining with LE on twelve backbone torsional angles. The resulting structural ensemble satisfies the experimental (3)J-coupling data better than the NMR model structure derived using conventional single-structure refinement based on these data. Thus, application of local-elevation search MD simulation in combination with biasing towards (3)J-coupling makes it possible to use (3)J-couplings quantitatively in structure determination of peptides.

  18. Data acquisition backbone core DABC release v1.0

    Energy Technology Data Exchange (ETDEWEB)

    Adamczewski-Musch, Joern; Essel, Hans G.; Kurz, Nikolaus; Linev, S. [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany)

    2010-07-01

    The new experiments at FAIR require new concepts of data acquisition systems for the distribution of self-triggered, time stamped data streams over high performance networks for event building. The Data Acquisition Backbone Core (DABC) is a general purpose software framework developed for the implementation of such data acquisition systems. A DABC application consists of functional components like data input, combiner, scheduler, event builder, filter, analysis and storage which can be configured at runtime. Application specific code including the support of all kinds of data channels (front-end systems) is implemented by C++ program plug-ins. DABC is also well suited as environment for various detector and readout components test beds. A set of DABC plug-ins has been developed for the FAIR experiment CBM (Compressed Baryonic Matter) at GSI. This DABC application is used as DAQ system for test beamtimes. Front-end boards equipped with n-XYTER ASICs and ADCs are connected to read-out controller boards (ROC). From there the data is sent over Ethernet (UDP), or over optics and PCIe interface cards into Linux PCs. DABC does the controlling, event building, archiving and data serving. The first release of DABC was published in 2009 and is available under GPL license.

  19. Distributed Prognostics based on Structural Model Decomposition

    Science.gov (United States)

    Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

    2014-01-01

    Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

  20. Deployable structures for a human lunar base

    Science.gov (United States)

    Gruber, Petra; Häuplik, Sandra; Imhof, Barbara; Özdemir, Kürsad; Waclavicek, Rene; Perino, Maria Antoinetta

    2007-06-01

    The study Lunar exploration architecture—deployable structures for a lunar base was performed within the Alcatel Alenia Space “Lunar Exploration Architecture” study for the European Space Agency. The purpose of the study was to investigate bionic concepts applicable to deployable structures and to interpret the findings for possible implementation concepts. The study aimed at finding innovative solutions for deployment possibilities. Translating folding/unfolding principles from nature, candidate geometries were developed and researched using models, drawings and visualisations. The use of materials, joints between structural elements and construction details were investigated for these conceptual approaches. Reference scenarios were used to identify the technical and environmental conditions, which served as design drivers. Mechanical issues and the investigation of deployment processes narrowed the selection down to six chosen concepts. Their applicability was evaluated at a conceptual stage in relation to the timescale of the mission.

  1. Electronic structure of Fe-based superconductors

    Indian Academy of Sciences (India)

    Kalobaran Maiti

    2015-06-01

    Fe-based superconductors have drawn much attention during the last decade due to the presence of superconductivity in materials containing the magnetic element, Fe, and the coexistence of superconductivity and magnetism. Extensive study of the electronic structure of these systems suggested the dominant role of states in their electronic properties, which is significantly different from the cuprate superconductors. In this article, some of our studies of the electronic structure of these fascinating systems employing high-resolution photoemission spectroscopy is reviewed. The combined effect of electron correlation and covalency reveals an interesting scenario in their electronic structure. The contribution of ligand states at the Fermi level is found to be much more significant than indicated in earlier studies. Temperature evolution of the energy bands reveals the signature of transition akin to Lifshitz transition in these systems.

  2. Backbone resonance assignments for G protein α(i3) subunit in the GDP-bound state.

    Science.gov (United States)

    Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2014-10-01

    Guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of G protein-coupled receptors (GPCRs) at the cell surface to intracellular responses. In the resting state, G protein forms a heterotrimer, consisting of the G protein α subunit with GDP (Gα·GDP) and the G protein βγ subunit (Gβγ). Ligand binding to GPCRs promotes the GDP-GTP exchange on Gα, leading to the dissociation of the GTP-bound form of Gα (Gα·GTP) and Gβγ. Then, Gα·GTP and Gβγ bind to their downstream effector enzymes or ion channels and regulate their activities, leading to a variety of cellular responses. Finally, Gα hydrolyzes the bound GTP to GDP and returns to the resting state by re-associating with Gβγ. The G proteins are classified with four major families based on the amino acid sequences of Gα: i/o, s, q/11, and 12/13. Here, we established the backbone resonance assignments of human Gαi3, a member of the i/o family with a molecular weight of 41 K, in complex with GDP. The chemical shifts were compared with those of Gα(i3) in complex with a GTP-analogue, GTPγS, which we recently reported, indicating that the residues with significant chemical shift differences are mostly consistent with the regions with the structural differences between the GDP- and GTPγS-bound states, as indicated in the crystal structures. The assignments of Gα(i3)·GDP would be useful for the analyses of the dynamics of Gα(i3) and its interactions with various target molecules.

  3. Collective prediction based on community structure

    Science.gov (United States)

    Jiang, Yasong; Li, Taisong; Zhang, Yan; Yan, Yonghong

    2017-01-01

    Collective prediction algorithms have been used to improve performances when network structures are involved in prediction tasks. The training dataset of such tasks often contain information of content, links and labels, while the testing dataset have only content and link information. Conventional collective prediction algorithms conduct predictions based on the content of a node and the information of its direct neighbors with a base classifier. However, the information of some direct neighbor nodes may be not consistent with the target one. In addition, the information of indirect neighbors can be helpful when that of direct neighbors is scant. In this paper, instead of using information of direct neighbors, we propose to apply community structures in networks to prediction tasks. A community detection method is aggregated into the collective prediction process to improve prediction performance. Experimental results show that the proposed algorithm outperforms a number of standard prediction algorithms specially under conditions that labeled training dataset are limited.

  4. Guideline based structured documentation: the final goal?

    Science.gov (United States)

    Bürkle, Thomas; Ganslandt, Thomas; Tübergen, Dirk; Menzel, Josef; Kucharzik, Torsten; Neumann, Klaus; Schlüter, Stefan; Müller, Marcel; Veltmann, Ursula; Prokosch, Hans-Ulrich

    2002-01-01

    Structured documentation of medical procedures facilitates information retrieval for research and therapy and may help to improve patient care. Most medical documents until today however consist mainly of unstructured narrative text. Here we present an application for endoscopy which is not only fully integrated into a comprehensive clinical information system, but which also supports various degrees of structuring examination reports. The application is used routinely in a German University hospital since summer 2000. We present the first unstructured version which permits storage of a free text report together with selected examination images. The next step added improved structure to the document using a catalogue of index terms. The practical advantages of selective patient retrieval are described. Today we use a version which supports fully structured, guideline based documentation of endoscopy reports in order to automatically generate essential classification codes and the narrative examination report All versions have advantages and disadvantages and we conclude that guideline based documentation may not be suitable for all endoscopy cases.

  5. A novel tree structure based watermarking algorithm

    Science.gov (United States)

    Lin, Qiwei; Feng, Gui

    2008-03-01

    In this paper, we propose a new blind watermarking algorithm for images which is based on tree structure. The algorithm embeds the watermark in wavelet transform domain, and the embedding positions are determined by significant coefficients wavelets tree(SCWT) structure, which has the same idea with the embedded zero-tree wavelet (EZW) compression technique. According to EZW concepts, we obtain coefficients that are related to each other by a tree structure. This relationship among the wavelet coefficients allows our technique to embed more watermark data. If the watermarked image is attacked such that the set of significant coefficients is changed, the tree structure allows the correlation-based watermark detector to recover synchronously. The algorithm also uses a visual adaptive scheme to insert the watermark to minimize watermark perceptibility. In addition to the watermark, a template is inserted into the watermarked image at the same time. The template contains synchronization information, allowing the detector to determine the geometric transformations type applied to the watermarked image. Experimental results show that the proposed watermarking algorithm is robust against most signal processing attacks, such as JPEG compression, median filtering, sharpening and rotating. And it is also an adaptive method which shows a good performance to find the best areas to insert a stronger watermark.

  6. Light weight cellular structures based on aluminium

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, O. [Indian Inst. of Tech., Kanpur (India); Embury, J.D.; Sinclair, C. [McMaster Univ., Hamilton, ON (Canada); Sang, H. [Queen`s Univ., Kingston, ON (Canada); Silvetti, P. [Cordoba Univ. Nacional (Argentina). Facultad de Ciencias Exactas, Fisicas y Naturales

    1997-02-01

    An interesting form of lightweight material which has emerged in the past 2 decades is metallic foam. This paper deals with the basic concepts of making metallic foams and a detailed study of foams produced from Al-SiC. In addition, some aspects of cellular solids based on honeycomb structures are outlined including the concept of producing both two-phase foams and foams with composite walls.

  7. General Structures of Block Based Interpolational Function

    Institute of Scientific and Technical Information of China (English)

    ZOU LE; TANG SHUO; Ma Fu-ming

    2012-01-01

    We construct general structures of one and two variable interpolation function,without depending on the existence of divided difference or inverse differences,and we also discuss the block based osculatory interpolation in one variable case.Clearly,our method offers many flexible interpolation schemes for choices.Error terms for the interpolation are determined and numerical examples are given to show the effectiveness of the results.

  8. Peptide Backbone Sampling Convergence with the Adaptive Biasing Force Algorithm

    Science.gov (United States)

    Faller, Christina E.; Reilly, Kyle A.; Hills, Ronald D.; Guvench, Olgun

    2013-01-01

    Complete Boltzmann sampling of reaction coordinates in biomolecular systems continues to be a challenge for unbiased molecular dynamics simulations. A growing number of methods have been developed for applying biases to biomolecular systems to enhance sampling while enabling recovery of the unbiased (Boltzmann) distribution of states. The Adaptive Biasing Force (ABF) algorithm is one such method, and works by canceling out the average force along the desired reaction coordinate(s) using an estimate of this force progressively accumulated during the simulation. Upon completion of the simulation, the potential of mean force, and therefore Boltzmann distribution of states, is obtained by integrating this average force. In an effort to characterize the expected performance in applications such as protein loop sampling, ABF was applied to the full ranges of the Ramachandran ϕ/ψ backbone dihedral reaction coordinates for dipeptides of the 20 amino acids using all-atom explicit-water molecular dynamics simulations. Approximately half of the dipeptides exhibited robust and rapid convergence of the potential of mean force as a function of ϕ/ψ in triplicate 50-ns simulations, while the remainder exhibited varying degrees of less complete convergence. The greatest difficulties in achieving converged ABF sampling were seen in the branched-sidechain amino acids threonine and valine, as well as the special case of proline. Proline dipeptide sampling was further complicated by trans-to-cis peptide bond isomerization not observed in unbiased control molecular dynamics simulations. Overall, the ABF method was found to be a robust means of sampling the entire ϕ/ψ reaction coordinate for the 20 amino acids, including high free-energy regions typically inaccessible in standard molecular dynamics simulations. PMID:23215032

  9. 1H, 15N and 13C backbone resonance assignments of the archetypal serpin α1-antitrypsin.

    Science.gov (United States)

    Nyon, Mun Peak; Kirkpatrick, John; Cabrita, Lisa D; Christodoulou, John; Gooptu, Bibek

    2012-10-01

    Alpha(1)-antitrypsin is a 45-kDa (394-residue) serine protease inhibitor synthesized by hepatocytes, which is released into the circulatory system and protects the lung from the actions of neutrophil elastase via a conformational transition within a dynamic inhibitory mechanism. Relatively common point mutations subvert this transition, causing polymerisation of α(1)-antitrypsin and deficiency of the circulating protein, predisposing carriers to severe lung and liver disease. We have assigned the backbone resonances of α(1)-antitrypsin using multidimensional heteronuclear NMR spectroscopy. These assignments provide the starting point for a detailed solution state characterization of the structural properties of this highly dynamic protein via NMR methods.

  10. Conformation-specific spectroscopy of capped glutamine-containing peptides: role of a single glutamine residue on peptide backbone preferences.

    Science.gov (United States)

    Walsh, Patrick S; Dean, Jacob C; McBurney, Carl; Kang, Hyuk; Gellman, Samuel H; Zwier, Timothy S

    2016-04-28

    The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse γ-turn in the peptide backbone by forming a pair of H-bonds that bridge the γ-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I β-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the β-turn not otherwise involved in a hydrogen bond. This β-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y β-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.

  11. Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins

    DEFF Research Database (Denmark)

    Maragakis, Paul; Lindorff-Larsen, Kresten; Eastwood, Michael P

    2008-01-01

    methods. However, apparent systematic discrepancies between order parameters extracted from simulations and experiments are common, particularly for elements of noncanonical secondary structure. In this paper, results from a 1.2 micros explicit solvent MD simulation of the protein ubiquitin are compared...... with previously determined backbone order parameters derived from NMR relaxation experiments [Tjandra, N.; Feller, S. E.; Pastor, R. W.; Bax, A. J. Am. Chem. Soc. 1995, 117, 12562-12566]. The simulation reveals fluctuations in three loop regions that occur on time scales comparable to or longer than...

  12. Structure-Based Design of Ricin Inhibitors

    Directory of Open Access Journals (Sweden)

    Jon D. Robertus

    2011-10-01

    Full Text Available Ricin is a potent cytotoxin easily purified in large quantities. It presents a significant public health concern due to its potential use as a bioterrorism agent. For this reason, extensive efforts have been underway to develop antidotes against this deadly poison. The catalytic A subunit of the heterodimeric toxin has been biochemically and structurally well characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA inhibitors have been identified; the most promising leads belonging to the pterin family. Development of these lead compounds into potent drug candidates is a challenging prospect for numerous reasons, including poor solubility of pterins, the large and highly polar secondary binding pocket of RTA, as well as the enzyme’s near perfect catalytic efficiency and tight binding affinity for its natural substrate, the eukaryotic ribosome. To date, the most potent RTA inhibitors developed using this approach are only modest inhibitors with apparent IC50 values in the 10−4 M range, leaving significant room for improvement. This review highlights the variety of techniques routinely employed in structure-based drug design projects, as well as the challenges faced in the design of RTA inhibitors.

  13. Protein Structure Network-based Drug Design.

    Science.gov (United States)

    Liang, Zhongjie; Hu, Guang

    2016-01-01

    Although structure-based drug design (SBDD) has become an indispensable tool in drug discovery for a long time, it continues to pose major challenges to date. With the advancement of "omics" techniques, systems biology has enriched SBDD into a new era, called polypharmacology, in which multi-targets drug or drug combination is designed to fight complex diseases. As a preliminary tool in systems biology, protein structure networks (PSNs) treat a protein as a set of residues linked by edges corresponding to the intramolecular interactions existing in folded structures between the residues. The PSN offers a computationally efficient tool to study the structure and function of proteins, and thus may facilitate structurebased drug design. Herein, we provide an overview of recent advances in PSNs, from predicting functionally important residues, to charactering protein-protein interactions and allosteric communication paths. Furthermore, we discuss potential pharmacological applications of PSN concepts and tools, and highlight the application to two families of drug targets, GPCRs and Hsp90. Although the application of PSNs as a framework for computer-aided drug discovery has been limited to date, we put forward the potential utility value in the near future and propose the PSNs could also serve as a new tool for polypharmacology research.

  14. Theoretical NMR correlations based Structure Discussion

    Directory of Open Access Journals (Sweden)

    Junker Jochen

    2011-07-01

    Full Text Available Abstract The constitutional assignment of natural products by NMR spectroscopy is usually based on 2D NMR experiments like COSY, HSQC, and HMBC. The actual difficulty of the structure elucidation problem depends more on the type of the investigated molecule than on its size. The moment HMBC data is involved in the process or a large number of heteroatoms is present, a possibility of multiple solutions fitting the same data set exists. A structure elucidation software can be used to find such alternative constitutional assignments and help in the discussion in order to find the correct solution. But this is rarely done. This article describes the use of theoretical NMR correlation data in the structure elucidation process with WEBCOCON, not for the initial constitutional assignments, but to define how well a suggested molecule could have been described by NMR correlation data. The results of this analysis can be used to decide on further steps needed to assure the correctness of the structural assignment. As first step the analysis of the deviation of carbon chemical shifts is performed, comparing chemical shifts predicted for each possible solution with the experimental data. The application of this technique to three well known compounds is shown. Using NMR correlation data alone for the description of the constitutions is not always enough, even when including 13C chemical shift prediction.

  15. Gas separation performance of 6FDA-based polyimides with different chemical structures

    KAUST Repository

    Qiu, Wulin

    2013-10-01

    This work reports the gas separation performance of several 6FDA-based polyimides with different chemical structures, to correlate chemical structure with gas transport properties with a special focus on CO2 and CH 4 transport and plasticization stability of the polyimides membranes relevant to natural gas purification. The consideration of the other gases (He, O2 and N2) provided additional insights regarding effects of backbone structure on detailed penetrant properties. The polyimides studied include 6FDA-DAM, 6FDA-mPDA, 6FDA-DABA, 6FDA-DAM:DABA (3:2), 6FDA-DAM:mPDA (3:2) and 6FDA-mPDA:DABA (3:2). Both pure and binary gas permeation were investigated. The packing density, which is tunable by adjusting monomer type and composition of the various samples, correlated with transport permeability and selectivity. The separation performance of the polyimides for various gas pairs were also plotted for comparison to the upper bound curves, and it was found that this family of materials shows attractive performance. The CO 2 plasticization responses for the un-cross-linked polyimides showed good plasticization resistance to CO2/CH4 mixed gas with 10% CO2; however, only the cross-linked polyimides showed good plasticization resistance under aggressive gas feed conditions (CO 2/CH4 mixed gas with 50% CO2 or pure CO 2). For future work, asymmetric hollow fibers and carbon molecular sieve membranes based on the most attractive members of the family will be considered. © 2013 Elsevier Ltd. All rights reserved.

  16. Ruthenium-catalyzed olefin metathesis accelerated by the steric effect of the backbone substituent in cyclic (alkyl)(amino) carbenes.

    Science.gov (United States)

    Zhang, Jun; Song, Shangfei; Wang, Xiao; Jiao, Jiajun; Shi, Min

    2013-10-21

    Three ruthenium complexes bearing backbone-monosubstituted CAACs were prepared and displayed dramatic improvement in catalytic efficiency not only in RCM reaction but also in the ethenolysis of methyl oleate, compared to those bearing backbone-disubstituted CAACs.

  17. Adaptive GOP structure based on motion coherence

    Science.gov (United States)

    Ma, Yanzhuo; Wan, Shuai; Chang, Yilin; Yang, Fuzheng; Wang, Xiaoyu

    2009-08-01

    Adaptive Group of Pictures (GOP) is helpful for increasing the efficiency of video encoding by taking account of characteristics of video content. This paper proposes a method for adaptive GOP structure selection for video encoding based on motion coherence, which extracts key frames according to motion acceleration, and assigns coding type for each key and non-key frame correspondingly. Motion deviation is then used instead of motion magnitude in the selection of the number of B frames. Experimental results show that the proposed method for adaptive GOP structure selection achieves performance gain of 0.2-1dB over the fixed GOP, and has the advantage of better transmission resilience. Moreover, this method can be used in real-time video coding due to its low complexity.

  18. Pseudo 5D HN(C)N Experiment to Facilitate the Assignment of Backbone Resonances in Proteins Exhibiting High Backbone Shift Degeneracy

    CERN Document Server

    Kumar, Dinesh; Shukla, Vaibhav Kumar; Pandey, Himanshu; Arora, Ashish; Guleria, Anupam

    2014-01-01

    Assignment of protein backbone resonances is most routinely carried out using triple resonance three dimensional NMR experiments involving amide 1H and 15N resonances. However for intrinsically unstructured proteins, alpha-helical proteins or proteins containing several disordered fragments, the assignment becomes problematic because of high degree of backbone shift degeneracy. In this backdrop, a novel reduced dimensionality (RD) experiment -(5,3)D-hNCO-CANH- is presented to facilitate (and/or to validate) the sequential backbone resonance assignment in such proteins. The proposed 3D NMR experiment makes use of the modulated amide 15N chemical shifts (resulting from the joint sampling along both its indirect dimensions) to resolve the ambiguity involved in connecting the neighboring amide resonances (i.e. HiNi and Hi-1Ni-1) for overlapping amide NH peaks. The experiment -encoding 5D spectral information- leads to a conventional 3D spectrum with significantly reduced spectral crowding and complexity. The impr...

  19. Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections

    Science.gov (United States)

    Nuccitelli, Annalisa; Cozzi, Roberta; Gourlay, Louise J.; Donnarumma, Danilo; Necchi, Francesca; Norais, Nathalie; Telford, John L.; Rappuoli, Rino; Bolognesi, Martino; Maione, Domenico; Grandi, Guido; Rinaudo, C. Daniela

    2011-01-01

    Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin subunits from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens. PMID:21593422

  20. Hydrogen-deuterium exchange mass spectrometry for investigation of backbone dynamics of oxidized and reduced cytochrome P450cam.

    Science.gov (United States)

    Hamuro, Yoshitomo; Molnar, Kathleen S; Coales, Stephen J; OuYang, Bo; Simorellis, Alana K; Pochapsky, Thomas C

    2008-02-01

    Backbone dynamics of the camphor monoxygenase cytochrome P450(cam) (CYP101) as a function of oxidation/ligation state of the heme iron were investigated via hydrogen/deuterium exchange (H/D exchange) as monitored by mass spectrometry. Main chain amide NH hydrogens can exchange readily with solvent and the rate of this exchange depends upon, among other things, dynamic fluctuations in local structural elements. A fluxional region of the polypeptide will exchange more quickly with solvent than one that is more constrained. In most regions of the enzyme, exchange rates were similar between oxidized high-spin camphor-bound and reduced camphor- and CO-bound CYP101 (CYP-S and CYP-S-CO, respectively). However, in regions of the protein that have previously been implicated in substrate access by structural and molecular dynamics investigations, the reduced enzyme shows significantly slower exchange rates than the oxidized CYP-S. This observation corresponds to increased flexibility of the oxidized enzyme relative to the reduced form. Structural features previously found to be perturbed in CYP-S-CO upon binding of the biologically relevant effector and reductant putidaredoxin (Pdx) as determined by nuclear magnetic resonance are also more protected from exchange in the reduced state. To our knowledge, this study represents the first experimental investigation of backbone dynamics within the P450 family using this methodology.

  1. A Distributed Virtual Backbone Formation for Wireless Ad Hoc and Sensor Networks

    Institute of Scientific and Technical Information of China (English)

    CAO Yong-tao; HE Chen; JIANG Ling-ge

    2007-01-01

    The virtual backbone is an approach for solving routing problems in wireless ad hoc and sensor networks. A connected dominating set (CDS) was proposed as a virtual backbone to improve the performance of wireless networks. The quality of a virtual backbone is measured not only by approximation factor, which is the ratio of its size to that of minimum CDS, but also time complexity and message complexity. In this paper, a distributed algorithm is presented to construct a minimum CDS for ad hoc and sensor networks. By destroying triangular loops in the virtual backbone, the proposed algorithm can effectively construct a CDS with smaller size. Moreover, our algorithm, which is fully localized, has a constant approximation ratio, linear message and time complexity, and low implementation complexity. The simulation results and theoretical analysis show that our algorithm has better efficiency and performance than conventional approaches.

  2. IMMUNOMODULATION OF SYNTHESIZED POLYMERS CONTAINING PHOSPHORUS IN THE BACKBONE —EFFECT ON THE PROLIFERATION OF LYMPHOCYTES

    Institute of Scientific and Technical Information of China (English)

    ZhuoRenxi; WangJun; 等

    1997-01-01

    The immunomodulation of several Charged synthetic polymers containing phosphorus in the backbone was studied in vitro through examining their inhibition or promotion effect on the proliferatioin of both T and B lymphocytes,It is found that polymers based on long chain alkyl ester of tyrosine exhibit immunomodulative activity.Negatively charged polymers show stimulative activity on LPS-induced B lymphocytes proliferation.Positively charged polymers exhibit inhibitory activity on both Con A-induced T lymphocytes and LPS-induced B lymplhyocytes proliferation.

  3. Benchmark quantum-chemical calculations on a complete set of rotameric families of the DNA sugar-phosphate backbone and their comparison with modern density functional theory.

    Science.gov (United States)

    Mládek, Arnošt; Krepl, Miroslav; Svozil, Daniel; Cech, Petr; Otyepka, Michal; Banáš, Pavel; Zgarbová, Marie; Jurečka, Petr; Sponer, Jiří

    2013-05-21

    The DNA sugar-phosphate backbone has a substantial influence on the DNA structural dynamics. Structural biology and bioinformatics studies revealed that the DNA backbone in experimental structures samples a wide range of distinct conformational substates, known as rotameric DNA backbone conformational families. Their correct description is essential for methods used to model nucleic acids and is known to be the Achilles heel of force field computations. In this study we report the benchmark database of MP2 calculations extrapolated to the complete basis set of atomic orbitals with aug-cc-pVTZ and aug-cc-pVQZ basis sets, MP2(T,Q), augmented by ΔCCSD(T)/aug-cc-pVDZ corrections. The calculations are performed in the gas phase as well as using a COSMO solvent model. This study includes a complete set of 18 established and biochemically most important families of DNA backbone conformations and several other salient conformations that we identified in experimental structures. We utilize an electronically sufficiently complete DNA sugar-phosphate-sugar (SPS) backbone model system truncated to prevent undesired intramolecular interactions. The calculations are then compared with other QM methods. The BLYP and TPSS functionals supplemented with Grimme's D3(BJ) dispersion term provide the best tradeoff between computational demands and accuracy and can be recommended for preliminary conformational searches as well as calculations on large model systems. Among the tested methods, the best agreement with the benchmark database has been obtained for the double-hybrid DSD-BLYP functional in combination with a quadruple-ζ basis set, which is, however, computationally very demanding. The new hybrid density functionals PW6B95-D3 and MPW1B95-D3 yield outstanding results and even slightly outperform the computationally more demanding PWPB95 double-hybrid functional. B3LYP-D3 is somewhat less accurate compared to the other hybrids. Extrapolated MP2(D,T) calculations are not as

  4. An Enhanced Backbone-Assisted Reliable Framework for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Amna Ali

    2010-03-01

    Full Text Available An extremely reliable source to sink communication is required for most of the contemporary WSN applications especially pertaining to military, healthcare and disaster-recovery. However, due to their intrinsic energy, bandwidth and computational constraints, Wireless Sensor Networks (WSNs encounter several challenges in reliable source to sink communication. In this paper, we present a novel reliable topology that uses reliable hotlines between sensor gateways to boost the reliability of end-to-end transmissions. This reliable and efficient routing alternative reduces the number of average hops from source to the sink. We prove, with the help of analytical evaluation, that communication using hotlines is considerably more reliable than traditional WSN routing. We use reliability theory to analyze the cost and benefit of adding gateway nodes to a backbone-assisted WSN. However, in hotline assisted routing some scenarios where source and the sink are just a couple of hops away might bring more latency, therefore, we present a Signature Based Routing (SBR scheme. SBR enables the gateways to make intelligent routing decisions, based upon the derived signature, hence providing lesser end-to-end delay between source to the sink communication. Finally, we evaluate our proposed hotline based topology with the help of a simulation tool and show that the proposed topology provides manifold increase in end-to-end reliability.

  5. A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR

    Science.gov (United States)

    Petkova, Aneta T.; Ishii, Yoshitaka; Balbach, John J.; Antzutkin, Oleg N.; Leapman, Richard D.; Delaglio, Frank; Tycko, Robert

    2002-01-01

    We present a structural model for amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1–40), based on a set of experimental constraints from solid state NMR spectroscopy. The model additionally incorporates the cross-β structural motif established by x-ray fiber diffraction and satisfies constraints on Aβ1–40 fibril dimensions and mass-per-length determined from electron microscopy. Approximately the first 10 residues of Aβ1–40 are structurally disordered in the fibrils. Residues 12–24 and 30–40 adopt β-strand conformations and form parallel β-sheets through intermolecular hydrogen bonding. Residues 25–29 contain a bend of the peptide backbone that brings the two β-sheets in contact through sidechain-sidechain interactions. A single cross-β unit is then a double-layered β-sheet structure with a hydrophobic core and one hydrophobic face. The only charged sidechains in the core are those of D23 and K28, which form salt bridges. Fibrils with minimum mass-per-length and diameter consist of two cross-β units with their hydrophobic faces juxtaposed. PMID:12481027

  6. Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope

    Energy Technology Data Exchange (ETDEWEB)

    Stanfield, Robyn L.; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S.; Zwick, Michael B.; Wilson, Ian A. (Scripps)

    2012-06-27

    Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K{sub d} of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

  7. Lagrangian based methods for coherent structure detection

    Energy Technology Data Exchange (ETDEWEB)

    Allshouse, Michael R., E-mail: mallshouse@chaos.utexas.edu [Center for Nonlinear Dynamics and Department of Physics, University of Texas at Austin, Austin, Texas 78712 (United States); Peacock, Thomas, E-mail: tomp@mit.edu [Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)

    2015-09-15

    There has been a proliferation in the development of Lagrangian analytical methods for detecting coherent structures in fluid flow transport, yielding a variety of qualitatively different approaches. We present a review of four approaches and demonstrate the utility of these methods via their application to the same sample analytic model, the canonical double-gyre flow, highlighting the pros and cons of each approach. Two of the methods, the geometric and probabilistic approaches, are well established and require velocity field data over the time interval of interest to identify particularly important material lines and surfaces, and influential regions, respectively. The other two approaches, implementing tools from cluster and braid theory, seek coherent structures based on limited trajectory data, attempting to partition the flow transport into distinct regions. All four of these approaches share the common trait that they are objective methods, meaning that their results do not depend on the frame of reference used. For each method, we also present a number of example applications ranging from blood flow and chemical reactions to ocean and atmospheric flows.

  8. Structure Based Antibody-Like Peptidomimetics

    Directory of Open Access Journals (Sweden)

    Mark I. Greene

    2012-02-01

    Full Text Available Biologics such as monoclonal antibodies (mAb and soluble receptors represent new classes of therapeutic agents for treatment of several diseases. High affinity and high specificity biologics can be utilized for variety of clinical purposes. Monoclonal antibodies have been used as diagnostic agents when coupled with radionuclide, immune modulatory agents or in the treatment of cancers. Among other limitations of using large molecules for therapy the actual cost of biologics has become an issue. There is an effort among chemists and biologists to reduce the size of biologics which includes monoclonal antibodies and receptors without a reduction of biological efficacy. Single chain antibody, camel antibodies, Fv fragments are examples of this type of deconstructive process. Small high-affinity peptides have been identified using phage screening. Our laboratory used a structure-based approach to develop small-size peptidomimetics from the three-dimensional structure of proteins with immunoglobulin folds as exemplified by CD4 and antibodies. Peptides derived either from the receptor or their cognate ligand mimics the functions of the parental macromolecule. These constrained peptides not only provide a platform for developing small molecule drugs, but also provide insight into the atomic features of protein-protein interactions. A general overview of the reduction of monoclonal antibodies to small exocyclic peptide and its prospects as a useful diagnostic and as a drug in the treatment of cancer are discussed.

  9. A Novel Method for Sampling Alpha-Helical Protein Backbones

    Science.gov (United States)

    Fain, Boris; Levitt, Michael

    2001-01-01

    We present a novel technique of sampling the configurations of helical proteins. Assuming knowledge of native secondary structure, we employ assembly rules gathered from a database of existing structures to enumerate the geometrically possible 3-D arrangements of the constituent helices. We produce a library of possible folds for 25 helical protein cores. In each case the method finds significant numbers of conformations close to the native structure. In addition we assign coordinates to all atoms for 4 of the 25 proteins. In the context of database driven exhaustive enumeration our method performs extremely well, yielding significant percentages of structures (0.02%--82%) within 6A of the native structure. The method's speed and efficiency make it a valuable contribution towards the goal of predicting protein structure.

  10. Structure-Based Algorithms for Microvessel Classification

    KAUST Repository

    Smith, Amy F.

    2015-02-01

    © 2014 The Authors. Microcirculation published by John Wiley & Sons Ltd. Objective: Recent developments in high-resolution imaging techniques have enabled digital reconstruction of three-dimensional sections of microvascular networks down to the capillary scale. To better interpret these large data sets, our goal is to distinguish branching trees of arterioles and venules from capillaries. Methods: Two novel algorithms are presented for classifying vessels in microvascular anatomical data sets without requiring flow information. The algorithms are compared with a classification based on observed flow directions (considered the gold standard), and with an existing resistance-based method that relies only on structural data. Results: The first algorithm, developed for networks with one arteriolar and one venular tree, performs well in identifying arterioles and venules and is robust to parameter changes, but incorrectly labels a significant number of capillaries as arterioles or venules. The second algorithm, developed for networks with multiple inlets and outlets, correctly identifies more arterioles and venules, but is more sensitive to parameter changes. Conclusions: The algorithms presented here can be used to classify microvessels in large microvascular data sets lacking flow information. This provides a basis for analyzing the distinct geometrical properties and modelling the functional behavior of arterioles, capillaries, and venules.

  11. Backbone, side chain and heme resonance assignments of cytochrome OmcF from Geobacter sulfurreducens.

    Science.gov (United States)

    Dantas, Joana M; Silva E Sousa, Marta; Salgueiro, Carlos A; Bruix, Marta

    2015-10-01

    Gene knockout studies on Geobacter sulfurreducens (Gs) cells showed that the outer membrane cytochrome OmcF is involved in respiratory pathways leading to the extracellular reduction of Fe(III) citrate and U(VI) oxide. In addition, microarray analysis of OmcF-deficient mutant versus the wild-type strain revealed that many of the genes with decreased transcript level were those whose expression is upregulated in cells grown with a graphite electrode as electron acceptor. This suggests that OmcF also regulates the electron transfer to electrode surfaces and the concomitant electrical current production by Gs in microbial fuel cells. Extracellular electron transfer processes (EET) constitute nowadays the foundations to develop biotechnological applications in biofuel production, bioremediation and bioenergy. Therefore, the structural characterization of OmcF is a fundamental step to understand the mechanisms underlying EET. Here, we report the complete assignment of the heme proton signals together with (1)H, (13)C and (15)N backbone and side chain assignments of the OmcF, excluding the hydrophobic residues of the N-terminal predicted lipid anchor.

  12. Navigating the massive world of reddit: using backbone networks to map user interests in social media

    Directory of Open Access Journals (Sweden)

    Randal S. Olson

    2015-05-01

    Full Text Available In the massive online worlds of social media, users frequently rely on organizing themselves around specific topics of interest to find and engage with like-minded people. However, navigating these massive worlds and finding topics of specific interest often proves difficult because the worlds are mostly organized haphazardly, leaving users to find relevant interests by word of mouth or using a basic search feature. Here, we report on a method using the backbone of a network to create a map of the primary topics of interest in any social network. To demonstrate the method, we build an interest map for the social news web site reddit and show how such a map could be used to navigate a social media world. Moreover, we analyze the network properties of the reddit social network and find that it has a scale-free, small-world, and modular community structure, much like other online social networks such as Facebook and Twitter. We suggest that the integration of interest maps into popular social media platforms will assist users in organizing themselves into more specific interest groups, which will help alleviate the overcrowding effect often observed in large online communities.

  13. Dependence of crystallite formation and preferential backbone orientations on the side chain pattern in PBDTTPD polymers

    KAUST Repository

    El Labban, Abdulrahman

    2014-11-26

    (Figure Presented) Alkyl substituents appended to the π-conjugated main chain account for the solution-processability and film-forming properties of most π-conjugated polymers for organic electronic device applications, including field-effect transistors (FETs) and bulk-heterojunction (BHJ) solar cells. Beyond film-forming properties, recent work has emphasized the determining role that side-chain substituents play on polymer self-assembly and thin-film nanostructural order, and, in turn, on device performance. However, the factors that determine polymer crystallite orientation in thin-films, implying preferential backbone orientation relative to the device substrate, are a matter of some debate, and these structural changes remain difficult to anticipate. In this report, we show how systematic changes in the side-chain pattern of poly(benzo[1,2-b:4,5-b′]dithiophene-alt-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers can (i) influence the propensity of the polymer to order in the π-stacking direction, and (ii) direct the preferential orientation of the polymer crystallites in thin films (e.g., "face-on" vs "edge-on"). Oriented crystallites, specifically crystallites that are well-ordered in the π-stacking direction, are believed to be a key contributor to improved thin-film device performance in both FETs and BHJ solar cells.

  14. Noise assisted excitation energy transfer in a linear model of a selectivity filter backbone strand.

    Science.gov (United States)

    Bassereh, Hassan; Salari, Vahid; Shahbazi, Farhad

    2015-07-15

    In this paper, we investigate the effect of noise and disorder on the efficiency of excitation energy transfer (EET) in a N = 5 sites linear chain with 'static' dipole-dipole couplings. In fact, here, the disordered chain is a toy model for one strand of the selectivity filter backbone in ion channels. It has recently been discussed that the presence of quantum coherence in the selectivity filter is possible and can play a role in mediating ion-conduction and ion-selectivity in the selectivity filter. The question is 'how a quantum coherence can be effective in such structures while the environment of the channel is dephasing (i.e. noisy)?' Basically, we expect that the presence of the noise should have a destructive effect in the quantum transport. In fact, we show that such expectation is valid for ordered chains. However, our results indicate that introducing the dephasing in the disordered chains leads to the weakening of the localization effects, arising from the multiple back-scatterings due to the randomness, and then increases the efficiency of quantum energy transfer. Thus, the presence of noise is crucial for the enhancement of EET efficiency in disordered chains. We also show that the contribution of both classical and quantum mechanical effects are required to improve the speed of energy transfer along the chain. Our analysis may help for better understanding of fast and efficient functioning of the selectivity filters in ion channels.

  15. Quantitative residue-specific protein backbone torsion angle dynamics from concerted measurement of 3J couplings.

    Science.gov (United States)

    Lee, Jung Ho; Li, Fang; Grishaev, Alexander; Bax, Ad

    2015-02-04

    Three-bond (3)J(C'C') and (3)J(HNHα) couplings in peptides and proteins are functions of the intervening backbone torsion angle ϕ. In well-ordered regions, (3)J(HNHα) is tightly correlated with (3)J(C'C'), but the presence of large ϕ angle fluctuations differentially affects the two types of couplings. Assuming the ϕ angles follow a Gaussian distribution, the width of this distribution can be extracted from (3)J(C'C') and (3)J(HNHα), as demonstrated for the folded proteins ubiquitin and GB3. In intrinsically disordered proteins, slow transverse relaxation permits measurement of (3)J(C'C') and (3)J(HNH) couplings at very high precision, and impact of factors other than the intervening torsion angle on (3)J will be minimal, making these couplings exceptionally valuable structural reporters. Analysis of α-synuclein yields rather homogeneous widths of 69 ± 6° for the ϕ angle distributions and (3)J(C'C') values that agree well with those of a recent maximum entropy analysis of chemical shifts, J couplings, and (1)H-(1)H NOEs. Data are consistent with a modest (≤30%) population of the polyproline II region.

  16. Dependence of crystallite formation and preferential backbone orientations on the side chain pattern in PBDTTPD polymers.

    Science.gov (United States)

    El Labban, Abdulrahman; Warnan, Julien; Cabanetos, Clément; Ratel, Olivier; Tassone, Christopher; Toney, Michael F; Beaujuge, Pierre M

    2014-11-26

    Alkyl substituents appended to the π-conjugated main chain account for the solution-processability and film-forming properties of most π-conjugated polymers for organic electronic device applications, including field-effect transistors (FETs) and bulk-heterojunction (BHJ) solar cells. Beyond film-forming properties, recent work has emphasized the determining role that side-chain substituents play on polymer self-assembly and thin-film nanostructural order, and, in turn, on device performance. However, the factors that determine polymer crystallite orientation in thin-films, implying preferential backbone orientation relative to the device substrate, are a matter of some debate, and these structural changes remain difficult to anticipate. In this report, we show how systematic changes in the side-chain pattern of poly(benzo[1,2-b:4,5-b']dithiophene-alt-thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers can (i) influence the propensity of the polymer to order in the π-stacking direction, and (ii) direct the preferential orientation of the polymer crystallites in thin films (e.g., "face-on" vs "edge-on"). Oriented crystallites, specifically crystallites that are well-ordered in the π-stacking direction, are believed to be a key contributor to improved thin-film device performance in both FETs and BHJ solar cells.

  17. Amino acid preference against beta sheet through allowing backbone hydration enabled by the presence of cation

    CERN Document Server

    Sharley, John N

    2016-01-01

    It is known that steric blocking by peptide sidechains of hydrogen bonding, HB, between water and peptide groups, PGs, in beta sheets accords with an amino acid intrinsic beta sheet preference. The present observations with Quantum Molecular Dynamics, QMD, simulation with quantum mechanical treatment of every water molecule solvating a beta sheet that would be transient in nature suggest that this steric blocking is not applicable in a hydrophobic region unless a cation is present, so that the amino acid beta sheet preference due to this steric blocking is only effective in the presence of a cation. We observed backbone hydration in a polyalanine and to a lesser extent polyvaline alpha helix without a cation being present, but a cation could increase the strength of these HBs. Parallel beta sheets have a greater tendency than antiparallel beta sheets of equivalent small size to retain regular structure in solvated QMD, and a 4 strand 4 inter-PG HB chain parallel beta sheet was used. Stability was reinforced b...

  18. Noise assisted excitation energy transfer in a linear model of a selectivity filter backbone strand

    Science.gov (United States)

    Bassereh, Hassan; Salari, Vahid; Shahbazi, Farhad

    2015-07-01

    In this paper, we investigate the effect of noise and disorder on the efficiency of excitation energy transfer (EET) in a N=5 sites linear chain with ‘static’ dipole-dipole couplings. In fact, here, the disordered chain is a toy model for one strand of the selectivity filter backbone in ion channels. It has recently been discussed that the presence of quantum coherence in the selectivity filter is possible and can play a role in mediating ion-conduction and ion-selectivity in the selectivity filter. The question is ‘how a quantum coherence can be effective in such structures while the environment of the channel is dephasing (i.e. noisy)?’ Basically, we expect that the presence of the noise should have a destructive effect in the quantum transport. In fact, we show that such expectation is valid for ordered chains. However, our results indicate that introducing the dephasing in the disordered chains leads to the weakening of the localization effects, arising from the multiple back-scatterings due to the randomness, and then increases the efficiency of quantum energy transfer. Thus, the presence of noise is crucial for the enhancement of EET efficiency in disordered chains. We also show that the contribution of both classical and quantum mechanical effects are required to improve the speed of energy transfer along the chain. Our analysis may help for better understanding of fast and efficient functioning of the selectivity filters in ion channels.

  19. Phylogenomics resolves a spider backbone phylogeny and rejects a prevailing paradigm for orb web evolution.

    Science.gov (United States)

    Bond, Jason E; Garrison, Nicole L; Hamilton, Chris A; Godwin, Rebecca L; Hedin, Marshal; Agnarsson, Ingi

    2014-08-04

    Spiders represent an ancient predatory lineage known for their extraordinary biomaterials, including venoms and silks. These adaptations make spiders key arthropod predators in most terrestrial ecosystems. Despite ecological, biomedical, and biomaterial importance, relationships among major spider lineages remain unresolved or poorly supported. Current working hypotheses for a spider "backbone" phylogeny are largely based on morphological evidence, as most molecular markers currently employed are generally inadequate for resolving deeper-level relationships. We present here a phylogenomic analysis of spiders including taxa representing all major spider lineages. Our robust phylogenetic hypothesis recovers some fundamental and uncontroversial spider clades, but rejects the prevailing paradigm of a monophyletic Orbiculariae, the most diverse lineage, containing orb-weaving spiders. Based on our results, the orb web either evolved much earlier than previously hypothesized and is ancestral for a majority of spiders or else it has multiple independent origins, as hypothesized by precladistic authors. Cribellate deinopoid orb weavers that use mechanically adhesive silk are more closely related to a diverse clade of mostly webless spiders than to the araneoid orb-weaving spiders that use adhesive droplet silks. The fundamental shift in our understanding of spider phylogeny proposed here has broad implications for interpreting the evolution of spiders, their remarkable biomaterials, and a key extended phenotype--the spider web.

  20. Selective Acid Hydrolysis Condition for the Composition and Linkage with a Fructofuranosyl Backbone of a Polysaccharide from Angelica sinensis (Oliv) Diels

    Institute of Scientific and Technical Information of China (English)

    Gui Yun XU; Yang CHEN; Ru Xian CHEN

    2006-01-01

    A new polysaccharide was extracted and purified from the roots of Angelica sinensis (Oliv) Diels (ASD). Its composition and linkage was elucidated by selective hydrolysis and GC/MS analysis of its derivatives. The polysaccharide was made of→1) Fruf(2→and→6) GlCp (1→as its backbone with highly branched structure. To our best knowledge, this is the first report of the fructose residue in polysaccharides from the roots of the ASD.

  1. Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

    Directory of Open Access Journals (Sweden)

    Lijian Yang

    Full Text Available Based on interactions among transcription factors, oncogenes, tumor suppressors and microRNAs, a Boolean model of cancer network regulated by miR-17-92 cluster is constructed, and the network is associated with the control of G1/S transition in the mammalian cell cycle. The robustness properties of this regulatory network are investigated by virtue of the Boolean network theory. It is found that, during G1/S transition in the cell cycle process, the regulatory networks are robustly constructed, and the robustness property is largely preserved with respect to small perturbations to the network. By using the unique process-based approach, the structure of this network is analyzed. It is shown that the network can be decomposed into a backbone motif which provides the main biological functions, and a remaining motif which makes the regulatory system more stable. The critical role of miR-17-92 in suppressing the G1/S cell cycle checkpoint and increasing the uncontrolled proliferation of the cancer cells by targeting a genetic network of interacting proteins is displayed with our model.

  2. Structure-based characterization of multiprotein complexes.

    Science.gov (United States)

    Wiederstein, Markus; Gruber, Markus; Frank, Karl; Melo, Francisco; Sippl, Manfred J

    2014-07-08

    Multiprotein complexes govern virtually all cellular processes. Their 3D structures provide important clues to their biological roles, especially through structural correlations among protein molecules and complexes. The detection of such correlations generally requires comprehensive searches in databases of known protein structures by means of appropriate structure-matching techniques. Here, we present a high-speed structure search engine capable of instantly matching large protein oligomers against the complete and up-to-date database of biologically functional assemblies of protein molecules. We use this tool to reveal unseen structural correlations on the level of protein quaternary structure and demonstrate its general usefulness for efficiently exploring complex structural relationships among known protein assemblies.

  3. Reliability Based Optimization of Structural Systems

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    1987-01-01

    The optimization problem to design structural systems such that the reliability is satisfactory during the whole lifetime of the structure is considered in this paper. Some of the quantities modelling the loads and the strength of the structure are modelled as random variables. The reliability...

  4. Earthquake Analysis of Structure by Base Isolation Technique in SAP

    OpenAIRE

    T. Subramani; J. Jothi

    2014-01-01

    This paper presents an overview of the present state of base isolation techniques with special emphasis and a brief on other techniques developed world over for mitigating earthquake forces on the structures. The dynamic analysis procedure for isolated structures is briefly explained. The provisions of FEMA 450 for base isolated structures are highlighted. The effects of base isolation on structures located on soft soils and near active faults are given in brief. Simple case s...

  5. Design, synthesis, and structure-property relationships of isoindigo-based conjugated polymers.

    Science.gov (United States)

    Lei, Ting; Wang, Jie-Yu; Pei, Jian

    2014-04-15

    Conjugated polymers have developed rapidly due to their promising applications in low-cost, lightweight, and flexible electronics. The development of the third-generation donor-acceptor (D-A) polymers greatly improved the device performance in organic solar cells (OSCs) and field-effect transistors (FETs). However, for further improvement of device performance, scientists need to develop new building blocks, in particular electron-deficient aromatics, and gain an in-depth understanding of the structure-property relationships. Recently, isoindigo has been used as a new acceptor of D-A conjugated polymers. An isomer of indigo, isoindigo is a less well-known dye and can be isolated as a by-product from certain biological processes. It has two lactam rings and exhibits strong electron-withdrawing character. This electron deficiency gives isoindigo-based polymers intriguing properties, such as broad absorption and high open circuit voltage in OSCs, as well as high mobility and good ambient stability in FETs. In this Account, we review our recent progress on the design, synthesis, and structure-property relationship study of isoindigo-based polymers for FETs. Starting with some discussion on carrier transport in polymer films, we provide some basic strategies towards high-performance polymer FETs. We discuss the stability issue of devices, the impediment of the alkyl side chains, and the choice of the donor part of conjugated polymers. We demonstrate that introducing the isoindigo core effectively lowers the HOMO levels of polymers and provides FETs with long-time stability. In addition, we have found that when we use inappropriate alkyl side chains or non-centrosymmetric donors, the device performance of isoindigo polymers suffers. To further improve device performance and ambient stability, we propose several design strategies, such as using farther branched alkyl chains, modulating polymer energy levels, and extending π-conjugated backbones. We have found that using

  6. Gender features of functional condition of backbone of teenagers with scoliotic posture

    Directory of Open Access Journals (Sweden)

    Sergiy Afanasiev

    2016-10-01

    Full Text Available Purpose: to study mobility of backbone, endurance of muscles of a trunk and to define gender features of functional condition of backbone at children of the middle school age with scoliotic posture depending on the direction of the top of arch of curvature of spine. Material & Methods: 40 girls and 40 boys, including 18 girls and 18 boys with the right-side deformation of backbone in the thoracic department, the left-side – 22 girls and 22 boys are examined. Results: features of changes of indicators, depending on sex of children and frontage of the top of arch of curvature of spine column, are revealed when studying the level of flexibility of backbone and endurance of muscles of a trunk at children of the middle school age with scoliotic posture. Conclusions: it is established that the level of decrease in flexibility of backbone is higher at boys, than at girls, whereas indicators of contractile ability and tone of muscles of "muscular corset" are higher at boys.

  7. Structure based alignment and clustering of proteins (STRALCP)

    Science.gov (United States)

    Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

    2013-06-18

    Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

  8. The Reticular Cell Network : A Robust Backbone for Immune Responses

    NARCIS (Netherlands)

    Textor, Johannes; Mandl, Judith N; de Boer, Rob J

    2016-01-01

    Lymph nodes are meeting points for circulating immune cells. A network of reticular cells that ensheathe a mesh of collagen fibers crisscrosses the tissue in each lymph node. This reticular cell network distributes key molecules and provides a structure for immune cells to move around on. During inf

  9. Protein secondary structure analysis with a coarse-grained model

    OpenAIRE

    Kneller, Gerald R.; Hinsen, Konrad

    2014-01-01

    The paper presents a geometrical model for protein secondary structure analysis which uses only the positions of the $C_{\\alpha}$-atoms. We construct a space curve connecting these positions by piecewise polynomial interpolation and describe the folding of the protein backbone by a succession of screw motions linking the Frenet frames at consecutive $C_{\\alpha}$-positions. Using the ASTRAL subset of the SCOPe data base of protein structures, we derive thresholds for the screw parameters of se...

  10. Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.

    Science.gov (United States)

    Pradhan, Mohan R; Pal, Arumay; Hu, Zhongqiao; Kannan, Srinivasaraghavan; Chee Keong, Kwoh; Lane, David P; Verma, Chandra S

    2016-02-01

    Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using "Dehydrons." "Dehydrons" are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein-protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non-conserved dehydron-residues) from other interaction interfaces (conserved dehydron-residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation.

  11. No-Enclave Percolation Corresponds to Holes in the Cluster Backbone

    Science.gov (United States)

    Hu, Hao; Ziff, Robert M.; Deng, Youjin

    2016-10-01

    The no-enclave percolation (NEP) model introduced recently by Sheinman et al. can be mapped to a problem of holes within a standard percolation backbone, and numerical measurements of such holes give the same size-distribution exponent τ =1.82 (1 ) as found for the NEP model. An argument is given that τ =1 +dB/2 ≈1.822 for backbone holes, where dB is the backbone dimension. On the other hand, a model of simple holes within a percolation cluster yields τ =1 +df/2 =187 /96 ≈1.948 , where df is the fractal dimension of the cluster, and this value is consistent with the experimental results of gel collapse of Sheinman et al., which give τ =1.91 (6 ). This suggests that the gel clusters are of the universality class of percolation cluster holes. Both models give a discontinuous maximum hole size at pc, signifying explosive percolation behavior.

  12. Constructing d-Hop 2-Connected Dominating Sets for Fault-Tolerant Backbone in Wireless Sensor Networks%无线传感器网络中d-Hop2-连通容错支配集的分布式构造算法

    Institute of Scientific and Technical Information of China (English)

    郑婵; 尹令; 孙世新

    2012-01-01

    Wireless sensor networks are self-maintaining and self-organizing structures with sensors nodes moving around. The virtual backbone base on connected dominating sets (CDS) helps to optimize multi-level hierarchical networks from flat models. However the size of CDS nodes is still large in large-scale wireless sensor networks. Thus d-hop CDS which is generalized from the concept of CDS can further reduce the virtual backbones. Otherwise virtual backbones are often very vulnerable due to frequent node failure and link broken,which are inherent in wireless networks. It is desirable that the virtual backbone is fault tolerant since the nodes in the virtual backbone need to carry other node's traffic. A distributed algorithm of d-hop 2-connected dominating set construction was proposed in unit disk graph network model in this paper. The major strategy we used was clustering partition. A d-hop dominating set was selected from each cluster firstly,and then some connector nodes were added to make final sub-solutions 2-connected.The complexity,approximation ratio and performance of the algorithm were given through theoretical analysis and simulations.%无线传感器网络随节点移动组成自我维持的自组织系统,采用连通支配集的虚拟骨干技术可使平面网络系统层次化而简化节点路由、管理和维护.但大规模无线传感器网络的连通支配集节点数目依然庞大,d-hop连通支配集可以大大减小支配集节点数目.另外,由于存在节点失效、链路断裂等无线特性,虚拟骨干网需要具备一定的容错性.在单位圆盘图网络模型中为构建精简且具有容错能力的虚拟骨干网,提出d-hop 2-连通支配集的分布式构造算法,先构造d-hop独立支配集后再连通形成d-hop 2-连通支配集.并从理论和仿真上对算法的复杂度、近似比和算法性能作了进一步探讨和验证.

  13. Protein structure mining using a structural alphabet.

    Science.gov (United States)

    Tyagi, M; de Brevern, A G; Srinivasan, N; Offmann, B

    2008-05-01

    We present a comprehensive evaluation of a new structure mining method called PB-ALIGN. It is based on the encoding of protein structure as 1D sequence of a combination of 16 short structural motifs or protein blocks (PBs). PBs are short motifs capable of representing most of the local structural features of a protein backbone. Using derived PB substitution matrix and simple dynamic programming algorithm, PB sequences are aligned the same way amino acid sequences to yield structure alignment. PBs are short motifs capable of representing most of the local structural features of a protein backbone. Alignment of these local features as sequence of symbols enables fast detection of structural similarities between two proteins. Ability of the method to characterize and align regions beyond regular secondary structures, for example, N and C caps of helix and loops connecting regular structures, puts it a step ahead of existing methods, which strongly rely on secondary structure elements. PB-ALIGN achieved efficiency of 85% in extracting true fold from a large database of 7259 SCOP domains and was successful in 82% cases to identify true super-family members. On comparison to 13 existing structure comparison/mining methods, PB-ALIGN emerged as the best on general ability test dataset and was at par with methods like YAKUSA and CE on nontrivial test dataset. Furthermore, the proposed method performed well when compared to flexible structure alignment method like FATCAT and outperforms in processing speed (less than 45 s per database scan). This work also establishes a reliable cut-off value for the demarcation of similar folds. It finally shows that global alignment scores of unrelated structures using PBs follow an extreme value distribution. PB-ALIGN is freely available on web server called Protein Block Expert (PBE) at http://bioinformatics.univ-reunion.fr/PBE/.

  14. Using Excel To Study The Relation Between Protein Dihedral Angle Omega And Backbone Length

    Science.gov (United States)

    Shew, Christopher; Evans, Samari; Tao, Xiuping

    How to involve the uninitiated undergraduate students in computational biophysics research? We made use of Microsoft Excel to carry out calculations of bond lengths, bond angles and dihedral angles of proteins. Specifically, we studied protein backbone dihedral angle omega by examining how its distribution varies with the length of the backbone length. It turns out Excel is a respectable tool for this task. An ordinary current-day desktop or laptop can handle the calculations for midsized proteins in just seconds. Care has to be taken to enter the formulas for the spreadsheet column after column to minimize the computing load. Supported in part by NSF Grant #1238795.

  15. Protein Structure-Function Correlation in Living Human Red Blood Cells Probed by Isotope Exchange-based Mass Spectrometry.

    Science.gov (United States)

    Narayanan, Sreekala; Mitra, Gopa; Muralidharan, Monita; Mathew, Boby; Mandal, Amit K

    2015-12-01

    To gain insight into the underlying mechanisms of various biological events, it is important to study the structure-function correlation of proteins within cells. Structural probes used in spectroscopic tools to investigate protein conformation are similar across all proteins. Therefore, structural studies are restricted to purified proteins in vitro and these findings are extrapolated in cells to correlate their functions in vivo. However, due to cellular complexity, in vivo and in vitro environments are radically different. Here, we show a novel way to monitor the structural transition of human hemoglobin upon oxygen binding in living red blood cells (RBCs), using hydrogen/deuterium exchange-based mass spectrometry (H/DX-MS). Exploiting permeability of D2O across cell membrane, the isotope exchange of polypeptide backbone amide hydrogens of hemoglobin was carried out inside RBCs and monitored using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). To explore the conformational transition associated with oxygenation of hemoglobin in vivo, the isotope exchange kinetics was simplified using the method of initial rates. RBC might be considered as an in vivo system of pure hemoglobin. Thus, as a proof-of-concept, the observed results were correlated with structural transition of hemoglobin associated with its function established in vitro. This is the first report on structural changes of a protein upon ligand binding in its endogenous environment. The proposed method might be applicable to proteins in their native state, irrespective of location, concentration, and size. The present in-cell approach opens a new avenue to unravel a plethora of biological processes like ligand binding, folding, and post-translational modification of proteins in living cells.

  16. Distributed Prognostics Based on Structural Model Decomposition

    Data.gov (United States)

    National Aeronautics and Space Administration — Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based...

  17. Identification and in vitro evaluation of new leads as selective and competitive glycogen synthase kinase-3β inhibitors through ligand and structure based drug design.

    Science.gov (United States)

    Darshit, B S; Balaji, B; Rani, P; Ramanathan, M

    2014-09-01

    Glycogen synthase kinase-3β elicits multi-functional effects on intracellular signaling pathways, thereby making the kinase a therapeutic target in multiple pathologies. Hence, it is important to selectively inhibit GSK-3β over structurally and biologically similar targets, such as CDK5. The current study was designed to identify and evaluate novel ATP-competitive GSK-3β inhibitors. The study was designed to identify new leads by ligand based drug design, structure based drug design and in vitro evaluation. The best validated pharmacophore model (AADRRR) identified using LBDD was derived from a dataset of 135 molecules. There were 357 primary hits within the SPECS database using this pharmacophore model. A SBDD approach to the GSK-3β and CDK5 proteins was applied to all primary hits, and 5 selective inhibitors were identified for GSK-3β. GSK-3β and CDK5 in vitro kinase inhibition assays were performed with these molecules to confirm their selectivity for GSK-3β. The molecules showed IC50 values ranging from 0.825μM to 1.116μM and were 23- to 57-fold selective for GSK-3β. Of all the molecules, molecule 3 had the lowest IC50 value of 0.825μM. Our research identified molecules possessing benzothiophene, isoquinoline, thiazolidinedione imidazo-isoquinoline and quinazolinone scaffolds. Potency of these molecules may be due to H-bond interaction with backbone residues of Val135, Asp133 and side chain interaction with Tyr134. Selectivity over CDK5 may be due to side chain interactions with Asp200, backbone of Val61, ionic interaction with Lys60 and π-cationic interaction with Arg141. These selective molecules were also exhibited small atom hydrophobicity and H-bond interaction with water molecule.

  18. Spectral backbone of excitation transport in ultracold Rydberg gases

    Science.gov (United States)

    Scholak, Torsten; Wellens, Thomas; Buchleitner, Andreas

    2014-12-01

    The spectral structure underlying excitonic energy transfer in ultracold Rydberg gases is studied numerically, in the framework of random matrix theory, and via self-consistent diagrammatic techniques. Rydberg gases are made up of randomly distributed, highly polarizable atoms that interact via strong dipolar forces. Dynamics in such a system is fundamentally different from cases in which the interactions are of short range, and is ultimately determined by the spectral and eigenvector structure. In the energy levels' spacing statistics, we find evidence for a critical energy that separates delocalized eigenstates from states that are localized at pairs or clusters of atoms separated by less than the typical nearest-neighbor distance. We argue that the dipole blockade effect in Rydberg gases can be leveraged to manipulate this transition across a wide range: As the blockade radius increases, the relative weight of localized states is reduced. At the same time, the spectral statistics, in particular, the density of states and the nearest-neighbor level-spacing statistics, exhibits a transition from approximately a 1-stable Lévy to a Gaussian orthogonal ensemble. Deviations from random matrix statistics are shown to stem from correlations between interatomic interaction strengths that lead to an asymmetry of the spectral density and profoundly affect localization properties. We discuss approximations to the self-consistent Matsubara-Toyozawa locator expansion that incorporate these effects.

  19. Backbone NxH compounds at high pressures.

    Science.gov (United States)

    Goncharov, Alexander F; Holtgrewe, Nicholas; Qian, Guangrui; Hu, Chaohao; Oganov, Artem R; Somayazulu, Maddury; Stavrou, Elissaios; Pickard, Chris J; Berlie, Adam; Yen, Fei; Mahmood, Mahmood; Lobanov, Sergey S; Konôpková, Zuzana; Prakapenka, Vitali B

    2015-06-01

    Optical and synchrotron x-ray diffraction diamond anvil cell experiments have been combined with first-principles theoretical structure predictions to investigate mixtures of N2 and H2 up to 55 GPa. Our experiments show the formation of structurally complex van der Waals compounds [see also D. K. Spaulding et al., Nat. Commun. 5, 5739 (2014)] above 10 GPa. However, we found that these NxH (0.5 < x < 1.5) compounds transform abruptly to new oligomeric materials through barochemistry above 47 GPa and photochemistry at pressures as low as 10 GPa. These oligomeric compounds can be recovered to ambient pressure at T < 130 K, whereas at room temperature, they can be metastable on pressure release down to 3.5 GPa. Extensive theoretical calculations show that such oligomeric materials become thermodynamically more stable in comparison to mixtures of N2, H2, and NH3 above approximately 40 GPa. Our results suggest new pathways for synthesis of environmentally benign high energy-density materials. These materials could also exist as alternative planetary ices.

  20. Backbone NxH compounds at high pressures

    Science.gov (United States)

    Goncharov, Alexander F.; Holtgrewe, Nicholas; Qian, Guangrui; Hu, Chaohao; Oganov, Artem R.; Somayazulu, Maddury; Stavrou, Elissaios; Pickard, Chris J.; Berlie, Adam; Yen, Fei; Mahmood, Mahmood; Lobanov, Sergey S.; Konôpková, Zuzana; Prakapenka, Vitali B.

    2015-06-01

    Optical and synchrotron x-ray diffraction diamond anvil cell experiments have been combined with first-principles theoretical structure predictions to investigate mixtures of N2 and H2 up to 55 GPa. Our experiments show the formation of structurally complex van der Waals compounds [see also D. K. Spaulding et al., Nat. Commun. 5, 5739 (2014)] above 10 GPa. However, we found that these NxH (0.5 < x < 1.5) compounds transform abruptly to new oligomeric materials through barochemistry above 47 GPa and photochemistry at pressures as low as 10 GPa. These oligomeric compounds can be recovered to ambient pressure at T < 130 K, whereas at room temperature, they can be metastable on pressure release down to 3.5 GPa. Extensive theoretical calculations show that such oligomeric materials become thermodynamically more stable in comparison to mixtures of N2, H2, and NH3 above approximately 40 GPa. Our results suggest new pathways for synthesis of environmentally benign high energy-density materials. These materials could also exist as alternative planetary ices.

  1. Combinatorics of RNA Secondary Structures with Base Triples.

    Science.gov (United States)

    Müller, Robert; Nebel, Markus E

    2015-07-01

    The structure of RNA has been the subject of intense research over the last decades due to its importance for the correct functioning of RNA molecules in biological processes. Hence, a large number of models for RNA folding and corresponding algorithms for structure prediction have been developed. However, previous models often only consider base pairs, although every base is capable of up to three edge-to-edge interactions with other bases. Recently, Höner zu Siederdissen et al. presented an extended model of RNA secondary structure, including base triples together with a folding algorithm-the first thermodynamics-based algorithm that allows the prediction of secondary structures with base triples. In this article, we investigate the search space processed by this new algorithm, that is, the combinatorics of extended RNA secondary structures with base triples. We present generalized definitions for structural motifs like hairpins, stems, bulges, or interior loops occurring in structures with base triples. Furthermore, we prove precise asymptotic results for the number of different structures (size of search space) and expectations for various parameters associated with structural motifs (typical shape of folding). Our analysis shows that the asymptotic number of secondary structures of size n increases exponentially to [Formula: see text] compared to the classic model by Stein and Waterman for which [Formula: see text] structures exist. A comparison with the classic model reveals large deviations in the expected structural appearance, too. The inclusion of base triples constitutes a significant refinement of the combinatorial model of RNA secondary structure, which, by our findings, is quantitatively characterized. Our results are of special theoretical interest, because a closer look at the numbers involved suggests that extended RNA secondary structures constitute a new combinatorial class not bijective with any other combinatorial objects studied so far.

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

    Directory of Open Access Journals (Sweden)

    Tsinoremas NF

    2007-05-01

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

  3. Purification, crystallization and preliminary crystallographic analysis of the SpaA backbone-pilin subunit from probiotic Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Singh, Deepak; von Ossowski, Ingemar; Palva, Airi; Krishnan, Vengadesan

    2013-10-01

    Lactobacillus rhamnosus GG, a widely used Gram-positive probiotic strain, is clinically well known for its perceived health-promoting effects. It has recently been shown to display proteinaceous pilus fibres (called SpaCBA) on its cell surface. Structurally, SpaCBA pili possess a characteristic three-pilin polymerized architecture, with repeating SpaA major pilins that form the backbone and two types of minor subunits (SpaB and SpaC). In this study, recombinant SpaA protein was purified, characterized and crystallized. The crystals diffracted to a resolution of 2.0 Å and belonged to space group C2, with unit-cell parameters a=227.9, b=63.2, c=104.3 Å, β=95.1°.

  4. Comparison of solid-state dipolar couplings and solution relaxation data provides insight into protein backbone dynamics.

    Science.gov (United States)

    Chevelkov, Veniamin; Xue, Yi; Linser, Rasmus; Skrynnikov, Nikolai R; Reif, Bernd

    2010-04-14

    Analyses of solution (15)N relaxation data and solid-state (1)H(N)-(15)N dipolar couplings from a small globular protein, alpha-spectrin SH3 domain, produce a surprisingly similar pattern of order parameters. This result suggests that there is little or no ns-mus dynamics throughout most of the sequence and, in particular, in the structured portion of the backbone. At the same time, evidence of ns-mus motions is found in the flexible loops and termini. These findings, corroborated by the MD simulations of alpha-spectrin SH3 in a hydrated crystalline environment and in solution, are consistent with the picture of protein dynamics that has recently emerged from the solution studies employing residual dipolar couplings.

  5. BEAMS: backbone extraction and merge strategy for the global many-to-many alignment of multiple PPI networks

    DEFF Research Database (Denmark)

    Alkan, Ferhat; Erten, Cesim

    2014-01-01

    MOTIVATION: Global many-to-many alignment of biological networks has been a central problem in comparative biological network studies. Given a set of biological interaction networks, the informal goal is to group together related nodes. For the case of protein-protein interaction networks...... are conserved across the input networks. We provide a formal definition of the global many-to-many alignment of multiple protein-protein interaction networks that captures this informal objective. We show the computational intractability of the suggested definition. We provide a heuristic method based...... on backbone extraction and merge strategy (BEAMS) for the problem. We finally show, through experiments based on biological significance tests, that the proposed BEAMS algorithm performs better than the state-of-the-art approaches. Furthermore, the computational burden of the BEAMS algorithm in terms...

  6. Building the backbone: the development and evolution of vertebral patterning.

    Science.gov (United States)

    Fleming, Angeleen; Kishida, Marcia G; Kimmel, Charles B; Keynes, Roger J

    2015-05-15

    The segmented vertebral column comprises a repeat series of vertebrae, each consisting of two key components: the vertebral body (or centrum) and the vertebral arches. Despite being a defining feature of the vertebrates, much remains to be understood about vertebral development and evolution. Particular controversy surrounds whether vertebral component structures are homologous across vertebrates, how somite and vertebral patterning are connected, and the developmental origin of vertebral bone-mineralizing cells. Here, we assemble evidence from ichthyologists, palaeontologists and developmental biologists to consider these issues. Vertebral arch elements were present in early stem vertebrates, whereas centra arose later. We argue that centra are homologous among jawed vertebrates, and review evidence in teleosts that the notochord plays an instructive role in segmental patterning, alongside the somites, and contributes to mineralization. By clarifying the evolutionary relationship between centra and arches, and their varying modes of skeletal mineralization, we can better appreciate the detailed mechanisms that regulate and diversify vertebral patterning.

  7. Synthesis and properties of polybenzazoles containing flexible methylene in backbone

    Institute of Scientific and Technical Information of China (English)

    Xiaohui XU; Xiaoyun LIU; Chengjun ZHOU; Qixin ZHUANG; Zhewen HAN

    2008-01-01

    A novel series of polybenzazoles with rigid-rod benzoxazole cycle and soft methylene segment was designed and synthesized via solution condensation poly-merizations from 4,6-diamino-l,3-benzenediol dipho-sphate, terephthalic acid and aliphatic dicarboxylic acid. The structures of polybenzazoles were characterized by means of FT-IR,1H NMR and Wide-angle X-ray diffrac-tion (WAXRD). All the polymers show excellent thermal stability and the TdS was above 471℃, The intrinsic vis-cosities [η] of the polymers ranged from 0.8 to 0.9. The UV-Vis absorption peaks of the polymers in MSA were blue-shifted from 429 nm for PBO to 291 nm for PBOC7, and the Stokes shifts in PL spectra enlarged.

  8. Characterizing structural transitions using localized free energy landscape analysis.

    Directory of Open Access Journals (Sweden)

    Nilesh K Banavali

    Full Text Available BACKGROUND: Structural changes in molecules are frequently observed during biological processes like replication, transcription and translation. These structural changes can usually be traced to specific distortions in the backbones of the macromolecules involved. Quantitative energetic characterization of such distortions can greatly advance the atomic-level understanding of the dynamic character of these biological processes. METHODOLOGY/PRINCIPAL FINDINGS: Molecular dynamics simulations combined with a variation of the Weighted Histogram Analysis Method for potential of mean force determination are applied to characterize localized structural changes for the test case of cytosine (underlined base flipping in a GTCAGCGCATGG DNA duplex. Free energy landscapes for backbone torsion and sugar pucker degrees of freedom in the DNA are used to understand their behavior in response to the base flipping perturbation. By simplifying the base flipping structural change into a two-state model, a free energy difference of upto 14 kcal/mol can be attributed to the flipped state relative to the stacked Watson-Crick base paired state. This two-state classification allows precise evaluation of the effect of base flipping on local backbone degrees of freedom. CONCLUSIONS/SIGNIFICANCE: The calculated free energy landscapes of individual backbone and sugar degrees of freedom expectedly show the greatest change in the vicinity of the flipping base itself, but specific delocalized effects can be discerned upto four nucleotide positions away in both 5' and 3' directions. Free energy landscape analysis thus provides a quantitative method to pinpoint the determinants of structural change on the atomic scale and also delineate the extent of propagation of the perturbation along the molecule. In addition to nucleic acids, this methodology is anticipated to be useful for studying conformational changes in all macromolecules, including carbohydrates, lipids, and proteins.

  9. Spatial interpolation approach based on IDW with anisotropic spatial structures

    Science.gov (United States)

    Li, Jia; Duan, Ping; Sheng, Yehua; Lv, Haiyang

    2015-12-01

    In many interpolation methods, with its simple interpolation principle, Inverse distance weighted (IDW) interpolation is one of the most common interpolation method. There are anisotropic spatial structures with actual geographical spatial phenomenon. When the IDW interpolation is used, anisotropic spatial structures should be considered. Geostatistical theory has a characteristics of exploring anisotropic spatial structures. In this paper, spatial interpolation approach based on IDW with anisotropic spatial structures is proposed. The DEM data is tested in this paper to prove reliability of the IDW interpolation considering anisotropic spatial structures. Experimental results show that IDW interpolation considering anisotropic spatial structures can improve interpolation precision when sampling data has anisotropic spatial structures feature.

  10. Structural Health Monitoring Using Neural Network Based Vibrational System Identification

    CERN Document Server

    Sofge, Donald A

    2007-01-01

    Composite fabrication technologies now provide the means for producing high-strength, low-weight panels, plates, spars and other structural components which use embedded fiber optic sensors and piezoelectric transducers. These materials, often referred to as smart structures, make it possible to sense internal characteristics, such as delaminations or structural degradation. In this effort we use neural network based techniques for modeling and analyzing dynamic structural information for recognizing structural defects. This yields an adaptable system which gives a measure of structural integrity for composite structures.

  11. Use of Just in Time Maintenance of Reinforced Concrete Bridge Structures based on Real Historical Data Deterioration Models

    Directory of Open Access Journals (Sweden)

    Abu-Tair A.

    2016-01-01

    Full Text Available Concrete is the backbone of any developed economy. Concrete can suffer from a large number of deleterious effects including physical, chemical and biological causes. Large owning bridge structures organizations are facing very serious questions when asking for maintenance budgets. The questions range from needing to justify the need for the work, its urgency, to also have to predict or show the consequences of delayed rehabilitation of a particular structure. There is therefore a need for a probabilistic model that can estimate the range of service lives of bridge populations and also the likelihood of level of deteriorations it can reached for every incremental time interval. A model was developed for such estimation based on statistical data from actual inspection records of a large reinforced concrete bridge portfolio. The method used both deterministic and stochastic methods to predict the service life of a bridge, using these service lives in combination with the just in time (JIT principle of management would enable maintenance managers to justify the need for action and the budgets needed, to intervene at the optimum time in the life of the structure and that of the deterioration. The paper will report on the model which is based on a large database of deterioration records of concrete bridges covering a period of over 60 years and include data from over 400 bridge structures. The paper will also illustrate how the service life model was developed and how these service lives combined with the JIT can be used to effectively allocate resources and use them to keep a major infrastructure asset moving with little disruption to the transport system and its users.

  12. Improving the prediction accuracy of residue solvent accessibility and real-value backbone torsion angles of proteins by guided-learning through a two-layer neural network.

    Science.gov (United States)

    Faraggi, Eshel; Xue, Bin; Zhou, Yaoqi

    2009-03-01

    This article attempts to increase the prediction accuracy of residue solvent accessibility and real-value backbone torsion angles of proteins through improved learning. Most methods developed for improving the backpropagation algorithm of artificial neural networks are limited to small neural networks. Here, we introduce a guided-learning method suitable for networks of any size. The method employs a part of the weights for guiding and the other part for training and optimization. We demonstrate this technique by predicting residue solvent accessibility and real-value backbone torsion angles of proteins. In this application, the guiding factor is designed to satisfy the intuitive condition that for most residues, the contribution of a residue to the structural properties of another residue is smaller for greater separation in the protein-sequence distance between the two residues. We show that the guided-learning method makes a 2-4% reduction in 10-fold cross-validated mean absolute errors (MAE) for predicting residue solvent accessibility and backbone torsion angles, regardless of the size of database, the number of hidden layers and the size of input windows. This together with introduction of two-layer neural network with a bipolar activation function leads to a new method that has a MAE of 0.11 for residue solvent accessibility, 36 degrees for psi, and 22 degrees for phi. The method is available as a Real-SPINE 3.0 server in http://sparks.informatics.iupui.edu.

  13. A maximum entropy approach to the study of residue-specific backbone angle distributions in α-synuclein, an intrinsically disordered protein

    Science.gov (United States)

    Mantsyzov, Alexey B; Maltsev, Alexander S; Ying, Jinfa; Shen, Yang; Hummer, Gerhard; Bax, Ad

    2014-01-01

    α-Synuclein is an intrinsically disordered protein of 140 residues that switches to an α-helical conformation upon binding phospholipid membranes. We characterize its residue-specific backbone structure in free solution with a novel maximum entropy procedure that integrates an extensive set of NMR data. These data include intraresidue and sequential HN–Hα and HN–HN NOEs, values for 3JHNHα, 1JHαCα, 2JCαN, and 1JCαN, as well as chemical shifts of 15N, 13Cα, and 13C′ nuclei, which are sensitive to backbone torsion angles. Distributions of these torsion angles were identified that yield best agreement to the experimental data, while using an entropy term to minimize the deviation from statistical distributions seen in a large protein coil library. Results indicate that although at the individual residue level considerable deviations from the coil library distribution are seen, on average the fitted distributions agree fairly well with this library, yielding a moderate population (20–30%) of the PPII region and a somewhat higher population of the potentially aggregation-prone β region (20–40%) than seen in the database. A generally lower population of the αR region (10–20%) is found. Analysis of 1H–1H NOE data required consideration of the considerable backbone diffusion anisotropy of a disordered protein. PMID:24976112

  14. A maximum entropy approach to the study of residue-specific backbone angle distributions in α-synuclein, an intrinsically disordered protein.

    Science.gov (United States)

    Mantsyzov, Alexey B; Maltsev, Alexander S; Ying, Jinfa; Shen, Yang; Hummer, Gerhard; Bax, Ad

    2014-09-01

    α-Synuclein is an intrinsically disordered protein of 140 residues that switches to an α-helical conformation upon binding phospholipid membranes. We characterize its residue-specific backbone structure in free solution with a novel maximum entropy procedure that integrates an extensive set of NMR data. These data include intraresidue and sequential H(N) − H(α) and H(N) − H(N) NOEs, values for (3) JHNHα, (1) JHαCα, (2) JCαN, and (1) JCαN, as well as chemical shifts of (15)N, (13)C(α), and (13)C' nuclei, which are sensitive to backbone torsion angles. Distributions of these torsion angles were identified that yield best agreement to the experimental data, while using an entropy term to minimize the deviation from statistical distributions seen in a large protein coil library. Results indicate that although at the individual residue level considerable deviations from the coil library distribution are seen, on average the fitted distributions agree fairly well with this library, yielding a moderate population (20-30%) of the PPII region and a somewhat higher population of the potentially aggregation-prone β region (20-40%) than seen in the database. A generally lower population of the αR region (10-20%) is found. Analysis of (1)H − (1)H NOE data required consideration of the considerable backbone diffusion anisotropy of a disordered protein.

  15. Risk Based Inspection Planning of Ageing Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Ersdal, Gerhard

    2008-01-01

    collapse of the structure. The importance of each component can be measured by the RIF (Residual Influence Factor) for each component and is illustrated by examples. When an installation becomes older then the number of fatigue critical components can be expected to increase. If the maximum acceptable....... Different approaches for updating inspection plans for older installations are considered in order to achieve decreased inspection intervals as the structure are ageing. The most promising method consists in increasing the rate of defects / crack initiation at the end of the expected lifetime. Different...

  16. Reliability-Based Design of Coastal Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.

    1997-01-01

    The objective of this paper is to introduce the application of reliability theory for conceptual design and evaluation of coastal structures. It is without the scope to discuss the validity and quality of the various design formulae available for coastal structures. The contents of the paper...... Engineering. Burcharth, H.F. (1993) Design of Breakwaters. Aalborg University. Department of Civil Engineering. Aalborg, Denmark. (Note). Burcbarth, H.F., Dalsgaard S9lrensen, J ., Cbristiani, E. (1995} Application for reliability analysis for optimal design of monolithic vertical wall breakwaters....... Proceedings Conference of Port and Coastal Engineering in developing countries. Rio de Janeiro, Brazil, 1995....

  17. Modal Based Fatigue Monitoring of Steel Structures

    DEFF Research Database (Denmark)

    Graugaard-Jensen, J.; Brincker, Rune; Hjelm, H. P.;

    2005-01-01

    compared with direct strain gauge measurements and it appears that the difference between the strains measured by strain gauges and the strains estimated by the presented technique is quite small. Looking at the fatigue of the lattice pylon it appears that the estimated damage is significantly smaller than...... by applying the mode shapes of the calibrated Finite Element model and strains are obtained using the shape functions for the actual elements. The technique has been applied on a model frame structure in the laboratory and on a wind loaded lattice pylon structure. In both cases the estimated stresses has been...

  18. Mnn10 Maintains Pathogenicity in Candida albicans by Extending α-1,6-Mannose Backbone to Evade Host Dectin-1 Mediated Antifungal Immunity.

    Directory of Open Access Journals (Sweden)

    Shi Qun Zhang

    2016-05-01

    Full Text Available The cell wall is a dynamic structure that is important for the pathogenicity of Candida albicans. Mannan, which is located in the outermost layer of the cell wall, has been shown to contribute to the pathogenesis of C. albicans, however, the molecular mechanism by which this occurs remains unclear. Here we identified a novel α-1,6-mannosyltransferase encoded by MNN10 in C. albicans. We found that Mnn10 is required for cell wall α-1,6-mannose backbone biosynthesis and polysaccharides organization. Deletion of MNN10 resulted in significant attenuation of the pathogenesis of C. albicans in a murine systemic candidiasis model. Inhibition of α-1,6-mannose backbone extension did not, however, impact the invasive ability of C. albicans in vitro. Notably, mnn10 mutant restored the invasive capacity in athymic nude mice, which further supports the notion of an enhanced host antifungal defense related to this backbone change. Mnn10 mutant induced enhanced Th1 and Th17 cell mediated antifungal immunity, and resulted in enhanced recruitment of neutrophils and monocytes for pathogen clearance in vivo. We also demonstrated that MNN10 could unmask the surface β-(1,3-glucan, a crucial pathogen-associated molecular pattern (PAMP of C. albicans recognized by host Dectin-1. Our results demonstrate that mnn10 mutant could stimulate an enhanced Dectin-1 dependent immune response of macrophages in vitro, including the activation of nuclear factor-κB, mitogen-activated protein kinase pathways, and secretion of specific cytokines such as TNF-α, IL-6, IL-1β and IL-12p40. In summary, our study indicated that α-1,6-mannose backbone is critical for the pathogenesis of C. albicans via shielding β-glucan from recognition by host Dectin-1 mediated immune recognition. Moreover, our work suggests that inhibition of α-1,6-mannose extension by Mnn10 may represent a novel modality to reduce the pathogenicity of C. albicans.

  19. Risk based design of civil structures

    NARCIS (Netherlands)

    Van Gelder, P.; Roos, A.; Vrijling, H.

    2001-01-01

    The Art and Science of Model Building: A Bayesian Approach, by Prof. A. Der Kiureghian; The talk will describe a Bayesian approach to developing models, with special emphasis on limit-state models for reinforced concrete structures. The formulation can incorporate all kinds of information (theoretic

  20. Reliability based Design of Coastal Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.

    2003-01-01

    , for example the expectation (mean) value of the 100-year return period event. However, this selection is often made without consideration of the involved uncertainties. In most cases the resistance is defined in terms of the load that causes a certain design impact or damage to the structure...

  1. Analysis of components of conserved "backbone sequences" among genomes of Shigella spp. strains

    Institute of Scientific and Technical Information of China (English)

    LIU Hong; PENG Junping; YANG Jian; SUN Lilian; CHEN Shuxia; Jin Qi

    2004-01-01

    Difference in the genomic compositions of prokaryotes is the basis of the diversity in their biological characters. However, besides their flora- or strain-specific genes, those floras with closer relationship in the evolution also have conserved "backbone sequences", which reveal the marks of their origin and evolution, and these "backbone sequences" are just the basis of their elementary living abilities and common biological properties. Shigella is very closely related to E. coli in the origin and evolution, and may turn out to belong to the same genus. In this study, a microarray containing E. coli K-12 whole genome and Sf301 specific ORFs is used to investigate the genomic components of four Shigella strains. The results indicate that 16%-22% K-12 ORFs sequences are not detected in the genome of Shigella strains while the genome of Shigella contains at least 2800 conserved ORFs, which compose the common "backbone sequences". Advanced analysis indicated that the "backbone sequences" are the essential components in maintaining the normal physiological activities of intestinal bacteria. Furthermore, only 20% Sf301-specific ORFs exist in other strains simultaneously, which demonstrate the great genome heterogeneity and the genetic diversity among the strains.

  2. Integrative technology of massage manipulations in physical rehabilitation of students with backbone pathology

    Directory of Open Access Journals (Sweden)

    Kotelevskiy V.I.

    2016-06-01

    Full Text Available Purpose: to analyze effectiveness of massage manipulations’ integrative technology in physical rehabilitation of higher educational establishments’ students with backbone pathology. Material: in the research 195 students of 19-20 years’ age participated. All students had periodical initial neurological symptoms of functional pathology and first stage osteochondrosis in different parts of backbone. We conducted a course of 10 sessions of therapeutic massage. Results: the sense of massage integrative technology is that every specialist shall have certain optimal set of skills and knowledge in technique of manipulation sessions of massage. Integrative technology of massage manipulations consists of psycho-corrective and manipulation parts. It considers psycho-somatic, mechanical and reflex rehabilitation aspects of patho-genesis of backbone functional disorders and vertebral osteochondrosis. Conclusions: depending on pathological process or backbone functional state of every person (peculiarities of his (her psycho-somatic status or, even, his (her bents. Individual approach in choice of strategy, tactic and methodological provisioning of massage session shall be used.

  3. Sequential insertion of three different organometallics into a versatile building block containing a PNA backbone.

    Science.gov (United States)

    Patra, Malay; Gasser, Gilles; Bobukhov, Dmytro; Merz, Klaus; Shtemenko, Alexander V; Metzler-Nolte, Nils

    2010-06-28

    In the view of developing a synthetic route for the controlled insertion of distinct organometallic moieties into peptide nucleic acid (PNA) oligomers, a proof-of-principle study of the chemoselective insertion of three different organometallics into a building block containing both a PNA backbone and an alkyne side-chain is presented in this study.

  4. Treatment Results of Injuries of Thoracic and Lumbar Backbone Departments at Osteoporosis Patients

    Directory of Open Access Journals (Sweden)

    D.Y. Sumin

    2009-06-01

    Full Text Available Information relates to radiologic (computer tomography manifestations providing the visualization of thoracic and lumbar backbone department injuries at osteoporotic patients. Contemporary methods of transcutaneous and trans-pedicle vertebroplasty with bone cement allows to obtain a stable positive healing effect against such pathologies.

  5. Synthesis of a Backbone Hexasaccharide Fragment of the Pectic Polysaccharide Rhamnogalacturonan I

    DEFF Research Database (Denmark)

    Zakharova, Alexandra N.; Madsen, Robert; Clausen, Mads H.

    2013-01-01

    Synthesis of the fully unprotected hexasaccharide backbone of the pectic polysaccharide rhamnogalacturonan I is described. The strategy relies on iterative coupling of a common pentenyl disaccharide glycosyl donor followed by a late-stage oxidation of the C-6 positions of the galactose residues. ...

  6. Interconnection and Competition Among Asymmetric Networks in the Internet Backbone Market

    NARCIS (Netherlands)

    Jahn, E.; Prüfer, J.

    2006-01-01

    We examine the interrelation between interconnection and competition in the internet backbone market.Networks asymmetric in size choose among different interconnection regimes and compete for end-users.We show that a direct interconnection regime, Peering, softens competition compared to indirect in

  7. Graduate Education in Kinesiology: Are We Part of "America's Backbone for Competitiveness and Innovation"?

    Science.gov (United States)

    DePauw, Karen P.

    2008-01-01

    Graduate education in the United States has been identified as being the backbone of American competitiveness and innovation in a recent report by the Council of Graduate Schools. The report provides a framework for examining the role of graduate education in partnership with business and government to advance an action agenda for achieving…

  8. CSTutor: A Sketch-Based Tool for Visualizing Data Structures

    Science.gov (United States)

    Buchanan, Sarah; Laviola, Joseph J., Jr.

    2014-01-01

    We present CSTutor, a sketch-based interface designed to help students understand data structures, specifically Linked Lists, Binary Search Trees, AVL Trees, and Heaps. CSTutor creates an environment that seamlessly combines a user's sketched diagram and code. In each of these data structure modes, the user can naturally sketch a data structure on…

  9. Elpipes for the High Capacity Backbone of an Asian Grid

    Institute of Scientific and Technical Information of China (English)

    Roger Faulkner

    2011-01-01

    Elpipes are polymer-insulated underground HVDC electric pipelines based on metallic conductors. Etpipes use relatively rigid extruded conductors designed for higher capacity and efficiency that are practical for overhead pow- er lines. Rigid insulation may be used. In this paper, we discuss the technical trade-offs for etpipes, and application of elpipes linking load centers to remote dispatchable hydro power, energy storage sites, and large dispatchable loads, to achieve load leveling through nonqocal storage and dispatchable loads, via the HVDC grid. Elpipes with voltage source converters (VSC) enable placing many AC/DC power taps on a single HVDC loop. It is advantageous to build up a continental scale HVDC grid from local loops that tie together 10-20 taps.

  10. Topology Optimization in Damping Structure Based on ESO

    Institute of Scientific and Technical Information of China (English)

    GUO Zhong-ze; CHEN Yu-ze; HOU Qiang

    2008-01-01

    The damping material optimal placement for the structure with damping layer is studied based on evolutionary structural optimization (ESO) to maximize modal loss factors. A mathematical model is constructed with the objective function defined as the maximum of modal loss factors of the structure and design constraints function defined as volume fraction ofdamping material. The optimal placement is found. Several examples are presented for verification. The results demonstratethat the method based on ESO is effective in solving the topology optimization of the structure with uncon-strained damping layer and constrained damping layer. This optimization method suits for free and constrained damping structures.

  11. Identification of protein superfamily from structure- based sequence motif

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The structure-based sequence motif of the distant proteins in evolution, protein tyrosine phosphatases (PTP) Ⅰ and Ⅱ superfamilies, as an example, has been defined by the structural comparison, structure-based sequence alignment and analyses on substitution patterns of residues in common sequence conserved regions. And the phosphatases Ⅰ and Ⅱ can be correctly identified together by the structure-based PTP sequence motif from SWISS-PROT and TrEBML databases. The results show that the correct rates of identification are over 98%. This is the first time to identify PTP Ⅰ and Ⅱ together by this motif.

  12. [Structuralization of digestive endoscopy report based on NLP].

    Science.gov (United States)

    Kong, Xiao-feng; Li, Ying; Li, Hao-min; Lu, Xu-dong

    2008-09-01

    This paper presents a method based on NLP to realize structuralization of digestive endoscopy reports. The method is taking advantage of existing NLP's processing technologies and introducing minimal standard terminology (MST) to transform a narrative gastroscopy report into the structuralization report based on MST, whose accuracy rate is 92.3%.

  13. Benefits of Risk Based Inspection Planning for Offshore Structures

    DEFF Research Database (Denmark)

    Straub, D.M.; Goyet, J.; Sørensen, John Dalsgaard

    2006-01-01

    The economical benefits of applying risk-based inspection planning (RBI) for offshore structures subject to fatigue are evaluated based on experiences from past industrial projects. To this end, the factors influencing the cost of inspection, repair and failure of structures are discussed......, the financial benefit of RBI is assessed....

  14. Dynamics-based Nondestructive Structural Monitoring Techniques

    Science.gov (United States)

    2012-06-21

    in the practice of non- destructive evaluation ( NDE ) and structural health monitoring (SHM). Guided wave techniques have several advantages over...conventional bulk wave ultrasonic NDE /SHM techniques. Some of these advantages are outlined in Table I. However, in addition to the advantages of...PVDF transducers for SHM applications with controlled guided wave modes and frequencies [7]. Wilcox used EMATs with circular coils in a guided wave

  15. Dynamics-based Nondestructive Structural Monitoring Teclrniques

    Science.gov (United States)

    2012-05-21

    destructive evaluation ( NDE ) and structural health monitoring (SHM). Guided wave techniques have several advantages over conventional bulk wave...ultrasonic NDE /SHM techniques. Some of these advantages are outlined in Table I. However, in addition to the advantages of guided waves comes an...PVDF transducers for SHM applications with controlled guided wave modes and frequencies [7]. Wilcox used EMATs with circular coils in a guided wave

  16. Modeling proteins using a super-secondary structure library and NMR chemical shift information.

    Science.gov (United States)

    Menon, Vilas; Vallat, Brinda K; Dybas, Joseph M; Fiser, Andras

    2013-06-04

    A remaining challenge in protein modeling is to predict structures for sequences with no sequence similarity to any experimentally solved structure. Based on earlier observations, the library of protein backbone supersecondary structure motifs (Smotifs) saturated about a decade ago. Therefore, it should be possible to build any structure from a combination of existing Smotifs with the help of limited experimental data that are sufficient to relate the backbone conformations of Smotifs between target proteins and known structures. Here, we present a hybrid modeling algorithm that relies on an exhaustive Smotif library and on nuclear magnetic resonance chemical shift patterns without any input of primary sequence information. In a test of 102 proteins, the algorithm delivered 90 homology-model-quality models, among them 24 high-quality ones, and a topologically correct solution for almost all cases. The current approach opens a venue to address the modeling of larger protein structures for which chemical shifts are available.

  17. RM-structure alignment based statistical machine translation model

    Institute of Scientific and Technical Information of China (English)

    Sun Jiadong; Zhao Tiejun

    2008-01-01

    A novel model based on structure alignments is proposed for statistical machine translation in this paper.Meta-structure and sequence of meta-structure for a parse tree are defined.During the translation process, a parse tree is decomposed to deal with the structure divergence and the alignments can be constructed at different levels of recombination of meta-structure (RM).This method can perform the structure mapping across the sub-tree structure between languages.As a result, we get not only the translation for the target language, but sequence of meta-structure of its parse tree at the same time.Experiments show that the model in the framework of log-linear model has better generative ability and significantly outperforms Pharaoh, a phrase-based system.

  18. Three-Dimensional Protein Fold Determination from Backbone Amide Pseudocontact Shifts Generated by Lanthanide Tags at Multiple Sites

    KAUST Repository

    Yagi, Hiromasa

    2013-06-01

    Site-specific attachment of paramagnetic lanthanide ions to a protein generates pseudocontact shifts (PCS) in the nuclear magnetic resonance (NMR) spectra of the protein that are easily measured as changes in chemical shifts. By labeling the protein with lanthanide tags at four different sites, PCSs are observed for most amide protons and accurate information is obtained about their coordinates in three-dimensional space. The approach is demonstrated with the chaperone ERp29, for which large differences have been reported between X-ray and NMR structures of the C-terminal domain, ERp29-C. The results unambiguously show that the structure of rat ERp29-C in solution is similar to the crystal structure of human ERp29-C. PCSs of backbone amides were the only structural restraints required. Because these can be measured for more dilute protein solutions than other NMR restraints, the approach greatly widens the range of proteins amenable to structural studies in solution. © 2013 Elsevier Ltd. All rights reserved.

  19. ON THE STRUCTURES OF RAM-BASED CHINESE CHARACTER LIBRARIES

    Institute of Scientific and Technical Information of China (English)

    钱培德

    1991-01-01

    The Chinese character library is one of the important data structures in the Chinese information Processing system.The behavior of the whole system depends directly on the reasonableness of design for its structure.This paper expounds the structures of RAM-based Chinese character libraries,static and dynamic ,The paper offers a descriptive method for this behavior and inquires into some algorithms related to the structures mentioned above.

  20. Structure-based bayesian sparse reconstruction

    KAUST Repository

    Quadeer, Ahmed Abdul

    2012-12-01

    Sparse signal reconstruction algorithms have attracted research attention due to their wide applications in various fields. In this paper, we present a simple Bayesian approach that utilizes the sparsity constraint and a priori statistical information (Gaussian or otherwise) to obtain near optimal estimates. In addition, we make use of the rich structure of the sensing matrix encountered in many signal processing applications to develop a fast sparse recovery algorithm. The computational complexity of the proposed algorithm is very low compared with the widely used convex relaxation methods as well as greedy matching pursuit techniques, especially at high sparsity. © 1991-2012 IEEE.

  1. Selecting Question-Specific Genes to Reduce Incongruence in Phylogenomics: A Case Study of Jawed Vertebrate Backbone Phylogeny.

    Science.gov (United States)

    Chen, Meng-Yun; Liang, Dan; Zhang, Peng

    2015-11-01

    Incongruence between different phylogenomic analyses is the main challenge faced by phylogeneticists in the genomic era. To reduce incongruence, phylogenomic studies normally adopt some data filtering approaches, such as reducing missing data or using slowly evolving genes, to improve the signal quality of data. Here, we assembled a phylogenomic data set of 58 jawed vertebrate taxa and 4682 genes to investigate the backbone phylogeny of jawed vertebrates under both concatenation and coalescent-based frameworks. To evaluate the efficiency of extracting phylogenetic signals among different data filtering methods, we chose six highly intractable internodes within the backbone phylogeny of jawed vertebrates as our test questions. We found that our phylogenomic data set exhibits substantial conflicting signal among genes for these questions. Our analyses showed that non-specific data sets that are generated without bias toward specific questions are not sufficient to produce consistent results when there are several difficult nodes within a phylogeny. Moreover, phylogenetic accuracy based on non-specific data is considerably influenced by the size of data and the choice of tree inference methods. To address such incongruences, we selected genes that resolve a given internode but not the entire phylogeny. Notably, not only can this strategy yield correct relationships for the question, but it also reduces inconsistency associated with data sizes and inference methods. Our study highlights the importance of gene selection in phylogenomic analyses, suggesting that simply using a large amount of data cannot guarantee correct results. Constructing question-specific data sets may be more powerful for resolving problematic nodes.

  2. The backbone of the post-synaptic density originated in a unicellular ancestor of choanoflagellates and metazoans

    Directory of Open Access Journals (Sweden)

    Manuel Michaël

    2010-02-01

    Full Text Available Abstract Background Comparative genomics of the early diverging metazoan lineages and of their unicellular sister-groups opens new window to reconstructing the genetic changes which preceded or accompanied the evolution of multicellular body plans. A recent analysis found that the genome of the nerve-less sponges encodes the homologues of most vertebrate post-synaptic proteins. In vertebrate excitatory synapses, these proteins assemble to form the post-synaptic density, a complex molecular platform linking membrane receptors, components of their signalling pathways, and the cytoskeleton. Newly available genomes from Monosiga brevicollis (a member of Choanoflagellata, the closest unicellular relatives of animals and Trichoplax adhaerens (a member of Placozoa: besides sponges, the only nerve-less metazoans offer an opportunity to refine our understanding of post-synaptic protein evolution. Results Searches for orthologous proteins and reconstruction of gene gains/losses based on the taxon phylogeny indicate that post-synaptic proteins originated in two main steps. The backbone scaffold proteins (Shank, Homer, DLG and some of their partners were acquired in a unicellular ancestor of choanoflagellates and metazoans. A substantial additional set appeared in an exclusive ancestor of the Metazoa. The placozoan genome contains most post-synaptic genes but lacks some of them. Notably, the master-scaffold protein Shank might have been lost secondarily in the placozoan lineage. Conclusions The time of origination of most post-synaptic proteins was not concomitant with the acquisition of synapses or neural-like cells. The backbone of the scaffold emerged in a unicellular context and was probably not involved in cell-cell communication. Based on the reconstructed protein composition and potential interactions, its ancestral function could have been to link calcium signalling and cytoskeleton regulation. The complex later became integrated into the evolving

  3. An in vitro recombination-based reverse genetic system for rapid mutagenesis of structural genes of the Japanese encephalitis virus

    Institute of Scientific and Technical Information of China (English)

    Ruikun; Du; Manli; Wang; Zhihong; Hu; Hualin; Wang; Fei; Deng

    2015-01-01

    Japanese encephalitis virus(JEV) is one of the most common pathogens of severe viral encephalitis, which is a severe threat to human health. Despite instability of the JEV genome in bacteria, many strategies have been developed to establish molecular clone systems of JEV, providing convenient tools for studying the virus life cycle and virus–host interactions. In this study, we adapted an In-Fusion enzyme-based in vitro recombination method to construct a reverse genetic system of JEV, thereby providing a rapid approach to introduce mutations into the structural genes. A truncated genome without the structural genes was constructed as the backbone, and the complementary segment containing the structural genes was recombined in vitro, which was then transfected directly into virus-permissive cells. The progeny of the infectious virus was successfully detected in the supernatant of the transfected cells, and showed an identical phenotype to its parental virus. To provide a proof-of-principle, the 12 conserved cysteine residues in the envelope(E) protein of JEV were respectively mutated using this approach, and all mutations resulted in a complete failure to generate infectious virus. However, a leucine-tophenylanine mutation at amino acid 107 of the E protein did not interfere with the production of the infectious virus. These results suggested that all 12 cysteines in the E protein are essential for the JEV life cycle. In summary, a novel reverse genetic system of JEV was established for rapidly introducing mutations into structural genes, which will serve as a useful tool for functional studies.

  4. Maximality-Based Structural Operational Semantics for Petri Nets

    Science.gov (United States)

    Saīdouni, Djamel Eddine; Belala, Nabil; Bouneb, Messaouda

    2009-03-01

    The goal of this work is to exploit an implementable model, namely the maximality-based labeled transition system, which permits to express true-concurrency in a natural way without splitting actions on their start and end events. One can do this by giving a maximality-based structural operational semantics for the model of Place/Transition Petri nets in terms of maximality-based labeled transition systems structures.

  5. CheShift-2 resolves a local inconsistency between two X-ray crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Vila, Jorge A. [Cornell University, Baker Laboratory of Chemistry and Chemical Biology (United States); Sue, Shih-Che [Scripps Research Institute, Department of Molecular Biology (United States); Fraser, James S. [University of California, California Institute of Quantitative Biosciences (QB3) and Department of Cellular and Molecular Pharmacology (United States); Scheraga, Harold A. [Cornell University, Baker Laboratory of Chemistry and Chemical Biology (United States); Dyson, H. Jane, E-mail: dyson@scripps.edu [Scripps Research Institute, Department of Molecular Biology (United States)

    2012-10-15

    Since chemical shifts provide important and relatively accessible information about protein structure in solution, a Web server, CheShift-2, was developed for structure interrogation, based on a quantum mechanics database of {sup 13}C{sup {alpha}} chemical shifts. We report the application of CheShift-2 to a local inconsistency between two X-ray crystal structures (PDB IDs 1IKN and 1NFI) of the complex between the p65/p50 heterodimer of NF{kappa}B and its inhibitor I{kappa}B{alpha}. The availability of NMR resonance assignments that included the region of the inconsistency provided an opportunity for independent validation of the CheShift-2 server. Application of the server showed that the {sup 13}C{sup {alpha}} chemical shifts measured for the Gly270-Pro281 sequence close to the C-terminus of I{kappa}B{alpha} were unequivocally consistent with the backbone structure modeled in the 1IKN structure, and were inconsistent with the 1NFI structure. Previous NOE measurements had demonstrated that the position of a tryptophan ring in the region immediately N-terminal in this region was not consistent with either structure. Subsequent recalculation of the local structure in this region, based on the electron density of the deposited structure factors for 1IKN, confirmed that the local backbone structure was best modeled by 1IKN, but that the rotamer of Trp258 is consistent with the 1NFI structure, including the presence of a hydrogen bond between the ring N{epsilon}H of Trp258 and the backbone carbonyl group of Gln278. The consensus between all of these measures suggests that the CheShift-2 server operates well under circumstances in which backbone chemical shifts are available but where local plasticity may render X-ray structural data ambiguous.

  6. Base pairing in RNA structures: A computational analysis of structural aspects and interaction energies

    Indian Academy of Sciences (India)

    Purshotam Sharma; Abhijit Mitra; Sitansh Sharma; Harjinder Singh

    2007-09-01

    The base pairing patterns in RNA structures are more versatile and completely different as compared to DNA. We present here results of ab-initio studies of structures and interaction energies of eight selected RNA base pairs reported in literature. Interaction energies, including BSSE correction, of hydrogen added crystal geometries of base pairs have been calculated at the HF/6-31G∗∗ level. The structures and interaction energies of the base pairs in the crystal geometry are compared with those obtained after optimization of the base pairs. We find that the base pairs become more planar on full optimization. No change in the hydrogen bonding pattern is seen. It is expected that the inclusion of appropriate considerations of many of these aspects of RNA base pairing would significantly improve the accuracy of RNA secondary structure prediction.

  7. Musical Structural Analysis Database Based on GTTM

    OpenAIRE

    Hamanaka, Masatoshi; Hirata, Keiji; Tojo, Satoshi

    2014-01-01

    This paper, we present the publication of our analysis data and analyzing tool based on the generative theory of tonal music (GTTM). Musical databases such as score databases, instrument sound databases, and musical pieces with standard MIDI files and annotated data are key to advancements in the field of music information technology. We started implementing the GTTM on a computer in 2004 and ever since have collected and publicized test data by musicologists in a step-by-step manner. In our ...

  8. Earthquake Analysis of Structure by Base Isolation Technique in SAP

    Directory of Open Access Journals (Sweden)

    T. Subramani

    2014-06-01

    Full Text Available This paper presents an overview of the present state of base isolation techniques with special emphasis and a brief on other techniques developed world over for mitigating earthquake forces on the structures. The dynamic analysis procedure for isolated structures is briefly explained. The provisions of FEMA 450 for base isolated structures are highlighted. The effects of base isolation on structures located on soft soils and near active faults are given in brief. Simple case study on natural base isolation using naturally available soils is presented. Also, the future areas of research are indicated. Earthquakes are one of nature IS greatest hazards; throughout historic time they have caused significant loss offline and severe damage to property, especially to man-made structures. On the other hand, earthquakes provide architects and engineers with a number of important design criteria foreign to the normal design process. From well established procedures reviewed by many researchers, seismic isolation may be used to provide an effective solution for a wide range of seismic design problems. The application of the base isolation techniques to protect structures against damage from earthquake attacks has been considered as one of the most effective approaches and has gained increasing acceptance during the last two decades. This is because base isolation limits the effects of the earthquake attack, a flexible base largely decoupling the structure from the ground motion, and the structural response accelerations are usually less than the ground acceleration. In general, the increase of additional viscous damping in the structure may reduce displacement and acceleration responses of the structure. This study also seeks to evaluate the effects of additional damping on the seismic response when compared with structures without additional damping for the different ground motions.

  9. Strengthening of Concrete Structures with cement based bonded composites

    DEFF Research Database (Denmark)

    Täljsten, Björn; Blanksvärd, Thomas

    2008-01-01

    Polymers). The method is very efficient and has achieved world wide attention. However, there are some drawbacks with the use of epoxy, e.g. working environment, compatibility and permeability. Substituting the epoxy adherent with a cement based bonding agent will render a strengthening system...... with improved working environment and better compatibility to the base concrete structure. This study gives an overview of different cement based systems, all with very promising results for structural upgrading. Studied parameters are structural retrofit for bending, shear and confinement. It is concluded...

  10. Structural Health Monitoring Based on Combined Structural Global and Local Frequencies

    Directory of Open Access Journals (Sweden)

    Jilin Hou

    2014-01-01

    Full Text Available This paper presents a parameter estimation method for Structural Health Monitoring based on the combined measured structural global frequencies and structural local frequencies. First, the global test is experimented to obtain the low order modes which can reflect the global information of the structure. Secondly, the mass is added on the member of structure to increase the local dynamic characteristic and to make the member have local primary frequency, which belongs to structural local frequency and is sensitive to local parameters. Then the parameters of the structure can be optimized accurately using the combined structural global frequencies and structural local frequencies. The effectiveness and accuracy of the proposed method are verified by the experiment of a space truss.

  11. Structure-based drug design and modern medicine

    Directory of Open Access Journals (Sweden)

    Vijayakrishnan R

    2009-01-01

    Full Text Available Drug discovery has evolved through various stages into more rational and evidence-based drug designing. Compared to conventional methods which were time consuming and less logical, new drug designing based on structure is rational, evidence based, faster and more scientific in nature. In the era of modern medicine, where newer insights into molecular level of disease processes are available, it is very essential that drug designing be based on molecular mechanism of pathologic processes. Structure-based drug designing has made tremendous contributions in the field of cancer chemotherapy, drug resistant infections, neurological diseases, to mention a few. New drug discovery methods are furthered by developments in the technology especially computers, bioassay techniques and calibrated instruments. Computational structure-based drug designing opens the door to novel treatments in modern medicine.

  12. Backbone cyclization of a recombinant cystine-knot peptide by engineered Sortase A.

    Science.gov (United States)

    Stanger, Karen; Maurer, Till; Kaluarachchi, Harini; Coons, Mary; Franke, Yvonne; Hannoush, Rami N

    2014-11-28

    Cyclotides belong to the family of cyclic cystine-knot peptides and have shown promise as scaffolds for protein engineering and pharmacological modulation of cellular protein activity. Cyclotides are characterized by a cystine-knotted topology and a head-to-tail cyclic polypeptide backbone. While they are primarily produced in plants, cyclotides have also been obtained by chemical synthesis. However, there is still a need for methods to generate cyclotides in high yields to near homogeneity. Here, we report a biomimetic approach which utilizes an engineered version of the enzyme Sortase A to catalyze amide backbone cyclization of the recombinant cyclotide MCoTI-II, thereby allowing the efficient production of active homogenous species in high yields. Our results provide proof of concept for using engineered Sortase A to produce cyclic MCoTI-II and should be generally applicable to generating other cyclic cystine-knot peptides.

  13. Protein and peptide alkoxyl radicals can give rise to C-terminal decarboxylation and backbone cleavage

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan

    1996-01-01

    when the free amino acid does not, and that hydroperoxides can be formed on both the backbone (at alpha-carbon positions) and the side chain. Decomposition of alpha-carbon hydroperoxides by Fe(II)-EDTA gives initially an alkoxyl radical via a pseudo-Fenton reaction; these radicals fragment rapidly...... with k estimated as > or = 10(7) s(-1). With N-acetyl amino acids and dipeptides beta-scission of an alkoxyl radical at the C-terminal alpha-carbon results in C-terminal decarboxylation, with release of CO2.-; the corresponding amides undergo deamidation with release of .C(O)NH2. Cyclic dipeptides...... undergo analogous reactions with cleavage of the alpha-carbon to carbonyl-carbon bond and formation of .C(O)NHR radicals. With substrates with large aliphatic side chains, radicals from side-chain hydroperoxides are also observed. C-terminal decarboxylation and backbone fragmentation are also observed...

  14. Aromatic Copolyamides with Anthrazoline Units in the Backbone: Synthesis, Characterization, Pervaporation Application

    Directory of Open Access Journals (Sweden)

    Galina A. Polotskaya

    2016-10-01

    Full Text Available Copolyamides with anthrazoline units in the backbone (coPA were synthesized and dense nonporous films were prepared by solvent evaporation. Glass transition temperature, density, and fractional free volume were determined for the dense nonporous films composed of polyamide and two of its copolymers containing 20 and 30 mol % anthrazoline units in the backbone. Transport properties of the polymer films were estimated by sorption and pervaporation tests toward methanol, toluene, and their mixtures. An increase in anthrazoline fragments content leads to an increasing degree of methanol sorption but to a decreasing degree of toluene sorption. Pervaporation of a methanol–toluene mixture was studied over a wide range of feed concentration (10–90 wt % methanol. Maximal separation factor was observed for coPA-20 containing 20 mol % fragments with anthrazoline units; maximal total flux was observed for coPA-30 with the highest fractional free volume.

  15. Graph-based linear scaling electronic structure theory

    CERN Document Server

    Niklasson, Anders M N; Negre, Christian F A; Cawkwell, Marc J; Swart, Pieter J; Mohd-Yusof, Jamal; Germann, Timothy C; Wall, Michael E; Bock, Nicolas; Djidjev, Hristo

    2016-01-01

    We show how graph theory can be combined with quantum theory to calculate the electronic structure of large complex systems. The graph formalism is general and applicable to a broad range of electronic structure methods and materials, including challenging systems such as biomolecules. The methodology combines well-controlled accuracy, low computational cost, and natural low-communication parallelism. This combination addresses substantial shortcomings of linear scaling electronic structure theory, in particular with respect to quantum-based molecular dynamics simulations.

  16. Structural Optimization of Machine Gun Based on Dynamic Stability Concept

    Institute of Scientific and Technical Information of China (English)

    LI Yong-jian; WANG Rui-lin; ZHANG Ben-jun

    2008-01-01

    Improving the firing accuracy is a final goal of structural optimization of machine guns. The main factors which affect the dispersion accuracy of machine gun are analyzed. Based on the concept of dynamic stability, a structural optimization model is built up, and the sensitivity of dispersion accuracy to design variables is analyzed. The optimization results of a type of machine gun show that the method is valid, feasible, and can be used as a guide to the structural optimization of other automatic weapons.

  17. [Computational chemistry in structure-based drug design].

    Science.gov (United States)

    Cao, Ran; Li, Wei; Sun, Han-Zi; Zhou, Yu; Huang, Niu

    2013-07-01

    Today, the understanding of the sequence and structure of biologically relevant targets is growing rapidly and researchers from many disciplines, physics and computational science in particular, are making significant contributions to modern biology and drug discovery. However, it remains challenging to rationally design small molecular ligands with desired biological characteristics based on the structural information of the drug targets, which demands more accurate calculation of ligand binding free-energy. With the rapid advances in computer power and extensive efforts in algorithm development, physics-based computational chemistry approaches have played more important roles in structure-based drug design. Here we reviewed the newly developed computational chemistry methods in structure-based drug design as well as the elegant applications, including binding-site druggability assessment, large scale virtual screening of chemical database, and lead compound optimization. Importantly, here we address the current bottlenecks and propose practical solutions.

  18. Industrial Utilization of Lignin Based on its Structure and Capability

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Chemical modification and industrial utilization of lignin based on its structure were reviewed in this paper. And its economic value and significance for the society and environmental protection were also evaluated.

  19. Structured-light Image Compression Based on Fractal Theory

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The method of fractal image compression is introduced which is applied to compress the line structured-light image. Based on the self-similarity of the structured-light image, we attain satisfactory compression ratio and higher peak signal-to-noise ratio (PSNR). The experimental results indicate that this method can achieve high performance.

  20. Miniature Microwave Bandpass Filter Based on EBG Structures

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy; Krozer, Viktor; Meincke, Peter

    2006-01-01

    A new design of a planar microwave filter, based on rejection band properties of an electrically small electromagnetic bandgap (EBG) structure, is proposed. The proposed EBG structure demonstrates effective impedance manipulation, exhibits a simple analysis, and is about three times smaller...

  1. Discrete Discriminant analysis based on tree-structured graphical models

    DEFF Research Database (Denmark)

    Perez de la Cruz, Gonzalo; Eslava, Guillermina

    The purpose of this paper is to illustrate the potential use of discriminant analysis based on tree{structured graphical models for discrete variables. This is done by comparing its empirical performance using estimated error rates for real and simulated data. The results show that discriminant...... analysis based on tree{structured graphical models is a simple nonlinear method competitive with, and sometimes superior to, other well{known linear methods like those assuming mutual independence between variables and linear logistic regression....

  2. An Analytic Method for the Kinematics and Dynamics of a Multiple-Backbone Continuum Robot

    Directory of Open Access Journals (Sweden)

    Bin He

    2013-01-01

    Full Text Available Continuum robots have been the subject of extensive research due to their potential use in a wide range of applications. In this paper, we propose a new continuum robot with three backbones, and provide a unified analytic method for the kinematics and dynamics of a multiple‐backbone continuum robot. The robot achieves actuation by independently pulling three backbones to carry out a bending motion of two‐degrees‐of‐freedom (DoF. A three‐dimensional CAD model of the robot is built and the kinematical equation is established on the basis of the Euler‐Bernoulli beam. The dynamical model of the continuum robot is constructed by using the Lagrange method. The simulation and the experiment’s validation results show the continuum robot can exactly bend into pre‐set angles in the two‐dimensional space (the maximum error is less than 5% of the robot length and can make a circular motion in three‐dimensional space. The results demonstrate that the proposed analytic method for the kinematics and dynamics of a continuum robot is feasible.

  3. Probability based high temperature engineering creep and structural fire resistance

    CERN Document Server

    Razdolsky, Leo

    2017-01-01

    This volume on structural fire resistance is for aerospace, structural, and fire prevention engineers; architects, and educators. It bridges the gap between prescriptive- and performance-based methods and simplifies very complex and comprehensive computer analyses to the point that the structural fire resistance and high temperature creep deformations will have a simple, approximate analytical expression that can be used in structural analysis and design. The book emphasizes methods of the theory of engineering creep (stress-strain diagrams) and mathematical operations quite distinct from those of solid mechanics absent high-temperature creep deformations, in particular the classical theory of elasticity and structural engineering. Dr. Razdolsky’s previous books focused on methods of computing the ultimate structural design load to the different fire scenarios. The current work is devoted to the computing of the estimated ultimate resistance of the structure taking into account the effect of high temperatur...

  4. RNA structural motif recognition based on least-squares distance.

    Science.gov (United States)

    Shen, Ying; Wong, Hau-San; Zhang, Shaohong; Zhang, Lin

    2013-09-01

    RNA structural motifs are recurrent structural elements occurring in RNA molecules. RNA structural motif recognition aims to find RNA substructures that are similar to a query motif, and it is important for RNA structure analysis and RNA function prediction. In view of this, we propose a new method known as RNA Structural Motif Recognition based on Least-Squares distance (LS-RSMR) to effectively recognize RNA structural motifs. A test set consisting of five types of RNA structural motifs occurring in Escherichia coli ribosomal RNA is compiled by us. Experiments are conducted for recognizing these five types of motifs. The experimental results fully reveal the superiority of the proposed LS-RSMR compared with four other state-of-the-art methods.

  5. Structures and photoelectric properties of five benzotrithiophene isomers-based donor-acceptor copolymers

    Science.gov (United States)

    Cheng, Na; Ma, Yuchen; Liu, Yongjun; Zhang, Changqiao; Liu, Chengbu

    2016-04-01

    In this paper, we have investigated the structures, electronic and optical properties of five conjugated copolymers (BTT1-BTz, BTT2-BTz, BTT3-BTz, BTT4-BTz and BTT5-BTz) featuring benzotrithiophene (BTT) isomers as donor units and benzothiadiazole (BTz) as acceptor units, linked through thiophene spacers, employing many-body perturbation theory (MBPT). We have explored the isomer effects by configuration of the sulfur atoms in BTT units, aimed to get insight into how the structural modifications to the conjugated backbone can influence the molecular structures and electronic properties of conjugated polymers. Using the trimer as the computational model, the calculated low and high energy absorption bands (660 and 413 nm) for BTT1-BTz agree well with the experimental ones (645 and 430 nm) with a small offset of ~ 15 nm. On the basis of our calculations, it is found that the backbones of these polymers display different coplanarities, with the dihedral angles between the two neighboring rings varying from 12.3° to 79.0°. Importantly, both BTT1-BTz and BTT2-BTz exhibit intense adsorption around 660 and 623 nm, indicating their promising application in solar cells, whereas BTT3-BTz and BTT4-BTz display the intense adsorption at 569 and 551 nm, which are also usable in the tandem solar cells. BTT5-BTz has narrow and weak adsorption in the visible and infrared region, implying it is not conducive to the sunlight absorption. The blue shift of about 150 nm from BTT1-BTz to BTT5-BTz is suggested to be originated from the shorter effective conjugation lengths.

  6. Crack detection in offshore platform structure based on structural intensity approach

    Science.gov (United States)

    Tian, Xiaojie; Liu, Guijie; Gao, Zhiming; Chen, Pengfei; Mu, Weilei

    2017-02-01

    Structural intensity approach is introduced to study the crack detection for offshore platform in the paper. The Line Spring Model (LSM) of surface crack is proposed based on plate crack structure, and thus the relationship between the additional angle, displacement and crack relative depth is achieved. Besides, the concept of appended structure-borne sound intensity is introduced. The expression of appended structural intensity for crack damage is derived. By observing the input energy, distribution, transmission and vibration performance of structure intensity, evidence is provided for detection of crack location. Vibration analysis is conducted on the whole platform under multi environment load. Using the structural intensity approach, the crack is detected on the key point easily. Moreover, the K-shape welded pipe point is detected using structural intensity approach, and the crack can be detected accurately. Therefore, development structural intensity approach would be extremely useful to spread out technologies that can be applied for offshore platform crack detection accurately.

  7. The latent structure of secure base script knowledge.

    Science.gov (United States)

    Waters, Theodore E A; Fraley, R Chris; Groh, Ashley M; Steele, Ryan D; Vaughn, Brian E; Bost, Kelly K; Veríssimo, Manuela; Coppola, Gabrielle; Roisman, Glenn I

    2015-06-01

    There is increasing evidence that attachment representations abstracted from childhood experiences with primary caregivers are organized as a cognitive script describing secure base use and support (i.e., the secure base script). To date, however, the latent structure of secure base script knowledge has gone unexamined-this despite that such basic information about the factor structure and distributional properties of these individual differences has important conceptual implications for our understanding of how representations of early experience are organized and generalized, as well as methodological significance in relation to maximizing statistical power and precision. In this study, we report factor and taxometric analyses that examined the latent structure of secure base script knowledge in 2 large samples. Results suggested that variation in secure base script knowledge-as measured by both the adolescent (N = 674) and adult (N = 714) versions of the Attachment Script Assessment-is generalized across relationships and continuously distributed.

  8. Base Stress of the Opened Bottom Cylinder Structures

    Institute of Scientific and Technical Information of China (English)

    刘建起; 孟晓娟

    2004-01-01

    The base stress of the opened bottom cylinder structure differs greatly from that of the structure with a closed bottom. By investigating the inner soil pressure on the cylinder wall and the base stress of the cylinder base, which were obtained from the model experiments, the interactions among the filler inside the cylinder,subsoil and cylinder are analyzed. The adjusting mechanism of frictional resistance between the inner filler and the wall of the cylinder during the overturning of the cylinder is discussed. Based on the experimental study, a method for calculating the base stress of the opened bottom cylinder structure is proposed. Meanwhile, the formulas for calculating the effective anti-overturning ratio of the opened bottom cylinder are derived.

  9. 基于噻吩和亚苯基合成的新物质的结构和电子性质%Structural and Electronic Properties of New Materials Based on Thiophene and Phenylene

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Theoretical study on the geometries and electronic properties of new conjugated compounds based on thiophene and phenylene was carried out. The theoretical ground-state geometries and electronic structures of the studied molecules were obtained using the density functional theory (DFT) method at B3LYP level with 6-31G(d) basis set. The electronic properties were determined by ZINDO/s, CIS/3-21G(d), and TD//B3LYP/3-21G(d) calculations performed on the B3LYP/6-31(d) optimized geometries. The effects of the ring structure and the substituents on the geometries and electronic properties of these materials were discussed. The results of this study indicate how the electronic properties can be tuned by the backbone ring or side group and suggest these compounds as good candidates for opro-electronic applications.

  10. Pre-Stressing Timber-Based Plate Tensegrity Structures

    DEFF Research Database (Denmark)

    Falk, Andreas; Kirkegaard, Poul Henning

    2012-01-01

    Tensile structures occur in numerous varieties utilising combinations of tension and compression. Introducing structural plates in the basic tensegrity unit and tensegric assemblies varies the range of feasible topologies and provides the structural system with an integrated surface. The present...... paper considers the concept of plate tensegrity based on CLT plates (cross-laminated timber). It combines the principles of tensegrity with the principles of plate shells and is characterised by a plate shell stabilised by struts and cables. The paper deals with material aspects and robustness of timber......-based plate shells and outlines needs, methods and effects of controlling cable stresses for secured capacity, form and function of plate tensegrity....

  11. Structural and Chemical Diversity of Tl-Based Cuprate Superconductors

    Institute of Scientific and Technical Information of China (English)

    信赢

    2003-01-01

    The Tl-based cuprate superconductor family is the largest family in crystal structure and chemical composition among all high Tc cuprate superconductors. The Tl family can be divided into two sub-families, the Tl single layer family and the Tl double layer family, based on their crystal structural characteristics. The Tl single layer family is an ideal material for investigating the evolution of crystalline formation, charge carrier density, chemical composition, transport properties, superconductivity and their relationships. The Tl family contains almostall possible crystal structures discovered in high-Tc cuprate superconductors. Tl cuprate superconductors are of great importance not only in studying high-temperature superconductivity but also in commercial applications.

  12. Structure of 2,4-Diaminopyrimidine - Theobromine Alternate Base Pairs

    Science.gov (United States)

    Gengeliczki, Zsolt; Callahan, Michael P.; Kabelac, Martin; Rijs, Anouk M.; deVries, Mattanjah S.

    2011-01-01

    We report the structure of clusters of 2,4-diaminopyrimidine with 3,7-dimethylxanthine (theobromine) in the gas phase determined by IR-UV double resonance spectroscopy in both the near-IR and mid-IR regions in combination with ab initio computations. These clusters represent potential alternate nucleobase pairs, geometrically equivalent to guanine-cytosine. We have found the four lowest energy structures, which include the Watson-Crick base pairing motif. This Watson-Crick structure has not been observed by resonant two-photon ionization (R2PI) in the gas phase for the canonical DNA base pairs.

  13. Protein structure prediction provides comparable performance to crystallographic structures in docking-based virtual screening.

    Science.gov (United States)

    Du, Hongying; Brender, Jeffrey R; Zhang, Jian; Zhang, Yang

    2015-01-01

    Structure based virtual screening has largely been limited to protein targets for which either an experimental structure is available or a strongly homologous template exists so that a high-resolution model can be constructed. The performance of state of the art protein structure predictions in virtual screening in systems where only weakly homologous templates are available is largely untested. Using the challenging DUD database of structural decoys, we show here that even using templates with only weak sequence homology (identity) structural models can be constructed by I-TASSER which achieve comparable enrichment rates to using the experimental bound crystal structure in the majority of the cases studied. For 65% of the targets, the I-TASSER models, which are constructed essentially in the apo conformations, reached 70% of the virtual screening performance of using the holo-crystal structures. A correlation was observed between the success of I-TASSER in modeling the global fold and local structures in the binding pockets of the proteins versus the relative success in virtual screening. The virtual screening performance can be further improved by the recognition of chemical features of the ligand compounds. These results suggest that the combination of structure-based docking and advanced protein structure modeling methods should be a valuable approach to the large-scale drug screening and discovery studies, especially for the proteins lacking crystallographic structures.

  14. Solution Structure and Backbone Dynamics of Human Liver Fatty Acid Binding Protein: Fatty Acid Binding Revisited

    OpenAIRE

    Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.

    2012-01-01

    Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the p...

  15. Aircraft detection based on probability model of structural elements

    Science.gov (United States)

    Chen, Long; Jiang, Zhiguo

    2014-11-01

    Detecting aircrafts is important in the field of remote sensing. In past decades, researchers used various approaches to detect aircrafts based on classifiers for overall aircrafts. However, with the development of high-resolution images, the internal structures of aircrafts should also be taken into consideration now. To address this issue, a novel aircrafts detection method for satellite images based on probabilistic topic model is presented. We model aircrafts as the connected structural elements rather than features. The proposed method contains two major steps: 1) Use Cascade-Adaboost classier to identify the structural elements of aircraft firstly. 2) Connect these structural elements to aircrafts, where the relationships between elements are estimated by hierarchical topic model. The model places strict spatial constraints on structural elements which can identify differences between similar features. The experimental results demonstrate the effectiveness of the approach.

  16. Towards fully automated structure-based function prediction in structural genomics: a case study.

    Science.gov (United States)

    Watson, James D; Sanderson, Steve; Ezersky, Alexandra; Savchenko, Alexei; Edwards, Aled; Orengo, Christine; Joachimiak, Andrzej; Laskowski, Roman A; Thornton, Janet M

    2007-04-13

    As the global Structural Genomics projects have picked up pace, the number of structures annotated in the Protein Data Bank as hypothetical protein or unknown function has grown significantly. A major challenge now involves the development of computational methods to assign functions to these proteins accurately and automatically. As part of the Midwest Center for Structural Genomics (MCSG) we have developed a fully automated functional analysis server, ProFunc, which performs a battery of analyses on a submitted structure. The analyses combine a number of sequence-based and structure-based methods to identify functional clues. After the first stage of the Protein Structure Initiative (PSI), we review the success of the pipeline and the importance of structure-based function prediction. As a dataset, we have chosen all structures solved by the MCSG during the 5 years of the first PSI. Our analysis suggests that two of the structure-based methods are particularly successful and provide examples of local similarity that is difficult to identify using current sequence-based methods. No one method is successful in all cases, so, through the use of a number of complementary sequence and structural approaches, the ProFunc server increases the chances that at least one method will find a significant hit that can help elucidate function. Manual assessment of the results is a time-consuming process and subject to individual interpretation and human error. We present a method based on the Gene Ontology (GO) schema using GO-slims that can allow the automated assessment of hits with a success rate approaching that of expert manual assessment.

  17. Evaluation Method of Web Site Based on Web Structure Mining

    Institute of Scientific and Technical Information of China (English)

    LiJun-e; ZhouDong-ru

    2003-01-01

    The structure of Web site became more complex than before. During the design period of a Web site, the lack of model and method results in improper Web structure,which depend on the designer's experience. From the point of view of software engineering, every period in the software life must be evaluated before starting the next period's work. It is very important and essential to search relevant methods for evaluating Web structure before the site is completed. In this work, after studying the related work about the Web structure mining and analyzing the major structure mining methods (Page-rank and Hub/Authority), a method based on the Page-rank for Web structure evaluation in design stage is proposed. A Web structure modeling language WSML is designed, and the implement strategies for evaluating system of the Web site structure are given out. Web structure mining has being used mainly in search engines before. It is the first time to employ the Web structure mining technology to evaluate a Web structure in the design period of a Web site. It contributes to the formalization of the design documents for Web site and the improving of software engineering for large scale Web site, and the evaluating system is a practical tool for Web site construction.

  18. Health monitoring of aeronautical structures based on vibrations measurements

    Science.gov (United States)

    Bovio, Igor; Lecce, Leonardo

    2006-03-01

    Purpose of the paper is to present an innovative application inside the Non Destructive Testing field based on vibrations measurements, developed by the authors during the last three years, and already tested for analysing damage of many structural elements. The proposed new method is based on the acquisition and comparison of Frequency Response Functions (FRFs) of the monitored structure before and after an occurred damage. Structural damage modify the dynamical behaviour of the structure such as mass, stiffened and damping, and consequently the FRFs of the damaged structure in comparison with the FRFs of the sound structure, making possible to identify, to localize and quantify a structural damage. The activities, presented in the paper, mostly focused on a new FRFs processing technique based on the determining of a representative "Damage Index" for identifying and analysing damage both on real scale aeronautical structural components, like large-scale fuselage reinforced panels, and on aeronautical composite panels. Besides it has been carried out a dedicated neural network algorithm aiming at obtaining a "recognition-based learning"; this kind of learning methodology permits to train the neural network in order to let it recognises only "positive" examples discarding as a consequence the "negative" ones. Within the structural NDT a "positive" example means "healthy" state of the analysed structural component and, obviously, a "negative" one means a "damaged" or perturbed state. From an architectural point of view piezoceramic patches have been tested as actuators and sensors. Besides it has been used a laser-scanning vibrometer system to validate the behaviour of the piezoceramic patches.

  19. Dynamic fracture modeling in shell structures based on XFEM

    NARCIS (Netherlands)

    Larsson, R.; Mediavilla, J.; Fagerström, M.

    2011-01-01

    Through-the-thickness crack propagation in thin-walled structures is dealt with in this paper. The formulation is based on the cohesive zone concept applied to a kinematically consistent shell model enhanced with an XFEM-based discontinuous kinematical representation. The resulting formulation compr

  20. Spectral analysis based on compressive sensing in nanophotonic structures.

    Science.gov (United States)

    Wang, Zhu; Yu, Zongfu

    2014-10-20

    A method of spectral sensing based on compressive sensing is shown to have the potential to achieve high resolution in a compact device size. The random bases used in compressive sensing are created by the optical response of a set of different nanophotonic structures, such as photonic crystal slabs. The complex interferences in these nanostructures offer diverse spectral features suitable for compressive sensing.

  1. High performance anodes with tailored catalytic properties for La5.6WO11.4-δ based proton conducting fuel cells

    DEFF Research Database (Denmark)

    Balaguer, M.; Solis, C.; Bozza, Francesco;

    2013-01-01

    A new generation of anodes for PC-SOFCs based on catalytically promoted La0.75Ce0.1Sr0.15CrO3−δ (LSCCe) is presented. LSCCe is selected as the electrode backbone structure, due to its superior total conductivity over that of LSC. The infiltration of catalytically highly active nickel nanoparticles...

  2. Photo-excited terahertz switch based on composite metamaterial structure

    Science.gov (United States)

    Wang, Guocui; Zhang, Jianna; Zhang, Bo; He, Ting; He, Yanan; Shen, Jingling

    2016-09-01

    A photo-excited terahertz switch based on a composite metamaterial structure was designed by integration of photoconductive silicon into the gaps of split-ring resonators. The conductivity of the silicon that was used to fill the gaps in the split-ring resonators was tuned dynamically as a function of the incident pump power using laser excitation, leading to a change in the composite metamaterial structure's properties. We studied the transmission characteristics of the composite metamaterial structure for various silicon conductivities, and the results indicated that this type of composite metamaterial structure could be used as a resonance frequency tunable terahertz metamaterial switch. We also designed other structures by filling different gaps with silicon, and proved that these structures could be used as terahertz metamaterial switches can change the working mode from a single frequency to multiple frequencies.

  3. Alkali metal salts of formazanate ligands: diverse coordination modes as a result of the nitrogen-rich [NNCNN] ligand backbone.

    Science.gov (United States)

    Travieso-Puente, Raquel; Chang, Mu-Chieh; Otten, Edwin

    2014-12-28

    Alkali metal salts of redox-active formazanate ligands were prepared, and their structures in the solid-state and in solution are determined. The nitrogen-rich [NNCNN] backbone of formazanates results in a varied coordination chemistry, with both the internal and terminal nitrogen atoms available for bonding with the alkali metal. The potassium salt K[PhNNC(p-tol)NNPh]·2THF (1-K) is dimeric in the solid state and even in THF solution, as a result of the K atom bridging via interaction with a terminal N atom and the aromatic ring of a second unit. Conversely, for the compounds Na[MesNNC(CN)NNMes]·2THF (2-Na) and Na[PhNNC((t)Bu)NNPh] (3-Na) polymeric and hexameric structures are found in the solid state respectively. The preference for binding the alkali metal through internal N atoms (1-K and 2-Na) to give a 4-membered chelate, or via internal/external N atoms (5-membered chelate in 3-Na), contrasts with the 6-membered chelate mode observed in our recently reported formazanate zinc complexes.

  4. N-H stretching modes around 3300 wavenumber from peptide backbones observed by chiral sum frequency generation vibrational spectroscopy.

    Science.gov (United States)

    Fu, Li; Wang, Zhuguang; Yan, Elsa C Y

    2014-09-01

    We present a detailed analysis of the molecular origin of the chiral sum frequency generation (SFG) signals of proteins and peptides at interfaces in the N-H stretching vibrational region. The N-H stretching can be a probe for investigating structural and functional properties of proteins, but remains technically difficult to analyze due to the overlapping with the O-H stretching of water molecules. Chiral SFG spectroscopy offers unique tools to study the N-H stretching from proteins at interfaces without interference from the water background. However, the molecular origin of the N-H stretching signals of proteins is still unclear. This work provides a justification of the origin of chiral N-H signals by analyzing the vibrational frequencies, examining chiral SFG theory, studying proton (hydrogen/deuterium) exchange kinetics, and performing optical control experiments. The results demonstrate that the chiral N-H stretching signals at ~3300 cm(-1) originate from the amide group of the protein backbones. This chiral N-H stretching signal offers an in situ, real-time, and background-free probe for interrogating the protein structures and dynamics at interfaces at the molecular level.

  5. High resolution 4D HPCH experiment for sequential assignment of {sup 13}C-labeled RNAs via phosphodiester backbone

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, Saurabh; Stanek, Jan [University of Warsaw, Faculty of Chemistry, Biological and Chemical Research Centre (Poland); Cevec, Mirko; Plavec, Janez [National Institute of Chemistry, Slovenian NMR Centre (Slovenia); Koźmiński, Wiktor, E-mail: kozmin@chem.uw.edu.pl [University of Warsaw, Faculty of Chemistry, Biological and Chemical Research Centre (Poland)

    2015-11-15

    The three-dimensional structure determination of RNAs by NMR spectroscopy requires sequential resonance assignment, often hampered by assignment ambiguities and limited dispersion of {sup 1}H and {sup 13}C chemical shifts, especially of C4′/H4′. Here we present a novel through-bond 4D HPCH NMR experiment involving phosphate backbone where C4′–H4′ correlations are resolved along the {sup 1}H3′–{sup 31}P spectral planes. The experiment provides high peak resolution and effectively removes ambiguities encountered during assignments. Enhanced peak dispersion is provided by the inclusion of additional {sup 31}P and {sup 1}H3′ dimensions and constant-time evolution of chemical shifts. High spectral resolution is obtained by using non-uniform sampling in three indirect dimensions. The experiment fully utilizes the isotopic {sup 13}C-labeling with evolution of C4′ carbons. Band selective {sup 13}C inversion pulses are used to achieve selectivity and prevent signal dephasing due to the C4′–C3′ and C4′–C5′ homonuclear couplings. Multiple quantum line narrowing is employed to minimize sensitivity loses. The 4D HPCH experiment is verified and successfully applied to a non-coding 34-nt RNA consisting typical structure elements and a 14-nt RNA hairpin capped by cUUCGg tetraloop.

  6. Earthquake Damage Assessment for RC Structures Based on Fuzzy Sets

    Directory of Open Access Journals (Sweden)

    Haoxiang He

    2013-01-01

    Full Text Available A global damage index based on multiple linear force-deformation curves in pushover analysis is presented to evaluate the integrated damage of reinforced concrete structure. The modified coefficient is provided considering the cyclic load and hysteresis energy. The number of inelastic cycles and the coefficient of hysteresis energy concentration are also introduced as damage indices. Hence, multiple damage indices about displacement and energy for performance-based design are considered. The relation of multiple damage indices or factors and the fuzzy damage set is presented by comprehensive fuzzy evaluation; hence, a performance-based multiple fuzzy seismic damage-assessment method for reinforced concrete frame structures is established. The method can be accomplished based on pushover analysis, code spectrum, and capacity spectrum method. The fuzzy seismic damage-assessment method is verified through nonlinear analysis four different structures and the corresponding results and assessment conclusions are accurate.

  7. Extended Kalman filter based structural damage detection for MR damper controlled structures

    Science.gov (United States)

    Jin, Chenhao; Jang, Shinae; Sun, Xiaorong; Jiang, Zhaoshuo; Christenson, Richard

    2016-04-01

    The Magneto-rheological (MR) dampers have been widely used in many building and bridge structures against earthquake and wind loadings due to its advantages including mechanical simplicity, high dynamic range, low power requirements, large force capacity, and robustness. However, research about structural damage detection methods for MR damper controlled structures is limited. This paper aims to develop a real-time structural damage detection method for MR damper controlled structures. A novel state space model of MR damper controlled structure is first built by combining the structure's equation of motion and MR damper's hyperbolic tangent model. In this way, the state parameters of both the structure and MR damper are added in the state vector of the state space model. Extended Kalman filter is then used to provide prediction for state variables from measurement data. The two techniques are synergistically combined to identify parameters and track the changes of both structure and MR damper in real time. The proposed method is tested using response data of a three-floor MR damper controlled linear building structure under earthquake excitation. The testing results show that the adaptive extended Kalman filter based approach is capable to estimate not only structural parameters such as stiffness and damping of each floor, but also the parameters of MR damper, so that more insights and understanding of the damage can be obtained. The developed method also demonstrates high damage detection accuracy and light computation, as well as the potential to implement in a structural health monitoring system.

  8. Chemical and structural effects of base modifications in messenger RNA

    Science.gov (United States)

    Harcourt, Emily M.; Kietrys, Anna M.; Kool, Eric T.

    2017-01-01

    A growing number of nucleobase modifications in messenger RNA have been revealed through advances in detection and RNA sequencing. Although some of the biochemical pathways that involve modified bases have been identified, research into the world of RNA modification -- the epitranscriptome -- is still in an early phase. A variety of chemical tools are being used to characterize base modifications, and the structural effects of known base modifications on RNA pairing, thermodynamics and folding are being determined in relation to their putative biological roles.

  9. Microstructure and structural phase transitions in iron-based superconductors

    Institute of Scientific and Technical Information of China (English)

    Wang Zhen; Cai Yao; Yang Huai-Xin; Tian Huan-Fang; Wang Zhi-Wei; Ma Chao; Chen Zhen

    2013-01-01

    Crystal structures and microstructural features,such as structural phase transitions,defect structures,and chemical and structural inhomogeneities,are known to have profound effects on the physical properties of superconducting materials.Recently,many studies on the structural properties of Fe-based high-Tc superconductors have been published.This review article will mainly focus on the typical microstructural features in samples that have been well characterized by physical measurements.(i) Certain common structural features are discussed,in particular,the crystal structural features for different superconducting families,the local structural distortions in the Fe2Pn2 (Pn =P,As,Sb) or Fe2Ch2 (Ch =S,Se,Te) blocks,and the structural transformations in the 122 system.(ii) In FeTe(Se) (11 family),the superconductivity,chemical and structural inhomogeneities are investigated and discussed in correlation with superconductivity.(iii) In the K0.8Fe1.6+xSe2 system,we focus on the typical compounds with emphasis on the Fe-vacancy order and phase separations.The microstructural features in other superconducting materials are also briefly discussed.

  10. Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone

    DEFF Research Database (Denmark)

    Jing, Xiaona; Yang, Mingjun; Kasimova, Marina Robertovna

    2012-01-01

    Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone were studied to ev...

  11. Oxidation Responsive Polymers with a Triggered Degradation via Arylboronate Self-Immolative Motifs on a Polyphosphazene Backbone

    Science.gov (United States)

    2017-01-01

    Oxidation responsive polymers with triggered degradation pathways have been prepared via attachment of self-immolative moieties onto a hydrolytically unstable polyphosphazene backbone. After controlled main-chain growth, postpolymerization functionalization allows the preparation of hydrolytically stable poly(organo)phosphazenes decorated with a phenylboronic ester caging group. In oxidative environments, triggered cleavage of the caging group is followed by self-immolation, exposing the unstable glycine-substituted polyphosphazene which subsequently undergoes to backbone degradation to low-molecular weight molecules. As well as giving mechanistic insights, detailed GPC and 1H and 31P NMR analysis reveal the polymers to be stable in aqueous solutions, but show a selective, fast degradation upon exposure to hydrogen peroxide containing solutions. Since the post-polymerization functionalization route allows simple access to polymer backbones with a broad range of molecular weights, the approach of using the inorganic backbone as a platform significantly expands the toolbox of polymers capable of stimuli-responsive degradation.

  12. Synthesis of novel cationic lipids with fully or partially non-scissile linkages between the hydrocarbon chains and pseudoglyceryl backbone

    Indian Academy of Sciences (India)

    Santanu Bhattacharya; Saubhik Haldar

    2002-06-01

    Five novel cationic lipids with fully or partially non-scissile linkage regions between the pseudoglyceryl backbone and the hydrocarbon chains have been synthesized. The membrane-forming properties of these new lipids are briefly presented.

  13. Structure-based classification and ontology in chemistry

    Directory of Open Access Journals (Sweden)

    Hastings Janna

    2012-04-01

    Full Text Available Abstract Background Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving relevant results from the available information, and organising those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures, while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies. Results We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches. Conclusion Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational

  14. First principles based multiparadigm modeling of electronic structures and dynamics

    Science.gov (United States)

    Xiao, Hai

    enabling the tunability of CBO. We predict that Na further improves the CBO through electrostatically elevating the valence levels to decrease the CBO, explaining the observed essential role of Na for high performance. Moreover we find that K leads to a dramatic decrease in the CBO to 0.05 eV, much better than Na. We suggest that the efficiency of CIGS devices might be improved substantially by tuning the ratio of Na to K, with the improved phase stability of Na balancing phase instability from K. All these defects reduce interfacial stability slightly, but not significantly. A number of exotic structures have been formed through high pressure chemistry, but applications have been hindered by difficulties in recovering the high pressure phase to ambient conditions (i.e., one atmosphere and room temperature). Here we use dispersion-corrected DFT (PBE-ulg flavor) to predict that above 60 GPa the most stable form of N2O (the laughing gas in its molecular form) is a 1D polymer with an all-nitrogen backbone analogous to cis-polyacetylene in which alternate N are bonded (ionic covalent) to O. The analogous trans-polymer is only 0.03-0.10 eV/molecular unit less stable. Upon relaxation to ambient conditions both polymers relax below 14 GPa to the same stable non-planar trans-polymer, accompanied by possible electronic structure transitions. The predicted phonon spectrum and dissociation kinetics validate the stability of this trans-poly-NNO at ambient conditions, which has potential applications as a new type of conducting polymer with all-nitrogen chains and as a high-energy oxidizer for rocket propulsion. This work illustrates in silico materials discovery particularly in the realm of extreme conditions. Modeling non-adiabatic electron dynamics has been a long-standing challenge for computational chemistry and materials science, and the eFF method presents a cost-efficient alternative. However, due to the deficiency of FSG representation, eFF is limited to low-Z elements with

  15. A Component-Based Debugging Approach for Detecting Structural Inconsistencies in Declarative Equation Based Models

    Institute of Scientific and Technical Information of China (English)

    Jian-Wan Ding; Li-Ping Chen; Fan-Li Zhou

    2006-01-01

    Object-oriented modeling with declarative equation based languages often unconsciously leads to structural inconsistencies. Component-based debugging is a new structural analysis approach that addresses this problem by analyzing the structure of each component in a model to separately locate faulty components. The analysis procedure is performed recursively based on the depth-first rule. It first generates fictitious equations for a component to establish a debugging environment, and then detects structural defects by using graph theoretical approaches to analyzing the structure of the system of equations resulting from the component. The proposed method can automatically locate components that cause the structural inconsistencies, and show the user detailed error messages. This information can be a great help in finding and localizing structural inconsistencies, and in some cases pinpoints them immediately.

  16. Research on Web-Based Product Structure and Configuration Management

    Institute of Scientific and Technical Information of China (English)

    CHENJi-zhong; TIANLing; XUXiao-hui

    2004-01-01

    An enhanced system architecture of Web-based product structure and configuration management system along with its, functions are is presented. The key techniques, such as construction of object models of product structure and product configuration, hybrid approach method in product configuration management, sharing and integration of heterogeneous product data, integration with other sub-systems, are discussed too. A prototype system is developed by J2EE technology.

  17. Structural Identification and Monitoring based on Uncertain/Limited Information

    Directory of Open Access Journals (Sweden)

    Chatzi Eleni N.

    2015-01-01

    Full Text Available The goal of the present study is to propose a structural identification framework able to exploit both vibrational response and operational condition information in extracting structural models, able to represent the systemspecific structural behavior in its complete operational spectrum. In doing so, a scheme need be derived for the extraction of salient features, which are indicative of structural condition. Such a scheme should account for variations attributed to operational effects, such as environmental and operational load variations, and which likely lie within regular structural condition bounds, versus variations which indicate short- or long-term damage effects. The latter may be achieved via coupling of sparse, yet diverse, monitoring information with appropriate stochastic tools, able to infer the underlying dependences between the monitored input and output data. This in turn allows for extraction of quantities, or features, relating to structural condition, which may further be utilized as performance indicators. The computational tool developed herein for realizing such a framework, termed the PCE-ICA scheme, is based on the use of Polynomial Chaos Expansion (PCE tool, along with an Independent Component Analysis (ICA algorithm. The benefits of additionally fusing a data-driven system model will further be discussed for the case of complex structural response. The method is assessed via implementation on field data acquired from diverse structural systems, namely a benchmark bridge case study and a wind turbine tower structure, revealing a robust condition assessment tool.

  18. Gradient-based adaptation of continuous dynamic model structures

    Science.gov (United States)

    La Cava, William G.; Danai, Kourosh

    2016-01-01

    A gradient-based method of symbolic adaptation is introduced for a class of continuous dynamic models. The proposed model structure adaptation method starts with the first-principles model of the system and adapts its structure after adjusting its individual components in symbolic form. A key contribution of this work is its introduction of the model's parameter sensitivity as the measure of symbolic changes to the model. This measure, which is essential to defining the structural sensitivity of the model, not only accommodates algebraic evaluation of candidate models in lieu of more computationally expensive simulation-based evaluation, but also makes possible the implementation of gradient-based optimisation in symbolic adaptation. The proposed method is applied to models of several virtual and real-world systems that demonstrate its potential utility.

  19. An RNA secondary structure prediction method based on minimum and suboptimal free energy structures.

    Science.gov (United States)

    Fu, Haoyue; Yang, Lianping; Zhang, Xiangde

    2015-09-07

    The function of an RNA-molecule is mainly determined by its tertiary structures. And its secondary structure is an important determinant of its tertiary structure. The comparative methods usually give better results than the single-sequence methods. Based on minimum and suboptimal free energy structures, the paper presents a novel method for predicting conserved secondary structure of a group of related RNAs. In the method, the information from the known RNA structures is used as training data in a SVM (Support Vector Machine) classifier. Our method has been tested on the benchmark dataset given by Puton et al. The results show that the average sensitivity of our method is higher than that of other comparative methods such as CentroidAlifold, MXScrana, RNAalifold, and TurboFold.

  20. Integrated Reliability-Based Optimal Design of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle

    1987-01-01

    the reliability decreases with time it is often necessary to design an inspection and repair programme. For example the reliability of offshore steel structures decreases with time due to corrosion and development of fatigue cracks. Until now most inspection and repair strategies are based on experience rather......In conventional optimal design of structural systems the weight or the initial cost of the structure is usually used as objective function. Further, the constraints require that the stresses and/or strains at some critical points have to be less than some given values. Finally, all variables...... and parameters are assumed to be deterministic quantities. In this paper a probabilistic formulation is used. Some of the quantities specifying the load and the strength of the structure are modelled as random variables, and the constraints specify that the reliability of the structure has to exceed some given...

  1. A wavelength demultiplexing structure based on graphene nanoribbon resonators

    Science.gov (United States)

    Zhuang, Huawei; Sheng, Shiwei; Kong, Fanmin; Li, Kang; Wang, Yuling

    2016-12-01

    A wavelength demultiplexing (WDM) structure based on graphene nanoribbon resonators is proposed and numerically investigated by the finite-difference time-domain (FDTD) method. The demultiplexing wavelength can be easily derived by adjusting the length of the resonator, which is accurately explained by the Fabry-Perot (F-P) resonant theory. Meanwhile, the transmission characteristics of the WDM structure are influenced by the coupling distance between the resonator and drop/bus waveguides, and the performance of the WDM device is analyzed at different nanoribbon width and chemical potential. In addition, in order to improve the transmission efficiency from the drop waveguide, a reflection structure is introduced at the end of the bus waveguide. The exact mechanism for the WDM structure is analyzed in detail using the temporal coupled-mode theory. The proposed structure will have potential applications in the field of ultra-compact WDM systems in highly integrated optical circuits.

  2. Vortical Structures in CT-based Breathing Lung Models

    Science.gov (United States)

    Choi, Jiwoong; Lee, Changhyun; Hoffman, Eric; Lin, Ching-Long

    2016-11-01

    The 1D-3D coupled computational fluid dynamics (CFD) lung model is applied to study vortical structures in the human airways during normal breathing cycles. During inhalation, small vortical structures form around the turbulent laryngeal jet and Taylor-Gőrtler-like vortices form near the curved walls in the supraglottal region and at airway bifurcations. On exhalation elongated vortical tubes are formed in the left main bronchus, whereas a relatively slower stream is observed in the right main bronchus. These structures result in helical motions in the trachea, producing long lasting high wall shear stress on the wall. The current study elucidates that the correct employment of image-based airway deformation and lung deflation information is crucial for capturing the physiologically consistent regional airflow structures. The pathophysiological implications of these structures in destruction of tracheal wall will be discussed.

  3. Secure data structures based on multi-party computation

    DEFF Research Database (Denmark)

    Toft, Tomas

    2011-01-01

    This work considers data structures based on multi-party computation (MPC) primitives: structuring secret (e.g. secret shared and potentially unknown) data such that it can both be queried and updated efficiently. Implementing an oblivious RAM (ORAM) using MPC allows any existing data structure...... to be realized using MPC primitives, however, by focusing on a specific example -- a priority queue -- it is shown that it is possible to achieve much better results than the generic solutions can provide. Moreover, the techniques differ significantly from existing ORAM constructions. Indeed it has recently been...

  4. A Sign-Based Phrase Structure Grammar for Turkish

    CERN Document Server

    Sehitoglu, O T

    1996-01-01

    This study analyses Turkish syntax from an informational point of view. Sign based linguistic representation and principles of HPSG (Head-driven Phrase Structure Grammar) theory are adapted to Turkish. The basic informational elements are nested and inherently sorted feature structures called signs. In the implementation, logic programming tool ALE (Attribute Logic Engine) which is primarily designed for implementing HPSG grammars is used. A type and structure hierarchy of Turkish language is designed. Syntactic phenomena such a s subcategorization, relative clauses, constituent order variation, adjuncts, nomina l predicates and complement-modifier relations in Turkish are analyzed. A parser is designed and implemented in ALE.

  5. Optical-based smart structures for tamper-indicating applications

    Energy Technology Data Exchange (ETDEWEB)

    Sliva, P.; Anheier, N.C.; Simmons, K.L.; Undem, H.A.

    1996-11-01

    This report is a compilation of several related projects performed from 1991 through 1996 concerning the design, construction, and application of optical-based smart structure to tamper-indicating and sensing secure containers. Due to several influences, the projects were carried through to varying degrees of completion. Cancellation of the overall project at the client level motivated the authors to gather all of the technology and ideas about smart structures developed during these several projects, whether completed or just conceptualized, into one document. Although each section individually discusses a specific project, the overall document is written chronologically with each successive section showing how increased smart structure complexity was integrated into the container.

  6. Structure based design of 11β-HSD1 inhibitors.

    Science.gov (United States)

    Singh, Suresh; Tice, Colin

    2010-11-01

    Controlling elevated tissue-specific levels of cortisol may provide a novel therapeutic approach for treating metabolic syndrome. This concept has spurred large scale medicinal chemistry efforts in the pharmaceutical industry for the design of 11β-HSD1 inhibitors. High resolution X-ray crystal structures of inhibitors in complex with the enzyme have facilitated the structure-based design of diverse classes of molecules. A summary of binding modes, trends in structure-activity relationships, and the pharmacodynamic data of inhibitors from each class is presented.

  7. SVM-based method for protein structural class prediction using secondary structural content and structural information of amino acids.

    Science.gov (United States)

    Mohammad, Tabrez Anwar Shamim; Nagarajaram, Hampapathalu Adimurthy

    2011-08-01

    The knowledge collated from the known protein structures has revealed that the proteins are usually folded into the four structural classes: all-α, all-β, α/β and α + β. A number of methods have been proposed to predict the protein's structural class from its primary structure; however, it has been observed that these methods fail or perform poorly in the cases of distantly related sequences. In this paper, we propose a new method for protein structural class prediction using low homology (twilight-zone) protein sequences dataset. Since protein structural class prediction is a typical classification problem, we have developed a Support Vector Machine (SVM)-based method for protein structural class prediction that uses features derived from the predicted secondary structure and predicted burial information of amino acid residues. The examination of different individual as well as feature combinations revealed that the combination of secondary structural content, secondary structural and solvent accessibility state frequencies of amino acids gave rise to the best leave-one-out cross-validation accuracy of ~81% which is comparable to the best accuracy reported in the literature so far.

  8. On structure-based priors in Bayesian geophysical inversion

    Science.gov (United States)

    de Pasquale, G.; Linde, N.

    2017-03-01

    Bayesian methods are extensively used to analyse geophysical data sets. A critical and somewhat overlooked component of high-dimensional Bayesian inversion is the definition of the prior probability density function that describes the joint probability of model parameters before considering available data sets. If insufficient prior information is available about model parameter correlations, then it is tempting to assume that model parameters are uncorrelated. When working with a spatially gridded model representation, this overparametrization leads to posterior realizations with far too much variability to be deemed realistic from a geological perspective. In this study, we introduce a new approach for structure-based prior sampling with Markov chain Monte Carlo that is suitable when only limited prior information is available. We evaluate our method using model structure measures related to standard roughness and damping metrics for l1- and l2-norms. We show that our structure-based prior approach is able to adequately sample the chosen prior distribution of model structure. The usefulness and applicability of the methodology is demonstrated on synthetic and field-based crosshole ground penetrating radar data. We find that our method provides posterior model realizations and statistics that are significantly more satisfactory than those based on underlying assumptions of uncorrelated model parameters or on explicit penalties on model structure within an empirical Bayes framework.

  9. ngs_backbone: a pipeline for read cleaning, mapping and SNP calling using Next Generation Sequence

    Directory of Open Access Journals (Sweden)

    Cañizares Joaquin

    2011-06-01

    Full Text Available Abstract Background The possibilities offered by next generation sequencing (NGS platforms are revolutionizing biotechnological laboratories. Moreover, the combination of NGS sequencing and affordable high-throughput genotyping technologies is facilitating the rapid discovery and use of SNPs in non-model species. However, this abundance of sequences and polymorphisms creates new software needs. To fulfill these needs, we have developed a powerful, yet easy-to-use application. Results The ngs_backbone software is a parallel pipeline capable of analyzing Sanger, 454, Illumina and SOLiD (Sequencing by Oligonucleotide Ligation and Detection sequence reads. Its main supported analyses are: read cleaning, transcriptome assembly and annotation, read mapping and single nucleotide polymorphism (SNP calling and selection. In order to build a truly useful tool, the software development was paired with a laboratory experiment. All public tomato Sanger EST reads plus 14.2 million Illumina reads were employed to test the tool and predict polymorphism in tomato. The cleaned reads were mapped to the SGN tomato transcriptome obtaining a coverage of 4.2 for Sanger and 8.5 for Illumina. 23,360 single nucleotide variations (SNVs were predicted. A total of 76 SNVs were experimentally validated, and 85% were found to be real. Conclusions ngs_backbone is a new software package capable of analyzing sequences produced by NGS technologies and predicting SNVs with great accuracy. In our tomato example, we created a highly polymorphic collection of SNVs that will be a useful resource for tomato researchers and breeders. The software developed along with its documentation is freely available under the AGPL license and can be downloaded from http://bioinf.comav.upv.es/ngs_backbone/ or http://github.com/JoseBlanca/franklin.

  10. Distance matrix-based approach to protein structure prediction.

    Science.gov (United States)

    Kloczkowski, Andrzej; Jernigan, Robert L; Wu, Zhijun; Song, Guang; Yang, Lei; Kolinski, Andrzej; Pokarowski, Piotr

    2009-03-01

    Much structural information is encoded in the internal distances; a distance matrix-based approach can be used to predict protein structure and dynamics, and for structural refinement. Our approach is based on the square distance matrix D = [r(ij)(2)] containing all square distances between residues in proteins. This distance matrix contains more information than the contact matrix C, that has elements of either 0 or 1 depending on whether the distance r (ij) is greater or less than a cutoff value r (cutoff). We have performed spectral decomposition of the distance matrices D = sigma lambda(k)V(k)V(kT), in terms of eigenvalues lambda kappa and the corresponding eigenvectors v kappa and found that it contains at most five nonzero terms. A dominant eigenvector is proportional to r (2)--the square distance of points from the center of mass, with the next three being the principal components of the system of points. By predicting r (2) from the sequence we can approximate a distance matrix of a protein with an expected RMSD value of about 7.3 A, and by combining it with the prediction of the first principal component we can improve this approximation to 4.0 A. We can also explain the role of hydrophobic interactions for the protein structure, because r is highly correlated with the hydrophobic profile of the sequence. Moreover, r is highly correlated with several sequence profiles which are useful in protein structure prediction, such as contact number, the residue-wise contact order (RWCO) or mean square fluctuations (i.e. crystallographic temperature factors). We have also shown that the next three components are related to spatial directionality of the secondary structure elements, and they may be also predicted from the sequence, improving overall structure prediction. We have also shown that the large number of available HIV-1 protease structures provides a remarkable sampling of conformations, which can be viewed as direct structural information about the

  11. Reliability-Based Structural Optimization of Wave Energy Converters

    DEFF Research Database (Denmark)

    Ambühl, Simon; Kramer, Morten; Sørensen, John Dalsgaard

    2014-01-01

    More and more wave energy converter (WEC) concepts are reaching prototype level. Once the prototype level is reached, the next step in order to further decrease the levelized cost of energy (LCOE) is optimizing the overall system with a focus on structural and maintenance (inspection) costs......, as well as on the harvested power from the waves. The target of a fully-developed WEC technology is not maximizing its power output, but minimizing the resulting LCOE. This paper presents a methodology to optimize the structural design of WECs based on a reliability-based optimization problem...

  12. Evaluation Method of Web Site Structure Based on Web Structure Mining

    Institute of Scientific and Technical Information of China (English)

    Li Jun-e; Zhou Dong-ru

    2003-01-01

    The structure of Web site hecarne more complex titan before. During the design period of a Web site, the lack of model and method results in improper Web structure,which depend on the designer's experience. From the point of view of software engineering, every period in the software life must be evaluated before starting the next period's work. It is very important and essential to search relevant methods for evaluating Web structure before the site is completed. In this work, after studying the related work about the Web struc lure mining and analyzing the major structure mining methods (Page-rank and Hub/Authority), a method based on the Page-rank for Web structure evaluation in design stage is proposecL A Web structure modeling language WSML is designed, and the implement strategies for evaluating system of the Web site structure are given out. Web structure mining has being used mainly in search engines before. It is the first time to employ the Web structure mining technology to evaluate a Web structure in the design period of a Web site. It contributes to the formalization of the design documents for Web site and the improving of software engineering for large scale Web site, and the evaluating system is a practical tool for Web site construction.

  13. SEVA Linkers: A Versatile and Automatable DNA Backbone Exchange Standard for Synthetic Biology

    DEFF Research Database (Denmark)

    Kim, Se Hyeuk; Cavaleiro, Mafalda; Rennig, Maja

    2016-01-01

    DNA vectors serve to maintain and select recombinant DNA in cell factories, and as design complexity increases, there is a greater need for well-characterized parts and methods for their assembly. Standards in synthetic biology are top priority, but standardizing molecular cloning contrasts...... flexibility, and different researchers prefer and master different molecular technologies. Here, we describe a new, highly versatile and automatable standard “SEVA linkers” for vector exchange. SEVA linkers enable backbone swapping with 20 combinations of classical enzymatic restriction/ligation, Gibson...... to the synthetic biology community....

  14. Synthesis of Aminophosphine Ligands with Binaphthyl Backbones for Silver(I)-catalyzed Enantioselective Allylation of Benzaldehyde

    Institute of Scientific and Technical Information of China (English)

    WANG,Yi(王以); JI,Bao-Ming(吉保明); DING,Kui-Ling(丁奎岭)

    2002-01-01

    A series of aminophosphine ligands was synthesized from 2amino-2′-hydroxy-1,1′-binaphthyl (NOBIN). Their asymmetric induction efficiency was examined for silver(I)catalyzed enantioselective allylation reaction of benzaldehyde with allyltributyltin.Under the optimized reaction conditions,quantitative yield as well as moderate ee value (54.5% ee)of product was achieved by the catalysis with silver(I)/3 complex. The effects of the binaphthyl backbone and the substituted situated at chelating N, Patoms on enantioselectivity of the reaction were also discussed.

  15. Relative specificities of water and ammonia losses from backbone fragments in collision-activated dissociation

    DEFF Research Database (Denmark)

    Savitski, Mikhail M; Kjeldsen, Frank; Nielsen, Michael L

    2007-01-01

    Analysis of a database containing over 20,000 high-resolution collision-activation mass spectra of tryptic peptide dications was employed to study the relative specificity of neutral losses from backbone fragments. The high resolution of the FTMS instrument allowed for the first time the first...... isotope of the water loss and the monoisotope of the ammonia loss to be distinguished. Contrary to a popular belief, water losses from y' ions are not specific enough to rely upon for detecting the presence of amino acids with oxygen in the side chains. At the same time, ammonia loss from b ions...

  16. Direct Formation of the C5′-Radical in the Sugar-Phosphate Backbone of DNA by High Energy Radiation

    Science.gov (United States)

    Adhikary, Amitava; Becker, David; Palmer, Brian J.; Heizer, Alicia N.; Sevilla, Michael D.

    2012-01-01

    Neutral sugar radicals formed in DNA sugar-phosphate backbone are well-established as precursors of biologically important damage such as DNA-strand scission and crosslinking. In this work, we present electron spin resonance (ESR) evidence showing that the sugar radical at C5′ (C5′•) is one of the most abundant (ca. 30%) sugar radicals formed by γ- and Ar ion-beam irradiated hydrated DNA samples. Taking dimethyl phosphate as a model of sugar-phosphate backbone, ESR and theoretical (DFT) studies of γ-irradiated dimethyl phosphate were carried out. CH3OP(O2−)OCH2• is formed via deprotonation from the methyl group of directly ionized dimethyl phosphate at 77 K. Formation of CH3OP(O2−)OCH2• is independent of dimethyl phosphate concentration (neat or in aqueous solution) or pH. ESR spectra of C5′• found in DNA and of CH3OP(O2−)OCH2• do not show an observable β-phosphorous hyperfine coupling (HFC). Further, C5′• found in DNA does not show a significant C4′-H β–proton HFC. Applying the DFT/B3LYP/6-31G(d) method, a study of conformational dependence of the phosphorous HFC in CH3OP(O2−)OCH2• shows that in its minimum energy conformation, CH3OP(O2−)OCH2• has a negligible β-phosphorous HFC. Based on these results, formation of radiation-induced C5′• is proposed to occur via a very rapid deprotonation from the directly ionized sugar-phosphate backbone and rate of this deprotonation must be faster than that of energetically downhill transfer of the unpaired spin (hole) from ionized sugar-phosphate backbone to the DNA bases. Moreover, C5′• in irradiated DNA is found to be in a conformation that does not exhibit β proton or β phosphorous HFCs. PMID:22553971

  17. Conformational energetics of cationic backbone rearrangements in triterpenoid biosynthesis provide an insight into enzymatic control of product.

    Science.gov (United States)

    Kürti, László; Chein, Rong-Jie; Corey, E J

    2008-07-16

    2,3-( S)-Oxidosqualene (C 30H 50O) serves as a versatile starting point for the remarkable biosynthesis of many isomeric naturally occurring triterpenoids of formula C 30H 50O. These biosyntheses all involve polycyclization via cationic intermediates. The fully cyclized primary products then are converted to various structures by cationic rearrangements involving the polycyclic backbone. The energetics of these rearrangements has been examined by B3LYP 6-31 G* DFT calculations and by ab initio Hartree-Fock calculations at the 6-31G* or 3-21G(*) level. The results have led to the conclusion that the biosynthesis of friedelin, the most drastically rearranged of the pentacyclic triterpenes, involves a complex nonstop process, with no stable intermediates between 2,3-( S)-oxidosqualene and friedelin. It is proposed that this single-reaction biosynthesis consists of pentacyclization to the lupanyl cation followed directly by a sequence of 10 suprafacial 1,2-shifts of carbon and hydrogen, driven by the large exergonicity of the pentacyclization and electrostatic acceleration of the rearrangement steps.

  18. Aggregation and Gelation of Aromatic Polyamides with Parallel and Anti-parallel Alignment of Molecular Dipole Along the Backbone

    Science.gov (United States)

    Zhu, Dan; Shang, Jing; Ye, Xiaodong; Shen, Jian

    2016-12-01

    The understanding of macromolecular structures and interactions is important but difficult, due to the facts that a macromolecules are of versatile conformations and aggregate states, which vary with environmental conditions and histories. In this work two polyamides with parallel or anti-parallel dipoles along the linear backbone, named as ABAB (parallel) and AABB (anti-parallel) have been studied. By using a combination of methods, the phase behaviors of the polymers during the aggregate and gelation, i.e., the forming or dissociation processes of nuclei and fibril, cluster of fibrils, and cluster-cluster aggregation have been revealed. Such abundant phase behaviors are dominated by the inter-chain interactions, including dispersion, polarity and hydrogen bonding, and correlatd with the solubility parameters of solvents, the temperature, and the polymer concentration. The results of X-ray diffraction and fast-mode dielectric relaxation indicate that AABB possesses more rigid conformation than ABAB, and because of that AABB aggregates are of long fibers while ABAB is of hairy fibril clusters, the gelation concentration in toluene is 1 w/v% for AABB, lower than the 3 w/v% for ABAB.

  19. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

    2016-06-01

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.

  20. Impairment assessment of orthogonal frequency division multiplexing over dispersion-managed links in backbone and backhaul networks

    Science.gov (United States)

    Tamilarasan, Ilavarasan; Saminathan, Brindha; Murugappan, Meenakshi

    2016-04-01

    The past decade has seen the phenomenal usage of orthogonal frequency division multiplexing (OFDM) in the wired as well as wireless communication domains, and it is also proposed in the literature as a future proof technique for the implementation of flexible resource allocation in cognitive optical networks. Fiber impairment assessment and adaptive compensation becomes critical in such implementations. A comprehensive analytical model for impairments in OFDM-based fiber links is developed. The proposed model includes the combined impact of laser phase fluctuations, fiber dispersion, self phase modulation, cross phase modulation, four-wave mixing, the nonlinear phase noise due to the interaction of amplified spontaneous emission with fiber nonlinearities, and the photodetector noises. The bit error rate expression for the proposed model is derived based on error vector magnitude estimation. The performance analysis of the proposed model is presented and compared for dispersion compensated and uncompensated backbone/backhaul links. The results suggest that OFDM would perform better for uncompensated links than the compensated links due to the negligible FWM effects and there is a need for flexible compensation. The proposed model can be employed in cognitive optical networks for accurate assessment of fiber-related impairments.

  1. Redox-controlled backbone dynamics of human cytochrome c revealed by {sup 15}N NMR relaxation measurements

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Koichi [Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810 (Japan); Kamiya, Masakatsu [Graduate School of Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Uchida, Takeshi [Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810 (Japan); Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan); Kawano, Keiichi [Graduate School of Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810 (Japan); Ishimori, Koichiro, E-mail: koichiro@sci.hokudai.ac.jp [Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810 (Japan); Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan)

    2010-07-23

    Research highlights: {yields} The dynamic parameters for the backbone dynamics in Cyt c were determined. {yields} The backbone mobility of Cyt c is highly restricted due to the covalently bound heme. {yields} The backbone mobility of Cyt c is more restricted upon the oxidation of the heme. {yields} The redox-dependent dynamics are shown in the backbone of Cyt c. {yields} The backbone dynamics of Cyt c would regulate the electron transfer from Cyt c. -- Abstract: Redox-controlled backbone dynamics in cytochrome c (Cyt c) were revealed by 2D {sup 15}N NMR relaxation experiments. {sup 15}N T{sub 1} and T{sub 2} values and {sup 1}H-{sup 15}N NOEs of uniformly {sup 15}N-labeled reduced and oxidized Cyt c were measured, and the generalized order parameters (S{sup 2}), the effective correlation time for internal motion ({tau}{sub e}), the {sup 15}N exchange broadening contributions (R{sub ex}) for each residue, and the overall correlation time ({tau}{sub m}) were estimated by model-free dynamics formalism. These dynamic parameters clearly showed that the backbone dynamics of Cyt c are highly restricted due to the covalently bound heme that functions as the stable hydrophobic core. Upon oxidation of the heme iron in Cyt c, the average S{sup 2} value was increased from 0.88 {+-} 0.01 to 0.92 {+-} 0.01, demonstrating that the mobility of the backbone is further restricted in the oxidized form. Such increases in the S{sup 2} values were more prominent in the loop regions, including amino acid residues near the thioether bonds to the heme moiety and positively charged region around Lys87. Both of the regions are supposed to form the interaction site for cytochrome c oxidase (CcO) and the electron pathway from Cyt c to CcO. The redox-dependent mobility of the backbone in the interaction site for the electron transfer to CcO suggests an electron transfer mechanism regulated by the backbone dynamics in the Cyt c-CcO system.

  2. Porous structures based on nanopolysaccharides for medical applications

    OpenAIRE

    2014-01-01

    Recently, the use of bio-based nanomaterials has attracted much interest in medical applications due to their cytocompatibility, good moisture stability, good mechanical properties, hydrophilic surfaces and their ability to form porous structures. The aim of this work is to develop porous nanocomposites based on nanochitin and nanocellulose with controlled pore size and porosity in order to facilitate cell growth and interconnectivity and to investigate their potential in wound dressing and c...

  3. Structure-based design of combinatorial mutagenesis libraries.

    Science.gov (United States)

    Verma, Deeptak; Grigoryan, Gevorg; Bailey-Kellogg, Chris

    2015-05-01

    The development of protein variants with improved properties (thermostability, binding affinity, catalytic activity, etc.) has greatly benefited from the application of high-throughput screens evaluating large, diverse combinatorial libraries. At the same time, since only a very limited portion of sequence space can be experimentally constructed and tested, an attractive possibility is to use computational protein design to focus libraries on a productive portion of the space. We present a general-purpose method, called "Structure-based Optimization of Combinatorial Mutagenesis" (SOCoM), which can optimize arbitrarily large combinatorial mutagenesis libraries directly based on structural energies of their constituents. SOCoM chooses both positions and substitutions, employing a combinatorial optimization framework based on library-averaged energy potentials in order to avoid explicitly modeling every variant in every possible library. In case study applications to green fluorescent protein, β-lactamase, and lipase A, SOCoM optimizes relatively small, focused libraries whose variants achieve energies comparable to or better than previous library design efforts, as well as larger libraries (previously not designable by structure-based methods) whose variants cover greater diversity while still maintaining substantially better energies than would be achieved by representative random library approaches. By allowing the creation of large-scale combinatorial libraries based on structural calculations, SOCoM promises to increase the scope of applicability of computational protein design and improve the hit rate of discovering beneficial variants. While designs presented here focus on variant stability (predicted by total energy), SOCoM can readily incorporate other structure-based assessments, such as the energy gap between alternative conformational or bound states.

  4. Density-Based and Transport-Based Core-Periphery Structures in Networks

    CERN Document Server

    Lee, Sang Hoon; Porter, Mason A

    2013-01-01

    Networks often possess mesoscale structures, and studying them can yield insights into both structure and function. It is most common to study community structure, but numerous other types of mesoscale structures also exist. In this paper, we examine core-periphery structures based on both density and transportation. In such structures, core network components are well-connected both among themselves and to peripheral components, which are not well-connected to anything. We examine core-periphery structures in a wide range of examples of transportation, social, and financial networks---including road networks in large urban areas, a rabbit warren, a dolphin social network, a European interbank network, and a migration network between counties in the United States. We illustrate that a recently developed transport-based notion of node coreness is very useful for characterizing transportation networks. We also generalize this notion to examine core versus peripheral edges, and we show that this new diagnostic i...

  5. Tunable, omnidirectional structural color on reflection based on metal-SiOx-metal structure

    Science.gov (United States)

    Yang, Chenying; Mao, Kening; Shen, Weidong; Fang, Bo; Fang, Xu; Zhang, Xing; Zhang, Yueguang; Liu, Xu

    2016-12-01

    An omnidirectional structural color based on the metal-SiOx-metal stack structure is proposed, which can present the same perceived color for a broad range of incidence angles. The tunable structural color can be obtained with adjustable intermediate dielectric layer by simply adjusting the deposition condition, especially the oxygen flow rate during the deposition processes. The resonance condition can be satisfied across the whole visible light region with this special dielectric. The strong absorption caused by the resonance within the metal-SiOx-metal structure accounts for the efficient spectral filtering feature, and the constant phase shift within the dielectric layer leads to angle insensitivity of this color filter. This simple color tuning method for omnidirectional structural colors can have a great potential in various applications such as displaying, imaging, colorful decoration, anti-counterfeiting and so forth.

  6. Crystal chemistry and structural design of iron-based superconductors

    Institute of Scientific and Technical Information of China (English)

    Jiang Hao; Sun Yun-Lei; Xu Zhu-An; Cao Guang-Han

    2013-01-01

    The second class of high-temperature superconductors (HTSCs),iron-based pnictides and chalcogenides,necessarily contain Fe2X2 (“X” refers to a pnictogen or a chalcogen element) layers,just like the first class of HTSCs which possess the essential CuO2 sheets.So far,dozens of iron-based HTSCs,classified into nine groups,have been discovered.In this article,the crystal-chemistry aspects of the known iron-based superconductors are reviewed and summarized by employing “hard and soft acids and bases (HSAB)” concept.Based on these understandings,we propose an alternative route to exploring new iron-based superconductors via rational structural design.

  7. Synthesis and Crystal Structures of Schiff Bases Bearing Ferrocenylphenyl Groups

    Institute of Scientific and Technical Information of China (English)

    Yan XU; Yong FU; Mao Ping SONG; Yang Jie WU

    2005-01-01

    The Schiff bases bearing ferrocenylphenyl and diferrocenylphenyl groups were synthesized by the reactions of m-ferrocenylaniline with salicylaldehyde or 1, 4-bis (2'-formylphenyl)-1, 4-dioxabutane. The title compounds were characterized by elemental analysis, IR, 1H NMR and X-ray structural determination.

  8. Nominal and Structural Subtyping in Component-Based Programming

    DEFF Research Database (Denmark)

    Ostermann, Klaus

    2007-01-01

    type. We analyze structural and different flavors of nominal subtyping from the perspective of component-based programming, where issues such as blame assignment and modular extensibility are important. Our analysis puts various existing subtyping mechanisms into a common frame of reference...

  9. Reliability-Based Inspection Planning for Structural Systems

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    1993-01-01

    A general model for reliability-based optimal inspection and repair strategies for structural systems is described. The total expected costs in the design lifetime is minimized with the number of inspections, the inspection times and efforts as decision variables. The equivalence of this model wi...

  10. Structural segmentation of music based on repeated harmonies

    NARCIS (Netherlands)

    de Haas, W.B.; Volk, A.; Wiering, F.

    2013-01-01

    In this paper we present a simple, yet powerful method for deriving the structural segmentation of a musical piece based on repetitions in chord sequences, called FORM. Repetition in harmony is a fundamental factor in constituting musical form. However, repeated pattern discovery in music still rema

  11. Electronic structure of Fe- vs. Ru-based dye molecules

    DEFF Research Database (Denmark)

    Johnson, Phillip S.; Cook, Peter L.; Zegkinoglou, Ioannis;

    2013-01-01

    In order to explore whether Ru can be replaced by inexpensive Fe in dye molecules for solar cells, the differences in the electronic structure of Fe- and Ru-based dyes are investigated by X-ray absorption spectroscopy and first-principles calculations. Molecules with the metal in a sixfold...

  12. Interactive Reliability-Based Optimization of Structural Systems

    DEFF Research Database (Denmark)

    Pedersen, Claus

    In order to introduce the basic concepts within the field of reliability-based structural optimization problems, this chapter is devoted to a brief outline of the basic theories. Therefore, this chapter is of a more formal nature and used as a basis for the remaining parts of the thesis. In secti...

  13. An improved AODV routing protocol based on tower structure

    Directory of Open Access Journals (Sweden)

    Li Yong Qiang

    2016-01-01

    Full Text Available The paper proposed a new routing protocol(IAODV based on tower structure in the Ad Hoc network for the problem which Location Routing Protocol need hardware and Complex algorithm. By the simulation, The complexity of the new routing protocol is reduced without reducing the performance of the network.

  14. Knowledge-based System Prototype in Structural Component Design Based on FM

    Institute of Scientific and Technical Information of China (English)

    JIANG; Tao; LI; Qing-fen; LI; Ming; FU; Wei

    2002-01-01

    A knowledge-based system in structural component design based on fracture mechanics is developed in this paper. The system consists of several functional parts: a general inference engine, a set of knowledge bases and data-bases, an interpretation engine, a bases administration system and the interface. It can simulate a human expert to make analysis and design scheme mainly for four kinds of typical structural components widely used in shipbuilding industry: pressure vessels, huge rotation constructions, pump-rod and welded structures. It is an open system which may be broadened and perfected to cover a wider range of engineering application through the modification and enlargement of knowledge bases and data-bases. It has a natural and friendly interface that may be easily operated. An on-line help service is also provided.

  15. Gradient based structural optimization with fatigue constraints of jacket structures for offshore wind turbines

    DEFF Research Database (Denmark)

    Oest, Jacob; Overgaard, Lars Christian; Lund, Erik

    2015-01-01

    Investigating the fatigue life of support structures of offshore wind turbines is imperative to avoid unexpected failure. Therefore, in the context of structural optimization, including fatigue constraints is crucial, as the optimized design will meet the design criteria early in the design process...... without the need for extensive manual post-processing. Ultimately, the optimized design may be lighter and thus reduce both production and installation cost. The aim of this work is to present such a gradient based optimization method with fatigue constraints of jacket structures for the preliminary...

  16. Inelastic Structural Control Based on MBC and FAM

    Directory of Open Access Journals (Sweden)

    Li Gang

    2011-01-01

    Full Text Available A complex structure has the characters of many degrees of freedom and intricate shape, especially inelastic behavior under strong external loadings. It is hard to apply the structural control technology to it. In this paper, a new method that combines the Market-Based Control (MBC strategy and Force Analogy Method (FAM is presented to analyze the inelastic behavior of structure with magnetorheological dampers. The MBC is used to reduce the structural vibration response, and FAM is proposed to perform the inelastic analysis. A numerical example is used to compare the control effect of the new method and LQR algorithm, which show the accuracy and efficiency of the proposed computational method.

  17. A fingerprint based metric for measuring similarities of crystalline structures

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Li; Fuhrer, Tobias; Schaefer, Bastian; Grauzinyte, Migle; Goedecker, Stefan, E-mail: stefan.goedecker@unibas.ch [Department of Physics, Universität Basel, Klingelbergstr. 82, 4056 Basel (Switzerland); Amsler, Maximilian [Department of Physics, Universität Basel, Klingelbergstr. 82, 4056 Basel (Switzerland); Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208 (United States); Faraji, Somayeh; Rostami, Samare; Ghasemi, S. Alireza [Institute for Advanced Studies in Basic Sciences, P.O. Box 45195-1159, Zanjan (Iran, Islamic Republic of); Sadeghi, Ali [Physics Department, Shahid Beheshti University, G. C., Evin, 19839 Tehran (Iran, Islamic Republic of); Wolverton, Chris [Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208 (United States)

    2016-01-21

    Measuring similarities/dissimilarities between atomic structures is important for the exploration of potential energy landscapes. However, the cell vectors together with the coordinates of the atoms, which are generally used to describe periodic systems, are quantities not directly suitable as fingerprints to distinguish structures. Based on a characterization of the local environment of all atoms in a cell, we introduce crystal fingerprints that can be calculated easily and define configurational distances between crystalline structures that satisfy the mathematical properties of a metric. This distance between two configurations is a measure of their similarity/dissimilarity and it allows in particular to distinguish structures. The new method can be a useful tool within various energy landscape exploration schemes, such as minima hopping, random search, swarm intelligence algorithms, and high-throughput screenings.

  18. A fingerprint based metric for measuring similarities of crystalline structures

    CERN Document Server

    Zhu, Li; Fuhrer, Tobias; Schaefer, Bastian; Faraji, Somayeh; Rostami, Samara; Ghasemi, S Alireza; Sadeghi, Ali; Grauzinyte, Migle; Wolverton, Christopher; Goedecker, Stefan

    2015-01-01

    Measuring similarities/dissimilarities between atomic structures is important for the exploration of potential energy landscapes. However, the cell vectors together with the coordinates of the atoms, which are generally used to describe periodic systems, are quantities not suitable as fingerprints to distinguish structures. Based on a characterization of the local environment of all atoms in a cell we introduce crystal fingerprints that can be calculated easily and allow to define configurational distances between crystalline structures that satisfy the mathematical properties of a metric. This distance between two configurations is a measure of their similarity/dissimilarity and it allows in particular to distinguish structures. The new method is an useful tool within various energy landscape exploration schemes, such as minima hopping, random search, swarm intelligence algorithms and high-throughput screenings.

  19. Optimization of multi-constrained structures based on optimality criteria

    Science.gov (United States)

    Rizzi, P.

    1976-01-01

    A weight-reduction algorithm is developed for the optimal design of structures subject to several multibehavioral inequality constraints. The structural weight is considered to depend linearly on the design variables. The algorithm incorporates a simple recursion formula derived from the Kuhn-Tucker necessary conditions for optimality, associated with a procedure to delete nonactive constraints based on the Gauss-Seidel iterative method for linear systems. A number of example problems is studied, including typical truss structures and simplified wings subject to static loads and with constraints imposed on stresses and displacements. For one of the latter structures, constraints on the fundamental natural frequency and flutter speed are also imposed. The results obtained show that the method is fast, efficient, and general when compared to other competing techniques. Extensions to the generality of the method to include equality constraints and nonlinear merit functions is discussed.

  20. Topography measurement of micro structure by modulation-based method

    Science.gov (United States)

    Zhou, Yi; Tang, Yan; Liu, Junbo; Deng, Qinyuan; Cheng, Yiguang; Hu, Song

    2016-10-01

    Dimensional metrology for micro structure plays an important role in addressing quality issues and observing the performance of micro-fabricated products. Different from the traditional white-light interferometry approach, the modulation-based method is expected to measure topography of micro structure by the obtained modulation of each interferometry image. Through seeking the maximum modulation of every pixel respectively in Z direction, the method could obtain the corresponding height of individual pixel and finally get topography of the structure. Owing to the characteristic of modulation, the proposed method which is not influenced by the change of background light intensity caused by instable light source and different reflection index of the structure could be widely applied with high stability. The paper both illustrates the principle of this novel method and conducts the experiment to verify the feasibility.

  1. Technology of structure damage monitoring based on multi-agent

    Institute of Scientific and Technical Information of China (English)

    Hongbing Sun; Shenfang Yuan; Xia Zhao; Hengbao Zhou; Dong Liang

    2010-01-01

    The health monitoring for large-scale structures need to resolve a large number of difficulties,such as the data transmission and distributing information handling.To solve these problems,the technology of multi-agent is a good candidate to be used in the field of structural health monitoring.A structural health monitoring system architecture based on multi-agent technology is proposed.The measurement system for aircraft airfoil is designed with FBG,strain gage,and corresponding signal processing circuit.The experiment to determine the location of the concentrate loading on the structure is carried on with the system combined with technologies of pattern recognition and multi-agent.The results show that the system can locate the concentrate loading of the aircraft airfoil at the accuracy of 91.2%.

  2. Modern earthquake engineering offshore and land-based structures

    CERN Document Server

    Jia, Junbo

    2017-01-01

    This book addresses applications of earthquake engineering for both offshore and land-based structures. It is self-contained as a reference work and covers a wide range of topics, including topics related to engineering seismology, geotechnical earthquake engineering, structural engineering, as well as special contents dedicated to design philosophy, determination of ground motions, shock waves, tsunamis, earthquake damage, seismic response of offshore and arctic structures, spatial varied ground motions, simplified and advanced seismic analysis methods, sudden subsidence of offshore platforms, tank liquid impacts during earthquakes, seismic resistance of non-structural elements, and various types of mitigation measures, etc. The target readership includes professionals in offshore and civil engineering, officials and regulators, as well as researchers and students in this field.

  3. Performance based investigations of structural systems under fire

    DEFF Research Database (Denmark)

    Gentili, Filippo; Crosti, Chiara; Giuliani, Luisa

    2010-01-01

    Prescriptive measures and procedures developed over the past here are mostly aimed at preventing structural failures of single elements for the time required for the evacuation. The response to fire and fire effects of the structural system as a whole remains often unknown and the survival...... of the construction after this time cannot always be granted. This is even more true in case of unaccounted events like human errors or rare but severe occurrence like a fire after explosion, which cannot be contemplated in the usual design. Even if a structure could be hardly designed to resist fully integer all...... these kinds of events, the mitigation of possible collapse induced by fire should be achieved. In this respect, a performance-based investigation of the structure aimed at highlight fire effects and fire-induced collapse mechanisms becomes of interest. In the paper collapse mechanisms of some simple...

  4. A new entropy based method for computing software structural complexity

    CERN Document Server

    Roca, J L

    2002-01-01

    In this paper a new methodology for the evaluation of software structural complexity is described. It is based on the entropy evaluation of the random uniform response function associated with the so called software characteristic function SCF. The behavior of the SCF with the different software structures and their relationship with the number of inherent errors is investigated. It is also investigated how the entropy concept can be used to evaluate the complexity of a software structure considering the SCF as a canonical representation of the graph associated with the control flow diagram. The functions, parameters and algorithms that allow to carry out this evaluation are also introduced. After this analytic phase follows the experimental phase, verifying the consistency of the proposed metric and their boundary conditions. The conclusion is that the degree of software structural complexity can be measured as the entropy of the random uniform response function of the SCF. That entropy is in direct relation...

  5. A fingerprint based metric for measuring similarities of crystalline structures.

    Science.gov (United States)

    Zhu, Li; Amsler, Maximilian; Fuhrer, Tobias; Schaefer, Bastian; Faraji, Somayeh; Rostami, Samare; Ghasemi, S Alireza; Sadeghi, Ali; Grauzinyte, Migle; Wolverton, Chris; Goedecker, Stefan

    2016-01-21

    Measuring similarities/dissimilarities between atomic structures is important for the exploration of potential energy landscapes. However, the cell vectors together with the coordinates of the atoms, which are generally used to describe periodic systems, are quantities not directly suitable as fingerprints to distinguish structures. Based on a characterization of the local environment of all atoms in a cell, we introduce crystal fingerprints that can be calculated easily and define configurational distances between crystalline structures that satisfy the mathematical properties of a metric. This distance between two configurations is a measure of their similarity/dissimilarity and it allows in particular to distinguish structures. The new method can be a useful tool within various energy landscape exploration schemes, such as minima hopping, random search, swarm intelligence algorithms, and high-throughput screenings.

  6. Peptide backbone orientation and dynamics in spider dragline silk and two-photon excitation in nuclear magnetic and quadrupole resonance

    Energy Technology Data Exchange (ETDEWEB)

    Eles, P.T

    2005-07-01

    In the first part of the dissertation, spider dragline silk is studied by solid state NMR techniques. The dependence of NMR frequency on molecular orientation is exploited using the DECODER experiment to determine the orientation of the protein backbone within the silk fibre. Practical experimental considerations require that the silk fibres be wound about a cylindrical axis perpendicular to the external magnetic field, complicating the reconstruction of the underlying orientation distribution and necessitating the development of numerical techniques for this purpose. A two-component model of silk incorporating static b-sheets and polyglycine II helices adequately fits the NMR data and suggests that the b-sheets are well aligned along the silk axis (20 FWHM) while the helices are poorly aligned (68 FWHM). The effects of fibre strain, draw rate and hydration on orientation are measured. Measurements of the time-scale for peptide backbone motion indicate that when wet, a strain-dependent fraction of the poorly aligned component becomes mobile. This suggests a mechanism for the supercontraction of silk involving latent entropic springs that undergo a local strain-dependent phase transition, driving supercontraction. In the second part of this dissertation a novel method is developed for exciting NMR and nuclear quadrupole resonance (NQR) by rf irradiation at multiple frequencies that sum to (or differ by) the resonance frequency. This is fundamentally different than traditional NMR experiments where irradiation is applied on-resonance. With excitation outside the detection bandwidth, two-photon excitation allows for detection of free induction signals during excitation, completely eliminating receiver dead-time. A theoretical approach to describing two-photon excitation is developed based on average Hamiltonian theory. An intuition for two-photon excitation is gained by analogy to the coherent absorption of multiple photons requiring conservation of total energy and

  7. Automatic assignment of protein backbone resonances by direct spectrum inspection in targeted acquisition of NMR data.

    Science.gov (United States)

    Wong, Leo E; Masse, James E; Jaravine, Victor; Orekhov, Vladislav; Pervushin, Konstantin

    2008-10-01

    The necessity to acquire large multidimensional datasets, a basis for assignment of NMR resonances, results in long data acquisition times during which substantial degradation of a protein sample might occur. Here we propose a method applicable for such a protein for automatic assignment of backbone resonances by direct inspection of multidimensional NMR spectra. In order to establish an optimal balance between completeness of resonance assignment and losses of cross-peaks due to dynamic processes/degradation of protein, assignment of backbone resonances is set as a stirring criterion for dynamically controlled targeted nonlinear NMR data acquisition. The result is demonstrated with the 12 kDa (13)C,(15) N-labeled apo-form of heme chaperone protein CcmE, where hydrolytic cleavage of 29 C-terminal amino acids is detected. For this protein, 90 and 98% of manually assignable resonances are automatically assigned within 10 and 40 h of nonlinear sampling of five 3D NMR spectra, respectively, instead of 600 h needed to complete the full time domain grid. In addition, resonances stemming from degradation products are identified. This study indicates that automatic resonance assignment might serve as a guiding criterion for optimal run-time allocation of NMR resources in applications to proteins prone to degradation.

  8. Automatic assignment of protein backbone resonances by direct spectrum inspection in targeted acquisition of NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Leo E. [Nanyang Technological University, School of Biological Sciences (Singapore); Masse, James E. [National Institutes of Health (United States); Jaravine, Victor [J. W. Goethe-University Frankfurt, Institute of Biophysical Chemistry (Germany); Orekhov, Vladislav [Gothenburg University, Swedish NMR Centre (Sweden); Pervushin, Konstantin [Nanyang Technological University, School of Biological Sciences (Singapore)], E-mail: kpervushin@ntu.edu.sg

    2008-10-15

    The necessity to acquire large multidimensional datasets, a basis for assignment of NMR resonances, results in long data acquisition times during which substantial degradation of a protein sample might occur. Here we propose a method applicable for such a protein for automatic assignment of backbone resonances by direct inspection of multidimensional NMR spectra. In order to establish an optimal balance between completeness of resonance assignment and losses of cross-peaks due to dynamic processes/degradation of protein, assignment of backbone resonances is set as a stirring criterion for dynamically controlled targeted nonlinear NMR data acquisition. The result is demonstrated with the 12 kDa {sup 13}C,{sup 15} N-labeled apo-form of heme chaperone protein CcmE, where hydrolytic cleavage of 29 C-terminal amino acids is detected. For this protein, 90 and 98% of manually assignable resonances are automatically assigned within 10 and 40 h of nonlinear sampling of five 3D NMR spectra, respectively, instead of 600 h needed to complete the full time domain grid. In addition, resonances stemming from degradation products are identified. This study indicates that automatic resonance assignment might serve as a guiding criterion for optimal run-time allocation of NMR resources in applications to proteins prone to degradation.

  9. Cellulose nanofiber backboned Prussian blue nanoparticles as powerful adsorbents for the selective elimination of radioactive cesium

    Science.gov (United States)

    Vipin, Adavan Kiliyankil; Fugetsu, Bunshi; Sakata, Ichiro; Isogai, Akira; Endo, Morinobu; Li, Mingda; Dresselhaus, Mildred S.

    2016-11-01

    On 11 March 2011, the day of the unforgettable disaster of the 9 magnitude Tohoku earthquake and quickly followed by the devastating Tsunami, a damageable amount of radionuclides had dispersed from the Fukushima Daiichi’s damaged nuclear reactors. Decontamination of the dispersed radionuclides from seawater and soil, due to the huge amounts of coexisting ions with competitive functionalities, has been the topmost difficulty. Ferric hexacyanoferrate, also known as Prussian blue (PB), has been the most powerful material for selectively trapping the radioactive cesium ions; its high tendency to form stable colloids in water, however, has made PB to be impossible for the open-field radioactive cesium decontamination applications. A nano/nano combinatorial approach, as is described in this study, has provided an ultimate solution to this intrinsic colloid formation difficulty of PB. Cellulose nanofibers (CNF) were used to immobilize PB via the creation of CNF-backboned PB. The CNF-backboned PB (CNF/PB) was found to be highly tolerant to water and moreover, it gave a 139 mg/g capability and a million (106) order of magnitude distribution coefficient (Kd) for absorbing of the radioactive cesium ion. Field studies on soil and seawater decontaminations in Fukushima gave satisfactory results, demonstrating high capabilities of CNF/PB for practical applications.

  10. Influence of Backbone Fluorination in Regioregular Poly(3-alkyl-4-fluoro)thiophenes

    KAUST Repository

    Fei, Zhuping

    2015-06-03

    © 2015 American Chemical Society. We report two strategies toward the synthesis of 3-alkyl-4-fluorothiophenes containing straight (hexyl and octyl) and branched (2-ethylhexyl) alkyl groups. We demonstrate that treatment of the dibrominated monomer with 1 equiv of alkyl Grignard reagent leads to the formation of a single regioisomer as a result of the pronounced directing effect of the fluorine group. Polymerization of the resulting species affords highly regioregular poly(3-alkyl-4-fluoro)thiophenes. Comparison of their properties to those of the analogous non-fluorinated polymers shows that backbone fluorination leads to an increase in the polymer ionization potential without a significant change in optical band gap. Fluorination also results in an enhanced tendency to aggregate in solution, which is ascribed to a more co-planar backbone on the basis of Raman and DFT calculations. Average charge carrier mobilities in field-effect transistors are found to increase by up to a factor of 5 for the fluorinated polymers.

  11. Improving VANETs Connectivity with a Totally Ad Hoc Living Mobile Backbone

    Directory of Open Access Journals (Sweden)

    Joilson Alves Junior

    2015-01-01

    Full Text Available The vehicular ad hoc network (VANET for intelligent transportation systems is an emerging concept to improve transportation security, reliability, and management. The network behavior can be totally different in topological aspects because of the mobility of vehicular nodes. The topology can be fully connected when the flow of vehicles is high and may have low connectivity or be invalid when the flow of vehicles is low or unbalanced. In big cities, the metropolitan buses that travel on exclusive lanes may be used to set up a metropolitan vehicular data network (backbone, raising the connectivity among the vehicles. Therefore, this paper proposes the implementation of a living mobile backbone, totally ad hoc (MOB-NET, which will provide infrastructure and raise the network connectivity. In order to show the viability of MOB-NET, statistical analyses were made with real data of express buses that travel through exclusive lanes, besides evaluations through simulations and analytic models. The statistic, analytic, and simulation results prove that the buses that travel through exclusive lanes can be used to build a communication network totally ad hoc and provide connectivity in more than 99% of the time, besides raising the delivery rate up to 95%.

  12. Comparison of backbone dynamics of the type III antifreeze protein and antifreeze-like domain of human sialic acid synthase

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yong-Geun [Gyeongsang National University, Department of Chemistry and Research Institute of Natural Science (Korea, Republic of); Park, Chin-Ju [Gwangju Institute of Science and Technology, Division of Liberal Arts and Sciences and Department of Chemistry (Korea, Republic of); Kim, Hee-Eun; Seo, Yeo-Jin; Lee, Ae-Ree; Choi, Seo-Ree; Lee, Shim Sung; Lee, Joon-Hwa, E-mail: joonhwa@gnu.ac.kr [Gyeongsang National University, Department of Chemistry and Research Institute of Natural Science (Korea, Republic of)

    2015-02-15

    Antifreeze proteins (AFPs) are found in a variety of cold-adapted (psychrophilic) organisms to promote survival at subzero temperatures by binding to ice crystals and decreasing the freezing temperature of body fluids. The type III AFPs are small globular proteins that consist of one α-helix, three 3{sub 10}-helices, and two β-strands. Sialic acids play important roles in a variety of biological functions, such as development, recognition, and cell adhesion and are synthesized by conserved enzymatic pathways that include sialic acid synthase (SAS). SAS consists of an N-terminal catalytic domain and a C-terminal antifreeze-like (AFL) domain, which is similar to the type III AFPs. Despite having very similar structures, AFL and the type III AFPs exhibit very different temperature-dependent stability and activity. In this study, we have performed backbone dynamics analyses of a type III AFP (HPLC12 isoform) and the AFL domain of human SAS (hAFL) at various temperatures. We also characterized the structural/dynamic properties of the ice-binding surfaces by analyzing the temperature gradient of the amide proton chemical shift and its correlation with chemical shift deviation from random coil. The dynamic properties of the two proteins were very different from each other. While HPLC12 was mostly rigid with a few residues exhibiting slow motions, hAFL showed fast internal motions at low temperature. Our results provide insight into the molecular basis of thermostability and structural flexibility in homologous psychrophilic HPLC12 and mesophilic hAFL proteins.

  13. Nonlinear feature identification of impedance-based structural health monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Rutherford, A. C. (Amanda C.); Park, G. H. (Gyu Hae); Sohn, H. (Hoon); Farrar, C. R. (Charles R.)

    2004-01-01

    The impedance-based structural health monitoring technique, which utilizes electromechanical coupling properties of piezoelectric materials, has shown feasibility for use in a variety of structural health monitoring applications. Relying on high frequency local excitations (typically > 30 kHz), this technique is very sensitive to minor changes in structural integrity in the near field of piezoelectric sensors. Several damage sensitive features have been identified and used coupled with the impedance methods. Most of these methods are, however, limited to linearity assumptions of a structure. This paper presents the use of experimentally identified nonlinear features, combined with impedance methods, for structural health monitoring. Their applicability to damage detection in various frequency ranges is demonstrated using actual impedance signals measured from a portal frame structure. The performance of the nonlinear feature is compared with those of conventional impedance methods. This paper reinforces the utility of nonlinear features in structural health monitoring and suggests that their varying sensitivity in different frequency ranges may be leveraged for certain applications.

  14. Rock burst prevention based on dissipative structure theory

    Institute of Scientific and Technical Information of China (English)

    Song Dazhao; Wang Enyuan; Li Nan; Jin Mingyue; Xue Shipeng

    2012-01-01

    Dynamic collapses of deeply mined coal rocks are severe.In order to explore new ideas for rock burst prevention,the relationship between entropy equations and dissipative structure was studied,and a concept-rock burst activity system (RAS) was proposed and its entropy was analyzed.The energy features of RAS were analyzed,and the relationship between electromagnetic radiation (EMR) intensity E and dissipated energy Ud was initially established.We suggest that rock burst normally happens only when d,S<< -des in RAS:RAS is the dissipative structure before collapse,and after which it become a new orderly structure,i.e.,a "dead",a statically orderly structure.We advanced that the effective way to prevent rock burst is to introduce entropy to the system for it keeps the system away from the dissipative structure.E and Ud of RAS are positively related,which is used as a bridge between dissipative structure theory and rock burst prevention engineering applications.Based on this.and using the data of rock burst prevention for working face No.250205up of Yanbei coal mine,an engineering verification for the dissipative structure of RAS was carried out,which showed good results.

  15. Statistical Pattern-Based Assessment of Structural Health Monitoring Data

    Directory of Open Access Journals (Sweden)

    Mohammad S. Islam

    2014-01-01

    Full Text Available In structural health monitoring (SHM, various sensors are installed at critical locations of a structure. The signals from sensors are either continuously or periodically analyzed to determine the state and performance of the structure. An objective comparison of the sensor data at different time ranges is essential for assessing the structural condition or excessive load experienced by the structure which leads to potential damage in the structure. The objectives of the current study are to establish a relationship between the data from various sensors to estimate the reliability of the data and potential damage using the statistical pattern matching techniques. In order to achieve these goals, new methodologies based on statistical pattern recognition techniques have been developed. The proposed methodologies have been developed and validated using sensor data obtained from an instrumented bridge and road test data from heavy vehicles. The application of statistical pattern matching techniques are relatively new in SHM data interpretation and current research demonstrates that it has high potential in assessing structural conditions, especially when the data are noisy and susceptible to environmental disturbances.

  16. Dissimilarity-based classification of anatomical tree structures

    DEFF Research Database (Denmark)

    Sørensen, Lauge Emil Borch Laurs; Lo, Pechin Chien Pau; Dirksen, Asger

    2011-01-01

    A novel method for classification of abnormality in anatomical tree structures is presented. A tree is classified based on direct comparisons with other trees in a dissimilarity-based classification scheme. The pair-wise dissimilarity measure between two trees is based on a linear assignment...... by including anatomical features in the branch feature vectors. The proposed approach is applied to classify airway trees in computed tomography images of subjects with and without chronic obstructive pulmonary disease (COPD). Using the wall area percentage (WA%), a common measure of airway abnormality in COPD...

  17. Significant Role of DNA Backbone in Mediating the Transition Origin of Electronic Excitations of B-DNA - Implication from Long Range Corrected TDDFT and Quantified NTO Analysis

    CERN Document Server

    Li, Jian-Hao; Guo, Guang-Yu; Hayashi, Michitoshi

    2011-01-01

    We systematically investigate the possible complex transition origin of electronic excitations of giant molecular systems by using the recently proposed QNTO analysis [J.-H. Li, J.-D. Chai, G. Y. Guo and M. Hayashi, Chem. Phys. Lett., 2011, 514, 362.] combined with long-range corrected TDDFT calculations. Thymine (Thy) related excitations of biomolecule B-DNA are then studied as examples, where the model systems have been constructed extracting from the perfect or a X-ray crystal (PDB code 3BSE) B-DNA structure with at least one Thy included. In the first part, we consider the systems composed of a core molecular segment (e.g. Thy, di-Thy) and a surrounding physical/chemical environment of interest (e.g. backbone, adjacent stacking nucleobases) and examine how the excitation properties of the core vary in response to the environment. We find that the orbitals contributed from DNA backbone and surrounding nucleobases often participate in a transition of Thy-related excitations affecting their composition, abso...

  18. Differential Gelation and Self-Sorting Properties of Two Isomeric Polyamides Due to the Parallel vs Anti-Parallel Alignment of Backbone Dipoles.

    Science.gov (United States)

    Leung, Chui-Fan; Chow, Hak-Fun

    2017-02-14

    Two isomeric bottlebrush polyamides P-1 and A-1 having the same repeating monomer dipole units aligned along the polymer backbone in pseudo-parallel and pseudo-anti-parallel, respectively, were synthesized and characterized. Both polymers can form thermoreversible gels with aromatic solvents but P-1 was found to show inferior gelation strength as compared to that of A-1. Furthermore, despite their close structural resemblance, a 1:1 mixture of the P-1 and A-1 polymers was shown to exhibit self-sorting in the gel state. Gel formation was found to be a kinetically trapped process via H-bonding, π-π stacking interactions and side chain interdigitation. The differential gelation and self-sorting properties can be explained by the local dipole-dipole interactions originated from the different modes of backbone dipole alignment. In single gel systems, the antiparallel-aligned dipoles in A-1 facilitated a more compact molecular packing due to the enthalpically more favorable polymer chain association. On the other hand, the parallel-aligned dipoles in P-1 gave rise to a less stable head-to-head packing, which had difficulties to convert to the more stable head-to-tail packing in a kinetically trapped environment. In the mixed gel system, it is the unfavorable hetero-polymer mismatch dipole-dipole interaction that inhibited the mixing of the A-1 and P-1 polymers and led to self-sorting.

  19. Rational design of a cytotoxic dinuclear Cu2 complex that binds by molecular recognition at two neighboring phosphates of the DNA backbone.

    Science.gov (United States)

    Jany, Thomas; Moreth, Alexander; Gruschka, Claudia; Sischka, Andy; Spiering, Andre; Dieding, Mareike; Wang, Ying; Samo, Susan Haji; Stammler, Anja; Bögge, Hartmut; Fischer von Mollard, Gabriele; Anselmetti, Dario; Glaser, Thorsten

    2015-03-16

    The mechanism of the cytotoxic function of cisplatin and related anticancer drugs is based on their binding to the nucleobases of DNA. The development of new classes of anticancer drugs requires establishing other binding modes. Therefore, we performed a rational design for complexes that target two neighboring phosphates of the DNA backbone by molecular recognition resulting in a family of dinuclear complexes based on 2,7-disubstituted 1,8-naphthalenediol. This rigid backbone preorganizes the two metal ions for molecular recognition at the distance of two neighboring phosphates in DNA of 6-7 Å. Additionally, bulky chelating pendant arms in the 2,7-position impede nucleobase complexation by steric hindrance. We successfully synthesized the Cu(II)2 complex of the designed family of dinuclear complexes and studied its binding to dsDNA by independent ensemble and single-molecule methods like gel electrophoresis, precipitation, and titration experiments followed by UV-vis spectroscopy, atomic force microscopy (AFM), as well as optical tweezers (OT) and magnetic tweezers (MT) DNA stretching. The observed irreversible binding of our dinuclear Cu(II)2 complex to dsDNA leads to a blocking of DNA synthesis as studied by polymerase chain reactions and cytotoxicity for human cancer cells.

  20. Insertions and the emergence of novel protein structure: a structure-based phylogenetic study of insertions

    Directory of Open Access Journals (Sweden)

    Blouin Christian

    2007-11-01

    Full Text Available Abstract Background In protein evolution, the mechanism of the emergence of novel protein domain is still an open question. The incremental growth of protein variable regions, which was produced by stochastic insertions, has the potential to generate large and complex sub-structures. In this study, a deterministic methodology is proposed to reconstruct phylogenies from protein structures, and to infer insertion events in protein evolution. The analysis was performed on a broad range of SCOP domain families. Results Phylogenies were reconstructed from protein 3D structural data. The phylogenetic trees were used to infer ancestral structures with a consensus method. From these ancestral reconstructions, 42.7% of the observed insertions are nested insertions, which locate in previous insert regions. The average size of inserts tends to increase with the insert rank or total number of insertions in the variable regions. We found that the structures of some nested inserts show complex or even domain-like fold patterns with helices, strands and loops. Furthermore, a basal level of structural innovation was found in inserts which displayed a significant structural similarity exclusively to themselves. The β-Lactamase/D-ala carboxypeptidase domain family is provided as an example to illustrate the inference of insertion events, and how the incremental growth of a variable region is capable to generate novel structural patterns. Conclusion Using 3D data, we proposed a method to reconstruct phylogenies. We applied the method to reconstruct the sequences of insertion events leading to the emergence of potentially novel structural elements within existing protein domains. The results suggest that structural innovation is possible via the stochastic process of insertions and rapid evolution within variable regions where inserts tend to be nested. We also demonstrate that the structure-based phylogeny enables the study of new questions relating to the

  1. Structural color-tunable mesoporous bragg stack layers based on graft copolymer self-assembly for high-efficiency solid-state dye-sensitized solar cells

    Science.gov (United States)

    Lee, Chang Soo; Park, Jung Tae; Kim, Jong Hak

    2016-08-01

    We present a facile fabrication route for structural color-tunable mesoporous Bragg stack (BS) layers based on the self-assembly of a cost-effective graft copolymer. The mesoporous BS layers are prepared through the alternating deposition of organized mesoporous-TiO2 (OM-TiO2) and -SiO2 (OM-SiO2) films on the non-conducting side of the counter electrode in dye-sensitized solar cells (DSSCs). The OM layers with controlled porosity, pore size, and refractive index are templated with amphiphilic graft copolymers consisting of poly(vinyl chloride) backbones and poly(oxyethylene methacrylate) side chains, i.e., PVC-g-POEM. The morphology and properties of the structural color-tunable mesoporous BS-functionalized electrodes are characterized using energy filtered transmission electron microscopy (EF-TEM), field emission-scanning electron microscopy (FE-SEM), spectroscopic ellipsometry, and reflectance spectroscopy. The solid-state DSSCs (ssDSSCs) based on a structural color-tunable mesoporous BS counter electrode with a single-component solid electrolyte show an energy conversion efficiency (η) of 7.1%, which is much greater than that of conventional nanocrystalline TiO2-based cells and one of the highest values for N719 dye-based ssDSSCs. The enhancement of η is due to the enhancement of current density (Jsc), attributed to the improved light harvesting properties without considerable decrease in fill factor (FF) or open-circuit voltage (Voc), as confirmed by incident photon-to-electron conversion efficiency (IPCE) and electrochemical impedance spectroscopy (EIS).

  2. Blind test of physics-based prediction of protein structures.

    Science.gov (United States)

    Shell, M Scott; Ozkan, S Banu; Voelz, Vincent; Wu, Guohong Albert; Dill, Ken A

    2009-02-01

    We report here a multiprotein blind test of a computer method to predict native protein structures based solely on an all-atom physics-based force field. We use the AMBER 96 potential function with an implicit (GB/SA) model of solvation, combined with replica-exchange molecular-dynamics simulations. Coarse conformational sampling is performed using the zipping and assembly method (ZAM), an approach that is designed to mimic the putative physical routes of protein folding. ZAM was applied to the folding of six proteins, from 76 to 112 monomers in length, in CASP7, a community-wide blind test of protein structure prediction. Because these predictions have about the same level of accuracy as typical bioinformatics methods, and do not utilize information from databases of known native structures, this work opens up the possibility of predicting the structures of membrane proteins, synthetic peptides, or other foldable polymers, for which there is little prior knowledge of native structures. This approach may also be useful for predicting physical protein folding routes, non-native conformations, and other physical properties from amino acid sequences.

  3. Single-Walled Carbon-Nanotubes-Based Organic Memory Structures

    Directory of Open Access Journals (Sweden)

    Sundes Fakher

    2016-09-01

    Full Text Available The electrical behaviour of organic memory structures, based on single-walled carbon-nanotubes (SWCNTs, metal–insulator–semiconductor (MIS and thin film transistor (TFT structures, using poly(methyl methacrylate (PMMA as the gate dielectric, are reported. The drain and source electrodes were fabricated by evaporating 50 nm gold, and the gate electrode was made from 50 nm-evaporated aluminium on a clean glass substrate. Thin films of SWCNTs, embedded within the insulating layer, were used as the floating gate. SWCNTs-based memory devices exhibited clear hysteresis in their electrical characteristics (capacitance–voltage (C–V for MIS structures, as well as output and transfer characteristics for transistors. Both structures were shown to produce reliable and large memory windows by virtue of high capacity and reduced charge leakage. The hysteresis in the output and transfer characteristics, the shifts in the threshold voltage of the transfer characteristics, and the flat-band voltage shift in the MIS structures were attributed to the charging and discharging of the SWCNTs floating gate. Under an appropriate gate bias (1 s pulses, the floating gate is charged and discharged, resulting in significant threshold voltage shifts. Pulses as low as 1 V resulted in clear write and erase states.

  4. A Network Flow Approach to Predict Protein Targets and Flavonoid Backbones to Treat Respiratory Syncytial Virus Infection

    Directory of Open Access Journals (Sweden)

    José Eduardo Vargas

    2015-01-01

    Full Text Available Background. Respiratory syncytial virus (RSV infection is the major cause of respiratory disease in lower respiratory tract in infants and young children. Attempts to develop effective vaccines or pharmacological treatments to inhibit RSV infection without undesired effects on human health have been unsuccessful. However, RSV infection has been reported to be affected by flavonoids. The mechanisms underlying viral inhibition induced by these compounds are largely unknown, making the development of new drugs difficult. Methods. To understand the mechanisms induced by flavonoids to inhibit RSV infection, a systems pharmacology-based study was performed using microarray data from primary culture of human bronchial cells infected by RSV, together with compound-proteomic interaction data available for Homo sapiens. Results. After an initial evaluation of 26 flavonoids, 5 compounds (resveratrol, quercetin, myricetin, apigenin, and tricetin were identified through topological analysis of a major chemical-protein (CP and protein-protein interacting (PPI network. In a nonclustered form, these flavonoids regulate directly the activity of two protein bottlenecks involved in inflammation and apoptosis. Conclusions. Our findings may potentially help uncovering mechanisms of action of early RSV infection and provide chemical backbones and their protein targets in the difficult quest to develop new effective drugs.

  5. Reliability-Based Structural Optimization of Wave Energy Converters

    Directory of Open Access Journals (Sweden)

    Simon Ambühl

    2014-12-01

    Full Text Available More and more wave energy converter (WEC concepts are reaching prototypelevel. Once the prototype level is reached, the next step in order to further decrease thelevelized cost of energy (LCOE is optimizing the overall system with a focus on structuraland maintenance (inspection costs, as well as on the harvested power from the waves.The target of a fully-developed WEC technology is not maximizing its power output,but minimizing the resulting LCOE. This paper presents a methodology to optimize thestructural design of WECs based on a reliability-based optimization problem and the intentto maximize the investor’s benefits by maximizing the difference between income (e.g., fromselling electricity and the expected expenses (e.g., structural building costs or failure costs.Furthermore, different development levels, like prototype or commercial devices, may havedifferent main objectives and will be located at different locations, as well as receive varioussubsidies. These points should be accounted for when performing structural optimizationsof WECs. An illustrative example on the gravity-based foundation of the Wavestar deviceis performed showing how structural design can be optimized taking target reliability levelsand different structural failure modes due to extreme loads into account.

  6. Electronic origin of structural transition in 122 Fe based superconductors

    Science.gov (United States)

    Ghosh, Haranath; Sen, Smritijit; Ghosh, Abyay

    2017-03-01

    Direct quantitative correlations between the orbital order and orthorhombicity is achieved in a number of Fe-based superconductors of 122 family. The former (orbital order) is calculated from first principles simulations using experimentally determined doping and temperature dependent structural parameters while the latter (the orthorhombicity) is taken from already established experimental studies; when normalized, both the above quantities quantitatively corresponds to each other in terms of their doping as well as temperature variations. This proves that the structural transition in Fe-based materials is electronic in nature due to orbital ordering. An universal correlations among various structural parameters and electronic structure are also obtained. Most remarkable among them is the mapping of two Fe-Fe distances in the low temperature orthorhombic phase, with the band energies Edxz, Edyz of Fe at the high symmetry points of the Brillouin zone. The fractional co-ordinate zAs of As which essentially determines anion height is inversely (directly) proportional to Fe-As bond distances (with exceptions of K doped BaFe2As2) for hole (electron) doped materials as a function of doping. On the other hand, Fe-As bond-distance is found to be inversely (directly) proportional to the density of states at the Fermi level for hole (electron) doped systems. Implications of these results to current issues of Fe based superconductivity are discussed.

  7. Graftig Copolymerization of Hydrophilic Monomers Onto Alginate for Modification it,s Structure

    Directory of Open Access Journals (Sweden)

    Mohammad Sadeghi

    2014-03-01

    Full Text Available In this research, we synthesize of a graft copolymer based on alginate via simultaneously graft copolymerization acrylamide (AAm and 2-acrylamido-2-methylpropanesulfonic acid (AMPS onto alginate backbones. The polymerization reaction was carried out in an aqueous medium and in the presence of ammonium persulfate (APS as an initiator. Infrared spectroscopy and TGA thermal analysis were carried out to confirm the chemical structure of the copolymer. A proposed mechanism for hydrogel formation was suggested.

  8. A new hybrid coding for protein secondary structure prediction based on primary structure similarity.

    Science.gov (United States)

    Li, Zhong; Wang, Jing; Zhang, Shunpu; Zhang, Qifeng; Wu, Wuming

    2017-03-16

    The coding pattern of protein can greatly affect the prediction accuracy of protein secondary structure. In this paper, a novel hybrid coding method based on the physicochemical properties of amino acids and tendency factors is proposed for the prediction of protein secondary structure. The principal component analysis (PCA) is first applied to the physicochemical properties of amino acids to construct a 3-bit-code, and then the 3 tendency factors of amino acids are calculated to generate another 3-bit-code. Two 3-bit-codes are fused to form a novel hybrid 6-bit-code. Furthermore, we make a geometry-based similarity comparison of the protein primary structure between the reference set and the test set before the secondary structure prediction. We finally use the support vector machine (SVM) to predict those amino acids which are not detected by the primary structure similarity comparison. Experimental results show that our method achieves a satisfactory improvement in accuracy in the prediction of protein secondary structure.

  9. Protein NMR Structure Refinement based on Bayesian Inference

    Science.gov (United States)

    Ikeya, Teppei; Ikeda, Shiro; Kigawa, Takanori; Ito, Yutaka; Güntert, Peter

    2016-03-01

    Nuclear Magnetic Resonance (NMR) spectroscopy is a tool to investigate threedimensional (3D) structures and dynamics of biomacromolecules at atomic resolution in solution or more natural environments such as living cells. Since NMR data are principally only spectra with peak signals, it is required to properly deduce structural information from the sparse experimental data with their imperfections and uncertainty, and to visualize 3D conformations by NMR structure calculation. In order to efficiently analyse the data, Rieping et al. proposed a new structure calculation method based on Bayes’ theorem. We implemented a similar approach into the program CYANA with some modifications. It allows us to handle automatic NOE cross peak assignments in unambiguous and ambiguous usages, and to create a prior distribution based on a physical force field with the generalized Born implicit water model. The sampling scheme for obtaining the posterior is performed by a hybrid Monte Carlo algorithm combined with Markov chain Monte Carlo (MCMC) by the Gibbs sampler, and molecular dynamics simulation (MD) for obtaining a canonical ensemble of conformations. Since it is not trivial to search the entire function space particularly for exploring the conformational prior due to the extraordinarily large conformation space of proteins, the replica exchange method is performed, in which several MCMC calculations with different temperatures run in parallel as replicas. It is shown with simulated data or randomly deleted experimental peaks that the new structure calculation method can provide accurate structures even with less peaks, especially compared with the conventional method. In particular, it dramatically improves in-cell structures of the proteins GB1 and TTHA1718 using exclusively information obtained in living Escherichia coli (E. coli) cells.

  10. A New Silicon-Based Ferroelectric Sandwich Structure

    Institute of Scientific and Technical Information of China (English)

    任天令; 张林涛; 刘理天; 李志坚

    2001-01-01

    A new silicon-based PbTiO3/Pb(Zr0.53 Ti0.47)O3/PbTiO3 sandwich structure is fabricated by a sol-gel method. Compared with other fabrication processes without PbTiO3 buffer layers, the annealing temperature is greatly reduced by as much as 100℃. Capacitance-voltage, polarization-electric field and dielectric-frequency properties of this sandwich structure are studied. The Pb(Zrx Ti1-x)O3 films are proved to have good dielectric and ferroelectric properties.

  11. Diode rectifier bridge-based structure for DFIG-based wind turbine

    DEFF Research Database (Denmark)

    Zhu, Rongwu; Chen, Zhe; Wu, Xiaojie

    2015-01-01

    This paper proposes a new structure for the doubly-fed induction generator (DFIG)-based wind turbine. The proposed structure consists of a DFIG controlled by a partial rated power converter in the rotor side, a three-phase diode rectifier bridge (DRB) connected to the stator, and a DC/AC full rated...... power inverter. As this structure could isolate the DFIG and the grid by a DC-link, the DFIG could avoid the direct influences from the grid, and achieve fault ride through requirement easily. Based on this structure, two control strategies are developed to control the DFIG and fulfill maximum power...... output. The simulation results based a MATALAB/Simulink using a 2MW DFIG compare the performances of DFIG system with the two control strategies. Further, the experimental results based on a scaled-down setup with a 7.5kW DFIG validate the correctness of the control strategies....

  12. A CADASTRAL SPATIAL DATA STORAGE STRUCTURE BASED ON RELATIONAL DATABASE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper presents a cadastral spatial data storage structure based on relational database,the method and the procedure to realize it.The paper consists of three parts.In the first part,some existing problems in some de veloped cadastral management systems are discussed.These problems are the fo llowing four.1) The security of cadastral spatial data is difficult to be assure d.2) It is difficult to varify cadastral data and the integrality of cadastral d ata is diffi cult to be kept.3) To transmit and share cadastral data is difficult.4) The effi ciency of data access is low.In the second part,t he feasibility of using relational database to store spatial data is analyzed an d a new cadastral spatial data storage structure is presented.At the same time, the related table structures and field descriptions are given,and then the merits and demerits of this storage structure are analyzed in detail.In th e last part,through a real example,the detailed methods to make the new storag e structure a reality are given.Moreover,some involving key techniques of the ne w storage structure are discussed.These techniques are:1) the application of database transaction,2) the application of database trigger,3) and the appl ication of secure recovery of database.

  13. Polarizable Simulations with Second order Interaction Model (POSSIM) force field: Developing parameters for alanine peptides and protein backbone

    Science.gov (United States)

    Ponomarev, Sergei Y.; Kaminski, George A.

    2011-01-01

    A previously introduced POSSIM (POlarizable Simulations with Second order Interaction Model) force field has been extended to include parameters for alanine peptides and protein backbones. New features were introduced into the fitting protocol, as compared to the previous generation of the polarizable force field for proteins. A reduced amount of quantum mechanical data was employed in fitting the electrostatic parameters. Transferability of the electrostatics between our recently developed NMA model and the protein backbone was confirmed. Binding energy and geometry for complexes of alanine dipeptide with a water molecule were estimated and found in a good agreement with high-level quantum mechanical results (for example, the intermolecular distances agreeing within ca. 0.06Å). Following the previously devised procedure, we calculated average errors in alanine di- and tetra-peptide conformational energies and backbone angles and found the agreement to be adequate (for example, the alanine tetrapeptide extended-globular conformational energy gap was calculated to be 3.09 kcal/mol quantim mechanically and 3.14 kcal/mol with the POSSIM force field). However, we have now also included simulation of a simple alpha-helix in both gas-phase and water as the ultimate test of the backbone conformational behavior. The resulting alanine and protein backbone force field is currently being employed in further development of the POSSIM fast polarizable force field for proteins. PMID:21743799

  14. Comb-type prepolymers consisting of a polyacrylamide backbone and poly(L-lysine) graft chains for multivalent ligands.

    Science.gov (United States)

    Asayama, S; Maruyama, A; Akaike, T

    1999-01-01

    The comb-type copolymers consisting of a polyacrylamide (PAAm) backbone and poly(L-lysine) (PLL) graft chains have been prepared as the "prepolymer" for designing multivalent ligands. To regulate the length and density of the clusters of primary amino groups, the Nalpha-carboxyanhydride of Nepsilon-carbobenzoxy (CBZ)-L-lysine was first polymerized using p-vinylbenzylamine as an initiator. The resulting poly(CBZ-L-lysine) macromonomer was then radically copolymerized with AAm, followed by the deprotection of amino groups. For the model study, the reactive clusters of primary amino groups were completely converted into anion clusters by the reaction with succinic anhydride. The model multivalent ligands having the biotin label on the PAAm backbone were prepared by the terpolymerization of the macromonomer, AAm, and the biotin derivative having a vinyl group. The enzyme-linked immunosorbent assay showed that the biotin with no spacer on the PAAm backbone was recognized by the avidin-peroxidase conjugate specifically. Therefore, the highly sensitive detection of the interaction between cells and various model multivalent ligands was possible. The selective labeling onto the PAAm backbone revealed that the converted anion clusters of graft chains interacted exclusively with the cell and that the backbone was inert to the interaction with the cell. These results indicate that the various PAAm-graft-PLL comb-type copolymers with the defined length and density of the PLL-grafts are the potential prepolymers to investigate and to optimize the affinity of the multivalent ligands for receptors.

  15. Integrated Teaching of Structure-Based Drug Design and Biopharmaceutics: A Computer-Based Approach

    Science.gov (United States)

    Sutch, Brian T.; Romero, Rebecca M.; Neamati, Nouri; Haworth, Ian S.

    2012-01-01

    Rational drug design requires expertise in structural biology, medicinal chemistry, physiology, and related fields. In teaching structure-based drug design, it is important to develop an understanding of the need for early recognition of molecules with "drug-like" properties as a key component. That is, it is not merely sufficient to teach…

  16. Solar Cells Based on Low-dimensional Nanocomposite Structures

    Directory of Open Access Journals (Sweden)

    S.L. Khrypko

    2016-12-01

    Full Text Available Converting solar energy into electric energy with using of solar batteries is a major task for developers and research teams. In this article we will look at the development of different generations of solar batteries for to create a nanocomposite structure. Production of solar batteries has gone through some steps, taking into account technological and economic aspects that have been associated with improved of their parameters. Thus the first generations of solar batteries have been based on the single-crystal silicon substrates (с-Si. The use of polycrystalline silicon and multi- crystalline allowed lower costs of modules, but due to the efficiency of solar energy conversion. The solar batteries of the second generation were based on thin-film technology, in which use different materials: silicon films based on amorphous silicon (a-Si, a film based on cadmium telluride (CdTe and film selenide copper-indium-gallium (CuInGaSe2, or CIGS. The use of such technology has allowed increasing the coefficient of performance (COP solar cell with a significant reduction in costs. The solar batteries of third-generation based on nanotechnology, nanocrystals and nano-sized clusters of semiconductors. The creation of such solar cells requires availability of a low-dimensional composite structure. Low-dimensional nanocomposite structures that are constructed on quantum dots and nano-porous materials have new modified optoelectronic properties. They can be used in solar elements, where absorption bands can be optimally adapted to the wavelength of radiation light. These structures could theoretically can lead to increased efficiency of solar energy conversion more than 65%, which can double practically current efficiency of solar batteries.

  17. Performance based analysis of hidden beams in reinforced concrete structures

    Directory of Open Access Journals (Sweden)

    Helou Samir H.

    2014-01-01

    Full Text Available Local and perhaps regional vernacular reinforced concrete building construction leans heavily against designing slabs with imbedded hidden beams for flooring systems in most structures including major edifices. The practice is distinctive in both framed and in shear wall structures. Hidden beams are favoured structural elements due to their many inherent features that characterize them; they save on floor height clearance; they also save on formwork, labour and material cost. Moreover, hidden beams form an acceptable aesthetic appearance that does not hinder efficient interior space partitioning. Such beams have the added advantage of clearing the way for horizontal electromechanical ductwork. However, seismic considerations, in all likelihood, are seldom seriously addressed. The mentioned structural system of shallow beams is adopted in ribbed slabs, waffle slabs and at times with solid slabs. Ribbed slabs and waffle slabs are more prone to hidden beam inclusion due to the added effective height of the concrete section. Due to the presence of a relatively high reinforcement ratio at the joints the sections at such location tend to become less ductile with unreliable contribution to spandrel force resistance. In the following study the structural influence of hidden beams within slabs is investigated. With the primary focus on a performance based analysis of such elements within a structure. This is investigated with due attention to shear wall contribution to the overall behaviour of such structures. Numerical results point in the direction that the function of hidden beams is not as adequate as desired. Therefore it is strongly believed that they are generally superfluous and maybe eliminated altogether. Conversely, shallow beams seem to render the overall seismic capacity of the structure unreliable. Since such an argument is rarely manifested within the linear analysis domain; a pushover analysis exercise is thus mandatory for behaviour

  18. Vaccines based on structure-based design provide protection against infectious diseases.

    Science.gov (United States)

    Thomas, Sunil; Luxon, Bruce A

    2013-11-01

    Vaccines elicit immune responses, provide protection against microorganisms and are considered as one of the most successful medical interventions against infectious diseases. Vaccines can be produced using attenuated virus or bacteria, recombinant proteins, bacterial polysaccharides, carbohydrates or plasmid DNA. Conventional vaccines rely on the induction of immune responses against antigenic proteins to be effective. The genetic diversity of microorganisms, coupled with the high degree of sequence variability in antigenic proteins, presents a challenge to developing broadly effective conventional vaccines. The observation that whole protein antigens are not necessarily essential for inducing immunity has led to the emergence of a new branch of vaccine design termed 'structural vaccinology'. Structure-based vaccines are designed on the rationale that protective epitopes should be sufficient to induce immune responses and provide protection against pathogens. Recent studies demonstrated that designing structure-based vaccine candidates with multiple epitopes induce a higher immune response. As yet there are no commercial vaccines available based on structure-based design and most of the structure-based vaccine candidates are in the preclinical stages of development. This review focuses on recent advances in structure-based vaccine candidates and their application in providing protection against infectious diseases.

  19. A protein relational database and protein family knowledge bases to facilitate structure-based design analyses.

    Science.gov (United States)

    Mobilio, Dominick; Walker, Gary; Brooijmans, Natasja; Nilakantan, Ramaswamy; Denny, R Aldrin; Dejoannis, Jason; Feyfant, Eric; Kowticwar, Rupesh K; Mankala, Jyoti; Palli, Satish; Punyamantula, Sairam; Tatipally, Maneesh; John, Reji K; Humblet, Christine

    2010-08-01

    The Protein Data Bank is the most comprehensive source of experimental macromolecular structures. It can, however, be difficult at times to locate relevant structures with the Protein Data Bank search interface. This is particularly true when searching for complexes containing specific interactions between protein and ligand atoms. Moreover, searching within a family of proteins can be tedious. For example, one cannot search for some conserved residue as residue numbers vary across structures. We describe herein three databases, Protein Relational Database, Kinase Knowledge Base, and Matrix Metalloproteinase Knowledge Base, containing protein structures from the Protein Data Bank. In Protein Relational Database, atom-atom distances between protein and ligand have been precalculated allowing for millisecond retrieval based on atom identity and distance constraints. Ring centroids, centroid-centroid and centroid-atom distances and angles have also been included permitting queries for pi-stacking interactions and other structural motifs involving rings. Other geometric features can be searched through the inclusion of residue pair and triplet distances. In Kinase Knowledge Base and Matrix Metalloproteinase Knowledge Base, the catalytic domains have been aligned into common residue numbering schemes. Thus, by searching across Protein Relational Database and Kinase Knowledge Base, one can easily retrieve structures wherein, for example, a ligand of interest is making contact with the gatekeeper residue.

  20. Optimization of Land Use Structure Based on Ecological GREEN Equivalent

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Optimization of land use structure consists of economic and social and ecological optimization.Applying the minds of system engineering and principles of ecology,this paper presents such thoughts:the optimal forest-coverage rate calculated according to the reality of a district is set as main standard of ecological rationality in the district;through considering the value of ecosystem services of the land with GREEN equivalent (mainly cultivated land and grassland)and based on the rule,GREEN equivalent,this paper introduces the area conversion between woodland and cultivated land,also between woodland and grassland;this paper establishes a multi-dimension controlling model of optimization of land use structure.In addition,a multi-objective linear programming model for optimization of land use structure is designed.In the end,this paper tests and verifies this theory of ecological optimization,taking Qionghai city in Hainan Province as an example.