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Sample records for constructing optimal backbone

  1. Constructing optimal backbone segments for joining fixed DNA base pairs.

    PubMed Central

    Mazur, J; Jernigan, R L; Sarai, A

    1996-01-01

    A method is presented to link a sequence of space-fixed base pairs by the sugar-phosphate segments of single nucleotides and to evaluate the effects in the backbone caused by this positioning of the bases. The entire computational unit comprises several nucleotides that are energy-minimized, subject to constraints imposed by the sugar-phosphate backbone segments being anchored to space-fixed base pairs. The minimization schemes are based on two stages, a conjugate gradient method followed by a Newton-Raphson algorithm. Because our purpose is to examine the response, or relaxation, of an artificially stressed backbone, it is essential to be able to obtain, as closely as possible, a lowest minimum energy conformation of the backbone segment in conformational space. For this purpose, an algorithm is developed that leads to the generation of an assembly of many local energy minima. From these sets of local minima, one conformation corresponding to the one with the lowest minimum is then selected and designated to represent the backbone segment at its minimum. The effective electrostatic potential of mean force is expressed in terms of adjustable parameters that incorporate solvent screening action in the Coulombic interactions between charged backbone atoms; these parameters are adjusted to obtain the best fit of the nearest-neighbor phosphorous atoms in an x-ray structure. PMID:8874023

  2. Constructing backbone network by using tinker algorithm

    NASA Astrophysics Data System (ADS)

    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.

  3. The optimization issues in an agile all-photonic backbone network

    NASA Astrophysics Data System (ADS)

    Zhang, Yiming; Yang, Oliver W.; Zhai, Yihua

    2005-02-01

    The Agile All-photonic Backbone Network (AAPN) architecture has been proposed by the telecommunication industry as a potential candidate for the ultra high speed Next Generation Optical Network (NGON) architecture. AAPN network structure is composed of adaptive optical core switches and edge routers in an overlaid star physical topology. In this paper, we examine various optimization issues for AAPN architectures. The optimization procedure is based on a Lagrangean relaxation and subgradient method. Based on the optimization methodology provided in the previous research, we propose a modified algorithm to optimize AAPN networks, with respect to the assumptions used in AAPN. The results for different network configurations are studied and the influence of network resources is also studied. Our algorithm is shown to be very computational effective on the AAPN networks, and the bounds generated are mostly within 1% of the final objective value.

  4. Constructing optimal entanglement witnesses

    SciTech Connect

    Chruscinski, Dariusz; Pytel, Justyna; Sarbicki, Gniewomir

    2009-12-15

    We provide a class of indecomposable entanglement witnesses. In 4x4 case, it reproduces the well-known Breuer-Hall witness. We prove that these witnesses are optimal and atomic, i.e., they are able to detect the 'weakest' quantum entanglement encoded into states with positive partial transposition. Equivalently, we provide a construction of indecomposable atomic maps in the algebra of 2kx2k complex matrices. It is shown that their structural physical approximations give rise to entanglement breaking channels. This result supports recent conjecture by Korbicz et al. [Phys. Rev. A 78, 062105 (2008)].

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

    NASA Astrophysics Data System (ADS)

    Choi, Eunwoo

    phenomenon was studied by powder X-ray diffraction and supported by gas adsorption and thermogravimetric analysis. Layered MOFs with metalloporphyrins with Zn, Cu, Co and Fe at their +2 oxidation states as struts were prepared to facilitate non-structural metal sites and tested for hydrogen adsorption and the binding enthalpies. Steep uptakes are indeed observed, but rather due to the optimal interlayer distance of 9 A for dihydrogen, and the binding enthalpies are 6.7 -- 7.6 kJ . mo1-1 which are not ·extraordinary. Although the metals did not seem to play a large role, a trend was observed where the binding enthalpies increase as the metals in the metalloporphyrins go from late to early transition metals. With the concept of conductive metal oxides, a journey of constructing conductive MOFs was taken by attempting the formation of metal-carbon bonds by linking transition metal ions with conjugated organic struts which are 1,4-benzenediisonitrile, 1,4-benzenediethynylide and p-cyanophenylethynylide. Among the attempted systems, a reaction of Cr(III) and 1,4-benzenediethynylide yielded an amorphous material with a BET (Brunauer-Emmett-Teller) surface area of 80 m2.g-1, hydrogen uptake of 47 cm 3. g-1 and a resistance of 20 MO. Also a crystalline compound was prepared by mimicking Prussian blue by using p-cyanophenylethynylide where one end can bind metal with ethynylic carbon and the other end with the cyano nitrogen by following the similar synthesis of Prussian blue analogues. The principles of reticular chemistry are demonstrated through each chapter and show how powerful and beneficial reticular chemistry is by allowing the predetermination of the structure and function. The details of the ways to approach an ideal compound and the synthetic aspects are also described in this dissertation.

  6. Backbone switch to abacavir/lamivudine fixed-dose combination: implications for antiretroviral therapy optimization.

    PubMed

    Fantauzzi, Alessandra; Floridia, Marco; Falasca, Francesca; Spanedda, Pierpaolo; Turriziani, Ombretta; Vullo, Vincenzo; Mezzaroma, Ivano

    2015-10-01

    Current guidelines recommend treatment optimization in virologically suppressed patients through switching/ simplification strategies to minimize long-term toxicities and improve adherence. The assessment of inflammation/ coagulation profiles may support therapeutic decisions. We undertook a prospective, non-randomized study to evaluate the efficacy and safety of switching to ABC/3TC from ZDV/3TC or TDF/FTC backbones, in 40 HIV-1 infected patients with HIV-RNA levels <37 copies/mL (>24 months). Main endpoints were viral load levels, CD4+ T cells and toxicities after 48 weeks. Serum inflammation/coagulation markers (ESR, CRP, D-dimer and fibrinogen) and pro-inflammatory cytokines (IL-6, TNF-α, adiponectin, resistin) were evaluated. Baseline characteristics were similar in the two arms, with significantly lower values of e-GFR in patients on TDF/FTC. Markers of inflammation/ coagulation and cytokine profile were also similar, except for higher values of resistin in patients on TDF/ FTC. During follow up, CD4+ T cells increased and viral load remained undetectable in both groups. Patient from ZDV/3TC had significantly greater changes in total cholesterol and serum creatinine. Markers of inflammation/ coagulation remained unchanged. Adiponectin significantly increased in patients from ZDV/3TC. Switching to ABC/3TC was effective and safe. Inflammatory markers remained low in both groups. Some changes in metabolic, kidney and cytokine profiles were apparently specific for baseline cART treatment.

  7. Lightweight mirror construction optimization

    NASA Astrophysics Data System (ADS)

    Mooney, J. T.; Allen, M. A.; Bolton, J.; Dahl, R. J.; Lintz, E. A.

    2015-10-01

    Large, lightweight mirrors are a critical component in space based imaging applications. These mirrors have traditionally required long manufacturing cycle times with associated high costs. In this paper, the key cost and schedule drivers for the production of large, lightweight mirrors will be reviewed along with enabling solutions that could provide significant cost and schedule reductions while maintaining the high quality performance required for these challenging applications. The technologies include advancements in replication, construction, and bonding. Initial feasibility tests and associated results will be presented.

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

    PubMed Central

    2016-01-01

    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. PMID:27559757

  9. Optimized Construction of SSR-enriched Libraries

    USDA-ARS?s Scientific Manuscript database

    We have developed a more efficient method to construct simple sequence repeat (SSR) libraries. We have designed and tested several new adapter. We changed the typical blunt-end ligation of adapters for the more effective sticky-end ligation. We optimized temperature, enzymes and length of each st...

  10. Sequestration of dyes from artificially prepared textile effluent using RSM-CCD optimized hybrid backbone based adsorbent-kinetic and equilibrium studies.

    PubMed

    Sukriti; Sharma, Jitender; Chadha, Amritpal Singh; Pruthi, Vaishali; Anand, Prerna; Bhatia, Jaspreet; Kaith, B S

    2017-04-01

    Present work reports the synthesis of semi-Interpenetrating Network Polymer (semi-IPN) using Gelatin-Gum xanthan hybrid backbone and polyvinyl alcohol in presence of l-tartaric acid and ammonium persulphate as the crosslinker-initiator system. Reaction parameters were optimized with Response Surface Methodology (RSM) in order to maximize the percent gel fraction of the synthesized sample. Polyvinyl alcohol, l-Tartaric acid, ammonium persulphate, reaction temperature, time and pH of the reaction medium were found to make an impact on the percentage gel fraction obtained. Incorporation of polyvinyl alcohol chains onto hybrid backbone and crosslinking between the different polymer chains were confirmed through techniques like FTIR, SEM-EDX and XRD. Semi-IPN was found to be very efficient in the removal of cationic dyes rhodamine-B (70%) and auramine-O (63%) from a mixture with an adsorbent dose of 700 mg, initial concentration of rhodamine-B 6 mgL(-1) and auramine-O 26 mgL(-1), at an time interval of 22-25 h and 30 °C temp. Further to determine the nature of adsorption Langmuir and Freundlich adsorption isotherm models were studied and it was found that Langmuir adsorption isotherm was the best fit model for the removal of mixture of dyes. Kinetic studies for the sorption of dyes favored the reaction mechanism to occur via a pseudo second order pathway with R(2) value about 0.99.

  11. Optimal atlas construction through hierarchical image registration

    NASA Astrophysics Data System (ADS)

    Grevera, George J.; Udupa, Jayaram K.; Odhner, Dewey; Torigian, Drew A.

    2016-03-01

    Atlases (digital or otherwise) are common in medicine. However, there is no standard framework for creating them from medical images. One traditional approach is to pick a representative subject and then proceed to label structures/regions of interest in this image. Another is to create a "mean" or average subject. Atlases may also contain more than a single representative (e.g., the Visible Human contains both a male and a female data set). Other criteria besides gender may be used as well, and the atlas may contain many examples for a given criterion. In this work, we propose that atlases be created in an optimal manner using a well-established graph theoretic approach using a min spanning tree (or more generally, a collection of them). The resulting atlases may contain many examples for a given criterion. In fact, our framework allows for the addition of new subjects to the atlas to allow it to evolve over time. Furthermore, one can apply segmentation methods to the graph (e.g., graph-cut, fuzzy connectedness, or cluster analysis) which allow it to be separated into "sub-atlases" as it evolves. We demonstrate our method by applying it to 50 3D CT data sets of the chest region, and by comparing it to a number of traditional methods using measures such as Mean Squared Difference, Mattes Mutual Information, and Correlation, and for rigid registration. Our results demonstrate that optimal atlases can be constructed in this manner and outperform other methods of construction using freely available software.

  12. Optimal construction of army ant living bridges.

    PubMed

    Graham, Jason M; Kao, Albert B; Wilhelm, Dylana A; Garnier, Simon

    2017-09-20

    Integrating the costs and benefits of collective behaviors is a fundamental challenge to understanding the evolution of group living. These costs and benefits can rarely be quantified simultaneously due to the complexity of the interactions within the group, or even compared to each other because of the absence of common metrics between them. The construction of 'living bridges' by New World army ants - which they use to shorten their foraging trails - is a unique example of a collective behavior where costs and benefits have been experimentally measured and related to each other. As a result, it is possible to make quantitative predictions about when and how the behavior will be observed. In this paper, we extend a previous mathematical model of these costs and benefits to much broader domain of applicability. Specifically, we exhibit a procedure for analyzing the optimal formation, and final configuration, of army ant living bridges given a means to express the geometrical configuration of foraging path obstructions. Using this procedure, we provide experimentally testable predictions of the final bridge position, as well as the optimal formation process for certain cases, for a wide range of scenarios, which more closely resemble common terrain obstacles that ants encounter in nature. As such, our framework offers a rare benchmark for determining the evolutionary pressures governing the evolution of a naturally occurring collective animal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. An Optimal CDS Construction Algorithm with Activity Scheduling in Ad Hoc Networks.

    PubMed

    Penumalli, Chakradhar; Palanichamy, Yogesh

    2015-01-01

    A new energy efficient optimal Connected Dominating Set (CDS) algorithm with activity scheduling for mobile ad hoc networks (MANETs) is proposed. This algorithm achieves energy efficiency by minimizing the Broadcast Storm Problem [BSP] and at the same time considering the node's remaining energy. The Connected Dominating Set is widely used as a virtual backbone or spine in mobile ad hoc networks [MANETs] or Wireless Sensor Networks [WSN]. The CDS of a graph representing a network has a significant impact on an efficient design of routing protocol in wireless networks. Here the CDS is a distributed algorithm with activity scheduling based on unit disk graph [UDG]. The node's mobility and residual energy (RE) are considered as parameters in the construction of stable optimal energy efficient CDS. The performance is evaluated at various node densities, various transmission ranges, and mobility rates. The theoretical analysis and simulation results of this algorithm are also presented which yield better results.

  14. Strike a Balance: Optimization of Backbone Torsion Parameters of AMBER Polarizable Force Field for Simulations of Proteins and Peptides

    PubMed Central

    WANG, ZHI-XIANG; ZHANG, WEI; WU, CHUN; LEI, HONGXING; CIEPLAK, PIOTR; DUAN, YONG

    2014-01-01

    Based on the AMBER polarizable model (ff02), we have reoptimized the parameters related to the main-chain (Φ, Ψ) torsion angles by fitting to the Boltzmann-weighted average quantum mechanical (QM) energies of the important regions (i.e., β, PII, αR, and αL regions). Following the naming convention of the AMBER force field series, this release will be called ff02pol.rl The force field has been assessed both by energetic comparison against the QM data and by the replica exchange molecular dynamics simulations of short alanine peptides in water. For Ace-Ala-Nme, the simulated populations in the β, PII and αR regions were approximately 30, 43, and 26%, respectively. For Ace-(Ala)7-Nme, the populations in these three regions were approximately 24, 49, and 26%. Both were in qualitative agreement with the NMR and CD experimental conclusions. In comparison with the previous force field, ff02pol.rl demonstrated good balance among these three important regions. The optimized torsion parameters, together with those in ff02, allow us to carry out simulations on proteins and peptides with the consideration of polarization. PMID:16526038

  15. Process Model Construction and Optimization Using Statistical Experimental Design,

    DTIC Science & Technology

    1988-04-01

    Memo No. 88-442 ~LECTE March 1988 31988 %,.. MvAY 1 98 0) PROCESS MODEL CONSTRUCTION AND OPTIMIZATION USING STATISTICAL EXPERIMENTAL DESIGN Emmanuel...Sachs and George Prueger Abstract A methodology is presented for the construction of process models by the combination of physically based mechanistic...253-8138. .% I " Process Model Construction and Optimization Using Statistical Experimental Design" by Emanuel Sachs Assistant Professor and George

  16. AbDesign: an algorithm for combinatorial backbone design guided by natural conformations and sequences

    PubMed Central

    Lapidoth, Gideon D.; Baran, Dror; Pszolla, Gabriele M.; Norn, Christoffer; Alon, Assaf; Tyka, Michael D.; Fleishman, Sarel J.

    2016-01-01

    Computational design of protein function has made substantial progress, generating new enzymes, binders, inhibitors, and nanomaterials not previously seen in nature. However, the ability to design new protein backbones for function – essential to exert control over all polypeptide degrees of freedom – remains a critical challenge. Most previous attempts to design new backbones computed the mainchain from scratch. Here, instead, we describe a combinatorial backbone and sequence optimization algorithm called AbDesign, which leverages the large number of sequences and experimentally determined molecular structures of antibodies to construct new antibody models, dock them against target surfaces and optimize their sequence and backbone conformation for high stability and binding affinity. We used the algorithm to produce antibody designs that target the same molecular surfaces as nine natural, high-affinity antibodies; in six the backbone conformation at the core of the antibody binding surface is similar to the natural antibody targets, and in several cases sequence and sidechain conformations recapitulate those seen in the natural antibodies. In the case of an anti-lysozyme antibody, designed antibody CDRs at the periphery of the interface, such as L1 and H2, show a greater backbone conformation diversity than the CDRs at the core of the interface, and increase the binding surface area compared to the natural antibody, which could enhance affinity and specificity. PMID:25670500

  17. Modular Protein Expression Toolbox (MoPET), a standardized assembly system for defined expression constructs and expression optimization libraries

    PubMed Central

    Birkenfeld, Jörg; Franz, Jürgen; Gritzan, Uwe; Linden, Lars; Trautwein, Mark

    2017-01-01

    The design and generation of an optimal expression construct is the first and essential step in in the characterization of a protein of interest. Besides evaluation and optimization of process parameters (e.g. selection of the best expression host or cell line and optimal induction conditions and time points), the design of the expression construct itself has a major impact. However, the path to this final expression construct is often not straight forward and includes multiple learning cycles accompanied by design variations and retesting of construct variants, since multiple, functional DNA sequences of the expression vector backbone, either coding or non-coding, can have a major impact on expression yields. To streamline the generation of defined expression constructs of otherwise difficult to express proteins, the Modular Protein Expression Toolbox (MoPET) has been developed. This cloning platform allows highly efficient DNA assembly of pre-defined, standardized functional DNA modules with a minimal cloning burden. Combining these features with a standardized cloning strategy facilitates the identification of optimized DNA expression constructs in shorter time. The MoPET system currently consists of 53 defined DNA modules divided into eight functional classes and can be flexibly expanded. However, already with the initial set of modules, 792,000 different constructs can be rationally designed and assembled. Furthermore, this starting set was used to generate small and mid-sized combinatorial expression optimization libraries. Applying this screening approach, variants with up to 60-fold expression improvement have been identified by MoPET variant library screening. PMID:28520717

  18. Genetic algorithms for the construction of D-optimal designs

    SciTech Connect

    Heredia-Langner, Alejandro; Carlyle, W M.; Montgomery, D C.; Borror, Connie M.; Runger, George C.

    2003-01-01

    Computer-generated designs are useful for situations where standard factorial, fractional factorial or response surface designs cannot be easily employed. Alphabetically-optimal designs are the most widely used type of computer-generated designs, and of these, the D-optimal (or D-efficient) class of designs are extremely popular. D-optimal designs are usually constructed by algorithms that sequentially add and delete points from a potential design based using a candidate set of points spaced over the region of interest. We present a technique to generate D-efficient designs using genetic algorithms (GA). This approach eliminates the need to explicitly consider a candidate set of experimental points and it can handle highly constrained regions while maintaining a level of performance comparable to more traditional design construction techniques.

  19. Optimization of amino acid type-specific 13C and 15N labeling for the backbone assignment of membrane proteins by solution- and solid-state NMR with the UPLABEL algorithm.

    PubMed

    Hefke, Frederik; Bagaria, Anurag; Reckel, Sina; Ullrich, Sandra Johanna; Dötsch, Volker; Glaubitz, Clemens; Güntert, Peter

    2011-02-01

    We present a computational method for finding optimal labeling patterns for the backbone assignment of membrane proteins and other large proteins that cannot be assigned by conventional strategies. Following the approach of Kainosho and Tsuji (Biochemistry 21:6273-6279 (1982)), types of amino acids are labeled with (13)C or/and (15)N such that cross peaks between (13)CO(i - 1) and (15)NH(i) result only for pairs of sequentially adjacent amino acids of which the first is labeled with (13)C and the second with (15)N. In this way, unambiguous sequence-specific assignments can be obtained for unique pairs of amino acids that occur exactly once in the sequence of the protein. To be practical, it is crucial to limit the number of differently labeled protein samples that have to be prepared while obtaining an optimal extent of labeled unique amino acid pairs. Our computer algorithm UPLABEL for optimal unique pair labeling, implemented in the program CYANA and in a standalone program, and also available through a web portal, uses combinatorial optimization to find for a given amino acid sequence labeling patterns that maximize the number of unique pair assignments with a minimal number of differently labeled protein samples. Various auxiliary conditions, including labeled amino acid availability and price, previously known partial assignments, and sequence regions of particular interest can be taken into account when determining optimal amino acid type-specific labeling patterns. The method is illustrated for the assignment of the human G-protein coupled receptor bradykinin B2 (B(2)R) and applied as a starting point for the backbone assignment of the membrane protein proteorhodopsin.

  20. Test problem construction for single-objective bilevel optimization.

    PubMed

    Sinha, Ankur; Malo, Pekka; Deb, Kalyanmoy

    2014-01-01

    In this paper, we propose a procedure for designing controlled test problems for single-objective bilevel optimization. The construction procedure is flexible and allows its user to control the different complexities that are to be included in the test problems independently of each other. In addition to properties that control the difficulty in convergence, the procedure also allows the user to introduce difficulties caused by interaction of the two levels. As a companion to the test problem construction framework, the paper presents a standard test suite of 12 problems, which includes eight unconstrained and four constrained problems. Most of the problems are scalable in terms of variables and constraints. To provide baseline results, we have solved the proposed test problems using a nested bilevel evolutionary algorithm. The results can be used for comparison, while evaluating the performance of any other bilevel optimization algorithm. The code related to the paper may be accessed from the website http://bilevel.org .

  1. On the Construction of Optimal Paths to Extinction

    DTIC Science & Technology

    2012-01-03

    dimensions. The algorithm relies on the calculation of nite-time Lyapunov exponents (FTLE), which provide a quantitative measure of how sensitively a...constructing, or growing, the optimal path to extinction in systems of arbitrary dimensions. The algorithm relies on the calculation of finite-time Lyapunov ...relies on the calculation of finite-time Lyapunov exponents (FTLE), which provide a quantitative measure of how sensitively a system’s behavior

  2. AbDesign: An algorithm for combinatorial backbone design guided by natural conformations and sequences.

    PubMed

    Lapidoth, Gideon D; Baran, Dror; Pszolla, Gabriele M; Norn, Christoffer; Alon, Assaf; Tyka, Michael D; Fleishman, Sarel J

    2015-08-01

    Computational design of protein function has made substantial progress, generating new enzymes, binders, inhibitors, and nanomaterials not previously seen in nature. However, the ability to design new protein backbones for function--essential to exert control over all polypeptide degrees of freedom--remains a critical challenge. Most previous attempts to design new backbones computed the mainchain from scratch. Here, instead, we describe a combinatorial backbone and sequence optimization algorithm called AbDesign, which leverages the large number of sequences and experimentally determined molecular structures of antibodies to construct new antibody models, dock them against target surfaces and optimize their sequence and backbone conformation for high stability and binding affinity. We used the algorithm to produce antibody designs that target the same molecular surfaces as nine natural, high-affinity antibodies; in five cases interface sequence identity is above 30%, and in four of those the backbone conformation at the core of the antibody binding surface is within 1 Å root-mean square deviation from the natural antibodies. Designs recapitulate polar interaction networks observed in natural complexes, and amino acid sidechain rigidity at the designed binding surface, which is likely important for affinity and specificity, is high compared to previous design studies. In designed anti-lysozyme antibodies, complementarity-determining regions (CDRs) at the periphery of the interface, such as L1 and H2, show greater backbone conformation diversity than the CDRs at the core of the interface, and increase the binding surface area compared to the natural antibody, potentially enhancing affinity and specificity.

  3. Optimization of circuits using a constructive learning algorithm

    SciTech Connect

    Beiu, V.

    1997-05-01

    The paper presents an application of a constructive learning algorithm to optimization of circuits. For a given Boolean function f. a fresh constructive learning algorithm builds circuits belonging to the smallest F{sub n,m} class of functions (n inputs and having m groups of ones in their truth table). The constructive proofs, which show how arbitrary Boolean functions can be implemented by this algorithm, are shortly enumerated An interesting aspect is that the algorithm can be used for generating both classical Boolean circuits and threshold gate circuits (i.e. analogue inputs and digital outputs), or a mixture of them, thus taking advantage of mixed analogue/digital technologies. One illustrative example is detailed The size and the area of the different circuits are compared (special cost functions can be used to closer estimate the area and the delay of VLSI implementations). Conclusions and further directions of research are ending the paper.

  4. Constructing DNA Barcode Sets based on Particle Swarm Optimization.

    PubMed

    Waang, Bin; Zheng, Xuedong; Zhou, Shihua; Zhou, Changjun; Wei, Xiaopeng; Zhang, Qiang; Wei, Ziqi

    2017-03-07

    Following the completion of the human genome project, a large amount of high-throughput bio-data was generated. To analyze these data, massively parallel sequencing, namely next-generation sequencing, was rapidly developed. DNA barcodes are used to identify the ownership between sequences and samples when they are attached at the beginning or end of sequencing reads. Constructing DNA barcode sets provides the candidate DNA barcodes for this application. To increase the accuracy of DNA barcode sets, a particle swarm optimization (PSO) algorithm has been modified and used to construct the DNA barcode sets in this paper. Compared with the extant results, some lower bounds of DNA barcode sets are improved. The results show that the proposed algorithm is effective in constructing DNA barcode sets.

  5. Underlying construct of empathy, optimism, and burnout in medical students.

    PubMed

    Hojat, Mohammadreza; Vergare, Michael; Isenberg, Gerald; Cohen, Mitchell; Spandorfer, John

    2015-01-29

    This study was designed to explore the underlying construct of measures of empathy, optimism, and burnout in medical students. Three instruments for measuring empathy (Jefferson Scale of Empathy, JSE); Optimism (the Life Orientation Test-Revised, LOT-R); and burnout (the Maslach Burnout Inventory, MBI, which includes three scales of Emotional Exhaustion, Depersonalization, and Personal Accomplishment) were administered to 265 third-year students at Sidney Kimmel (formerly Jefferson) Medical College at Thomas Jefferson University. Data were subjected to factor analysis to examine relationships among measures of empathy, optimism, and burnout in a multivariate statistical model. Factor analysis (principal component with oblique rotation) resulted in two underlying constructs, each with an eigenvalue greater than one. The first factor involved "positive personality attributes" (factor coefficients greater than .58 for measures of empathy, optimism, and personal accomplishment). The second factor involved "negative personality attributes" (factor coefficients greater than .78 for measures of emotional exhaustion, and depersonalization). Results confirmed that an association exists between empathy in the context of patient care and personality characteristics that are conducive to relationship building, and considered to be "positive personality attributes," as opposed to personality characteristics that are considered as "negative personality attributes" that are detrimental to interpersonal relationships. Implications for the professional development of physicians-in-training and in-practice are discussed.

  6. Underlying construct of empathy, optimism, and burnout in medical students

    PubMed Central

    Vergare, Michael; Isenberg, Gerald; Cohen, Mitchell; Spandorfer, John

    2015-01-01

    Objectives This study was designed to explore the underlying construct of measures of empathy, optimism, and burnout in medical students. Methods Three instruments for measuring empathy (Jefferson Scale of Empathy, JSE); Optimism (the Life Orientation Test-Revised, LOT-R); and burnout (the Maslach Burnout Inventory, MBI, which includes three scales of Emotional Exhaustion, Depersonalization, and Personal Accomplishment) were administered to 265 third-year students at Sidney Kimmel (formerly Jefferson) Medical College at Thomas Jefferson University. Data were subjected to factor analysis to examine relationships among measures of empathy, optimism, and burnout in a multivariate statistical model.  Results Factor analysis (principal component with oblique rotation) resulted in two underlying constructs, each with an eigenvalue greater than one. The first factor involved “positive personality attributes” (factor coefficients greater than .58 for measures of empathy, optimism, and personal accomplishment). The second factor involved “negative personality attributes” (factor coefficients greater than .78 for measures of emotional exhaustion, and depersonalization). Conclusions Results confirmed that an  association exists between empathy in the context of patient care and personality characteristics that are conducive to relationship building, and considered to be  “positive personality attributes,” as opposed to personality characteristics that are considered as “negative personality attributes” that are detrimental to interpersonal relationships. Implications for the professional development of physicians-in-training and in-practice are discussed. PMID:25633650

  7. Constructal method to optimize solar thermochemical reactor design

    SciTech Connect

    Tescari, S.; Mazet, N.; Neveu, P.

    2010-09-15

    The objective of this study is the geometrical optimization of a thermochemical reactor, which works simultaneously as solar collector and reactor. The heat (concentrated solar radiation) is supplied on a small peripheral surface and has to be dispersed in the entire reactive volume in order to activate the reaction all over the material. A similarity between this study and the point to volume problem analyzed by the constructal approach (Bejan, 2000) is evident. This approach was successfully applied to several domains, for example for the coupled mass and conductive heat transfer (Azoumah et al., 2004). Focusing on solar reactors, this work aims to apply constructal analysis to coupled conductive and radiative heat transfer. As a first step, the chemical reaction is represented by a uniform heat sink inside the material. The objective is to optimize the reactor geometry in order to maximize its efficiency. By using some hypothesis, a simplified solution is found. A parametric study provides the influence of different technical and operating parameters on the maximal efficiency and on the optimal shape. Different reactor designs (filled cylinder, cavity and honeycomb reactors) are compared, in order to determine the most efficient structure according to the operating conditions. Finally, these results are compared with a CFD model in order to validate the assumptions. (author)

  8. Construction and preliminary investigation of a novel dengue serotype 4 chimeric virus using Japanese encephalitis vaccine strain SA14-14-2 as the backbone.

    PubMed

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

    2014-10-13

    For the purpose of developing a novel dengue vaccine candidate, recombinant plasmids were constructed which contained the full length cDNA clone of Japanese encephalitis (JE) vaccine strain SA14-14-2 with its premembrane (PreM) and envelope (E) genes replaced by the counterparts of dengue virus type 4 (DENV4). By transfecting the in vitro transcription products of the recombinant plasmids into BHK-21 cells, a chimeric virus JEV/DENV4 was successfully recovered. The chimeric virus was identified by complete genome sequencing, Western blot and immunofluorescent staining. Growth characteristics revealed it was well adapted to primary hamster kidney (PHK) cells. Its genetic stability was investigated and only one unintentional mutation in 5'-untranslated region (5'-UTR) was found after 20 passages in PHK cells. Neurotropism, neurovirulence and immunogenicity of the chimeric virus were tested in mice. Besides, the influence of JE vaccine pre-immunization on the neutralizing antibody level induced by the chimeric virus was illuminated. To our knowledge, this is the first chimeric virus incorporating the JE vaccine stain SA14-14-2 and DENV4. It is probably a potential candidate to compose a tetravalent dengue chimeric vaccine.

  9. [Diagnostics of work motivation (DIAMO): optimization and construct validity].

    PubMed

    Ranft, Andreas; Fiedler, Rolf; Greitemann, Bernhard; Heuft, Gereon

    2009-01-01

    Faced with increasing cost pressure of the social insurance system the carriers of rehabilitation programs focus on the efficacy of their measures. The diagnostic instrument for work motivation (DIAMO) has been developed to assess the influence of job-related motivation on the rehabilitation outcome. The inner structure of the instrument was validated and optimized in a cohort of medical rehabilitation patients (n = 422). Construct validity was further tested by using established instruments. Ten scales related to self-image, intention of action and goodness of fit show good psychometric qualities (Cronbachs alpha: 0.72 - 0.86). The constructs correlate moderately-to-strongly with personality-oriented scales while correlation with disease-related contents is low. The DIAMO is a generic and not disease oriented instrument. It would be expected to facilitate the development of vocational interventions to increase the rehabilitation outcome.

  10. On some Methods for Constructing Optimal Subset Selection Procedures

    DTIC Science & Technology

    1976-09-01

    Reproduction in whole or in part is permitted for any purpose of the United States Government. cc-I U On Some Methods for Constructing Optimal...Reproduction in whole or in part is permitted for any purpose of the United States Government. 2/ LL-mma 1. A Family of’ distributions P, has SIP in...if" E ,,(X) , Eep(X) for,9 - _3 - - 𔃽 - al I non-decre:asin integralle function ip(x) and all (3 < It is ea;v to generalize Alam’s result in [1] as

  11. [Optimization of aerobic/anaerobic subsurface flow constructed wetlands].

    PubMed

    Li, Feng-Min; Shan, Shi; Li, Yuan-Yuan; Li, Yang; Wang, Zheng-Yu

    2012-02-01

    Previous studies showed that setting aerobic and anaerobic paragraph segments in the subsurface constructed wetlands (SFCWs) can improve the COD, NH4(+)-N, and TN removal rate, whereas the oxygen enrichment environment which produced by the artificial aeration could restrain the NO3(-)-N and NO2(-)-N removal process, and to a certain extent, inhibit the denitrification in SFCWs Therefore, in this research the structure and technology of SFCW with aerobic and anaerobic paragraph segments were optimized, by using the multi-point water inflow and setting the corresponding section for the extra pollutant removal. Results showed that with the hydraulic load of 0.06 m3 x (m2 x d)(-1), the COD, NH4(+)-N and TN removal efficiencies in the optimized SFCW achieved 91.6%, 100% and 87.7% respectively. COD/N increased to 10 speedily after the inflow supplement. The multi-point water inflow could add carbon sources, and simultaneously maximum utilization of wetland to remove pollutants. The optimized SFCW could achieve the purposes of purification process optimization, and provide theoretical basis and application foundation for improving the total nitrogen removal efficiency.

  12. Construction of optimal resources for concatenated quantum protocols

    NASA Astrophysics Data System (ADS)

    Pirker, A.; Wallnöfer, J.; Briegel, H. J.; Dür, W.

    2017-06-01

    We consider the explicit construction of resource states for measurement-based quantum information processing. We concentrate on special-purpose resource states that are capable to perform a certain operation or task, where we consider unitary Clifford circuits as well as non-trace-preserving completely positive maps, more specifically probabilistic operations including Clifford operations and Pauli measurements. We concentrate on 1 →m and m →1 operations, i.e., operations that map one input qubit to m output qubits or vice versa. Examples of such operations include encoding and decoding in quantum error correction, entanglement purification, or entanglement swapping. We provide a general framework to construct optimal resource states for complex tasks that are combinations of these elementary building blocks. All resource states only contain input and output qubits, and are hence of minimal size. We obtain a stabilizer description of the resulting resource states, which we also translate into a circuit pattern to experimentally generate these states. In particular, we derive recurrence relations at the level of stabilizers as key analytical tool to generate explicit (graph) descriptions of families of resource states. This allows us to explicitly construct resource states for encoding, decoding, and syndrome readout for concatenated quantum error correction codes, code switchers, multiple rounds of entanglement purification, quantum repeaters, and combinations thereof (such as resource states for entanglement purification of encoded states).

  13. First-principle optimal local pseudopotentials construction via optimized effective potential method

    NASA Astrophysics Data System (ADS)

    Mi, Wenhui; Zhang, Shoutao; Wang, Yanchao; Ma, Yanming; Miao, Maosheng

    2016-04-01

    The local pseudopotential (LPP) is an important component of orbital-free density functional theory, a promising large-scale simulation method that can maintain information on a material's electron state. The LPP is usually extracted from solid-state density functional theory calculations, thereby it is difficult to assess its transferability to cases involving very different chemical environments. Here, we reveal a fundamental relation between the first-principles norm-conserving pseudopotential (NCPP) and the LPP. On the basis of this relationship, we demonstrate that the LPP can be constructed optimally from the NCPP for a large number of elements using the optimized effective potential method. Specially, our method provides a unified scheme for constructing and assessing the LPP within the framework of first-principles pseudopotentials. Our practice reveals that the existence of a valid LPP with high transferability may strongly depend on the element.

  14. Optimal deployment of emissions reduction technologies for construction equipment.

    PubMed

    Bari, Muhammad Ehsanul; Zietsman, Josias; Quadrifoglio, Luca; Farzaneh, Mohamadreza

    2011-06-01

    The objective of this research was to develop a multiobjective optimization model to deploy emissions reduction technologies for nonroad construction equipment to reduce emissions in a cost-effective and optimal manner. Given a fleet of construction equipment emitting different pollutants in the nonattainment (NA) and near -nonattainment (NNA) counties of a state and a set of emissions reduction technologies available for installation on equipment to control pollution/emissions, the model assists in determining the mix of technologies to be deployed so that maximum emissions reduction and fuel savings are achieved within a given budget. Three technologies considered for emissions reduction were designated as X, Y, and Z to keep the model formulation general so that it can be applied for any other set of technologies. Two alternative methods of deploying these technologies on a fleet of equipment were investigated with the methods differing in the technology deployment preference in the NA and NNA counties. The model having a weighted objective function containing emissions reduction benefits and fuel-saving benefits was programmed with C++ and ILOG-CPLEX. For demonstration purposes, the model was applied for a selected construction equipment fleet owned by the Texas Department of Transportation, located in NA and NNA counties of Texas, assuming the three emissions reduction technologies X, Y, and Z to represent, respectively, hydrogen enrichment, selective catalytic reduction, and fuel additive technologies. Model solutions were obtained for varying budget amounts to test the sensitivity of emissions reductions and fuel-savings benefits with increasing the budget. Different mixes of technologies producing maximum oxides of nitrogen (NO(x)) reductions and total combined benefits (emissions reductions plus fuel savings) were indicated at different budget ranges. The initial steep portion of the plots for NO(x) reductions and total combined benefits against budgets

  15. Optimizing the Construction of the A1 Collaboration Neutron Detector

    NASA Astrophysics Data System (ADS)

    Chinn, Edward; A1 Collaboration

    2016-09-01

    We report on the design and construction of a frame designed to optimize both the time efficiency and construction quality of the large scintillator elements These elements will be assembled to form a neutron detector for use by the A1 Collaboration at the Institute for Nuclear Physics in Mainz, Germany. The design had to provide adequate support for the 20 kg scintillator bars while gluing light guides and photomultiplier tubes to both sides of the bars using optical cement. The optical cement requires approximately 24 hours to dry and 100 bars have to be glued with this apparatus. To address each of these issues, several different prototypes were designed and reviewed. The selected apparatus minimized size to meet space constraints, with reduced material cost and provided the most time-efficient way to build the neutron detector. Once the schematic design was selected, we produced technical drawings in AutoDesk Inventor. Assembled the structure and completed gluing of the first batch of scintillators, in order to verify the performance. This apparatus was successful at producing high quality scintillators which were evaluated using cosmic rays. National Science Foundation Grant No. IIA-1358175.

  16. Fluid management in the optimization of space construction

    NASA Technical Reports Server (NTRS)

    Snyder, Howard

    1990-01-01

    Fluid management impacts strongly on the optimization of space construction. Large quantities of liquids are needed for propellants and life support. The mass of propellant liquids is comparable to that required for the structures. There may be a strong dynamic interaction between the stored liquids and the space structure unless the design minimizes the interaction. The constraints of cost and time required optimization of the supply/resupply strategy. The proper selection and design of the fluid management methods for: slosh control; stratification control; acquisition; transfer; gauging; venting; dumping; contamination control; selection of tank configuration and size; the storage state and the control system can improve the entire system performance substantially. Our effort consists of building mathematical/computer models of the various fluid management methods and testing them against the available experimental data. The results of the models are used as inputs to the system operations studies. During the past year, the emphasis has been on modeling: the transfer of cryogens; sloshing and the storage configuration. The work has been intermeshed with ongoing NASA design and development studies to leverage the funds provided by the Center.

  17. Fluid management in the optimization of space construction

    NASA Technical Reports Server (NTRS)

    Snyder, Howard

    1990-01-01

    Fluid management impacts strongly on the optimization of space construction. Large quantities of liquids are needed for propellants and life support. The mass of propellant liquids is comparable to that required for the structures. There may be a strong dynamic interaction between the stored liquids and the space structure unless the design minimizes the interaction. The constraints of cost and time required optimization of the supply/resupply strategy. The proper selection and design of the fluid management methods for: slosh control; stratification control; acquisition; transfer; gauging; venting; dumping; contamination control; selection of tank configuration and size; the storage state and the control system can improve the entire system performance substantially. Our effort consists of building mathematical/computer models of the various fluid management methods and testing them against the available experimental data. The results of the models are used as inputs to the system operations studies. During the past year, the emphasis has been on modeling: the transfer of cryogens; sloshing and the storage configuration. The work has been intermeshed with ongoing NASA design and development studies to leverage the funds provided by the Center.

  18. 96 Week Follow-Up of HIV-Infected Patients in Rescue with Raltegravir Plus Optimized Backbone Regimens: A Multicentre Italian Experience

    PubMed Central

    Capetti, Amedeo; Landonio, Simona; Meraviglia, Paola; Di Biagio, Antonio; Lo Caputo, Sergio; Sterrantino, Gaetana; Ammassari, Adriana; Menzaghi, Barbara; Franzetti, Marco; De Socio, Giuseppe Vittorio; Pellicanò, Giovanni; Mazzotta, Elena; Soria, Alessandro; Meschiari, Marianna; Trezzi, Michele; Sasset, Lolita; Celesia, Benedetto Maurizio; Zucchi, Patrizia; Melzi, Sara; Ricci, Elena; Rizzardini, Giuliano

    2012-01-01

    Background Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings. Methods Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96. Results Out of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm3; 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA <50 copies/mL). When analyzing the immuno-virologic outcome according to the number of drugs used in the regimen, 2 (n = 45), 3 (n = 111), 4 (n = 124), or >4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL. Conclusions In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events. PMID:22808029

  19. Employing Social Network Construction and Analysis in Web Structure Optimization

    NASA Astrophysics Data System (ADS)

    Xagi, Mohamad; Guerbas, Abdelghani; Kianmehr, Keivan; Karampelas, Panagiotis; Ridley, Mick; Alhajj, Reda; Rokne, Jon

    The world wide web is growing continuously and rapidly; it is quickly facilitating the migration of tasks of the daily life into web-based. This trend shows time will come when everyone is forced to use the web for daily activities. Naive users arc the major concern of such a shift; so, it is necessary to have the web ready to serve them. We argue that this requires well optimized websites for users to quickly locate the information they arc looking for. This, on the other hand, becomes more and more important due to the widespread reliance on the many services available on the Internet nowadays. It is true that search engines can facilitate the task of finding the information one is looking for. However, search engines will never replace but do complement the optimization of a website's internal structure based on previously recorded user behavior. In this chapter, wc will present a novel approach for identifying problematic structures in websites. This method consists of two phases. The first phase compares user behavior, derived via web log mining techniques, to a combined analysis of the website's link structure obtained by applying three methods leading to more robust framework and hence strong and consistent outcome: (1) constructing and analyzing a social network of the pages constituting the website by considering both the structure and the usage information; (2) applying the Weighted PageRank algorithm; and (3) applying the Hypertext Induced Topic Selection (HITS) method. In the second phase, we use the term frequency-inverse document frequency (TFIDF) measure to investigate further the correlation between the page that contains the link and the linked to pages in order to further support the findings of the first phase of our approach. We will then show how to use these intermediate results in order to point out problematic website structures to the website owner.

  20. Automatic Construction and Global Optimization of a Multisentiment Lexicon

    PubMed Central

    Zhang, Zhongqiu; Mo, Yuting; Li, Lianbei

    2016-01-01

    Manual annotation of sentiment lexicons costs too much labor and time, and it is also difficult to get accurate quantification of emotional intensity. Besides, the excessive emphasis on one specific field has greatly limited the applicability of domain sentiment lexicons (Wang et al., 2010). This paper implements statistical training for large-scale Chinese corpus through neural network language model and proposes an automatic method of constructing a multidimensional sentiment lexicon based on constraints of coordinate offset. In order to distinguish the sentiment polarities of those words which may express either positive or negative meanings in different contexts, we further present a sentiment disambiguation algorithm to increase the flexibility of our lexicon. Lastly, we present a global optimization framework that provides a unified way to combine several human-annotated resources for learning our 10-dimensional sentiment lexicon SentiRuc. Experiments show the superior performance of SentiRuc lexicon in category labeling test, intensity labeling test, and sentiment classification tasks. It is worth mentioning that, in intensity label test, SentiRuc outperforms the second place by 21 percent. PMID:28042290

  1. Automatic Construction and Global Optimization of a Multisentiment Lexicon.

    PubMed

    Yang, Xiaoping; Zhang, Zhongxia; Zhang, Zhongqiu; Mo, Yuting; Li, Lianbei; Yu, Li; Zhu, Peican

    2016-01-01

    Manual annotation of sentiment lexicons costs too much labor and time, and it is also difficult to get accurate quantification of emotional intensity. Besides, the excessive emphasis on one specific field has greatly limited the applicability of domain sentiment lexicons (Wang et al., 2010). This paper implements statistical training for large-scale Chinese corpus through neural network language model and proposes an automatic method of constructing a multidimensional sentiment lexicon based on constraints of coordinate offset. In order to distinguish the sentiment polarities of those words which may express either positive or negative meanings in different contexts, we further present a sentiment disambiguation algorithm to increase the flexibility of our lexicon. Lastly, we present a global optimization framework that provides a unified way to combine several human-annotated resources for learning our 10-dimensional sentiment lexicon SentiRuc. Experiments show the superior performance of SentiRuc lexicon in category labeling test, intensity labeling test, and sentiment classification tasks. It is worth mentioning that, in intensity label test, SentiRuc outperforms the second place by 21 percent.

  2. Constructing optimized binary masks for reservoir computing with delay systems

    NASA Astrophysics Data System (ADS)

    Appeltant, Lennert; van der Sande, Guy; Danckaert, Jan; Fischer, Ingo

    2014-01-01

    Reservoir computing is a novel bio-inspired computing method, capable of solving complex tasks in a computationally efficient way. It has recently been successfully implemented using delayed feedback systems, allowing to reduce the hardware complexity of brain-inspired computers drastically. In this approach, the pre-processing procedure relies on the definition of a temporal mask which serves as a scaled time-mutiplexing of the input. Originally, random masks had been chosen, motivated by the random connectivity in reservoirs. This random generation can sometimes fail. Moreover, for hardware implementations random generation is not ideal due to its complexity and the requirement for trial and error. We outline a procedure to reliably construct an optimal mask pattern in terms of multipurpose performance, derived from the concept of maximum length sequences. Not only does this ensure the creation of the shortest possible mask that leads to maximum variability in the reservoir states for the given reservoir, it also allows for an interpretation of the statistical significance of the provided training samples for the task at hand.

  3. Large-scale measurement and modeling of backbone Internet traffic

    NASA Astrophysics Data System (ADS)

    Roughan, Matthew; Gottlieb, Joel

    2002-07-01

    There is a brewing controversy in the traffic modeling community concerning how to model backbone traffic. The fundamental work on self-similarity in data traffic appears to be contradicted by recent findings that suggest that backbone traffic is smooth. The traffic analysis work to date has focused on high-quality but limited-scope packet trace measurements; this limits its applicability to high-speed backbone traffic. This paper uses more than one year's worth of SNMP traffic data covering an entire Tier 1 ISP backbone to address the question of how backbone network traffic should be modeled. Although the limitations of SNMP measurements do not permit us to comment on the fine timescale behavior of the traffic, careful analysis of the data suggests that irrespective of the variation at fine timescales, we can construct a simple traffic model that captures key features of the observed traffic. Furthermore, the model's parameters are measurable using existing network infrastructure, making this model practical in a present-day operational network. In addition to its practicality, the model verifies basic statistical multiplexing results, and thus sheds deep insight into how smooth backbone traffic really is.

  4. ANSS Backbone Station Quality Assessment

    NASA Astrophysics Data System (ADS)

    Leeds, A.; McNamara, D.; Benz, H.; Gee, L.

    2006-12-01

    In this study we assess the ambient noise levels of the broadband seismic stations within the United States Geological Survey's (USGS) Advanced National Seismic System (ANSS) backbone network. The backbone consists of stations operated by the USGS as well as several regional network stations operated by universities. We also assess the improved detection capability of the network due to the installation of 13 additional backbone stations and the upgrade of 26 existing stations funded by the Earthscope initiative. This assessment makes use of probability density functions (PDF) of power spectral densities (PSD) (after McNamara and Buland, 2004) computed by a continuous noise monitoring system developed by the USGS- ANSS and the Incorporated Research Institutions in Seismology (IRIS) Data Management Center (DMC). We compute the median and mode of the PDF distribution and rank the stations relative to the Peterson Low noise model (LNM) (Peterson, 1993) for 11 different period bands. The power of the method lies in the fact that there is no need to screen the data for system transients, earthquakes or general data artifacts since they map into a background probability level. Previous studies have shown that most regional stations, instrumented with short period or extended short period instruments, have a higher noise level in all period bands while stations in the US network have lower noise levels at short periods (0.0625-8.0 seconds), high frequencies (8.0- 0.125Hz). The overall network is evaluated with respect to accomplishing the design goals set for the USArray/ANSS backbone project which were intended to increase broadband performance for the national monitoring network.

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

    NASA Astrophysics Data System (ADS)

    Schumann, Frank; Varadan, Ranjani; Tayakuniyil, Praveen; Grossman, Jennifer; Camarero, Julio; Fushman, David

    2015-04-01

    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.

  6. The backbone of a city

    NASA Astrophysics Data System (ADS)

    Scellato, S.; Cardillo, A.; Latora, V.; Porta, S.

    2006-03-01

    Recent studies have revealed the importance of centrality measures to analyze various spatial factors affecting human life in cities. Here we show how it is possible to extract the backbone of a city by deriving spanning trees based on edge betweenness and edge information. By using as sample cases the cities of Bologna and San Francisco, we show how the obtained trees are radically different from those based on edge lengths, and allow an extended comprehension of the “skeleton” of most important routes that so much affects pedestrian/vehicular flows, retail commerce vitality, land-use separation, urban crime and collective dynamical behaviours.

  7. Optimism and pessimism in the context of health: bipolar opposites or separate constructs?

    PubMed

    Kubzansky, Laura D; Kubzansky, Philip E; Maselko, Joanna

    2004-08-01

    One difficulty plaguing research on dispositional optimism and health is whether optimism and pessimism are bipolar opposites or constitute distinct constructs. The present study examined the Life Orientation Test to determine whether the two-factor structure is explained by method bias (due to measurement) or substantive differences. The authors compared three measurement models: bipolar, bivariate, and method artifact. Optimism and pessimism emerged as distinct constructs due to substantive differences. The authors also considered the validity of optimism and pessimism, examining their relations with psychological and physical health outcomes. Optimism and pessimism were more similar in relation to psychological health than to other health-related behavior or physical health outcomes. However, a strongly interpretable pattern for the relation of optimism and pessimism to the health outcomes did not emerge. Further research may benefit from considering optimism and pessimism as bivariate and also should consider the conceptual components and behavioral mechanisms specific to each variable.

  8. Constructing optimal entanglement witnesses. II. Witnessing entanglement in 4Nx4N systems

    SciTech Connect

    Chruscinski, Dariusz; Pytel, Justyna

    2010-11-15

    We provide a class of optimal nondecomposable entanglement witnesses for 4Nx4N composite quantum systems or, equivalently, another construction of nondecomposable positive maps in the algebra of 4Nx4N complex matrices. This construction provides natural generalization of the Robertson map. It is shown that their structural physical approximations give rise to entanglement breaking channels.

  9. Optimal measurement model is crucial to identify distinct constructs.

    PubMed

    Gandhi, Pranav

    2010-06-01

    This is a Brief Commentary in response to article-"Steinsbekk, S., Jozefiak, T., Ødegård, R., & Wichstrøm, L. (2009). Impaired parent-reported quality of life in treatment-seeking children with obesity is mediated with high levels of psychopathology. Quality of Life Research, 18(9), 1159-1167. doi: 10.1007/s11136-009-9535-6 ." The commentary states that the investigation of the hypothesis if quality of life and psychopathology are two separate constructs may have been hampered by the use of a suboptimal measurement model.

  10. Split Bregman's optimization method for image construction in compressive sensing

    NASA Astrophysics Data System (ADS)

    Skinner, D.; Foo, S.; Meyer-Bäse, A.

    2014-05-01

    The theory of compressive sampling (CS) was reintroduced by Candes, Romberg and Tao, and D. Donoho in 2006. Using a priori knowledge that a signal is sparse, it has been mathematically proven that CS can defY Nyquist sampling theorem. Theoretically, reconstruction of a CS image relies on the minimization and optimization techniques to solve this complex almost NP-complete problem. There are many paths to consider when compressing and reconstructing an image but these methods have remained untested and unclear on natural images, such as underwater sonar images. The goal of this research is to perfectly reconstruct the original sonar image from a sparse signal while maintaining pertinent information, such as mine-like object, in Side-scan sonar (SSS) images. Goldstein and Osher have shown how to use an iterative method to reconstruct the original image through a method called Split Bregman's iteration. This method "decouples" the energies using portions of the energy from both the !1 and !2 norm. Once the energies are split, Bregman iteration is used to solve the unconstrained optimization problem by recursively solving the problems simultaneously. The faster these two steps or energies can be solved then the faster the overall method becomes. While the majority of CS research is still focused on the medical field, this paper will demonstrate the effectiveness of the Split Bregman's methods on sonar images.

  11. Optimized in situ construction of oligomers on an array surface

    PubMed Central

    Tolonen, Andrew C.; Albeanu, Dinu F.; Corbett, Julia F.; Handley, Heather; Henson, Charlotte; Malik, Pratap

    2002-01-01

    Oligonucleotide arrays are powerful tools to study changes in gene expression for whole genomes. These arrays can be synthesized by adapting photolithographic techniques used in microelectronics. Using this method, oligonucleotides are built base by base directly on the array surface by numerous cycles of photodeprotection and nucleotide addition. In this paper we examine strategies to reduce the number of synthesis cycles required to construct oligonucleotide arrays. By computer modeling oligonucleotide synthesis, we found that the number of required synthesis cycles could be significantly reduced by focusing upon how oligonucleotides are chosen from within genes and upon the order in which nucleotides are deposited on the array. The methods described here could provide a more efficient strategy to produce oligonucleotide arrays. PMID:12384609

  12. New optimal asymmetric quantum codes constructed from constacyclic codes

    NASA Astrophysics Data System (ADS)

    Xu, Gen; Li, Ruihu; Guo, Luobin; Lü, Liangdong

    2017-02-01

    In this paper, we propose the construction of asymmetric quantum codes from two families of constacyclic codes over finite field 𝔽q2 of code length n, where for the first family, q is an odd prime power with the form 4t + 1 (t ≥ 1 is integer) or 4t ‑ 1 (t ≥ 2 is integer) and n1 = q2+1 2; for the second family, q is an odd prime power with the form 10t + 3 or 10t + 7 (t ≥ 0 is integer) and n2 = q2+1 5. As a result, families of new asymmetric quantum codes [[n,k,dz/dx

  13. Combined holographic-mechanical optical tweezers: construction, optimization, and calibration.

    PubMed

    Hanes, Richard D L; Jenkins, Matthew C; Egelhaaf, Stefan U

    2009-08-01

    A spatial light modulator (SLM) and a pair of galvanometer-mounted mirrors (GMM) were combined into an optical tweezers setup. This provides great flexibility as the SLM creates an array of traps, which can be moved smoothly and quickly with the GMM. To optimize performance, the effect of the incidence angle on the SLM with respect to phase and intensity response was investigated. Although it is common to use the SLM at an incidence angle of 45 degrees, smaller angles give a full 2pi phase shift and an output intensity which is less dependent on the magnitude of the phase shift. The traps were calibrated using an active oscillatory technique and a passive probability distribution method.

  14. Combined holographic-mechanical optical tweezers: Construction, optimization, and calibration

    SciTech Connect

    Hanes, Richard D. L.; Jenkins, Matthew C.; Egelhaaf, Stefan U.

    2009-08-15

    A spatial light modulator (SLM) and a pair of galvanometer-mounted mirrors (GMM) were combined into an optical tweezers setup. This provides great flexibility as the SLM creates an array of traps, which can be moved smoothly and quickly with the GMM. To optimize performance, the effect of the incidence angle on the SLM with respect to phase and intensity response was investigated. Although it is common to use the SLM at an incidence angle of 45 deg., smaller angles give a full 2{pi} phase shift and an output intensity which is less dependent on the magnitude of the phase shift. The traps were calibrated using an active oscillatory technique and a passive probability distribution method.

  15. The Backbone of the Climate Networks

    NASA Astrophysics Data System (ADS)

    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.

  16. Removal of antibiotics from urban wastewater by constructed wetland optimization.

    PubMed

    Hijosa-Valsero, María; Fink, Guido; Schlüsener, Michael P; Sidrach-Cardona, Ricardo; Martín-Villacorta, Javier; Ternes, Thomas; Bécares, Eloy

    2011-04-01

    Seven mesocosm-scale constructed wetlands (CWs), differing in their design characteristics, were set up in the open air to assess their efficiency to remove antibiotics from urban raw wastewater. A conventional wastewater treatment plant (WWTP) was simultaneously monitored. The experiment took place in autumn. An analytical methodology including HPLC-MS/MS was developed to measure antibiotic concentrations in the soluble water fraction, in the suspended solids fraction and in the WWTP sludge. Considering the soluble water fraction, the only easily eliminated antibiotics in the WWTP were doxycycline (61±38%) and sulfamethoxazole (60±26%). All the studied types of CWs were efficient for the removal of sulfamethoxazole (59±30-87±41%), as found in the WWTP, and, in addition, they removed trimethoprim (65±21-96±29%). The elimination of other antibiotics in CWs was limited by the specific system-configuration: amoxicillin (45±15%) was only eliminated by a free-water (FW) subsurface flow (SSF) CW planted with Typha angustifolia; doxycycline was removed in FW systems planted with T. angustifolia (65±34-75±40%), in a Phragmites australis-floating macrophytes system (62±31%) and in conventional horizontal SSF-systems (71±39%); clarithromycin was partially eliminated by an unplanted FW-SSF system (50±18%); erythromycin could only be removed by a P. australis-horizontal SSF system (64±30%); and ampicillin was eliminated by a T. angustifolia-floating macrophytes system (29±4%). Lincomycin was not removed by any of the systems (WWTP or CWs). The presence or absence of plants, the vegetal species (T. angustifolia or P. australis), the flow type and the CW design characteristics regulated the specific removal mechanisms. Therefore, CWs are not an overall solution to remove antibiotics from urban wastewater during cold seasons. However, more studies are needed to assess their ability in warmer periods and to determine the behaviour of full-scale systems. Copyright

  17. Flexible backbone aromatic polyimide adhesives

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.; St. Clair, Terry L.

    1989-01-01

    Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

  18. Flexible backbone aromatic polyimide adhesives

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.; St.clair, Terry L.

    1988-01-01

    Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

  19. Flexible backbone aromatic polyimide adhesives

    NASA Technical Reports Server (NTRS)

    Progar, Donald J.; St. Clair, Terry L.

    1989-01-01

    Continuing research at Langley Research Center on the synthesis and development of new inexpensive flexible aromatic polyimides as adhesives has resulted in a material identified as LARC-F-SO2 with similarities to polyimidesulfone, PISO2, and other flexible backbone polyimides recently reported by Progar and St. Clair. Also prepared and evaluated was an endcapped version of PISO2. These two polymers were compared with LARC-TPI and LARC-STPI, polyimides research in our laboratory and reported in the literature. The adhesive evaluation, primarily based on lap shear strength (LSS) tests at RT, 177 C and 204 C, involved preparing adhesive tapes, conducting bonding studies and exposing lap shear specimens to 204 C air for up to 1000 hrs and to a 72-hour water boil. The type of adhesive failure as well as the Tg was determined for the fractured specimens. The results indicate that LARC-TPI provides the highest LSSs. LARC-F-SO2, LARC-TPI and LARC-STPI all retain their strengths after thermal exposure for 1000 hrs and PISO2 retains greater than 80 percent of its control strengths. After a 72-hr water boil exposure, most of the four adhesive systems showed reduced strengths for all test temperatures although still retaining a high percentage of their original strength (greater than 60 percent) except for one case. The predominant failure type was cohesive with no significant change in the Tgs.

  20. Power Grid Construction Project Portfolio Optimization Based on Bi-level programming model

    NASA Astrophysics Data System (ADS)

    Zhao, Erdong; Li, Shangqi

    2017-08-01

    As the main body of power grid operation, county-level power supply enterprises undertake an important emission to guarantee the security of power grid operation and safeguard social power using order. The optimization of grid construction projects has been a key issue of power supply capacity and service level of grid enterprises. According to the actual situation of power grid construction project optimization of county-level power enterprises, on the basis of qualitative analysis of the projects, this paper builds a Bi-level programming model based on quantitative analysis. The upper layer of the model is the target restriction of the optimal portfolio; the lower layer of the model is enterprises’ financial restrictions on the size of the enterprise project portfolio. Finally, using a real example to illustrate operation proceeding and the optimization result of the model. Through qualitative analysis and quantitative analysis, the bi-level programming model improves the accuracy and normative standardization of power grid enterprises projects.

  1. Generalized Lions-Peetre interpolation construction and optimal embedding theorems for Sobolev spaces

    SciTech Connect

    Ovchinnikov, V I

    2014-01-31

    In the paper, a new description of the generalized Lions-Peetre method of means is found, which enables one to evaluate the interpolation orbits of spaces constructed by this method. The list of these spaces includes all Lorentz spaces with functional parameters, Orlicz spaces, and spaces close to them. This leads in turn to new optimal embedding theorems for Sobolev spaces produced using the Lions-Peetre construction in rearrangement invariant spaces. It turns out that the optimal space of the embedding is also a generalized Lions-Peetre space whose parameters are explicitly evaluated. Bibliography: 18 titles.

  2. External Tank - The Structure Backbone

    NASA Technical Reports Server (NTRS)

    Welzyn, Kenneth; Pilet, Jeffrey C.; Diecidue-Conners, Dawn; Worden, Michelle; Guillot, Michelle

    2011-01-01

    The External Tank forms the structural backbone of the Space Shuttle in the launch configuration. Because the tank flies to orbital velocity with the Space Shuttle Orbiter, minimization of weight is mandatory, to maximize payload performance. Choice of lightweight materials both for structure and thermal conditioning was necessary. The tank is large, and unique manufacturing facilities, tooling, handling, and transportation operations were required. Weld processes and tooling evolved with the design as it matured through several block changes, to reduce weight. Non Destructive Evaluation methods were used to assure integrity of welds and thermal protection system materials. The aluminum-lithium alloy was used near the end of the program and weld processes and weld repair techniques had to be refined. Development and implementation of friction stir welding was a substantial technology development incorporated during the Program. Automated thermal protection system application processes were developed for the majority of the tank surface. Material obsolescence was an issue throughout the 40 year program. The final configuration and tank weight enabled international space station assembly in a high inclination orbit allowing international cooperation with the Russian Federal Space Agency. Numerous process controls were implemented to assure product quality, and innovative proof testing was accomplished prior to delivery. Process controls were implemented to assure cleanliness in the production environment, to control contaminants, and to preclude corrosion. Each tank was accepted via rigorous inspections, including non-destructive evaluation techniques, proof testing, and all systems testing. In the post STS-107 era, the project focused on ascent debris risk reduction. This was accomplished via stringent process controls, post flight assessment using substantially improved imagery, and selective redesigns. These efforts were supported with a number of test programs to

  3. Triazole linkages and backbone branches in nucleic acids for biological and extra-biological applications

    NASA Astrophysics Data System (ADS)

    Paredes, Eduardo

    The recently increasing evidence of nucleic acids' alternative roles in biology and potential as useful nanomaterials and therapeutic agents has enabled the development of useful probes, elaborate nanostructures and therapeutic effectors based on nucleic acids. The study of alternative nucleic acid structure and function, particularly RNA, hinges on the ability to introduce site-specific modifications that either provide clues to the nucleic acid structure function relationship or alter the nucleic acid's function. Although the available chemistries allow for the conjugation of useful labels and molecules, their limitations lie in their tedious conjugation conditions or the lability of the installed probes. The development and optimization of click chemistry with RNA now provides the access to a robust and orthogonal conjugation methodology while providing stable conjugates. Our ability to introduce click reactive groups enzymatically, rather than only in the solid-phase, allows for the modification of larger, more cell relevant RNAs. Additionally, ligation of modified RNAs with larger RNA constructs through click chemistry represents an improvement over traditional ligation techniques. We determined that the triazole linkage generated through click chemistry is compatible in diverse nucleic acid based biological systems. Click chemistry has also been developed for extra-biological applications, particularly with DNA. We have expanded its use to generate useful polymer-DNA conjugates which can form controllable soft nanoparticles which take advantage of DNA's properties, i.e. DNA hybridization and computing. Additionally, we have generated protein-DNA conjugates and assembled protein-polymer hybrids mediated by DNA hybridization. The use of click chemistry in these reactions allows for the facile synthesis of these unnatural conjugates. We have also developed backbone branched DNA through click chemistry and showed that these branched DNAs are useful in generating

  4. Teacher's Academic Optimism: The Development and Test of a New Construct

    ERIC Educational Resources Information Center

    Hoy, Anita Woolfolk; Hoy, Wayne K.; Kurz, Nan M.

    2008-01-01

    The objective of this exploratory study of teacher beliefs was twofold: first, to determine whether the construct of academic optimism could be defined and measured as an individual teacher characteristic as it has been at the collective school level, and second, to identify sets of teacher beliefs and practices that were good predictors of…

  5. Different effects of economic and structural performance indexes on model construction of structural topology optimization

    NASA Astrophysics Data System (ADS)

    Yi, G. L.; Sui, Y. K.

    2015-10-01

    The objective and constraint functions related to structural optimization designs are classified into economic and performance indexes in this paper. The influences of their different roles in model construction of structural topology optimization are also discussed. Furthermore, two structural topology optimization models, optimizing a performance index under the limitation of an economic index, represented by the minimum compliance with a volume constraint (MCVC) model, and optimizing an economic index under the limitation of a performance index, represented by the minimum weight with a displacement constraint (MWDC) model, are presented. Based on a comparison of numerical example results, the conclusions can be summarized as follows: (1) under the same external loading and displacement performance conditions, the results of the MWDC model are almost equal to those of the MCVC model; (2) the MWDC model overcomes the difficulties and shortcomings of the MCVC model; this makes the MWDC model more feasible in model construction; (3) constructing a model of minimizing an economic index under the limitations of performance indexes is better at meeting the needs of practical engineering problems and completely satisfies safety and economic requirements in mechanical engineering, which have remained unchanged since the early days of mechanical engineering.

  6. Optimization of Structural Design for Sustainable Construction of Transmission Tower Based on Topographical Algorithm

    NASA Astrophysics Data System (ADS)

    Che Muda, Zakaria; Nasharuddin Mustapha, Kamal; Che Omar, Rohayu; Usman, Fathoni; Ashrafu Alam, Md; Thiruchelvam, Sivadass

    2013-06-01

    Optimization of transmission tower structures is traditionally based on either optimization of members sizes with fixed topographical shape or based on structural analysis modelling strategies without taking cognizance of fabrication and constructability issue facing the contractors . This paper look into an integrated optimum design approach strategies whereby size, shape and topology are combined together with the fabrication issues in the construction of the transmission tower. The topographical algorithm is based on changing the inclination degree of the legs of the tower at first with optimum individual members sizing and later rationalized member sizes are performed through member groupings for the ease fabrication and construction of the transmission tower. The optimum weight using topographical algorithm obtained for the transmission tower is 10,924 kg for singular members and 18,430 kg for element grouping at 10° inclination angle.

  7. DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals.

    PubMed

    Chen, Xiulai; Gao, Cong; Guo, Liang; Hu, Guipeng; Luo, Qiuling; Liu, Jia; Nielsen, Jens; Chen, Jian; Liu, Liming

    2017-04-26

    Chemical synthesis is a well established route for producing many chemicals on a large scale, but some drawbacks still exist in this process, such as unstable intermediates, multistep reactions, complex process control, etc. Biobased production provides an attractive alternative to these challenges, but how to make cells into efficient factories is challenging. As a key enabling technology to develop efficient cell factories, design-construction-evaluation-optimization (DCEO) biotechnology, which incorporates the concepts and techniques of pathway design, pathway construction, pathway evaluation, and pathway optimization at the systems level, offers a conceptual and technological framework to exploit potential pathways, modify existing pathways and create new pathways for the optimal production of desired chemicals. Here, we summarize recent progress of DCEO biotechnology and examples of its application, and provide insights as to when, what and how different strategies should be taken. In addition, we highlight future perspectives of DCEO biotechnology for the successful establishment of biorefineries.

  8. Constructing Optimal Prediction Intervals by Using Neural Networks and Bootstrap Method.

    PubMed

    Khosravi, Abbas; Nahavandi, Saeid; Srinivasan, Dipti; Khosravi, Rihanna

    2015-08-01

    This brief proposes an efficient technique for the construction of optimized prediction intervals (PIs) by using the bootstrap technique. The method employs an innovative PI-based cost function in the training of neural networks (NNs) used for estimation of the target variance in the bootstrap method. An optimization algorithm is developed for minimization of the cost function and adjustment of NN parameters. The performance of the optimized bootstrap method is examined for seven synthetic and real-world case studies. It is shown that application of the proposed method improves the quality of constructed PIs by more than 28% over the existing technique, leading to narrower PIs with a coverage probability greater than the nominal confidence level.

  9. Cervical Exercise: The Backbone of Spine Treatment

    MedlinePlus

    Cervical Exercise: The Backbone of Spine Treatment How important is it? What can be done? North American Spine Society Public Education Series ... flow comes to the area to help repair injury. Your ability to function in your daily activities ...

  10. Cervical Exercise: The Backbone of Spine Treatment

    MedlinePlus

    Cervical Exercise: The Backbone of Spine Treatment How important is it? What can be done? North American Spine Society ... you should see your physician before starting any exercises. The Importance of Exercise for the Neck Spine ...

  11. Construction schedule simulation of a diversion tunnel based on the optimized ventilation time.

    PubMed

    Wang, Xiaoling; Liu, Xuepeng; Sun, Yuefeng; An, Juan; Zhang, Jing; Chen, Hongchao

    2009-06-15

    Former studies, the methods for estimating the ventilation time are all empirical in construction schedule simulation. However, in many real cases of construction schedule, the many factors have impact on the ventilation time. Therefore, in this paper the 3D unsteady quasi-single phase models are proposed to optimize the ventilation time with different tunneling lengths. The effect of buoyancy is considered in the momentum equation of the CO transport model, while the effects of inter-phase drag, lift force, and virtual mass force are taken into account in the momentum source of the dust transport model. The prediction by the present model for airflow in a diversion tunnel is confirmed by the experimental values reported by Nakayama [Nakayama, In-situ measurement and simulation by CFD of methane gas distribution at a heading faces, Shigen-to-Sozai 114 (11) (1998) 769-775]. The construction ventilation of the diversion tunnel of XinTangfang power station in China is used as a case. The distributions of airflow, CO and dust in the diversion tunnel are analyzed. A theory method for GIS-based dynamic visual simulation for the construction processes of underground structure groups is presented that combines cyclic operation network simulation, system simulation, network plan optimization, and GIS-based construction processes' 3D visualization. Based on the ventilation time the construction schedule of the diversion tunnel is simulated by the above theory method.

  12. Simulation of value stream mapping and discrete optimization of energy consumption in modular construction

    NASA Astrophysics Data System (ADS)

    Chowdhury, Md Mukul

    With the increased practice of modularization and prefabrication, the construction industry gained the benefits of quality management, improved completion time, reduced site disruption and vehicular traffic, and improved overall safety and security. Whereas industrialized construction methods, such as modular and manufactured buildings, have evolved over decades, core techniques used in prefabrication plants vary only slightly from those employed in traditional site-built construction. With a focus on energy and cost efficient modular construction, this research presents the development of a simulation, measurement and optimization system for energy consumption in the manufacturing process of modular construction. The system is based on Lean Six Sigma principles and loosely coupled system operation to identify the non-value adding tasks and possible causes of low energy efficiency. The proposed system will also include visualization functions for demonstration of energy consumption in modular construction. The benefits of implementing this system include a reduction in the energy consumption in production cost, decrease of energy cost in the production of lean-modular construction, and increase profit. In addition, the visualization functions will provide detailed information about energy efficiency and operation flexibility in modular construction. A case study is presented to validate the reliability of the system.

  13. Extended weak bonding interactions in DNA: pi-stacking (base-base), base-backbone, and backbone-backbone interactions.

    PubMed

    Matta, Chérif F; Castillo, Norberto; Boyd, Russell J

    2006-01-12

    We report on several weak interactions in nucleic acids, which, collectively, can make a nonnegligible contribution to the structure and stability of these molecules. Fragments of DNA were obtained from previously determined accurate experimental geometries and their electron density distributions calculated using density functional theory (DFT). The electron densities were analyzed topologically according to the quantum theory of atoms in molecules (AIM). A web of closed-shell bonding interactions is shown to connect neighboring base pairs in base-pair duplexes and in dinuleotide steps. This bonding underlies the well-known pi-stacking interaction between adjacent nucleic acid bases and is characterized topologically for the first time. Two less widely appreciated modes of weak closed-shell interactions in nucleic acids are also described: (i) interactions between atoms in the bases and atoms belonging to the backbone (base-backbone) and (ii) interactions among atoms within the backbone itself (backbone-backbone). These interactions include hydrogen bonding, dihydrogen bonding, hydrogen-hydrogen bonding, and several other weak closed-shell X-Y interactions (X, Y = O, N, C). While each individual interaction is very weak and typically accompanied by perhaps 0.5-3 kcal/mol, the sum total of these interactions is postulated to play a role in stabilizing the structure of nucleic acids. The Watson-and-Crick hydrogen bonding is also characterized in detail at the experimental geometries as a prelude to the discussion of the modes of interactions listed in the title.

  14. Spatial optimization in perfusion bioreactors improves bone tissue-engineered construct quality attributes.

    PubMed

    Papantoniou, Ioannis; Guyot, Yann; Sonnaert, Maarten; Kerckhofs, Greet; Luyten, Frank P; Geris, Liesbet; Schrooten, Jan

    2014-12-01

    Perfusion bioreactors have shown great promise for tissue engineering applications providing a homogeneous and consistent distribution of nutrients and flow-induced shear stresses throughout tissue-engineered constructs. However, non-uniform fluid-flow profiles found in the perfusion chamber entrance region have been shown to affect tissue-engineered construct quality characteristics during culture. In this study a whole perfusion and construct, three dimensional (3D) computational fluid dynamics approach was used in order to optimize a critical design parameter such as the location of the regular pore scaffolds within the perfusion bioreactor chamber. Computational studies were coupled to bioreactor experiments for a case-study flow rate. Two cases were compared in the first instance seeded scaffolds were positioned immediately after the perfusion chamber inlet while a second group was positioned at the computationally determined optimum distance were a steady state flow profile had been reached. Experimental data showed that scaffold location affected significantly cell content and neo-tissue distribution, as determined and quantified by contrast enhanced nanoCT, within the constructs both at 14 and 21 days of culture. However, gene expression level of osteopontin and osteocalcin was not affected by the scaffold location. This study demonstrates that the bioreactor chamber environment, incorporating a scaffold and its location within it, affects the flow patterns within the pores throughout the scaffold requiring therefore dedicated optimization that can lead to bone tissue engineered constructs with improved quality attributes. © 2014 Wiley Periodicals, Inc.

  15. Construction and application of particle swarm optimization algorithm for ecological spatial data mining

    NASA Astrophysics Data System (ADS)

    Fu, ZhongLiang; Wan, Bin

    2009-10-01

    The research of the regional ecological environment becomes more important to regional Sustainable Development in order to achieve the harmonious relationship between the person and the nature. The advent of spatial information technologies, such as GIS, GPS and RS, have great enhanced our capabilities to collect and capture spatial data. How to discover potentially useful information and knowledge from massive amounts of spatial data is becoming a crucial project for spatial analysis and spatial decision making. Particle Swarm Optimization has a powerful ability for reasoning and semantic representation, which combined with qualitative analysis and quantitative analysis, with prior knowledge and observed data, and provides an effective way to spatial data mining. This paper focuses on construction and learning a Particle Swarm Optimization model for spatial data mining. Firstly, the theory of spatial data mining is introduced and the characteristics of Particle Swarm Optimization are discussed. A framework and process of spatial data mining is proposed. Then we construct a Particle Swarm Optimization model for spatial data mining with the given dataset. The research area is focused on the distribution of pollution sources in Wuhan City. The experimental results demonstrate the feasibility and practical of the proposed approach to spatial data mining. Finally, draw a conclusion and show further avenues for research. Through the empirical study, it has been proved that Particle Swarm Optimization algorithm is feasible and the conclusion can provide instruction for local environmental planning.

  16. Sub-optimal pit construction in predatory ant lion larvae (Myrmeleon sp.).

    PubMed

    Burgess, Matthew G

    2009-10-07

    The impacts on energy gains of two aspects of ant lion pit architecture were investigated in a natural population of pit-building ant lion larvae (Myrmeleon sp.) in Costa Rica. Field and laboratory settings were used to examine the impacts of circumference and depth of the pit on net energy gain rate. An optimization model predicted a point optimum circumference and angle of depression in an unconstrained system, and positive correlations between body mass, pit circumference, and pit angle of depression in the presence of physiological constraints on both measures. Such a physiological constraint is possible in this system due to a large one-time construction cost. All of these correlations were observed in a lab setting with filtered substrate and no competition; though none were significant in the field. Individuals additionally constructed wider, shallower pits in the field. These results are consistent with an angle of depression that is limited by the angle of repose of the substrate in the field, rather than physiology. These results provided suggestive evidence for sub-optimal pit dimensions in Myrmeleon sp., and for the importance of substrate type in understanding the architecture of natural ant lion pits. The model predicted that the frequency of relocation would not affect the optimal angle of depression, but it would affect the optimal pit circumference to a degree proportional to the square root of the change in the average time an ant lion occupies a single pit. These findings challenge the widely held assumption of adaptive optimality in animal foraging.

  17. Rapid convergence of optimal control in NMR using numerically-constructed toggling frames

    NASA Astrophysics Data System (ADS)

    Coote, Paul; Anklin, Clemens; Massefski, Walter; Wagner, Gerhard; Arthanari, Haribabu

    2017-08-01

    We present a numerical method for rapidly solving the Bloch equation for an arbitrary time-varying spin-1/2 Hamiltonian. The method relies on fast, vectorized computations such as summation and quaternion multiplication, rather than slow computations such as matrix exponentiation. A toggling frame is constructed in which the Hamiltonian is time-invariant, and therefore has a simple analytical solution. The key insight is that constructing this frame is faster than solving the system dynamics in the original frame. Rapidly solving the Bloch equations for an arbitrary Hamiltonian is particularly useful in the context of NMR optimal control. Optimal control theory can be used to design pulse shapes for a range of tasks in NMR spectroscopy. However, it requires multiple simulations of the Bloch equations at each stage of the algorithm, and for each relevant set of parameters (e.g. chemical shift frequencies). This is typically time consuming. We demonstrate that by working in an appropriate toggling frame, optimal control pulses can be generated much faster. We present a new alternative to the well-known GRAPE algorithm to continuously update the toggling-frame as the optimal pulse is generated, and demonstrate that this approach is extremely fast. The use and benefit of rapid optimal pulse generation is demonstrated for 19F fragment screening experiments.

  18. Rapid convergence of optimal control in NMR using numerically-constructed toggling frames.

    PubMed

    Coote, Paul; Anklin, Clemens; Massefski, Walter; Wagner, Gerhard; Arthanari, Haribabu

    2017-08-01

    We present a numerical method for rapidly solving the Bloch equation for an arbitrary time-varying spin-1/2 Hamiltonian. The method relies on fast, vectorized computations such as summation and quaternion multiplication, rather than slow computations such as matrix exponentiation. A toggling frame is constructed in which the Hamiltonian is time-invariant, and therefore has a simple analytical solution. The key insight is that constructing this frame is faster than solving the system dynamics in the original frame. Rapidly solving the Bloch equations for an arbitrary Hamiltonian is particularly useful in the context of NMR optimal control. Optimal control theory can be used to design pulse shapes for a range of tasks in NMR spectroscopy. However, it requires multiple simulations of the Bloch equations at each stage of the algorithm, and for each relevant set of parameters (e.g. chemical shift frequencies). This is typically time consuming. We demonstrate that by working in an appropriate toggling frame, optimal control pulses can be generated much faster. We present a new alternative to the well-known GRAPE algorithm to continuously update the toggling-frame as the optimal pulse is generated, and demonstrate that this approach is extremely fast. The use and benefit of rapid optimal pulse generation is demonstrated for 19F fragment screening experiments. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Recurrent construction of optimal entanglement witnesses for 2N-qubit systems

    NASA Astrophysics Data System (ADS)

    Zwolak, Justyna P.; Chruściński, Dariusz

    2014-05-01

    We provide a recurrent construction of entanglement witnesses for a bipartite systems living in a Hilbert space corresponding to 2N qubits (N qubits in each subsystem). Our construction provides a method of generalization of the Robertson map that naturally meshes with 2N-qubit systems, i.e., its structure respects the 22N growth of the state space. We prove that for N >1 these witnesses are indecomposable and optimal. As a byproduct we provide a family of PPT (Positive Partial Transpose) entangled states.

  20. N-acetyl-L-aspartic acid-N'-methylamide with side-chain orientation capable of external hydrogen bonding . Backbone and side-chain folding, studied at the DFT level of quantum theory

    NASA Astrophysics Data System (ADS)

    Koo, J. C. P.; Chass, G. A.; Perczel, A.; Farkas, Ö.; Varro, A.; Torday, L. L.; Papp, J. Gy.; Csizmadia, I. G.

    2002-09-01

    In this study, we generated and analyzed the side-chain conformational potential energy hypersurfaces for each of the nine possible backbone conformers for N-acetyl-L-aspartic acid-N' methylamide. We found a total of 27 out of the 81 possible conformers optimized at the B3LYP/6-31G(d) level of theory. The relative energies, as well as the stabilization energies exerted by the side-chain on the backbone, have been calculated for each of the 27 optimized conformers at this level of theory. Various backbone-backbone (N H{\\cdot}{\\cdot}{\\cdot}O=C) and backbone-side-chain (N H{\\cdot}{\\cdot}{\\cdot}O=C; N H{\\cdot}{\\cdot}{\\cdot}OH) hydrogen bonds were analyzed. The appearance of the notoriously absent \\varepsilon_L backbone conformer may be attributed to such side-chain-backbone (SC/BB) and backbone-backbone (BB/BB) hydrogen bonds.

  1. Understanding traffic dynamics at a backbone POP

    NASA Astrophysics Data System (ADS)

    Taft, Nina; Bhattacharyya, Supratik; Jetcheva, Jorjeta; Diot, Christophe

    2001-07-01

    Spatial and temporal information about traffic dynamics is central to the design of effective traffic engineering practices for IP backbones. In this paper we study backbone traffic dynamics using data collected at a major POP on a tier-1 IP backbone. We develop a methodology that combines packet-level traces from access links in the POP and BGP routing information to build components of POP-to-POP traffic matrices. Our results show that there is wide disparity in the volume of traffic headed towards different egress POPs. At the same time, we find that current routing practices in the backbone tend to constrain traffic between ingress-egress POP pairs to a small number of paths. As a result, there is a wide variation in the utilization level of links in the backbone. Frequent capacity upgrades of the heavily used links are expensive; the need for such upgrades can be reduced by designing load balancing policies that will route more traffic over less utilized links. We identify traffic aggregates based on destination address prefixes and find that this set of criteria isolates a few aggregates that account for an overwhelmingly large portion of inter-POP traffic. We also demonstrate that these aggregates exhibit stability throughout the day on per-hour time scales, and thus they form a natural basis for splitting traffic over multiple paths in order to improve load balancing.

  2. Computational protein design with backbone plasticity

    PubMed Central

    MacDonald, James T.; Freemont, Paul S.

    2016-01-01

    The computational algorithms used in the design of artificial proteins have become increasingly sophisticated in recent years, producing a series of remarkable successes. The most dramatic of these is the de novo design of artificial enzymes. The majority of these designs have reused naturally occurring protein structures as ‘scaffolds’ onto which novel functionality can be grafted without having to redesign the backbone structure. The incorporation of backbone flexibility into protein design is a much more computationally challenging problem due to the greatly increased search space, but promises to remove the limitations of reusing natural protein scaffolds. In this review, we outline the principles of computational protein design methods and discuss recent efforts to consider backbone plasticity in the design process. PMID:27911735

  3. A novel approach to phylogenetic tree construction using stochastic optimization and clustering

    PubMed Central

    Qin, Ling; Chen, Yixin; Pan, Yi; Chen, Ling

    2006-01-01

    Background The problem of inferring the evolutionary history and constructing the phylogenetic tree with high performance has become one of the major problems in computational biology. Results A new phylogenetic tree construction method from a given set of objects (proteins, species, etc.) is presented. As an extension of ant colony optimization, this method proposes an adaptive phylogenetic clustering algorithm based on a digraph to find a tree structure that defines the ancestral relationships among the given objects. Conclusion Our phylogenetic tree construction method is tested to compare its results with that of the genetic algorithm (GA). Experimental results show that our algorithm converges much faster and also achieves higher quality than GA. PMID:17217517

  4. Construction of optimal laws of variation of the angular momentum vector of a rigid body

    NASA Astrophysics Data System (ADS)

    Biryukov, V. G.; Chelnokov, Yu. N.

    2014-09-01

    We consider the problem of constructing optimal preset laws of variation of the angular momentum vector of a rigid body taking the body from an arbitrary initial angular position to the required terminal angular position in a given time. We minimize an integral quadratic performance functional whose integrand is a weighted sum of squared projections of the angular momentum vector of the rigid body. We use the Pontryagin maximum principle to derive necessary optimality conditions. In the case of a spherically symmetric rigid body, the problem has a well-known analytic solution. In the case where the body has a dynamic symmetry axis, the obtained boundary value optimization problem is reduced to a system of two nonlinear algebraic equations. For a rigid body with an arbitrarymass distribution, optimal control laws are obtained in the form of elliptic functions. We discuss the laws of controlled motion and applications of the constructed preset laws in systems of attitude control by external control torques or rotating flywheels.

  5. The role of molecular structure of sugar-phosphate backbone and nucleic acid bases in the formation of single-stranded and double-stranded DNA structures.

    PubMed

    Poltev, Valeri; Anisimov, Victor M; Danilov, Victor I; Garcia, Dolores; Sanchez, Carolina; Deriabina, Alexandra; Gonzalez, Eduardo; Rivas, Francisco; Polteva, Nina

    2014-06-01

    Our previous DFT computations of deoxydinucleoside monophosphate complexes with Na(+)-ions (dDMPs) have demonstrated that the main characteristics of Watson-Crick (WC) right-handed duplex families are predefined in the local energy minima of dDMPs. In this work, we study the mechanisms of contribution of chemically monotonous sugar-phosphate backbone and the bases into the double helix irregularity. Geometry optimization of sugar-phosphate backbone produces energy minima matching the WC DNA conformations. Studying the conformational variability of dDMPs in response to sequence permutation, we found that simple replacement of bases in the previously fully optimized dDMPs, e.g. by constructing Pyr-Pur from Pur-Pyr, and Pur-Pyr from Pyr-Pur sequences, while retaining the backbone geometry, automatically produces the mutual base position characteristic of the target sequence. Based on that, we infer that the directionality and the preferable regions of the sugar-phosphate torsions, combined with the difference of purines from pyrimidines in ring shape, determines the sequence dependence of the structure of WC DNA. No such sequence dependence exists in dDMPs corresponding to other DNA conformations (e.g., Z-family and Hoogsteen duplexes). Unlike other duplexes, WC helix is unique by its ability to match the local energy minima of the free single strand to the preferable conformations of the duplex.

  6. ExScal Backbone Network Architecture

    DTIC Science & Technology

    2005-01-01

    802.11 battery powered nodes was laid over the sensor network. We adopted the Stargate platform for the backbone tier to serve as the basis for...its head. XSS Hardware and Network: XSS stands for eXtreme Scaling Stargate . A stargate is a linux-based single board computer. It has a 400 MHz

  7. Construction and optimization of a quantum analog of the Carnot cycle.

    PubMed

    Xiao, Gaoyang; Gong, Jiangbin

    2015-07-01

    The quantum analog of Carnot cycles in few-particle systems consists of two quantum adiabatic steps and two isothermal steps. This construction is formally justified by use of a minimum work principle. It is then shown, using minimal assumptions of work or heat in nanoscale systems, that the heat-to-work efficiency of such quantum heat engine cycles can be further optimized via two conditions regarding the expectation value of some generalized force operators evaluated at equilibrium states. In general the optimized efficiency is system specific, lower than the Carnot efficiency, and dependent upon both temperatures of the cold and hot reservoirs. Simple computational examples are used to illustrate our theory. The results should be an important guide towards the design of favorable working conditions of a realistic quantum heat engine.

  8. Construction and optimization of a quantum analog of the Carnot cycle

    NASA Astrophysics Data System (ADS)

    Xiao, Gaoyang; Gong, Jiangbin

    2015-07-01

    The quantum analog of Carnot cycles in few-particle systems consists of two quantum adiabatic steps and two isothermal steps. This construction is formally justified by use of a minimum work principle. It is then shown, using minimal assumptions of work or heat in nanoscale systems, that the heat-to-work efficiency of such quantum heat engine cycles can be further optimized via two conditions regarding the expectation value of some generalized force operators evaluated at equilibrium states. In general the optimized efficiency is system specific, lower than the Carnot efficiency, and dependent upon both temperatures of the cold and hot reservoirs. Simple computational examples are used to illustrate our theory. The results should be an important guide towards the design of favorable working conditions of a realistic quantum heat engine.

  9. Optimizations on supply and distribution of dissolved oxygen in constructed wetlands: A review.

    PubMed

    Liu, Huaqing; Hu, Zhen; Zhang, Jian; Ngo, Huu Hao; Guo, Wenshan; Liang, Shuang; Fan, Jinlin; Lu, Shaoyong; Wu, Haiming

    2016-08-01

    Dissolved oxygen (DO) is one of the most important factors that can influence pollutants removal in constructed wetlands (CWs). However, problems of insufficient oxygen supply and inappropriate oxygen distribution commonly exist in traditional CWs. Detailed analyses of DO supply and distribution characteristics in different types of CWs were introduced. It can be concluded that atmospheric reaeration (AR) served as the promising point on oxygen intensification. The paper summarized possible optimizations of DO in CWs to improve its decontamination performance. Process (tidal flow, drop aeration, artificial aeration, hybrid systems) and parameter (plant, substrate and operating) optimizations are particularly discussed in detail. Since economic and technical defects are still being cited in current studies, future prospects of oxygen research in CWs terminate this review.

  10. Construction and parameterization of all static and dynamic H2-optimal state feedback solutions, optimal fixed modes, and fixed decoupling zeros

    NASA Technical Reports Server (NTRS)

    Chen, Ben M.; Saberi, Ali; Sannuti, Peddapullaiah; Shamash, Yacov

    1993-01-01

    This paper considers an H2 optimization problem via state feedback. The class of problems dealt with here are general singular type which have a left invertible transfer matrix function from the control input to the controlled output. This class subsumes the regular H2 optimization problems. The paper constructs and parameterizes all the static and dynamic H2 optimal state feedback solutions. Moreover, all the eigenvalues of an optimal closed-loop system are characterized. All optimal closed-loop systems share a set of eigenvalues which are termed here as the optimal fixed modes. Every H2 optimal controller must assign among the closed-loop eigenvalues the set of optimal fixed modes. This set of optimal fixed modes includes a set of optimal fixed decoupling zeros which shows the minimum absolutely necessary number and locations of pole-zero cancellations present in any H2 optimal design. It is shown that both the sets of optimal fixed modes and optimal fixed decoupling zeros do not vary depending upon whether the static or the dynamic controllers are used.

  11. A web-based Decision Support System for the optimal management of construction and demolition waste.

    PubMed

    Banias, G; Achillas, Ch; Vlachokostas, Ch; Moussiopoulos, N; Papaioannou, I

    2011-12-01

    Wastes from construction activities constitute nowadays the largest by quantity fraction of solid wastes in urban areas. In addition, it is widely accepted that the particular waste stream contains hazardous materials, such as insulating materials, plastic frames of doors, windows, etc. Their uncontrolled disposal result to long-term pollution costs, resource overuse and wasted energy. Within the framework of the DEWAM project, a web-based Decision Support System (DSS) application - namely DeconRCM - has been developed, aiming towards the identification of the optimal construction and demolition waste (CDW) management strategy that minimises end-of-life costs and maximises the recovery of salvaged building materials. This paper addresses both technical and functional structure of the developed web-based application. The web-based DSS provides an accurate estimation of the generated CDW quantities of twenty-one different waste streams (e.g. concrete, bricks, glass, etc.) for four different types of buildings (residential, office, commercial and industrial). With the use of mathematical programming, the DeconRCM provides also the user with the optimal end-of-life management alternative, taking into consideration both economic and environmental criteria. The DSS's capabilities are illustrated through a real world case study of a typical five floor apartment building in Thessaloniki, Greece.

  12. Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization.

    PubMed

    Li, Min; Zhang, John Zenghui; Xia, Fei

    2016-04-12

    Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules. The defined residual in FM-CG converges to a maximal value as the number of CG sites increases, allowing an optimal CG model to be rigorously defined on the basis of the maximum. More importantly, we developed a robust algorithm called stepwise local iterative optimization (SLIO) to accelerate the process of coarse-graining large biomolecules. By means of the efficient SLIO algorithm, the computational cost of coarse-graining large biomolecules is reduced to within the time scale of seconds, which is far lower than that of conventional simulated annealing. The coarse-graining of two huge systems, chaperonin GroEL and lengsin, indicates that our new methods can coarse-grain huge biomolecular systems with up to 10,000 residues within the time scale of minutes. The further parametrization of CG sites derived from FM-CG allows us to construct the corresponding CG models for studies of the functions of huge biomolecular systems.

  13. ANSS Backbone Station Installation and Site Characterization

    NASA Astrophysics Data System (ADS)

    Meremonte, M.; Leeds, A.; Overturf, D.; McMillian, J.; Allen, J.; McNamara, D.

    2004-12-01

    During 2004 several new broadband seismic stations have been deployed as a part of the USGS's Advanced National Seismic System (ANSS) backbone and regional networks. New stations include: ERPA, MNTX, OGLA, AMTX, NATX, KCCO, BMO, MARC, TZTN, LAO, DGMT, REDW, KSU1, MOOW, TPAW, LOHW, RAMW. Permanent station locations were chosen to minimize the local noise conditions by recording continuous data and using a quantitative analysis of the statistical distribution of noise power estimates. For each one-hour segment of continuous data, a power spectral density (PSD) is estimated and smoothed in full octave averages at 1/8 octave intervals. Powers for each 1/8 period interval were then accumulated in one dB power bins. A statistical analysis of power bins yields probability density functions (PDFs) as a function of noise power for each of the octave bands at each station and component. Examination of earthquake signal, artifacts related to station operation and episodic cultural noise in the PDFs allow us to estimate both the overall station quality and the level of earth noise at each potential backbone site. The main function of a seismic network, such as the ANSS, is to provide high quality data for earthquake monitoring, source studies, and Earth structure research. The utility of seismic data is greatly increased when noise levels are reduced. A good quantification and understanding of seismic noise is a first step at reducing noise levels in seismic data and improving overall data quality from the ANSS backbone network.

  14. Homogeneous Canine Chest Phantom Construction: A Tool for Image Quality Optimization

    PubMed Central

    2016-01-01

    Digital radiographic imaging is increasing in veterinary practice. The use of radiation demands responsibility to maintain high image quality. Low doses are necessary because workers are requested to restrain the animal. Optimizing digital systems is necessary to avoid unnecessary exposure, causing the phenomenon known as dose creep. Homogeneous phantoms are widely used to optimize image quality and dose. We developed an automatic computational methodology to classify and quantify tissues (i.e., lung tissue, adipose tissue, muscle tissue, and bone) in canine chest computed tomography exams. The thickness of each tissue was converted to simulator materials (i.e., Lucite, aluminum, and air). Dogs were separated into groups of 20 animals each according to weight. Mean weights were 6.5 ± 2.0 kg, 15.0 ± 5.0 kg, 32.0 ± 5.5 kg, and 50.0 ± 12.0 kg, for the small, medium, large, and giant groups, respectively. The one-way analysis of variance revealed significant differences in all simulator material thicknesses (p < 0.05) quantified between groups. As a result, four phantoms were constructed for dorsoventral and lateral views. In conclusion, the present methodology allows the development of phantoms of the canine chest and possibly other body regions and/or animals. The proposed phantom is a practical tool that may be employed in future work to optimize veterinary X-ray procedures. PMID:27101001

  15. Homogeneous Canine Chest Phantom Construction: A Tool for Image Quality Optimization.

    PubMed

    Pavan, Ana Luiza Menegatti; Rosa, Maria Eugênia Dela; Giacomini, Guilherme; Bacchim Neto, Fernando Antonio; Yamashita, Seizo; Vulcano, Luiz Carlos; Duarte, Sergio Barbosa; Miranda, José Ricardo de Arruda; de Pina, Diana Rodrigues

    2016-01-01

    Digital radiographic imaging is increasing in veterinary practice. The use of radiation demands responsibility to maintain high image quality. Low doses are necessary because workers are requested to restrain the animal. Optimizing digital systems is necessary to avoid unnecessary exposure, causing the phenomenon known as dose creep. Homogeneous phantoms are widely used to optimize image quality and dose. We developed an automatic computational methodology to classify and quantify tissues (i.e., lung tissue, adipose tissue, muscle tissue, and bone) in canine chest computed tomography exams. The thickness of each tissue was converted to simulator materials (i.e., Lucite, aluminum, and air). Dogs were separated into groups of 20 animals each according to weight. Mean weights were 6.5 ± 2.0 kg, 15.0 ± 5.0 kg, 32.0 ± 5.5 kg, and 50.0 ± 12.0 kg, for the small, medium, large, and giant groups, respectively. The one-way analysis of variance revealed significant differences in all simulator material thicknesses (p < 0.05) quantified between groups. As a result, four phantoms were constructed for dorsoventral and lateral views. In conclusion, the present methodology allows the development of phantoms of the canine chest and possibly other body regions and/or animals. The proposed phantom is a practical tool that may be employed in future work to optimize veterinary X-ray procedures.

  16. Optimized single-number quantity for rating the airborne sound insulation of constructions: Living sounds.

    PubMed

    Virjonen, Petra; Hongisto, Valtteri; Oliva, David

    2016-12-01

    ISO 717-1 [(1996). International Organization for Standardization, Geneva, Switzerland] and ASTM 413 [(2010). American Society for Testing and Materials International] define various single-number quantities (SNQs) that are commonly used to rate objectively airborne sound insulation of constructions. Recent psychoacoustic evidence suggests that none of them is appropriate for a wide range of living sound stimuli. The purpose of the study was to develop an alternative compromising SNQ for the frequency range 50-5000 Hz that explains well the annoyance caused by various airborne living sounds transmitted from the neighboring dwelling. Optimal reference spectra for different living sounds were found by mathematical optimization. Experimental data from a psychoacoustic laboratory study [Hongisto, Oliva, and Keränen (2014). Acta Acust. Acust. 100, 848-863] were utilized. The subjects (n = 59) had evaluated the disturbance of living sounds that were electrically filtered to mimic transmission through commonly used wall structures. To find a high-performing reference spectrum for living sounds in general, the optimized reference spectra were averaged over all sound types. The resulting SNQ was called Rw + Copt. The related reference spectrum deviates significantly from the reference spectrum for living activities, C50-5000, below 315 Hz. The suggested SNQ correlates better with the subjective disturbance caused by living sounds than any of the present standardized SNQs of ISO 717-1 or ASTM 413.

  17. Towards environmental construct validity in animal models of CNS disorders: optimizing translation of preclinical studies.

    PubMed

    Burrows, Emma L; Hannan, Anthony J

    2013-08-01

    There is an enormous demand for new therapeutic interventions for a range of major disorders. The majority of clinical trials in recent years have been unsuccessful despite highly promising preclinical data. Therefore, an urgent issue confronting both the academic and commercial medical research sectors is how to optimize translation of preclinical studies. The vast majority of preclinical studies are currently performed using laboratory mice and rats. We will discuss the various opportunities for optimization of animal models of CNS disorders. One limitation of current approaches is that most studies are conducted on sedentary, unstimulated animals with unlimited access to food in the home cage, thus leading to metabolic and physiological compromise. Environmental enrichment, which enhances sensory stimulation, cognitive activity and physical exercise, has been demonstrated to induce dramatic effects on brain and behavior in both wild-type and genetically modified rodent models, relative to standard-housed littermate controls. Environmental enrichment also exerts beneficial effects outside the CNS, such as a reduction in excess body fat. We propose that therapeutic interventions which are found to show promise in standard-housed preclinical models should be subsequently tested under conditions of greater environmental enrichment to identify therapeutics which continue to show efficacy in housing contexts of superior 'environmental construct validity'. Other possible approaches to optimize the quality, validity and reporting of preclinical studies in animal models are also discussed.

  18. Incorporation of Biological Pathway Knowledge in the Construction of Priors for Optimal Bayesian Classification.

    PubMed

    Esfahani, Mohammad Shahrokh; Dougherty, Edward R

    2014-01-01

    Small samples are commonplace in genomic/proteomic classification, the result being inadequate classifier design and poor error estimation. The problem has recently been addressed by utilizing prior knowledge in the form of a prior distribution on an uncertainty class of feature-label distributions. A critical issue remains: how to incorporate biological knowledge into the prior distribution. For genomics/proteomics, the most common kind of knowledge is in the form of signaling pathways. Thus, it behooves us to find methods of transforming pathway knowledge into knowledge of the feature-label distribution governing the classification problem. In this paper, we address the problem of prior probability construction by proposing a series of optimization paradigms that utilize the incomplete prior information contained in pathways (both topological and regulatory). The optimization paradigms employ the marginal log-likelihood, established using a small number of feature-label realizations (sample points) regularized with the prior pathway information about the variables. In the special case of a Normal-Wishart prior distribution on the mean and inverse covariance matrix (precision matrix) of a Gaussian distribution, these optimization problems become convex. Companion website: gsp.tamu.edu/Publications/supplementary/shahrokh13a.

  19. A Synthetic HIV-1 Subtype C Backbone Generates Comparable PR and RT Resistance Profiles to a Subtype B Backbone in a Recombinant Virus Assay

    PubMed Central

    Nauwelaers, David; Van Houtte, Margriet; Winters, Bart; Steegen, Kim; Van Baelen, Kurt; Chi, Ellen; Zhou, Mimi; Steiner, Derek; Bonesteel, Rachelle; Aston, Colin; Stuyver, Lieven J.

    2011-01-01

    In order to determine phenotypic protease and reverse transcriptase inhibitor-associated resistance in HIV subtype C virus, we have synthetically constructed an HIV-1 subtype C (HIV-1-C) viral backbone for use in a recombinant virus assay. The in silico designed viral genome was divided into 4 fragments, which were chemically synthesized and joined together by conventional subcloning. Subsequently, gag-protease-reverse-transcriptase (GPRT) fragments from 8 HIV-1 subtype C-infected patient samples were RT-PCR-amplified and cloned into the HIV-1-C backbone (deleted for GPRT) using In-Fusion reagents. Recombinant viruses (1 to 5 per patient sample) were produced in MT4-eGFP cells where cyto-pathogenic effect (CPE), p24 and Viral Load (VL) were monitored. The resulting HIV-1-C recombinant virus stocks (RVS) were added to MT4-eGFP cells in the presence of serial dilutions of antiretroviral drugs (PI, NNRTI, NRTI) to determine the fold-change in IC50 compared to the IC50 of wild-type HIV-1 virus. Additionally, viral RNA was extracted from the HIV-1-C RVS and the amplified GPRT products were used to generate recombinant virus in a subtype B backbone. Phenotypic resistance profiles in a subtype B and subtype C backbone were compared. The following observations were made: i) functional, infectious HIV-1 subtype C viruses were generated, confirmed by VL and p24 measurements; ii) their rate of infection was slower than viruses generated in the subtype B backbone; iii) they did not produce clear CPE in MT4 cells; and iv) drug resistance profiles generated in both backbones were very similar, including re-sensitizing effects like M184V on AZT. PMID:21629677

  20. Construction Performance Optimization toward Green Building Premium Cost Based on Greenship Rating Tools Assessment with Value Engineering Method

    NASA Astrophysics Data System (ADS)

    Latief, Yusuf; Berawi, Mohammed Ali; Basten, Van; Riswanto; Budiman, Rachmat

    2017-07-01

    Green building concept becomes important in current building life cycle to mitigate environment issues. The purpose of this paper is to optimize building construction performance towards green building premium cost, achieving green building rating tools with optimizing life cycle cost. Therefore, this study helps building stakeholder determining building fixture to achieve green building certification target. Empirically the paper collects data of green building in the Indonesian construction industry such as green building fixture, initial cost, operational and maintenance cost, and certification score achievement. After that, using value engineering method optimized green building fixture based on building function and cost aspects. Findings indicate that construction performance optimization affected green building achievement with increasing energy and water efficiency factors and life cycle cost effectively especially chosen green building fixture.

  1. An Optimal Parallel Algorithm for Constructing a Spanning Tree on Circular Permutation Graphs

    NASA Astrophysics Data System (ADS)

    Honma, Hirotoshi; Honma, Saki; Masuyama, Shigeru

    The spanning tree problem is to find a tree that connects all the vertices of G. This problem has many applications, such as electric power systems, computer network design and circuit analysis. Klein and Stein demonstrated that a spanning tree can be found in O(log n) time with O(n + m) processors on the CRCW PRAM. In general, it is known that more efficient parallel algorithms can be developed by restricting classes of graphs. Circular permutation graphs properly contain the set of permutation graphs as a subclass and are first introduced by Rotem and Urrutia. They provided O(n2.376) time recognition algorithm. Circular permutation graphs and their models find several applications in VLSI layout. In this paper, we propose an optimal parallel algorithm for constructing a spanning tree on circular permutation graphs. It runs in O(log n) time with O(n/ log n) processors on the EREW PRAM.

  2. Towards Clinically Optimized MRI-guided Surgical Manipulator for Minimally Invasive Prostate Percutaneous Interventions: Constructive Design.

    PubMed

    Eslami, Sohrab; Fischer, Gregory S; Song, Sang-Eun; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M; Iordachita, Iulian

    2013-12-31

    This paper undertakes the modular design and development of a minimally invasive surgical manipulator for MRI-guided transperineal prostate interventions. Severe constraints for the MRI-compatibility to hold the minimum artifact on the image quality and dimensions restraint of the bore scanner shadow the design procedure. Regarding the constructive design, the manipulator kinematics has been optimized and the effective analytical needle workspace is developed and followed by proposing the workflow for the manual needle insertion. A study of the finite element analysis is established and utilized to improve the mechanism weaknesses under some inevitable external forces to ensure the minimum structure deformation. The procedure for attaching a sterile plastic drape on the robot manipulator is discussed. The introduced robotic manipulator herein is aimed for the clinically prostate biopsy and brachytherapy applications.

  3. Towards Clinically Optimized MRI-guided Surgical Manipulator for Minimally Invasive Prostate Percutaneous Interventions: Constructive Design*

    PubMed Central

    Eslami, Sohrab; Fischer, Gregory S.; Song, Sang-Eun; Tokuda, Junichi; Hata, Nobuhiko; Tempany, Clare M.; Iordachita, Iulian

    2013-01-01

    This paper undertakes the modular design and development of a minimally invasive surgical manipulator for MRI-guided transperineal prostate interventions. Severe constraints for the MRI-compatibility to hold the minimum artifact on the image quality and dimensions restraint of the bore scanner shadow the design procedure. Regarding the constructive design, the manipulator kinematics has been optimized and the effective analytical needle workspace is developed and followed by proposing the workflow for the manual needle insertion. A study of the finite element analysis is established and utilized to improve the mechanism weaknesses under some inevitable external forces to ensure the minimum structure deformation. The procedure for attaching a sterile plastic drape on the robot manipulator is discussed. The introduced robotic manipulator herein is aimed for the clinically prostate biopsy and brachytherapy applications. PMID:24683502

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

    PubMed

    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.

  5. Optimization of the choice of unmanned aerial vehicles used to monitor the implementation of selected construction projects

    NASA Astrophysics Data System (ADS)

    Skorupka, Dariusz; Duchaczek, Artur; Waniewska, Agnieszka; Kowacka, Magdalena

    2017-07-01

    Due to their properties unmanned aerial vehicles have huge number of possibilities for application in construction engineering. The nature and extent of construction works performedmakes the decision to purchase the right equipment significant for the possibility for its further use while monitoring the implementation of these works. Technical factors, such as the accuracy and quality of the applied measurement instruments are especially important when monitoring the realization of construction projects. The paper presents the optimization of the choice of unmanned aerial vehicles using the Bellinger method. The decision-making analysis takes into account criteria that are particularly crucial by virtue of the range of monitoring of ongoing construction works.

  6. Design and construction of miniature artificial ecosystem based on dynamic response optimization

    NASA Astrophysics Data System (ADS)

    Hu, Dawei; Liu, Hong; Tong, Ling; Li, Ming; Hu, Enzhu

    The miniature artificial ecosystem (MAES) is a combination of man, silkworm, salad and mi-croalgae to partially regenerate O2 , sanitary water and food, simultaneously dispose CO2 and wastes, therefore it have a fundamental life support function. In order to enhance the safety and reliability of MAES and eliminate the influences of internal variations and external dis-turbances, it was necessary to configure MAES as a closed-loop control system, and it could be considered as a prototype for future bioregenerative life support system. However, MAES is a complex system possessing large numbers of parameters, intricate nonlinearities, time-varying factors as well as uncertainties, hence it is difficult to perfectly design and construct a prototype through merely conducting experiments by trial and error method. Our research presented an effective way to resolve preceding problem by use of dynamic response optimiza-tion. Firstly the mathematical model of MAES with first-order nonlinear ordinary differential equations including parameters was developed based on relevant mechanisms and experimental data, secondly simulation model of MAES was derived on the platform of MatLab/Simulink to perform model validation and further digital simulations, thirdly reference trajectories of de-sired dynamic response of system outputs were specified according to prescribed requirements, and finally optimization for initial values, tuned parameter and independent parameters was carried out using the genetic algorithm, the advanced direct search method along with parallel computing methods through computer simulations. The result showed that all parameters and configurations of MAES were determined after a series of computer experiments, and its tran-sient response performances and steady characteristics closely matched the reference curves. Since the prototype is a physical system that represents the mathematical model with reason-able accuracy, so the process of designing and

  7. Pyridoxamine Protects Protein Backbone from Oxidative Fragmentation

    PubMed Central

    Chetyrkin, Sergei; Mathis, Missy; McDonald, W. Hayes; Shackelford, Xavier; Hudson, Billy; Voziyan, Paul

    2011-01-01

    Oxidative damage to proteins is one of the major pathogenic mechanisms in many chronic diseases. Therefore, inhibition of this oxidative damage can be an important part of therapeutic strategies. Pyridoxamine (PM), a prospective drug for treatment of diabetic nephropathy, has been previously shown to inhibit several oxidative and glycoxidative pathways, thus protecting amino acid side chains of the proteins from oxidative damage. Here, we demonstrated that PM can also protect protein backbone from fragmentation induced via different oxidative mechanisms including autoxidation of glucose. This protection was due to hydroxyl radical scavenging by PM and may contribute to PM therapeutic effects shown in clinical trials. PMID:21763683

  8. Telephone wire is backbone of security system

    SciTech Connect

    Brede, K.; Rackson, L.T.

    1995-09-01

    Video provides a variety of low-cost, high-quality solutions in today`s security environment. Cost-conscious managers of power generation stations, casinos, prison facilities, military bases and office buildings are considering using regular telephone wire (unshielded twisted pair-UTP) within their existing systems as the backbone of a video to the PC, personal and video-conferencing and training are other areas where phone wire in a building can save money and provide an alternative to coax or fiber for video. More and more, businesses and government agencies are meeting their needs efficiently by using telephone wires for more than just telephones.

  9. DisMeta – a Meta Server for Construct Design and Optimization

    PubMed Central

    Huang, Yuanpeng Janet; Acton, Thomas B.; Montelione, Gaetano T.

    2014-01-01

    Summary Intrinsically disordered or unstructured regions in proteins are both common and biologically important, particularly in regulation, signaling and modulating intermolecular recognition processes. From a practical point of view, however, such disordered regions often can pose significant challenges for crystallization. Disordered regions are also detrimental to NMR spectral quality, complicating the analysis of resonance assignments and three-dimensional protein structures by NMR methods. The DisMeta Server has been used by Northeastern Structural Genomics Consortium (NESG) as a primary tool for construct design and optimization in preparing samples for both NMR and crystallization studies. It is a meta-server that generates a consensus analysis of eight different sequence-based disorder predictors to identify regions that are likely to be disordered. DisMeta also identifies predicted secretion signal peptides, trans-membrane segments, and low complexity regions. Identification of disordered regions, by either experimental or computational methods, is an important step in the NESG structure production pipeline, allowing the rational design of protein constructs that have improved expression and solubility, improved crystallization, and better quality NMR spectra. PMID:24203321

  10. Geminal embedding scheme for optimal atomic basis set construction in correlated calculations

    NASA Astrophysics Data System (ADS)

    Sorella, S.; Devaux, N.; Dagrada, M.; Mazzola, G.; Casula, M.

    2015-12-01

    We introduce an efficient method to construct optimal and system adaptive basis sets for use in electronic structure and quantum Monte Carlo calculations. The method is based on an embedding scheme in which a reference atom is singled out from its environment, while the entire system (atom and environment) is described by a Slater determinant or its antisymmetrized geminal power (AGP) extension. The embedding procedure described here allows for the systematic and consistent contraction of the primitive basis set into geminal embedded orbitals (GEOs), with a dramatic reduction of the number of variational parameters necessary to represent the many-body wave function, for a chosen target accuracy. Within the variational Monte Carlo method, the Slater or AGP part is determined by a variational minimization of the energy of the whole system in presence of a flexible and accurate Jastrow factor, representing most of the dynamical electronic correlation. The resulting GEO basis set opens the way for a fully controlled optimization of many-body wave functions in electronic structure calculation of bulk materials, namely, containing a large number of electrons and atoms. We present applications on the water molecule, the volume collapse transition in cerium, and the high-pressure liquid hydrogen.

  11. Geminal embedding scheme for optimal atomic basis set construction in correlated calculations

    SciTech Connect

    Sorella, S.; Devaux, N.; Dagrada, M.; Mazzola, G.; Casula, M.

    2015-12-28

    We introduce an efficient method to construct optimal and system adaptive basis sets for use in electronic structure and quantum Monte Carlo calculations. The method is based on an embedding scheme in which a reference atom is singled out from its environment, while the entire system (atom and environment) is described by a Slater determinant or its antisymmetrized geminal power (AGP) extension. The embedding procedure described here allows for the systematic and consistent contraction of the primitive basis set into geminal embedded orbitals (GEOs), with a dramatic reduction of the number of variational parameters necessary to represent the many-body wave function, for a chosen target accuracy. Within the variational Monte Carlo method, the Slater or AGP part is determined by a variational minimization of the energy of the whole system in presence of a flexible and accurate Jastrow factor, representing most of the dynamical electronic correlation. The resulting GEO basis set opens the way for a fully controlled optimization of many-body wave functions in electronic structure calculation of bulk materials, namely, containing a large number of electrons and atoms. We present applications on the water molecule, the volume collapse transition in cerium, and the high-pressure liquid hydrogen.

  12. Geometric construction of eighth-order optimal families of Ostrowski's method.

    PubMed

    Behl, Ramandeep; Motsa, S S

    2015-01-01

    Based on well-known fourth-order Ostrowski's method, we proposed many new interesting optimal families of eighth-order multipoint methods without memory for obtaining simple roots. Its geometric construction consists in approximating fn' at zn in such a way that its average with the known tangent slopes fn' at xn and yn is the same as the known weighted average of secant slopes and then we apply weight function approach. The adaptation of this strategy increases the convergence order of Ostrowski's method from four to eight and its efficiency index from 1.587 to 1.682. Finally, a number of numerical examples are also proposed to illustrate their accuracy by comparing them with the new existing optimal eighth-order methods available in the literature. It is found that they are very useful in high precision computations. Further, it is also noted that larger basins of attraction belong to our methods although the other methods are slow and have darker basins while some of the methods are too sensitive upon the choice of the initial value.

  13. Construction and Optimization of a Large Gene Coexpression Network in Maize Using RNA-Seq Data.

    PubMed

    Huang, Ji; Vendramin, Stefania; Shi, Lizhen; McGinnis, Karen M

    2017-09-01

    With the emergence of massively parallel sequencing, genomewide expression data production has reached an unprecedented level. This abundance of data has greatly facilitated maize research, but may not be amenable to traditional analysis techniques that were optimized for other data types. Using publicly available data, a gene coexpression network (GCN) can be constructed and used for gene function prediction, candidate gene selection, and improving understanding of regulatory pathways. Several GCN studies have been done in maize (Zea mays), mostly using microarray datasets. To build an optimal GCN from plant materials RNA-Seq data, parameters for expression data normalization and network inference were evaluated. A comprehensive evaluation of these two parameters and a ranked aggregation strategy on network performance, using libraries from 1266 maize samples, were conducted. Three normalization methods and 10 inference methods, including six correlation and four mutual information methods, were tested. The three normalization methods had very similar performance. For network inference, correlation methods performed better than mutual information methods at some genes. Increasing sample size also had a positive effect on GCN. Aggregating single networks together resulted in improved performance compared to single networks. © 2017 American Society of Plant Biologists. All Rights Reserved.

  14. Backbone dependency further improves side chain prediction efficiency in the Energy-based Conformer Library (bEBL).

    PubMed

    Subramaniam, Sabareesh; Senes, Alessandro

    2014-11-01

    Side chain optimization is an integral component of many protein modeling applications. In these applications, the conformational freedom of the side chains is often explored using libraries of discrete, frequently occurring conformations. Because side chain optimization can pose a computationally intensive combinatorial problem, the nature of these conformer libraries is important for ensuring efficiency and accuracy in side chain prediction. We have previously developed an innovative method to create a conformer library with enhanced performance. The Energy-based Library (EBL) was obtained by analyzing the energetic interactions between conformers and a large number of natural protein environments from crystal structures. This process guided the selection of conformers with the highest propensity to fit into spaces that should accommodate a side chain. Because the method requires a large crystallographic data-set, the EBL was created in a backbone-independent fashion. However, it is well established that side chain conformation is strongly dependent on the local backbone geometry, and that backbone-dependent libraries are more efficient in side chain optimization. Here we present the backbone-dependent EBL (bEBL), whose conformers are independently sorted for each populated region of Ramachandran space. The resulting library closely mirrors the local backbone-dependent distribution of side chain conformation. Compared to the EBL, we demonstrate that the bEBL uses fewer conformers to produce similar side chain prediction outcomes, thus further improving performance with respect to the already efficient backbone-independent version of the library.

  15. Construction and evaluation of plasmid vectors optimized for constitutive and regulated gene expression in Burkholderia cepacia complex isolates.

    PubMed

    Lefebre, Matthew D; Valvano, Miguel A

    2002-12-01

    Genetic studies with Burkholderia cepacia complex isolates are hampered by the limited availability of cloning vectors and by the inherent resistance of these isolates to the most common antibiotics used for genetic selection. Also, some of the promoters widely employed for gene expression in Escherichia coli are inefficient in B. cepacia. In this study, we have utilized the backbone of the vector pME6000, a derivative of the pBBR1 plasmid that was originally isolated from Bordetella bronchiseptica, to construct a set of vectors useful for gene expression in B. cepacia. These vectors contain either the constitutive promoter of the S7 ribosomal protein gene from Burkholderia sp. strain LB400 or the arabinose-inducible P(BAD) promoter from E. coli. Promoter sequences were placed immediately upstream of multiple cloning sites in combination with the minimal sequence of pME6000 required for plasmid maintenance and mobilization. The functionality of both vectors was assessed by cloning the enhanced green fluorescent protein gene (e-gfp) and determining the levels of enhanced green fluorescent protein expression and fluorescence emission for a variety of clinical and environmental isolates of the B. cepacia complex. We also demonstrate that B. cepacia carrying these constructs can readily be detected intracellularly by fluorescence microscopy following the infection of Acanthamoeba polyphaga.

  16. Advanced routing in interplanetary backbone network

    NASA Astrophysics Data System (ADS)

    Xu, Ge; Sheng, Min; Wu, Chengke

    2007-11-01

    Interplanetary (IPN) Internet is a communication infrastructure providing communication services for scientific data delivery and navigation services for the explorer spacecrafts and orbiters of the future deep space missions. The interplanetary backbone network has the unique characteristics hence routing through the backbone network present many challenges that are not presented in traditional networks. Some routing algorithms have been proposed, in which, LPDB integrates the shortest path algorithm and the directional broadcast method to guarantee fast and reliable message delivery. Through this mutipath routing strategy, unpredictable link failures is addressed, but additional network overhead is introduced. In this paper, we propose an improvement of the LPDB named ALPDB in which the source could adaptively decide the next-hop nodes according to the link condition, hence reduce the network overhead. We model this algorithm on the network simulation platform of OPNET and compare it with other applicable algorithms in data passing ratio, data delay and network overhead. The result indicates that the ALPDB algorithm could not only guarantee reliable message delivery, but also decrease the cost significantly.

  17. Nonlinear backbone torsional pair correlations in proteins

    NASA Astrophysics Data System (ADS)

    Long, Shiyang; Tian, Pu

    2016-10-01

    Protein allostery requires dynamical structural correlations. Physical origin of which, however, remain elusive despite intensive studies during last two and half decades. Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are mainly spatially long-ranged and are dominantly executed by loop residues, exist extensively in most analyzed proteins. Examination of torsional motion for correlated BTPs suggested that such nonlinear correlations are mainly associated aharmonic torsional state transitions and in some cases strongly anisotropic local torsional motion of participating torsions, and occur on widely different and relatively longer time scales. In contrast, correlations between backbone torsions in stable α helices and β strands are mainly linear and spatially short-ranged, and are more likely to associate with harmonic local torsional motion. Further analysis revealed that the direct cause of nonlinear contributions are heterogeneous linear correlations. These findings implicate a general search strategy for novel allosteric modulation sites of protein activities.

  18. Nonlinear backbone torsional pair correlations in proteins

    PubMed Central

    Long, Shiyang; Tian, Pu

    2016-01-01

    Protein allostery requires dynamical structural correlations. Physical origin of which, however, remain elusive despite intensive studies during last two and half decades. Based on analysis of molecular dynamics (MD) simulation trajectories for ten proteins with different sizes and folds, we found that nonlinear backbone torsional pair (BTP) correlations, which are mainly spatially long-ranged and are dominantly executed by loop residues, exist extensively in most analyzed proteins. Examination of torsional motion for correlated BTPs suggested that such nonlinear correlations are mainly associated aharmonic torsional state transitions and in some cases strongly anisotropic local torsional motion of participating torsions, and occur on widely different and relatively longer time scales. In contrast, correlations between backbone torsions in stable α helices and β strands are mainly linear and spatially short-ranged, and are more likely to associate with harmonic local torsional motion. Further analysis revealed that the direct cause of nonlinear contributions are heterogeneous linear correlations. These findings implicate a general search strategy for novel allosteric modulation sites of protein activities. PMID:27708342

  19. Improved design and optimization of subsurface flow constructed wetlands and sand filters

    NASA Astrophysics Data System (ADS)

    Brovelli, A.; Carranza-Díaz, O.; Rossi, L.; Barry, D. A.

    2010-05-01

    Subsurface flow constructed wetlands and sand filters are engineered systems capable of eliminating a wide range of pollutants from wastewater. These devices are easy to operate, flexible and have low maintenance costs. For these reasons, they are particularly suitable for small settlements and isolated farms and their use has substantially increased in the last 15 years. Furthermore, they are also becoming used as a tertiary - polishing - step in traditional treatment plants. Recent work observed that research is however still necessary to understand better the biogeochemical processes occurring in the porous substrate, their mutual interactions and feedbacks, and ultimately to identify the optimal conditions to degrade or remove from the wastewater both traditional and anthropogenic recalcitrant pollutants, such as hydrocarbons, pharmaceuticals, personal care products. Optimal pollutant elimination is achieved if the contact time between microbial biomass and the contaminated water is sufficiently long. The contact time depends on the hydraulic residence time distribution (HRTD) and is controlled by the hydrodynamic properties of the system. Previous reports noted that poor hydrodynamic behaviour is frequent, with water flowing mainly through preferential paths resulting in a broad HRTD. In such systems the flow rate must be decreased to allow a sufficient proportion of the wastewater to experience the minimum residence time. The pollutant removal efficiency can therefore be significantly reduced, potentially leading to the failure of the system. The aim of this work was to analyse the effect of the heterogeneous distribution of the hydraulic properties of the porous substrate on the HRTD and treatment efficiency, and to develop an improved design methodology to reduce the risk of system failure and to optimize existing systems showing poor hydrodynamics. Numerical modelling was used to evaluate the effect of substrate heterogeneity on the breakthrough curves of

  20. Construction of Optimally Reduced Empirical Model by Spatially Distributed Climate Data

    NASA Astrophysics Data System (ADS)

    Gavrilov, A.; Mukhin, D.; Loskutov, E.; Feigin, A.

    2016-12-01

    We present an approach to empirical reconstruction of the evolution operator in stochastic form by space-distributed time series. The main problem in empirical modeling consists in choosing appropriate phase variables which can efficiently reduce the dimension of the model at minimal loss of information about system's dynamics which consequently leads to more robust model and better quality of the reconstruction. For this purpose we incorporate in the model two key steps. The first step is standard preliminary reduction of observed time series dimension by decomposition via certain empirical basis (e. g. empirical orthogonal function basis or its nonlinear or spatio-temporal generalizations). The second step is construction of an evolution operator by principal components (PCs) - the time series obtained by the decomposition. In this step we introduce a new way of reducing the dimension of the embedding in which the evolution operator is constructed. It is based on choosing proper combinations of delayed PCs to take into account the most significant spatio-temporal couplings. The evolution operator is sought as nonlinear random mapping parameterized using artificial neural networks (ANN). Bayesian approach is used to learn the model and to find optimal hyperparameters: the number of PCs, the dimension of the embedding, the degree of the nonlinearity of ANN. The results of application of the method to climate data (sea surface temperature, sea level pressure) and their comparing with the same method based on non-reduced embedding are presented. The study is supported by Government of Russian Federation (agreement #14.Z50.31.0033 with the Institute of Applied Physics of RAS).

  1. Sofosbuvir as backbone of interferon free treatments.

    PubMed

    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. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  2. Organ sample generator for expected treatment dose construction and adaptive inverse planning optimization

    SciTech Connect

    Nie Xiaobo; Liang Jian; Yan Di

    2012-12-15

    Purpose: To create an organ sample generator (OSG) for expected treatment dose construction and adaptive inverse planning optimization. The OSG generates random samples of organs of interest from a distribution obeying the patient specific organ variation probability density function (PDF) during the course of adaptive radiotherapy. Methods: Principle component analysis (PCA) and a time-varying least-squares regression (LSR) method were used on patient specific geometric variations of organs of interest manifested on multiple daily volumetric images obtained during the treatment course. The construction of the OSG includes the determination of eigenvectors of the organ variation using PCA, and the determination of the corresponding coefficients using time-varying LSR. The coefficients can be either random variables or random functions of the elapsed treatment days depending on the characteristics of organ variation as a stationary or a nonstationary random process. The LSR method with time-varying weighting parameters was applied to the precollected daily volumetric images to determine the function form of the coefficients. Eleven h and n cancer patients with 30 daily cone beam CT images each were included in the evaluation of the OSG. The evaluation was performed using a total of 18 organs of interest, including 15 organs at risk and 3 targets. Results: Geometric variations of organs of interest during h and n cancer radiotherapy can be represented using the first 3 {approx} 4 eigenvectors. These eigenvectors were variable during treatment, and need to be updated using new daily images obtained during the treatment course. The OSG generates random samples of organs of interest from the estimated organ variation PDF of the individual. The accuracy of the estimated PDF can be improved recursively using extra daily image feedback during the treatment course. The average deviations in the estimation of the mean and standard deviation of the organ variation PDF for h

  3. Construction

    DTIC Science & Technology

    2002-01-01

    Harbor Deepening Project, Jacksonville, FL Palm Valley Bridge Project, Jacksonville, FL Rotary Club of San Juan, San Juan, PR Tren Urbano Subway...David. What is nanotechnology? What are its implications for construction?, Foresight/CRISP Workshop on Nanotechnology, Royal Society of Arts

  4. Construction

    DTIC Science & Technology

    2002-01-01

    San Juan, PR Tren Urbano Subway Project, San Juan, PR U.S. Army South, San Juan, PR U.S. Coast Guard Housing Project, San Juan, PR U.S. Coast Guard...construction?, Foresight/CRISP Workshop on Nanotechnology, Royal Society of Arts . Cheltenham, England: 2001, p.5. 56 Concrete Proposals, Economist, July 24

  5. Selective mapping: a strategy for optimizing the construction of high-density linkage maps.

    PubMed Central

    Vision, T J; Brown, D G; Shmoys, D B; Durrett, R T; Tanksley, S D

    2000-01-01

    Historically, linkage mapping populations have consisted of large, randomly selected samples of progeny from a given pedigree or cell lines from a panel of radiation hybrids. We demonstrate that, to construct a map with high genome-wide marker density, it is neither necessary nor desirable to genotype all markers in every individual of a large mapping population. Instead, a reduced sample of individuals bearing complementary recombinational or radiation-induced breakpoints may be selected for genotyping subsequent markers from a large, but sparsely genotyped, mapping population. Choosing such a sample can be reduced to a discrete stochastic optimization problem for which the goal is a sample with breakpoints spaced evenly throughout the genome. We have developed several different methods for selecting such samples and have evaluated their performance on simulated and actual mapping populations, including the Lister and Dean Arabidopsis thaliana recombinant inbred population and the GeneBridge 4 human radiation hybrid panel. Our methods quickly and consistently find much-reduced samples with map resolution approaching that of the larger populations from which they are derived. This approach, which we have termed selective mapping, can facilitate the production of high-quality, high-density genome-wide linkage maps. PMID:10790413

  6. Construction of a Compact, Low-Inductance, 100 J Dense Plasma Focus for Yield Optimization Studies

    NASA Astrophysics Data System (ADS)

    Cooper, Christopher; Povilus, Alex; Chapman, Steven; Falabella, Steve; Podpaly, Yuri; Shaw, Brian; Liu, Jason; Schmidt, Andrea

    2016-10-01

    A new 100 J mini dense plasma focus (DPF) is constructed to optimize neutron yields for a variety of plasma conditions and anode shapes. The device generates neutrons by leveraging instabilities that occur during a z-pinch in a plasma sheath to accelerate a beam of deuterium ions into a background deuterium gas target. The features that distinguish this miniDPF from previous 100 J devices are a compact, engineered electrode geometry and a low-impedance driver. The driving circuit inductance is minimized by mounting the capacitors close to the back of the anode and cathode < 20 cm away, increasing the breakdown current and yields. The anode can rapidly be changed out to test new designs. The neutron yield and 2D images of the visible light emission are compared to simulations with the hybrid kinetic code LSP which can directly simulate the device and anode designs. Initial studies of the sheath physics and neutron yields for a scaling of discharge voltages and neutral fill pressures are presented. Prepared by LLNL under Contract DE-AC52-07NA27344.

  7. Evaluation of impact of backbone outages in IP networks

    NASA Astrophysics Data System (ADS)

    Kogan, Yaakov; Choudhury, Gagan L.; Tarapore, Percy

    2004-09-01

    Nationwide IP networks typically include nodes in major cities and the following elements: customer equipment, access routers, backbone routers, peering routers, access links connecting customer equipment to access routers, access routers to backbone routers, and backbone links interconnecting backbone routers. The part of this network consisting of backbone routers and related interconnecting links is referred to as the "backbone". We develop a new approach for accurately computing the Availability measure of IP networks by directly simulating each type of backbone outage event and its impact on traffic loss. We use this approach to quantify availability improvement as a result of introducing various technological changes in the network such as IGP tuning, high availability router architecture, MPLS-TE and Fast Reroute. A situation, where operational backbone links do not have enough spare capacity to carry additional traffic during the outage time, is referred to as bandwidth loss. We concentrate on one unidirectional backbone link and derive asymptotic approximations for the expected bandwidth loss in the framework of generalized Erlang and Engset models when the total number of resource units and request arrival rates are proportionally large. Simulation results demonstrate good accuracy of the approximations.

  8. Construction

    DTIC Science & Technology

    2003-01-01

    hot water, appliances, lightening and misc.66 Average and efficient energy costs were determined for each base. The collection of average and...data and the appropriate regional median condominium87 and apartment O&M costs . For new housing projects the energy efficient utility costs were used...supply of domestic skilled laborers and the increasing cost of insurance. The construction industry has always contracted and expanded based

  9. Multi-objective evolutionary optimization for constructing neural networks for virtual reality visual data mining: application to geophysical prospecting.

    PubMed

    Valdés, Julio J; Barton, Alan J

    2007-05-01

    A method for the construction of virtual reality spaces for visual data mining using multi-objective optimization with genetic algorithms on nonlinear discriminant (NDA) neural networks is presented. Two neural network layers (the output and the last hidden) are used for the construction of simultaneous solutions for: (i) a supervised classification of data patterns and (ii) an unsupervised similarity structure preservation between the original data matrix and its image in the new space. A set of spaces are constructed from selected solutions along the Pareto front. This strategy represents a conceptual improvement over spaces computed by single-objective optimization. In addition, genetic programming (in particular gene expression programming) is used for finding analytic representations of the complex mappings generating the spaces (a composition of NDA and orthogonal principal components). The presented approach is domain independent and is illustrated via application to the geophysical prospecting of caves.

  10. Expected treatment dose construction and adaptive inverse planning optimization: Implementation for offline head and neck cancer adaptive radiotherapy

    SciTech Connect

    Yan Di; Liang Jian

    2013-02-15

    Purpose: To construct expected treatment dose for adaptive inverse planning optimization, and evaluate it on head and neck (h and n) cancer adaptive treatment modification. Methods: Adaptive inverse planning engine was developed and integrated in our in-house adaptive treatment control system. The adaptive inverse planning engine includes an expected treatment dose constructed using the daily cone beam (CB) CT images in its objective and constrains. Feasibility of the adaptive inverse planning optimization was evaluated retrospectively using daily CBCT images obtained from the image guided IMRT treatment of 19 h and n cancer patients. Adaptive treatment modification strategies with respect to the time and the number of adaptive inverse planning optimization during the treatment course were evaluated using the cumulative treatment dose in organs of interest constructed using all daily CBCT images. Results: Expected treatment dose was constructed to include both the delivered dose, to date, and the estimated dose for the remaining treatment during the adaptive treatment course. It was used in treatment evaluation, as well as in constructing the objective and constraints for adaptive inverse planning optimization. The optimization engine is feasible to perform planning optimization based on preassigned treatment modification schedule. Compared to the conventional IMRT, the adaptive treatment for h and n cancer illustrated clear dose-volume improvement for all critical normal organs. The dose-volume reductions of right and left parotid glands, spine cord, brain stem and mandible were (17 {+-} 6)%, (14 {+-} 6)%, (11 {+-} 6)%, (12 {+-} 8)%, and (5 {+-} 3)% respectively with the single adaptive modification performed after the second treatment week; (24 {+-} 6)%, (22 {+-} 8)%, (21 {+-} 5)%, (19 {+-} 8)%, and (10 {+-} 6)% with three weekly modifications; and (28 {+-} 5)%, (25 {+-} 9)%, (26 {+-} 5)%, (24 {+-} 8)%, and (15 {+-} 9)% with five weekly modifications. Conclusions

  11. Efficient expression of nattokinase in Bacillus licheniformis: host strain construction and signal peptide optimization.

    PubMed

    Wei, Xuetuan; Zhou, Yinhua; Chen, Jingbang; Cai, Dongbo; Wang, Dan; Qi, Gaofu; Chen, Shouwen

    2015-02-01

    Nattokinase (NK) possesses the potential for prevention and treatment of thrombus-related diseases. In this study, high-level expression of nattokinase was achieved in Bacillus licheniformis WX-02 via host strain construction and signal peptides optimization. First, ten genes (mpr, vpr, aprX, epr, bpr, wprA, aprE, bprA, hag, amyl) encoding for eight extracellular proteases, a flagellin and an amylase were deleted to obtain B. licheniformis BL10, which showed no extracellular proteases activity in gelatin zymography. Second, the gene fragments of P43 promoter, Svpr, nattokinase and TamyL were combined into pHY300PLK to form the expression vector pP43SNT. In BL10 (pP43SNT), the fermentation activity and product activity per unit of biomass of nattokinase reached 14.33 FU/mL and 2,187.71 FU/g respectively, which increased by 39 and 156 % compared to WX-02 (pP43SNT). Last, Svpr was replaced with SsacC and SbprA, and the maximum fermentation activity (33.83 FU/mL) was achieved using SsacC, which was 229 % higher than that of WX-02 (pP43SNT). The maximum NK fermentation activity in this study reaches the commercial production level of solid state fermentation, and this study provides a promising engineered strain for industrial production of nattokinase, as well as a potential platform host for expression of other target proteins.

  12. High Speed Fibre Optic Backbone LAN

    NASA Astrophysics Data System (ADS)

    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.

  13. Free backbone carbonyls mediate rhodopsin activation

    PubMed Central

    Kimata, Naoki; Pope, Andreyah; Sanchez-Reyes, Omar B.; Eilers, Markus; Opefi, Chikwado A.; Ziliox, Martine; Reeves, Philip J.; Smith, Steven O.

    2016-01-01

    Conserved prolines in the transmembrane helices of G protein-coupled receptors (GPCRs) are often considered to function as hinges that divide the helix into two segments capable of independent motion. Depending on their potential to hydrogen-bond, the free C=O groups associated with these prolines can facilitate conformational flexibility, conformational switching or stabilize receptor structure. To address the role of conserved prolines in family A GPCRs, we focus on bovine rhodopsin, a GPCR in the visual receptor subfamily, using solid-state NMR spectroscopy. The free backbone C=O groups on helices H5 and H7 are found to stabilize the inactive rhodopsin structure through hydrogen-bonds to residues on adjacent helices. In response to light-induced isomerization of the retinal chromophore, hydrogen-bonding interactions involving these C=O groups are released facilitating H5 and H7 repacking onto the transmembrane core of the receptor. These results provide insights into the multiple structural and functional roles prolines play in membrane proteins. PMID:27376589

  14. Extracting the Information Backbone in Online System

    PubMed Central

    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. PMID:23690946

  15. Detecting the Significant Flux Backbone of Escherichia coli metabolism.

    PubMed

    Güell, Oriol; Sagués, Francesc; Serrano, M Ángeles

    2017-04-09

    The heterogeneity of computationally predicted reaction fluxes in metabolic networks within a single flux state can be exploited to detect their significant flux backbone. Here, we disclose the backbone of Escherichia coli, and compare it with the backbones of other bacteria. We find that, in general, the core of the backbones is mainly composed of reactions in energy metabolism corresponding to ancient pathways. In E. coli, the synthesis of nucleotides and the metabolism of lipids form smaller cores which rely critically on energy metabolism. Moreover, the consideration of different media leads to the identification of pathways sensitive to environmental changes. The metabolic backbone of an organism is thus useful for tracing, simultaneously, both its evolution and adaptation fingerprints. This article is protected by copyright. All rights reserved.

  16. Construction of pore network models for Berea and Fontainebleau sandstones using non-linear programing and optimization techniques

    NASA Astrophysics Data System (ADS)

    Sharqawy, Mostafa H.

    2016-12-01

    Pore network models (PNM) of Berea and Fontainebleau sandstones were constructed using nonlinear programming (NLP) and optimization methods. The constructed PNMs are considered as a digital representation of the rock samples which were based on matching the macroscopic properties of the porous media and used to conduct fluid transport simulations including single and two-phase flow. The PNMs consisted of cubic networks of randomly distributed pores and throats sizes and with various connectivity levels. The networks were optimized such that the upper and lower bounds of the pore sizes are determined using the capillary tube bundle model and the Nelder-Mead method instead of guessing them, which reduces the optimization computational time significantly. An open-source PNM framework was employed to conduct transport and percolation simulations such as invasion percolation and Darcian flow. The PNM model was subsequently used to compute the macroscopic properties; porosity, absolute permeability, specific surface area, breakthrough capillary pressure, and primary drainage curve. The pore networks were optimized to allow for the simulation results of the macroscopic properties to be in excellent agreement with the experimental measurements. This study demonstrates that non-linear programming and optimization methods provide a promising method for pore network modeling when computed tomography imaging may not be readily available.

  17. Peptide backbone circularization enhances antifreeze protein thermostability.

    PubMed

    Stevens, Corey A; Semrau, Joanna; Chiriac, Dragos; Litschko, Morgan; Campbell, Robert L; Langelaan, David N; Smith, Steven P; Davies, Peter L; Allingham, John S

    2017-10-01

    Antifreeze proteins (AFPs) are a class of ice-binding proteins that promote survival of a variety of cold-adapted organisms by decreasing the freezing temperature of bodily fluids. A growing number of biomedical, agricultural, and commercial products, such as organs, foods, and industrial fluids, have benefited from the ability of AFPs to control ice crystal growth and prevent ice recrystallization at subzero temperatures. One limitation of AFP use in these latter contexts is their tendency to denature and irreversibly lose activity at the elevated temperatures of certain industrial processing or large-scale AFP production. Using the small, thermolabile type III AFP as a model system, we demonstrate that AFP thermostability is dramatically enhanced via split intein-mediated N- and C-terminal end ligation. To engineer this circular protein, computational modeling and molecular dynamics simulations were applied to identify an extein sequence that would fill the 20-Å gap separating the free ends of the AFP, yet impose little impact on the structure and entropic properties of its ice-binding surface. The top candidate was then expressed in bacteria, and the circularized protein was isolated from the intein domains by ice-affinity purification. This circularized AFP induced bipyramidal ice crystals during ice growth in the hysteresis gap and retained 40% of this activity even after incubation at 100°C for 30 min. NMR analysis implicated enhanced thermostability or refolding capacity of this protein compared to the noncyclized wild-type AFP. These studies support protein backbone circularization as a means to expand the thermostability and practical applications of AFPs. © 2017 The Protein Society.

  18. Identical repeated backbone of the human genome

    PubMed Central

    2010-01-01

    Background Identical sequences with a minimal length of about 300 base pairs (bp) have been involved in the generation of various meiotic/mitotic genomic rearrangements through non-allelic homologous recombination (NAHR) events. Genomic disorders and structural variation, together with gene remodelling processes have been associated with many of these rearrangements. Based on these observations, we identified and integrated all the 100% identical repeats of at least 300 bp in the NCBI version 36.2 human genome reference assembly into non-overlapping regions, thus defining the Identical Repeated Backbone (IRB) of the reference human genome. Results The IRB sequences are distributed all over the genome in 66,600 regions, which correspond to ~2% of the total NCBI human genome reference assembly. Important structural and functional elements such as common repeats, segmental duplications, and genes are contained in the IRB. About 80% of the IRB bp overlap with known copy-number variants (CNVs). By analyzing the genes embedded in the IRB, we were able to detect some identical genes not previously included in the Ensembl release 50 annotation of human genes. In addition, we found evidence of IRB gene copy-number polymorphisms in raw sequence reads of two diploid sequenced genomes. Conclusions In general, the IRB offers new insight into the complex organization of the identical repeated sequences of the human genome. It provides an accurate map of potential NAHR sites which could be used in targeting the study of novel CNVs, predicting DNA copy-number variation in newly sequenced genomes, and improve genome annotation. PMID:20096123

  19. Radiation safety system (RSS) backbones: Design, engineering, fabrication and installation

    SciTech Connect

    Wilmarth, J.E.; Sturrock, J.C.; Gallegos, F.R.

    1998-12-01

    The Radiation Safety System (RSS) Backbones are part of an electrical/electronic/mechanical system insuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS Backbones control the safety fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low energy beam transport. The Backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the Backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two Linac Backbone segments and experimental area segments form a continuous cable plant over 3,500 feet from beam plugs to the tip on the longest tail. The Backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

  20. Radiation Safety System (RSS) backbones: Design, engineering, fabrication, and installation

    SciTech Connect

    Wilmarth, J.E.; Sturrock, J.C.; Gallegos, F.R.

    1998-12-01

    The Radiation Safety System (RSS) backbones are part of an electrical/electronic/mechanical system ensuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS backbones control the safety-fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low-energy beam transport. The backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two linac backbone segments and the experimental area segments form a continuous cable plant over 3500 feet from the beam plugs to the tip on the longest tail. The backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely. {copyright} {ital 1998 American Institute of Physics.}

  1. Radiation Safety System (RSS) backbones: Design, engineering, fabrication, and installation

    SciTech Connect

    Wilmarth, J. E.; Sturrock, J. C.; Gallegos, F. R.

    1998-12-10

    The Radiation Safety System (RSS) backbones are part of an electrical/electronic/mechanical system ensuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS backbones control the safety-fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low-energy beam transport. The backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two linac backbone segments and the experimental area segments form a continuous cable plant over 3500 feet from the beam plugs to the tip on the longest tail. The backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

  2. Radiation Safety System (RSS) backbones: Design, engineering, fabrication, and installation

    NASA Astrophysics Data System (ADS)

    Wilmarth, J. E.; Sturrock, J. C.; Gallegos, F. R.

    1998-12-01

    The Radiation Safety System (RSS) backbones are part of an electrical/electronic/mechanical system ensuring safe access and exclusion of personnel to areas at the Los Alamos Neutron Science Center (LANSCE) accelerator. The RSS backbones control the safety-fusible beam plugs which terminate transmission of accelerated ion beams in response to predefined conditions. Any beam or access fault of the backbone inputs will cause insertion of the beam plugs in the low-energy beam transport. The backbones serve the function of tying the beam plugs to the access control systems, beam spill monitoring systems and current-level limiting systems. In some ways the backbones may be thought of as a spinal column with beam plugs at the head and nerve centers along the spinal column. The two linac backbone segments and the experimental area segments form a continuous cable plant over 3500 feet from the beam plugs to the tip on the longest tail. The backbones were installed in compliance with current safety standards, such as installation of the two segments in separate conduits or tray. Monitoring for ground-faults and input wiring verification was an added enhancement to the system. The system has the capability to be tested remotely.

  3. A method to combine hydrodynamics and constructive design in the optimization of the runner blades of Kaplan turbines

    NASA Astrophysics Data System (ADS)

    Miclosina, C. O.; Balint, D. I.; Campian, C. V.; Frunzaverde, D.; Ion, I.

    2012-11-01

    This paper deals with the optimization of the axial hydraulic turbines of Kaplan type. The optimization of the runner blade is presented systematically from two points of view: hydrodynamic and constructive. Combining these aspects in order to gain a safer operation when unsteady effects occur in the runner of the turbine is attempted. The design and optimization of the runner blade is performed with QTurbo3D software developed at the Center for Research in Hydraulics, Automation and Thermal Processes (CCHAPT) from "Eftimie Murgu" University of Resita, Romania. QTurbo3D software offers possibilities to design the meridian channel of hydraulic turbines design the blades and optimize the runner blade. 3D modeling and motion analysis of the runner blade operating mechanism are accomplished using SolidWorks software. The purpose of motion study is to obtain forces, torques or stresses in the runner blade operating mechanism, necessary to estimate its lifetime. This paper clearly states the importance of combining the hydrodynamics with the structural design in the optimization procedure of the runner of hydraulic turbines.

  4. A backbone lever-arm effect enhances polymer mechanochemistry.

    PubMed

    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.

  5. A backbone lever-arm effect enhances polymer mechanochemistry

    NASA Astrophysics Data System (ADS)

    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.

  6. Design Optimization and Structural Performance Evaluation of Plate Girder Bridge Constructed Using a Turn-Over Process

    PubMed Central

    Eom, Gi-Ha; Kim, Sung Jae; Lee, Tae-Hee; Kim, Jang-Ho Jay

    2017-01-01

    A recent trend in bridge construction has been the optimization of the cost-to-performance ratio. The most effective way to optimize the cost-to-performance ratio is to maximize the efficiency of the superstructure. Currently, many bridge engineers and designers favor two- or three- girder plate superstructures, due to their cost advantages. However, research on the performance enhancements of the I-type girder in two- or three- girder plate bridges is lacking. One of the most important performance improvement technologies for the I-type girder is the “preflex” method. In the preflex method, the specimen is inverted during the construction process to apply prestressed cambering to the specimen by using self-weight. However, a problem with the preflex construction method is difficulty with inverting the girder/plate system during the concrete curing process. Therefore, a new inverting system called Turn-Over (TO) wheel was proposed. Using TO wheels, wider variations to the I-type girder design can be achieved. Using this TO construction method, various cross sectional designs of girder plate systems can be considered due to its easiness in inverting the girder/plate system. In this study, the location of concrete confinement sections between the steel I-beams and concrete plates was varied in an I-girder cross-sectional design. Design parameters included effective height, flange thickness, flange width, confining concrete section width, etc. From this study, the optimum cross-sectional design of the I-girder/concrete plate system was achieved. Then, a single 20 m TO girder/plate system and two 20 m TO girder bridges were constructed and tested to evaluate their performance. From the test, failure behavior, load carrying capacity, crack pattern, etc., are obtained. The results are discussed in detail in this paper. PMID:28772644

  7. Design Optimization and Structural Performance Evaluation of Plate Girder Bridge Constructed Using a Turn-Over Process.

    PubMed

    Eom, Gi-Ha; Kim, Sung Jae; Lee, Tae-Hee; Kim, Jang-Ho Jay

    2017-03-13

    A recent trend in bridge construction has been the optimization of the cost-to-performance ratio. The most effective way to optimize the cost-to-performance ratio is to maximize the efficiency of the superstructure. Currently, many bridge engineers and designers favor two- or three- girder plate superstructures, due to their cost advantages. However, research on the performance enhancements of the I-type girder in two- or three- girder plate bridges is lacking. One of the most important performance improvement technologies for the I-type girder is the "preflex" method. In the preflex method, the specimen is inverted during the construction process to apply prestressed cambering to the specimen by using self-weight. However, a problem with the preflex construction method is difficulty with inverting the girder/plate system during the concrete curing process. Therefore, a new inverting system called Turn-Over (TO) wheel was proposed. Using TO wheels, wider variations to the I-type girder design can be achieved. Using this TO construction method, various cross sectional designs of girder plate systems can be considered due to its easiness in inverting the girder/plate system. In this study, the location of concrete confinement sections between the steel I-beams and concrete plates was varied in an I-girder cross-sectional design. Design parameters included effective height, flange thickness, flange width, confining concrete section width, etc. From this study, the optimum cross-sectional design of the I-girder/concrete plate system was achieved. Then, a single 20 m TO girder/plate system and two 20 m TO girder bridges were constructed and tested to evaluate their performance. From the test, failure behavior, load carrying capacity, crack pattern, etc., are obtained. The results are discussed in detail in this paper.

  8. Construction and Optimization of a Heterologous Pathway for Protocatechuate Catabolism in Escherichia coli Enables Bioconversion of Model Aromatic Compounds.

    PubMed

    Clarkson, Sonya M; Giannone, Richard J; Kridelbaugh, Donna M; Elkins, James G; Guss, Adam M; Michener, Joshua K

    2017-09-15

    The production of biofuels from lignocellulose yields a substantial lignin by-product stream that currently has few applications. Biological conversion of lignin-derived compounds into chemicals and fuels has the potential to improve the economics of lignocellulose-derived biofuels, but few microbes are able both to catabolize lignin-derived aromatic compounds and to generate valuable products. While Escherichia coli has been engineered to produce a variety of fuels and chemicals, it is incapable of catabolizing most aromatic compounds. Therefore, we engineered E. coli to catabolize protocatechuate, a common intermediate in lignin degradation, as the sole source of carbon and energy via heterologous expression of a nine-gene pathway from Pseudomonas putida KT2440. We next used experimental evolution to select for mutations that increased growth with protocatechuate more than 2-fold. Increasing the strength of a single ribosome binding site in the heterologous pathway was sufficient to recapitulate the increased growth. After optimization of the core pathway, we extended the pathway to enable catabolism of a second model compound, 4-hydroxybenzoate. These engineered strains will be useful platforms to discover, characterize, and optimize pathways for conversions of lignin-derived aromatics.IMPORTANCE Lignin is a challenging substrate for microbial catabolism due to its polymeric and heterogeneous chemical structure. Therefore, engineering microbes for improved catabolism of lignin-derived aromatic compounds will require the assembly of an entire network of catabolic reactions, including pathways from genetically intractable strains. Constructing defined pathways for aromatic compound degradation in a model host would allow rapid identification, characterization, and optimization of novel pathways. We constructed and optimized one such pathway in E. coli to enable catabolism of a model aromatic compound, protocatechuate, and then extended the pathway to a related

  9. Side-chain and backbone ordering in a polypeptide.

    PubMed

    Wei, Yanjie; Nadler, Walter; Hansmann, Ulrich H E

    2006-10-28

    We report results from multicanonical simulations of polyglutamic acid chains of length of ten residues. For this simple polypeptide we observe a decoupling of backbone and side-chain ordering in the folding process. While the details of the two transitions vary between the peptide in gas phase and in an implicit solvent, our results indicate that, independent of the specific surroundings, upon continuously lowering the temperature side-chain ordering occurs only after the backbone topology is completely formed.

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

    PubMed

    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.

  11. Comb-type prepolymers consisting of a polyacrylamide backbone and poly(L-lysine) graft chains for multivalent ligands.

    PubMed

    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.

  12. Some Approaches Towards Constructing Optimally Efficient Multigrid Solvers for the Inviscid Flow Equations

    NASA Technical Reports Server (NTRS)

    Sidilkover, David

    1997-01-01

    Some important advances took place during the last several years in the development of genuinely multidimensional upwind schemes for the compressible Euler equations. In particular, a robust, high-resolution genuinely multidimensional scheme which can be used for any of the flow regimes computations was constructed. This paper summarizes briefly these developments and outlines the fundamental advantages of this approach.

  13. Evaluation of Precast Panels for Airfield Pavement Repair. Phase 1: System Optimization and Test Section Construction

    DTIC Science & Technology

    2013-06-01

    installation for emergency and contingency portland cement concrete (PCC) pavement repairs. Seven precast concrete panels were fabricated for use in an...the investigation were used to develop fabrication and installation procedures and to determine the supplies and equipment required to construct...86  5  Fabrication of Precast Panels

  14. How to Construct More Accurate Student Models: Comparing and Optimizing Knowledge Tracing and Performance Factor Analysis

    ERIC Educational Resources Information Center

    Gong, Yue; Beck, Joseph E.; Heffernan, Neil T.

    2011-01-01

    Student modeling is a fundamental concept applicable to a variety of intelligent tutoring systems (ITS). However, there is not a lot of practical guidance on how to construct and train such models. This paper compares two approaches for student modeling, Knowledge Tracing (KT) and Performance Factors Analysis (PFA), by evaluating their predictive…

  15. How to Construct More Accurate Student Models: Comparing and Optimizing Knowledge Tracing and Performance Factor Analysis

    ERIC Educational Resources Information Center

    Gong, Yue; Beck, Joseph E.; Heffernan, Neil T.

    2011-01-01

    Student modeling is a fundamental concept applicable to a variety of intelligent tutoring systems (ITS). However, there is not a lot of practical guidance on how to construct and train such models. This paper compares two approaches for student modeling, Knowledge Tracing (KT) and Performance Factors Analysis (PFA), by evaluating their predictive…

  16. Weighting and Aggregation in Composite Indicator Construction: A Multiplicative Optimization Approach

    ERIC Educational Resources Information Center

    Zhou, P.; Ang, B. W.; Zhou, D. Q.

    2010-01-01

    Composite indicators (CIs) have increasingly been accepted as a useful tool for benchmarking, performance comparisons, policy analysis and public communication in many different fields. Several recent studies show that as a data aggregation technique in CI construction the weighted product (WP) method has some desirable properties. However, a…

  17. Weighting and Aggregation in Composite Indicator Construction: A Multiplicative Optimization Approach

    ERIC Educational Resources Information Center

    Zhou, P.; Ang, B. W.; Zhou, D. Q.

    2010-01-01

    Composite indicators (CIs) have increasingly been accepted as a useful tool for benchmarking, performance comparisons, policy analysis and public communication in many different fields. Several recent studies show that as a data aggregation technique in CI construction the weighted product (WP) method has some desirable properties. However, a…

  18. Construction of a large synthetic human Fab antibody library on yeast cell surface by optimized yeast mating.

    PubMed

    Baek, Du-San; Kim, Yong-Sung

    2014-03-28

    Yeast surface-displayed antibody libraries provide an efficient and quantitative screening resource for given antigens, but suffer from typically modest library sizes owing to low yeast transformation efficiency. Yeast mating is an attractive method for overcoming the limit of yeast transformation to construct a large, combinatorial antibody library, but the optimal conditions have not been reported. Here, we report a large synthetic human Fab (antigen binding fragment) yeast surface-displayed library generated by stepwise optimization of yeast mating conditions. We first constructed HC (heavy chain) and LC (light chain) libraries, where all of the six CDRs (complementarity-determining regions) of the variable domains were diversified mimicking the human germline antibody repertoires by degenerate codons, onto single frameworks of VH3-23 and Vkappa1-16 germline sequences, in two haploid cells of opposite mating types. Yeast mating conditions were optimized in the order of cell density, media pH, and cell growth phase, yielding a mating efficiency of ~58% between the two haploid cells carrying HC and LC libraries. We constructed two combinatorial Fab libraries with CDR-H3 of 9 or 11 residues in length with colony diversities of more than 10(9) by one round of yeast mating between the two haploid HC and LC libraries, with modest diversity sizes of ~10(7). The synthetic human Fab yeast-displayed libraries exhibited relative amino acid compositions in each position of the six CDRs that were very similar to those of the designed repertoires, suggesting that they are a promising source for human Fab antibody screening.

  19. Integrated and Optimized Energy-Efficient Construction Package for a Community of Production Homes in the Mixed-Humid Climate

    SciTech Connect

    Mallay, D.; Wiehagen, J.; Del Bianco, M.

    2014-10-01

    This research high performance home analyzes how a set of advanced technologies can be integrated into a durable and energy-efficient house in the mixed-humid climate while remaining affordable to homeowners. The technical solutions documented in this report are the cornerstone of the builder's entire business model based on delivering high-performance homes on a production basis as a standard product offering to all price segments of the residential market. Home Innovation Research Labs partnered with production builder Nexus EnergyHomes (CZ 4) and they plan to adopt the successful components of the energy solution package for all 55 homes in the community. The research objective was to optimize the builder's energy solution package based on energy performance and construction costs. All of the major construction features, including envelope upgrades, space conditioning system, hot water system, and solar electric system were analyzed.

  20. Life-management strategies of selection, optimization, and compensation: measurement by self-report and construct validity.

    PubMed

    Freund, Alexandra M; Baltes, Paul B

    2002-04-01

    The authors examined the usefulness of a self-report measure for elective selection, loss-based selection. optimization, and compensation (SOC) as strategies of life management. The expected 4-factor solution was obtained in 2 independent samples (N = 218, 14-87 years; N = 181, 18-89 years) exhibiting high retest stability across 4 weeks (r(tt) = .74-82). As expected, middle-aged adults showed higher endorsement of SOC than younger and older adults. Moreover, SOC showed meaningful convergent and divergent associations to other psychological constructs (e.g., thinking styles, NEO) and evinced positive correlations with measures of well-being which were maintained after other personality and motivational constructs were controlled for. Initial evidence on behavioral associations involving SOC obtained in other studies is summarized.

  1. Blind Optimism: A Cross-Cultural Study of Students' Temporal Constructs and Their Schooling Engagements

    ERIC Educational Resources Information Center

    Rossatto, Cesar Augusto

    2004-01-01

    This article examines students' perceptions and usage of time, their sense of optimism or lack of it, especially related to schooling. Positionality, or perceptions about life and projections of the future, has great impact on students' success in school. How they interpret the past, live in the present and foresee the future is significantly…

  2. Optimal planar flow network designs for tissue engineered constructs with built-in vasculature.

    PubMed

    Janakiraman, Vijayakumar; Mathur, Kamlesh; Baskaran, Harihara

    2007-03-01

    Convective delivery of nutrients is important to enhance mass transport within tissue engineered (TE) products. Depending on the target tissue, an ideal TE product will have an integrated microvasculature that will eliminate mass transport limitations that can occur during product growth in vitro and integration in vivo. A synthetic approach to develop microvasculature involves development of network designs with efficient mass transfer characteristics. In this paper, utilizing a planar bifurcating network as a basis, we develop an approach to design optimal flow networks that have maximum mass transport efficiency for a given pressure drop. We formulated the optimization problem for a TE skin product, incorporating two types of duct flow, rectangular and square, and solved using a generalized reduced gradient algorithm. Under the conditions of this study, we found that rectangular ducts have superior mass transport characteristics than square ducts. Microvascular area per volume values obtained in this work are significantly greater than those reported in the literature. We discuss the effect of network variables such as porosity and generations on the optimal designs. This research forms the engineering basis for the rational development of TE products with built-in microvasculature and will pave the way to design complex flow networks with optimal mass transfer characteristics.

  3. Optimal Planar Flow Network Designs for Tissue Engineered Constructs with Built-in Vasculature

    PubMed Central

    Janakiraman, Vijayakumar; Mathur, Kamlesh; Baskaran, Harihara

    2008-01-01

    Convective delivery of nutrients is important to enhance mass transport within tissue engineered (TE) products. Depending on the target tissue, an ideal TE product will have an integrated microvasculature that will eliminate mass transport limitations that can occur during product growth in vitro and integration in vivo. A synthetic approach to develop microvasculature involves development of network designs with efficient mass transfer characteristics. In this paper, utilizing a planar bifurcating network as a basis, we develop an approach to design optimal flow networks that have maximum mass transport efficiency for a given pressure drop. We formulated the optimization problem for a TE skin product, incorporating two types of duct flow, rectangular and square, and solved using a generalized reduced gradient algorithm. Under the conditions of this study, we found that rectangular ducts have superior mass transport characteristics than square ducts. Microvascular area per volume values obtained in this work are significantly greater than those recorded in the literature. We discuss the effect of network variables such as porosity and generations on the optimal designs. This research forms the engineering basis for the rational development of TE products with built-in microvasculature and will pave the way to design complex flow networks with optimal mass transfer characteristics. PMID:17203399

  4. Padé spectrum decompositions of quantum distribution functions and optimal hierarchical equations of motion construction for quantum open systems

    NASA Astrophysics Data System (ADS)

    Hu, Jie; Luo, Meng; Jiang, Feng; Xu, Rui-Xue; Yan, YiJing

    2011-06-01

    Padé spectrum decomposition is an optimal sum-over-poles expansion scheme of Fermi function and Bose function [J. Hu, R. X. Xu, and Y. J. Yan, J. Chem. Phys. 133, 101106 (2010)], 10.1063/1.3484491. In this work, we report two additional members to this family, from which the best among all sum-over-poles methods could be chosen for different cases of application. Methods are developed for determining these three Padé spectrum decomposition expansions at machine precision via simple algorithms. We exemplify the applications of present development with optimal construction of hierarchical equations-of-motion formulations for nonperturbative quantum dissipation and quantum transport dynamics. Numerical demonstrations are given for two systems. One is the transient transport current to an interacting quantum-dots system, together with the involved high-order co-tunneling dynamics. Another is the non-Markovian dynamics of a spin-boson system.

  5. Optimization of self-study room open problem based on green and low-carbon campus construction

    NASA Astrophysics Data System (ADS)

    Liu, Baoyou

    2017-04-01

    The optimization of self-study room open arrangement problem in colleges and universities is conducive to accelerate the fine management of the campus and promote green and low-carbon campus construction. Firstly, combined with the actual survey data, the self-study area and living area were divided into different blocks, and the electricity consumption in each self-study room and distance between different living and studying areas were normalized. Secondly, the minimum of total satisfaction index and the minimum of the total electricity consumption were selected as the optimization targets respectively. The mathematical models of linear programming were established and resolved by LINGO software. The results showed that the minimum of total satisfaction index was 4055.533 and the total minimum electricity consumption was 137216 W. Finally, some advice had been put forward on how to realize the high efficient administration of the study room.

  6. Padé spectrum decompositions of quantum distribution functions and optimal hierarchical equations of motion construction for quantum open systems.

    PubMed

    Hu, Jie; Luo, Meng; Jiang, Feng; Xu, Rui-Xue; Yan, Yijing

    2011-06-28

    Padé spectrum decomposition is an optimal sum-over-poles expansion scheme of Fermi function and Bose function [J. Hu, R. X. Xu, and Y. J. Yan, J. Chem. Phys. 133, 101106 (2010)]. In this work, we report two additional members to this family, from which the best among all sum-over-poles methods could be chosen for different cases of application. Methods are developed for determining these three Padé spectrum decomposition expansions at machine precision via simple algorithms. We exemplify the applications of present development with optimal construction of hierarchical equations-of-motion formulations for nonperturbative quantum dissipation and quantum transport dynamics. Numerical demonstrations are given for two systems. One is the transient transport current to an interacting quantum-dots system, together with the involved high-order co-tunneling dynamics. Another is the non-Markovian dynamics of a spin-boson system.

  7. Algorithmic co-optimization of genetic constructs and growth conditions: application to 6-ACA, a potential nylon-6 precursor.

    PubMed

    Zhou, Hui; Vonk, Brenda; Roubos, Johannes A; Bovenberg, Roel A L; Voigt, Christopher A

    2015-12-02

    Optimizing bio-production involves strain and process improvements performed as discrete steps. However, environment impacts genotype and a strain that is optimal under one set of conditions may not be under different conditions. We present a methodology to simultaneously vary genetic and process factors, so that both can be guided by design of experiments (DOE). Advances in DNA assembly and gene insulation facilitate this approach by accelerating multi-gene pathway construction and the statistical interpretation of screening data. This is applied to a 6-aminocaproic acid (6-ACA) pathway in Escherichia coli consisting of six heterologous enzymes. A 32-member fraction factorial library is designed that simultaneously perturbs expression and media composition. This is compared to a 64-member full factorial library just varying expression (0.64 Mb of DNA assembly). Statistical analysis of the screening data from these libraries leads to different predictions as to whether the expression of enzymes needs to increase or decrease. Therefore, if genotype and media were varied separately this would lead to a suboptimal combination. This is applied to the design of a strain and media composition that increases 6-ACA from 9 to 48 mg/l in a single optimization step. This work introduces a generalizable platform to co-optimize genetic and non-genetic factors.

  8. Algorithmic co-optimization of genetic constructs and growth conditions: application to 6-ACA, a potential nylon-6 precursor

    PubMed Central

    Zhou, Hui; Vonk, Brenda; Roubos, Johannes A.; Bovenberg, Roel A.L.; Voigt, Christopher A.

    2015-01-01

    Optimizing bio-production involves strain and process improvements performed as discrete steps. However, environment impacts genotype and a strain that is optimal under one set of conditions may not be under different conditions. We present a methodology to simultaneously vary genetic and process factors, so that both can be guided by design of experiments (DOE). Advances in DNA assembly and gene insulation facilitate this approach by accelerating multi-gene pathway construction and the statistical interpretation of screening data. This is applied to a 6-aminocaproic acid (6-ACA) pathway in Escherichia coli consisting of six heterologous enzymes. A 32-member fraction factorial library is designed that simultaneously perturbs expression and media composition. This is compared to a 64-member full factorial library just varying expression (0.64 Mb of DNA assembly). Statistical analysis of the screening data from these libraries leads to different predictions as to whether the expression of enzymes needs to increase or decrease. Therefore, if genotype and media were varied separately this would lead to a suboptimal combination. This is applied to the design of a strain and media composition that increases 6-ACA from 9 to 48 mg/l in a single optimization step. This work introduces a generalizable platform to co-optimize genetic and non-genetic factors. PMID:26519464

  9. A homotopy approach for combined control-structure optimization - Constructive analysis and numerical examples

    NASA Technical Reports Server (NTRS)

    Scheid, R. E.; Milman, M. H.; Salama, M.; Bruno, R.; Gibson, J. S.

    1990-01-01

    This paper outlines the development of methods for the combined control-structure optimization of physical systems encountered in the technology of large space structures. The objectives of the approach taken in this paper is not to produce the 'best' optimized design, but rather to efficiently produce a family of design options so as to assist in early trade studies, typically before hard design constraints are imposed. The philosophy is that these are candidate designs to be passed on for further considerations, and their function is more to guide the development of the system design rather than to represent the ultimate product. A homotopy approach involving multi-objective functions is developed for this purpose. Analytical and numerical examples are also presented.

  10. Meta-Heuristics in Short Scale Construction: Ant Colony Optimization and Genetic Algorithm.

    PubMed

    Schroeders, Ulrich; Wilhelm, Oliver; Olaru, Gabriel

    2016-01-01

    The advent of large-scale assessment, but also the more frequent use of longitudinal and multivariate approaches to measurement in psychological, educational, and sociological research, caused an increased demand for psychometrically sound short scales. Shortening scales economizes on valuable administration time, but might result in inadequate measures because reducing an item set could: a) change the internal structure of the measure, b) result in poorer reliability and measurement precision, c) deliver measures that cannot effectively discriminate between persons on the intended ability spectrum, and d) reduce test-criterion relations. Different approaches to abbreviate measures fare differently with respect to the above-mentioned problems. Therefore, we compare the quality and efficiency of three item selection strategies to derive short scales from an existing long version: a Stepwise COnfirmatory Factor Analytical approach (SCOFA) that maximizes factor loadings and two metaheuristics, specifically an Ant Colony Optimization (ACO) with a tailored user-defined optimization function and a Genetic Algorithm (GA) with an unspecific cost-reduction function. SCOFA compiled short versions were highly reliable, but had poor validity. In contrast, both metaheuristics outperformed SCOFA and produced efficient and psychometrically sound short versions (unidimensional, reliable, sensitive, and valid). We discuss under which circumstances ACO and GA produce equivalent results and provide recommendations for conditions in which it is advisable to use a metaheuristic with an unspecific out-of-the-box optimization function.

  11. Meta-Heuristics in Short Scale Construction: Ant Colony Optimization and Genetic Algorithm

    PubMed Central

    Schroeders, Ulrich; Wilhelm, Oliver; Olaru, Gabriel

    2016-01-01

    The advent of large-scale assessment, but also the more frequent use of longitudinal and multivariate approaches to measurement in psychological, educational, and sociological research, caused an increased demand for psychometrically sound short scales. Shortening scales economizes on valuable administration time, but might result in inadequate measures because reducing an item set could: a) change the internal structure of the measure, b) result in poorer reliability and measurement precision, c) deliver measures that cannot effectively discriminate between persons on the intended ability spectrum, and d) reduce test-criterion relations. Different approaches to abbreviate measures fare differently with respect to the above-mentioned problems. Therefore, we compare the quality and efficiency of three item selection strategies to derive short scales from an existing long version: a Stepwise COnfirmatory Factor Analytical approach (SCOFA) that maximizes factor loadings and two metaheuristics, specifically an Ant Colony Optimization (ACO) with a tailored user-defined optimization function and a Genetic Algorithm (GA) with an unspecific cost-reduction function. SCOFA compiled short versions were highly reliable, but had poor validity. In contrast, both metaheuristics outperformed SCOFA and produced efficient and psychometrically sound short versions (unidimensional, reliable, sensitive, and valid). We discuss under which circumstances ACO and GA produce equivalent results and provide recommendations for conditions in which it is advisable to use a metaheuristic with an unspecific out-of-the-box optimization function. PMID:27893845

  12. Improving Water Quality in Construction Site Runoff: Optimal Mixing Time and Dose for Flocculating Suspended Sediment with Polyacrylamide

    NASA Astrophysics Data System (ADS)

    Zare, A. H.

    2015-12-01

    Sediment, a major water pollutant, can harm ecosystems and water resources. Sediment in construction site runoff can be controlled through flocculation using anionic, linear polyacrylamide (PAM), but there is little information on optimizing these applications. We conducted laboratory experiments to determine the optimal mixing times for varying concentrations of two types of polyacrylamide, APS 705 and FA 920, which are blends of polymers with a range of molecular weights that are anionic and neutral, respectively. These were selected from a variety of PAMs previously screened for flocculation potential. Soil from three active construction sites in the Piedmont region of North Carolina were used in the testing. A mixing speed of 300 revolutions per minute (RPM), the maximum available for the paddle mixer we used, was the most effective at reducing turbidity with PAM. Turbidity was reduced with increased mixing times up to a point, after which little additional benefit was evident. For all three soils tested, turbidity decreased as mixing time reached 1-2 minutes at polymer doses of 1, 5 and 10 mg L-1, with no substantial reduction with further mixing. At a polymer dose of 0.5 mg L-1, however, turbidity tended to increase beyond 5 minutes of mixing time, possibly because excessive shear forces destroyed sparsely linked floc. For both PAMs, 1 mg L-1 and a mixing time of 2-3 min appeared to be sufficient to achieve the most effective turbidity reduction.

  13. Optimization of operating parameters of hybrid vertical down-flow constructed wetland systems for domestic sewerage treatment.

    PubMed

    Huang, Zhujian; Zhang, Xianning; Cui, Lihua; Yu, Guangwei

    2016-09-15

    In this work, three hybrid vertical down-flow constructed wetland (HVDF-CW) systems with different compound substrates were fed with domestic sewage and their pollutants removal performance under different hydraulic loading and step-feeding ratio was investigated. The results showed that the hydraulic loading and step-feeding ratio were two crucial factors determining the removal efficiency of most pollutants, while substrate types only significantly affected the removal of COD and NH4(+)-N. Generally, the lower the hydraulic loading, the better removal efficiency of all contaminants, except for TN. By contrast, the increase of step-feeding ratio would slightly reduce the removal rate of ammonium and TP but obviously promoted the TN removal. Therefore, the optimal operation of this CWs could be achieved with low hydraulic loading combined with 50% of step-feeding ratio when TN removal is the priority, whereas medium or low hydraulic loading without step-feeding would be suitable when TN removal is not taken into consideration. The obtained results in this study can provide us with a guideline for design and optimization of hybrid vertical flow constructed wetland systems to improve the pollutants removal from domestic sewage.

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

    NASA Astrophysics Data System (ADS)

    Krokhotin, Andrey; Niemi, Antti J.; Peng, Xubiao

    2013-05-01

    We construct an energy function that describes the crystallographic structure of sperm whale 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 nonlinear Schrödinger equation. Likewise, ours supports topological solitons as local minimum energy configurations. We describe the 1ABS backbone in terms of topological 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 topological multi-soliton solution to extensive numerical heating and cooling experiments, over a very wide range of temperatures. We concentrate in particular to temperatures above 300 K and below the Θ-point unfolding temperature, which is around 348 K. We confirm that the behavior of the topological multi-soliton is fully consistent with Anfinsen's thermodynamic principle, up to very high temperatures. We observe that the structure responds to an increase of temperature consistently in a very similar manner. This enables us to characterize the onset of thermally induced conformational changes in terms of three distinct backbone ligand gates. One of the gates is made of the helix F and the helix E. The two other gates are chosen similarly, when open they provide a direct access route for a ligand to reach the heme. We find that out of the three gates we investigate, the one which is formed by helices B and G is the most sensitive to thermally induced conformational changes. Our approach provides a novel perspective to the important problem of ligand entry and exit.

  15. a New Methodology for the Construction of Optimized RUNGE-KUTTA-NYSTRÖM Methods

    NASA Astrophysics Data System (ADS)

    Papadopoulos, D. F.; Simos, T. E.

    In this paper, a new Runge-Kutta-Nyström method of fourth algebraic order is developed. The new method has zero phase-lag, zero amplification error and zero first integrals of the previous properties. Numerical results indicate that the new method is very efficient for solving numerically the Schrödinger equation. We note that for the first time in the literature we use the requirement of vanishing the first integrals of phase-lag and amplification error in the construction of efficient methods for the numerical solution of the Schrödinger equation.

  16. Optimization in differentiable manifolds in order to determine the method of construction of prehistoric wall paintings.

    PubMed

    Arabadjis, Dimitris; Rousopoulos, Panayiotis; Papaodysseus, Constantin; Exarhos, Michalis; Panagopoulos, Michail; Papazoglou-Manioudaki, Lena

    2011-11-01

    In this paper, a general methodology is introduced for the determination of potential prototype curves used for the drawing of prehistoric wall paintings. The approach includes 1) preprocessing of the wall-paintings contours to properly partition them, according to their curvature, 2) choice of prototype curves families, 3) analysis and optimization in 4-manifold for a first estimation of the form of these prototypes, 4) clustering of the contour parts and the prototypes to determine a minimal number of potential guides, and 5) further optimization in 4-manifold, applied to each cluster separately, in order to determine the exact functional form of the potential guides, together with the corresponding drawn contour parts. The methodology introduced simultaneously deals with two problems: 1) the arbitrariness in data-points orientation and 2) the determination of one proper form for a prototype curve that optimally fits the corresponding contour data. Arbitrariness in orientation has been dealt with a novel curvature based error, while the proper forms of curve prototypes have been exhaustively determined by embedding curvature deformations of the prototypes into 4-manifolds. Application of this methodology to celebrated wall paintings excavated at Tyrins, Greece, and the Greek island of Thera manifests that it is highly probable that these wall paintings were drawn by means of geometric guides that correspond to linear spirals and hyperbolae. These geometric forms fit the drawings’ lines with an exceptionally low average error, less than 0.39 mm. Hence, the approach suggests the existence of accurate realizations of complicated geometric entities more than 1,000 years before their axiomatic formulation in the Classical Ages.

  17. Mesh optimization for microbial fuel cell cathodes constructed around stainless steel mesh current collectors

    NASA Astrophysics Data System (ADS)

    Zhang, Fang; Merrill, Matthew D.; Tokash, Justin C.; Saito, Tomonori; Cheng, Shaoan; Hickner, Michael A.; Logan, Bruce E.

    Mesh current collectors made of stainless steel (SS) can be integrated into microbial fuel cell (MFC) cathodes constructed of a reactive carbon black and Pt catalyst mixture and a poly(dimethylsiloxane) (PDMS) diffusion layer. It is shown here that the mesh properties of these cathodes can significantly affect performance. Cathodes made from the coarsest mesh (30-mesh) achieved the highest maximum power of 1616 ± 25 mW m -2 (normalized to cathode projected surface area; 47.1 ± 0.7 W m -3 based on liquid volume), while the finest mesh (120-mesh) had the lowest power density (599 ± 57 mW m -2). Electrochemical impedance spectroscopy showed that charge transfer and diffusion resistances decreased with increasing mesh opening size. In MFC tests, the cathode performance was primarily limited by reaction kinetics, and not mass transfer. Oxygen permeability increased with mesh opening size, accounting for the decreased diffusion resistance. At higher current densities, diffusion became a limiting factor, especially for fine mesh with low oxygen transfer coefficients. These results demonstrate the critical nature of the mesh size used for constructing MFC cathodes.

  18. Integrated and Optimized Energy-Efficient Construction Package for a Community of Production Homes in the Mixed-Humid Climate

    SciTech Connect

    Mallay, D.; Wiehagen, J.; Del Bianco, M.

    2014-10-01

    Selection and integration of high performance home features are two sides of the same coin in energy efficient sustainable construction. Many advanced technologies are available for selection, but it is in the integration of these technologies into an affordable set of features that can be used on a production basis by builders, that ensures whole-house performance meets expectations. This research high performance home analyzes how a set of advanced technologies can be integrated into a durable and energy efficient house in the mixed-humid climate while remaining affordable to homeowners. The technical solutions documented in this report are the cornerstone of the builder's entire business model based on delivering high-performance homes on a production basis as a standard product offering to all price segments of the residential market. Home Innovation Research Labs partnered with production builder Nexus EnergyHomes (CZ 4). The builder plans to adopt the successful components of the energy solution package for all 55 homes in the community. The research objective was to optimize the builder's energy solution package based on energy performance and construction costs. All of the major construction features, including envelope upgrades, space conditioning system, hot water system, and solar electric system were analyzed. The information in this report can be used by builders and designers to evaluate options, and the integration of options, for increasing the efficiency of home designs in climate zone 4. The data also provide a point of reference for evaluating estimates of energy savings and costs for specific features.

  19. Structural dependencies of protein backbone 2JNC' couplings.

    PubMed

    Juranić, Nenad; Dannenberg, J J; Cornilescu, Gabriel; Salvador, Pedro; Atanasova, Elena; Ahn, Hee-Chul; Macura, Slobodan; Markley, John L; Prendergast, Franklyn G

    2008-04-01

    Protein folding can introduce strain in peptide covalent geometry, including deviations from planarity that are difficult to detect, especially for a protein in solution. We have found dependencies in protein backbone (2)J(NC') couplings on the planarity and the relative orientation of the sequential peptide planes. These dependences were observed in experimental (2)J(NC') couplings from seven proteins, and also were supported by DFT calculations for a model tripeptide. Findings indicate that elevated (2)J(NC') couplings may serve as reporters of structural strain in the protein backbone imposed by protein folds. Such information, supplemented with the H-bond strengths derived from (h3)J(NC') couplings, provides useful insight into the overall energy profile of the protein backbone in solution.

  20. Structural dependencies of protein backbone 2JNC′ couplings

    PubMed Central

    Juranić, Nenad; Dannenberg, J.J.; Cornilescu, Gabriel; Salvador, Pedro; Atanasova, Elena; Ahn, Hee-Chul; Macura, Slobodan; Markley, John L.; Prendergast, Franklyn G.

    2008-01-01

    Protein folding can introduce strain in peptide covalent geometry, including deviations from planarity that are difficult to detect, especially for a protein in solution. We have found dependencies in protein backbone 2JNC′ couplings on the planarity and the relative orientation of the sequential peptide planes. These dependences were observed in experimental 2JNC′ couplings from seven proteins, and also were supported by DFT calculations for a model tripeptide. Findings indicate that elevated 2JNC′ couplings may serve as reporters of structural strain in the protein backbone imposed by protein folds. Such information, supplemented with the H-bond strengths derived from h3JNC′ couplings, provides useful insight into the overall energy profile of the protein backbone in solution. PMID:18305196

  1. Trauma system: the backbone of disaster preparedness.

    PubMed

    Cryer, H Gill; Hiatt, Jonathan R

    2009-08-01

    To describe the Los Angeles County trauma system response to disasters. Review of trauma system structure and multicasualty events. The Los Angeles County trauma system is made up of 13 level I and II trauma centers with defined catchment areas that serve 10 million people in 88 cites over 4,000 square miles and receive more than 20,000 trauma activations annually. There is an organized disaster plan, which is orchestrated through the Medical Alert Center that coordinates the distribution of casualties from the scene of a multicasualty event, with the most critically injured patients going to level I centers by air, severe injuries to level I and II centers by ground and air and less severe injuries to local community hospitals by ground. The plan has been used in several multicasualty events over the last 25 years, the most recent of which occurred 6 hours after this paper was presented. The system allows for all critically injured patients to be distributed to several trauma centers, so that all can be cared for in a timely fashion without overwhelming any one trauma center and without critically injured patients being taken to nontrauma centers where they cannot receive optimal care. The answer to disaster preparedness in our country is to develop this kind of trauma system in every state. Doing so will improve access of our population to excellent care on a daily basis and will provide a network of trauma centers that can be mobilized to most effectively care for victims of multicasualty events.

  2. Impact of HIV-1 Backbone on Neutralization Sensitivity: Neutralization Profiles of Heterologous Envelope Glycoproteins Expressed in Native Subtype C and CRF01_AE Backbone

    PubMed Central

    Sanders-Buell, Eric; Wesberry, Maggie; Towle, Teresa; Pillis, Devin M.; Molnar, Sebastian; McLinden, Robert; Edmonds, Tara; Hirsch, Ivan; O’Connell, Robert; McCutchan, Francine E.; Montefiori, David C.; Ochsenbauer, Christina; Kappes, John C.; Kim, Jerome H.; Polonis, Victoria R.; Tovanabutra, Sodsai

    2013-01-01

    Standardized assays to assess vaccine and antiviral drug efficacy are critical for the development of protective HIV-1 vaccines and drugs. These immune assays will be advanced by the development of standardized viral stocks, such as HIV-1 infectious molecular clones (IMC), that i) express a reporter gene, ii) are representative of globally diverse subtypes and iii) are engineered to easily exchange envelope (env) genes for expression of sequences of interest. Thus far, a subtype B IMC backbone expressing Renilla luciferase (LucR), and into which the ectodomain of heterologous env coding sequences can be expressed has been successfully developed but as execution of HIV-1 vaccine efficacy trials shifts increasingly to non-subtype B epidemics (Southern African and Southeast Asia), non-subtype B HIV-1 reagents are needed to support vaccine development. Here we describe two IMCs derived from subtypes C and CRF01_AE HIV-1 primary isolates expressing LucR (IMC.LucR) that were engineered to express heterologous gp160 Envs. 18 constructs expressing various subtypes C and CRF01_AE Envs, mostly acute, in subtype-matched and –unmatched HIV backbones were tested for functionality and neutralization sensitivity. Our results suggest a possible effect of non-env HIV-1 genes on the interaction of Env and neutralizing antibodies and highlight the need to generate a library of IMCs representative of the HIV-1 subtype spectrum to be used as standardized neutralization assay reagents for assessing HIV-1 vaccine efficacy. PMID:24312165

  3. Disorder prediction-based construct optimization improves activity and catalytic efficiency of Bacillus naganoensis pullulanase

    PubMed Central

    Wang, Xinye; Nie, Yao; Mu, Xiaoqing; Xu, Yan; Xiao, Rong

    2016-01-01

    Pullulanase is a well-known starch-debranching enzyme. However, the production level of pullulanase is yet low in both wide-type strains and heterologous expression systems. We predicted the disorder propensities of Bacillus naganoensis pullulanase (PUL) using the bioinformatics tool, Disorder Prediction Meta-Server. On the basis of disorder prediction, eight constructs, including PULΔN5, PULΔN22, PULΔN45, PULΔN64, PULΔN78 and PULΔN106 by deleting the first 5, 22, 45, 64, 78 and 106 residues from the N-terminus, and PULΔC9 and PULΔC36 by deleting the last 9 and 36 residues from the C-terminus, were cloned into the recombinant expression vector pET-28a-PelB and auto-induced in Escherichia coli BL21 (DE3) cells. All constructs were evaluated in production level, specific activities and kinetic parameters. Both PULΔN5 and PULΔN106 gave higher production levels of protein than the wide type and displayed increased specific activities. Kinetic studies showed that substrate affinities of the mutants were improved in various degrees and the catalytic efficiency of PULΔN5, PULΔN45, PULΔN78, PULΔN106 and PULΔC9 were enhanced. However, the truncated mutations did not change the advantageous properties of the enzyme involving optimum temperature and pH for further application. Therefore, Disorder prediction-based truncation would be helpful to efficiently improve the enzyme activity and catalytic efficiency. PMID:27091115

  4. Optimal conditions for chlorothalonil and dissolved organic carbon in horizontal subsurface flow constructed wetlands.

    PubMed

    Rìos-Montes, Karina A; Casas-Zapata, Juan C; Briones-Gallardo, Roberto; Peñuela, Gustavo

    2017-01-13

    The most efficient system of horizontal subsurface flow constructed wetlands (HSSFCW) for removing dissolved organic carbon (DOC) in the presence of chlorothalonil pesticide (CLT) present in synthetic domestic wastewater was determined using the macrophyte Phragmites australis. Two concentrations of CLT (85 and 385 μg L(-1)) and one concentration of glucose (20 mg L(-1)) were evaluated in four pilot scale horizontal surface flow constructed wetlands coupled with two sizes of silica gravel, igneous gravel, fine chalky gravel (3.18-6.35 mm), coarse gravel (12.70-25.40 mm) and two water surface heights (20 and 40 cm). For a month, wetlands were acclimated with domestic wastewater. Some groups of bacteria were also identified in the biofilm attached to the gravel. In each treatment periodic samplings were conducted in the influent and effluent. Chlorothalonil was quantified by gas chromatography (GC-ECD m), DOC by an organic carbon analyzer and bacterial groups using conventional microbiology in accordance with Standard Methods. The largest removals of DOC (85.82%-85.31%) were found when using fine gravel (3.18-6.35 mm) and the lower layer of water (20 cm). The bacterial groups quantified in the biofilm were total heterotrophic, revivable heterotrophic, Pseudomonas and total coliforms. The results of this study indicate that fine grain gravel (3.18-6.35 mm) and both water levels (20 to 40 cm) can be used in the removal of organic matter and for the treatment of agricultural effluents contaminated with organo-chloride pesticides like CLT in HSSFCW.

  5. [Construction of optimal combined chemotherapy of anti-tumor drugs based on chronotherapy].

    PubMed

    To, Hideto

    2006-06-01

    Metastatic breast cancer (MBC) is almost always incurable, and the median survival is of the order on 18-24 months. Combination therapy with adriamycin (ADR) and docetaxel (DOC) is more effective against MBC than the previous therapy due to differences between their mechanisms. However, the combination of ADR and DOC induces severe adverse effects, limiting its clinical use in many patients with MBC. The biologic functions of most living organisms are organized along an approximate 24 h time cycle or circadian rhythm. Chronotherapy is defined as the administration of medications using biological rhythms to optimize the therapeutic outcomes and/or control adverse effects. To decrease adverse effects, many antitumor drugs have been particularly studied in humans and animals. The toxicities of ADR and DOC have also been found to depend on dosing-time in animals and humans. This study was to establish the most suitable dosing schedule to relieve severe adverse effects and improve antitumor effects by considering a chronopharmacological approach, dosing-interval and dosing-sequence to the combination chemotherapy of ADR and DOC in mice. In the results, we demonstrate that the dosing schedule based on dosing-sequence, dosing-interval and dosing-time not only significantly reduced leukopenia and toxic death but also significantly increased the inhibition rate of tumor growth compared with the dosing schedule without an interval between each injection, commonly used in clinical practice. These findings suggest that the therapeutic index of combined chemotherapy can be improved by choosing an optimal dosing-schedule (dosing-interval, dosing-sequence and dosing-time).

  6. Choice and optimization of ratio of components to develop fast-mounted thermostable heat-insulating constructions

    NASA Astrophysics Data System (ADS)

    Loginova, N. A.; Grigor'ev, S. V.; Lapin, E. E.; Pogorelov, S. I.; Ryzhenkov, A. V.

    2016-05-01

    Fast-mounted heat-insulating constructions based on foamed synthetic rubbers, polyethylene, and polyurethane are characterized by a thermostability up to 150°C and emit toxic substances when burnt. However, there is a need for heat insulation of surfaces with higher coolant temperatures, such as pipelines, equipment of nuclear and thermal power plants, and heating systems with remote heat sources. One of the most promising types of heat insulation materials for creation of fast-mounted heat insulation constructions is the syntactic foams or thin-film multilayer heat-insulating coatings (TFMHIC), which are created using hollow microspheres and various types of binders. The formation of TFMHIC on the heat-insulating surface is carried out mostly by means of spraying methods that have well proven themselves at coating on flat and cylindrical surfaces of large area, but they turned out ineffective for cylindrical surfaces with a diameter of 300 mm and less, since they are characterized by a large degree of carryover of composite material. This article analyzed the binders and microspheres promising to create the fast-mounted heat-insulating constructions based on TFMHIC with high thermostability. Based on the analysis, a conclusion is drawn that organicsilicon binding and glass microspheres are promising for use in the heat-insulating constructions with thermostability up to 300°C. The results of experimental research are given that point to the possibility of predicting the optimal composition of heat-insulating material characterized by a high degree of filling with microspheres with maintaining the mechanical strength, by means of performing the analysis of rheological characteristics of nonpolymerized liquid compositions of heat-insulation material. The index of tensile strength in bending was the criterion for evaluating the mechanical strength of heat-insulating material. The critical volume concentrations of filling the heat-insulating material with glass

  7. Construction typification as the tool for optimizing the functioning of a robotized manufacturing system

    NASA Astrophysics Data System (ADS)

    Gwiazda, A.; Banas, W.; Sekala, A.; Foit, K.; Hryniewicz, P.; Kost, G.

    2015-11-01

    Process of workcell designing is limited by different constructional requirements. They are related to technological parameters of manufactured element, to specifications of purchased elements of a workcell and to technical characteristics of a workcell scene. This shows the complexity of the design-constructional process itself. The results of such approach are individually designed workcell suitable to the specific location and specific production cycle. Changing this parameters one must rebuild the whole configuration of a workcell. Taking into consideration this it is important to elaborate the base of typical elements of a robot kinematic chain that could be used as the tool for building Virtual modelling of kinematic chains of industrial robots requires several preparatory phase. Firstly, it is important to create a database element, which will be models of industrial robot arms. These models could be described as functional primitives that represent elements between components of the kinematic pairs and structural members of industrial robots. A database with following elements is created: the base kinematic pairs, the base robot structural elements, the base of the robot work scenes. The first of these databases includes kinematic pairs being the key component of the manipulator actuator modules. Accordingly, as mentioned previously, it includes the first stage rotary pair of fifth stage. This type of kinematic pairs was chosen due to the fact that it occurs most frequently in the structures of industrial robots. Second base consists of structural robot elements therefore it allows for the conversion of schematic structures of kinematic chains in the structural elements of the arm of industrial robots. It contains, inter alia, the structural elements such as base, stiff members - simple or angular units. They allow converting recorded schematic three-dimensional elements. Last database is a database of scenes. It includes elements of both simple and complex

  8. Optimization of performance assessment and design characteristics in constructed wetlands for the removal of organic matter.

    PubMed

    Hijosa-Valsero, María; Sidrach-Cardona, Ricardo; Martín-Villacorta, Javier; Bécares, Eloy

    2010-10-01

    Some of the most used constructed wetland (CW) configurations [conventional and modified free-water (FW) flow, surface flow, conventional horizontal subsurface flow (SSF) and soilless systems with floating macrophytes (FM)] were assessed in order to compare their efficiencies for the removal of organic pollutants [COD, filtered COD (FCOD), BOD and total suspended solids (TSS)] from urban sewage under the same climatic and wastewater conditions. The removal performance was calculated using three approaches: effluent concentrations, areal removed loads and mass removal. Results were very different depending on the approach, which indicates that the way to present CW efficiency should be considered carefully. All CW-configurations obtained BOD effluent concentrations below 25 mg L(-1) in summer, with a FW-CW with effluent leaving through the bottom of the tank being the only one maintaining low BOD effluent concentrations even in winter and under high organic loading conditions. In this kind of CW, the presence of plants favoured pollutant removal. SSF-CWs were the most efficient for the removal of COD. FM systems can be as efficient as some gravel bed CWs. Typhaangustifolia worked better than Phragmitesaustralis, at least when the systems were at the beginning of their operation period.

  9. Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks

    PubMed Central

    Navlakha, Saket; Barth, Alison L.; Bar-Joseph, Ziv

    2015-01-01

    Robust, efficient, and low-cost networks are advantageous in both biological and engineered systems. During neural network development in the brain, synapses are massively over-produced and then pruned-back over time. This strategy is not commonly used when designing engineered networks, since adding connections that will soon be removed is considered wasteful. Here, we show that for large distributed routing networks, network function is markedly enhanced by hyper-connectivity followed by aggressive pruning and that the global rate of pruning, a developmental parameter not previously studied by experimentalists, plays a critical role in optimizing network structure. We first used high-throughput image analysis techniques to quantify the rate of pruning in the mammalian neocortex across a broad developmental time window and found that the rate is decreasing over time. Based on these results, we analyzed a model of computational routing networks and show using both theoretical analysis and simulations that decreasing rates lead to more robust and efficient networks compared to other rates. We also present an application of this strategy to improve the distributed design of airline networks. Thus, inspiration from neural network formation suggests effective ways to design distributed networks across several domains. PMID:26217933

  10. How to construct the optimal Bayesian measurement in quantum statistical decision theory

    NASA Astrophysics Data System (ADS)

    Tanaka, Fuyuhiko

    Recently, much more attention has been paid to the study aiming at the application of fundamental properties in quantum theory to information processing and technology. In particular, modern statistical methods have been recognized in quantum state tomography (QST), where we have to estimate a density matrix (positive semidefinite matrix of trace one) representing a quantum system from finite data collected in a certain experiment. When the dimension of the density matrix gets large (from a few hundred to millions), it gets a nontrivial problem. While a specific measurement is often given and fixed in QST, we are also able to choose a measurement itself according to the purpose of QST by using qunatum statistical decision theory. Here we propose a practical method to find the best projective measurement in the Bayesian sense. We assume that a prior distribution (e.g., the uniform distribution) and a convex loss function (e.g., the squared error) are given. In many quantum experiments, these assumptions are not so restrictive. We show that the best projective measurement and the best statistical inference based on the measurement outcome exist and that they are obtained explicitly by using the Monte Carlo optimization. The Grant-in-Aid for Scientific Research (B) (No. 26280005).

  11. Evolution of Robust Network Topologies: Emergence of Central Backbones

    NASA Astrophysics Data System (ADS)

    Peixoto, Tiago P.; Bornholdt, Stefan

    2012-09-01

    We model the robustness against random failure or an intentional attack of networks with an arbitrary large-scale structure. We construct a block-based model which incorporates—in a general fashion—both connectivity and interdependence links, as well as arbitrary degree distributions and block correlations. By optimizing the percolation properties of this general class of networks, we identify a simple core-periphery structure as the topology most robust against random failure. In such networks, a distinct and small “core” of nodes with higher degree is responsible for most of the connectivity, functioning as a central “backbone” of the system. This centralized topology remains the optimal structure when other constraints are imposed, such as a given fraction of interdependence links and fixed degree distributions. This distinguishes simple centralized topologies as the most likely to emerge, when robustness against failure is the dominant evolutionary force.

  12. Backbone fractal dimension and fractal hybrid orbital of protein structure

    NASA Astrophysics Data System (ADS)

    Peng, Xin; Qi, Wei; Wang, Mengfan; Su, Rongxin; He, Zhimin

    2013-12-01

    Fractal geometry analysis provides a useful and desirable tool to characterize the configuration and structure of proteins. In this paper we examined the fractal properties of 750 folded proteins from four different structural classes, namely (1) the α-class (dominated by α-helices), (2) the β-class (dominated by β-pleated sheets), (3) the (α/β)-class (α-helices and β-sheets alternately mixed) and (4) the (α + β)-class (α-helices and β-sheets largely segregated) by using two fractal dimension methods, i.e. "the local fractal dimension" and "the backbone fractal dimension" (a new and useful quantitative parameter). The results showed that the protein molecules exhibit a fractal behavior in the range of 1 ⩽ N ⩽ 15 (N is the number of the interval between two adjacent amino acid residues), and the value of backbone fractal dimension is distinctly greater than that of local fractal dimension for the same protein. The average value of two fractal dimensions decreased in order of α > α/β > α + β > β. Moreover, the mathematical formula for the hybrid orbital model of protein based on the concept of backbone fractal dimension is in good coincidence with that of the similarity dimension. So it is a very accurate and simple method to analyze the hybrid orbital model of protein by using the backbone fractal dimension.

  13. The Graphical Representation of the Digital Astronaut Physiology Backbone

    NASA Technical Reports Server (NTRS)

    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.

  14. Impact of template backbone heterogeneity on RNA polymerase II transcription

    PubMed Central

    Xu, Liang; Wang, Wei; Zhang, Lu; Chong, Jenny; Huang, Xuhui; Wang, Dong

    2015-01-01

    Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3′-5′ or 2′-5′ orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary ‘imperfect’ DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA. PMID:25662224

  15. Cooperative UAV-Based Communications Backbone for Sensor Networks

    SciTech Connect

    Roberts, R S

    2001-10-07

    The objective of this project is to investigate the use of unmanned air vehicles (UAVs) as mobile, adaptive communications backbones for ground-based sensor networks. In this type of network, the UAVs provide communication connectivity to sensors that cannot communicate with each other because of terrain, distance, or other geographical constraints. In these situations, UAVs provide a vertical communication path for the sensors, thereby mitigating geographic obstacles often imposed on networks. With the proper use of UAVs, connectivity to a widely disbursed sensor network in rugged terrain is readily achieved. Our investigation has focused on networks where multiple cooperating UAVs are used to form a network backbone. The advantage of using multiple UAVs to form the network backbone is parallelization of sensor connectivity. Many widely spaced or isolated sensors can be connected to the network at once using this approach. In these networks, the UAVs logically partition the sensor network into sub-networks (subnets), with one UAV assigned per subnet. Partitioning the network into subnets allows the UAVs to service sensors in parallel thereby decreasing the sensor-to-network connectivity. A UAV services sensors in its subnet by flying a route (path) through the subnet, uplinking data collected by the sensors, and forwarding the data to a ground station. An additional advantage of using multiple UAVs in the network is that they provide redundancy in the communications backbone, so that the failure of a single UAV does not necessarily imply the loss of the network.

  16. Design, construction, and optimization of a novel, modular, and scalable incubation chamber for continuous viral inactivation.

    PubMed

    Orozco, Raquel; Godfrey, Scott; Coffman, Jon; Amarikwa, Linus; Parker, Stephanie; Hernandez, Lindsay; Wachuku, Chinenye; Mai, Ben; Song, Brian; Hoskatti, Shashidhar; Asong, Jinkeng; Shamlou, Parviz; Bardliving, Cameron; Fiadeiro, Marcus

    2017-02-11

    We designed, built or 3D printed, and screened tubular reactors that minimize axial dispersion to serve as incubation chambers for continuous virus inactivation of biological products. Empirical residence time distribution data were used to derive each tubular design's volume equivalent to a theoretical plate (VETP) values at a various process flow rates. One design, the Jig in a Box (JIB), yielded the lowest VETP, indicating optimal radial mixing and minimal axial dispersion. A minimum residence time (MRT) approach was employed, where the MRT is the minimum time the product spends in the tubular reactor. This incubation time is typically 60 minutes in a batch process. We provide recommendations for combinations of flow rates and device dimensions for operation of the JIB connected in series that will meet a 60-min MRT. The results show that under a wide range of flow rates and corresponding volumes, it takes 75 ± 3 min for 99% of the product to exit the reactor while meeting the 60-min MRT criterion and fulfilling the constraint of keeping a differential pressure drop under 5 psi. Under these conditions, the VETP increases slightly from 3 to 5 mL though the number of theoretical plates stays constant at about 1326 ± 88. We also demonstrated that the final design volume was only 6% ± 1% larger than the ideal plug flow volume. Using such a device would enable continuous viral inactivation in a truly continuous process or in the effluent of a batch chromatography column. Viral inactivation studies would be required to validate such a design. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 2017.

  17. Construction and optimization of an efficient amplification method of a random ssDNA library by asymmetric emulsion PCR.

    PubMed

    Shao, Keke; Shi, Xinhui; Zhu, Xiangjun; Cui, Leilei; Shao, Qixiang; Ma, Da

    2015-12-16

    Construction of a random ssDNA sublibrary is an important step of the aptamer screening process. The available construction methods include asymmetric PCR, biotin-streptavidin separation, and lambda exonuclease digestions, in which PCR amplification is a key step. The main drawback of PCR amplification is overamplification increasing nonspecific hybridization among different products and by-products, which may cause the loss of potential high-quality aptamers, inefficient screening, and even screening failure. Cycle number optimization in PCR amplification is the main way to avoid overamplification but does not fundamentally eliminate the nonspecific hybridization, and the decreased cycle number may lead to insufficient product amounts. Here, we developed a new method, "asymmetric emulsion PCR," which could overcome the shortcomings of conventional PCR. In asymmetric emulsion PCR, different templates were separated by emulsion particles, allowing single-molecule PCR, in which each template was separately amplified, and the nonspecific hybridization was avoided. Overamplification or formation of by-products was not observed. The method is so simple that direct amplification of 40 or more cycles can provide a high-quality ssDNA library. Therefore, the asymmetric emulsion PCR would improve the screening efficiency of systematic evolution of ligands by exponential enrichment.

  18. Construction of a directed hammerhead ribozyme library: towards the identification of optimal target sites for antisense-mediated gene inhibition.

    PubMed Central

    Pierce, M L; Ruffner, D E

    1998-01-01

    Antisense-mediated gene inhibition uses short complementary DNA or RNA oligonucleotides to block expression of any mRNA of interest. A key parameter in the success or failure of an antisense therapy is the identification of a suitable target site on the chosen mRNA. Ultimately, the accessibility of the target to the antisense agent determines target suitability. Since accessibility is a function of many complex factors, it is currently beyond our ability to predict. Consequently, identification of the most effective target(s) requires examination of every site. Towards this goal, we describe a method to construct directed ribozyme libraries against any chosen mRNA. The library contains nearly equal amounts of ribozymes targeting every site on the chosen transcript and the library only contains ribozymes capable of binding to that transcript. Expression of the ribozyme library in cultured cells should allow identification of optimal target sites under natural conditions, subject to the complexities of a fully functional cell. Optimal target sites identified in this manner should be the most effective sites for therapeutic intervention. PMID:9801305

  19. Construction of plasmids with tunable copy numbers in Saccharomyces cerevisiae and their applications in pathway optimization and multiplex genome integration.

    PubMed

    Lian, Jiazhang; Jin, Run; Zhao, Huimin

    2016-11-01

    The CEN/ARS-based low-copy plasmids and 2 μ-based high-copy plasmids have been broadly used for both fundamental studies and practical applications in Saccharomyces cerevisiae. However, the relative low copy numbers and narrow dynamic range limit their applications in many cases. In this study, the expression level of the selection marker proteins was engineered to increase the plasmid copy numbers. A series of plasmids with step-wise increased copy numbers were constructed. The copy number of the plasmids with engineered dominant markers (5-100 copies per cell) showed a positive correlation with the concentration of antibiotics supplemented to the growth media. Based on this finding, we developed a simple yet highly efficient strategy, named Pathway Optimization by Tuning Antibiotic Concentrations (POTAC) to rapidly balance the flux of multi-gene pathways at the DNA level in S. cerevisiae. As proof of concept, POTAC was used to optimize the lycopene and n-butanol biosynthetic pathways, increasing the production of lycopene and n-butanol by 10- and 100-fold, respectively. Additionally, multiplex genome integration with controllable copy numbers was attempted by combining the engineered dominant markers with the CRISPR/Cas9 system. Biotechnol. Bioeng. 2016;113: 2462-2473. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Optimization of Maternal Magnesium Sulfate Administration for Fetal Neuroprotection: Application of a Prospectively Constructed Pharmacokinetic Model to the BEAM Cohort.

    PubMed

    Brookfield, Kathleen F; Elkomy, Mohammed; Su, Felice; Drover, David R; Carvalho, Brendan

    2017-06-06

    The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy. Among 1905 women who met inclusion criteria, the incidence of cerebral palsy in the cohort was 3.6% for women who had received magnesium sulfate and 6.4% for controls. The simulated maternal serum concentration at delivery associated with the lowest probability of delivering an infant with cerebral palsy was 4.1 mg/dL (95%CI 3.7 to 4.4). Our population-based estimates of magnesium disposition suggest that to optimize fetal neuroprotection and prevent cerebral palsy, magnesium sulfate administration should target a maternal serum magnesium level between 3.7 and 4.4 mg/dL at delivery. © 2017, The American College of Clinical Pharmacology.

  1. Backbone flexibility of CDR3 and immune recognition of antigens.

    PubMed

    Haidar, Jaafar N; Zhu, Wei; Lypowy, Jacqueline; Pierce, Brian G; Bari, Amtul; Persaud, Kris; Luna, Xenia; Snavely, Marshall; Ludwig, Dale; Weng, Zhiping

    2014-04-03

    Conformational entropy is an important component of protein-protein interactions; however, there is no reliable method for computing this parameter. We have developed a statistical measure of residual backbone entropy in folded proteins by using the ϕ-ψ distributions of the 20 amino acids in common secondary structures. The backbone entropy patterns of amino acids within helix, sheet or coil form clusters that recapitulate the branching and hydrogen bonding properties of the side chains in the secondary structure type. The same types of residues in coil and sheet have identical backbone entropies, while helix residues have much smaller conformational entropies. We estimated the backbone entropy change for immunoglobulin complementarity-determining regions (CDRs) from the crystal structures of 34 low-affinity T-cell receptors and 40 high-affinity Fabs as a result of the formation of protein complexes. Surprisingly, we discovered that the computed backbone entropy loss of only the CDR3, but not all CDRs, correlated significantly with the kinetic and affinity constants of the 74 selected complexes. Consequently, we propose a simple algorithm to introduce proline mutations that restrict the conformational flexibility of CDRs and enhance the kinetics and affinity of immunoglobulin interactions. Combining the proline mutations with rationally designed mutants from a previous study led to 2400-fold increase in the affinity of the A6 T-cell receptor for Tax-HLAA2. However, this mutational scheme failed to induce significant binding changes in the already-high-affinity C225-Fab/huEGFR interface. Our results will serve as a roadmap to formulate more effective target functions to design immune complexes with improved biological functions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Constructing optimal ensemble projections for predictive environmental modelling in Northern Eurasia

    NASA Astrophysics Data System (ADS)

    Anisimov, Oleg; Kokorev, Vasily

    2013-04-01

    Large uncertainties in climate impact modelling are associated with the forcing climate data. This study is targeted at the evaluation of the quality of GCM-based climatic projections in the specific context of predictive environmental modelling in Northern Eurasia. To accomplish this task, we used the output from 36 CMIP5 GCMs from the IPCC AR-5 data base for the control period 1975-2005 and calculated several climatic characteristics and indexes that are most often used in the impact models, i.e. the summer warmth index, duration of the vegetation growth period, precipitation sums, dryness index, thawing degree-day sums, and the annual temperature amplitude. We used data from 744 weather stations in Russia and neighbouring countries to analyze the spatial patterns of modern climatic change and to delineate 17 large regions with coherent temperature changes in the past few decades. GSM results and observational data were averaged over the coherent regions and compared with each other. Ultimately, we evaluated the skills of individual models, ranked them in the context of regional impact modelling and identified top-end GCMs that "better than average" reproduce modern regional changes of the selected meteorological parameters and climatic indexes. Selected top-end GCMs were used to compose several ensembles, each combining results from the different number of models. Ensembles were ranked using the same algorithm and outliers eliminated. We then used data from top-end ensembles for the 2000-2100 period to construct the climatic projections that are likely to be "better than average" in predicting climatic parameters that govern the state of environment in Northern Eurasia. The ultimate conclusions of our study are the following. • High-end GCMs that demonstrate excellent skills in conventional atmospheric model intercomparison experiments are not necessarily the best in replicating climatic characteristics that govern the state of environment in Northern Eurasia

  3. SV-AUTOPILOT: optimized, automated construction of structural variation discovery and benchmarking pipelines.

    PubMed

    Leung, Wai Yi; Marschall, Tobias; Paudel, Yogesh; Falquet, Laurent; Mei, Hailiang; Schönhuth, Alexander; Maoz Moss, Tiffanie Yael

    2015-03-25

    Many tools exist to predict structural variants (SVs), utilizing a variety of algorithms. However, they have largely been developed and tested on human germline or somatic (e.g. cancer) variation. It seems appropriate to exploit this wealth of technology available for humans also for other species. Objectives of this work included: a) Creating an automated, standardized pipeline for SV prediction. b) Identifying the best tool(s) for SV prediction through benchmarking. c) Providing a statistically sound method for merging SV calls. The SV-AUTOPILOT meta-tool platform is an automated pipeline for standardization of SV prediction and SV tool development in paired-end next-generation sequencing (NGS) analysis. SV-AUTOPILOT comes in the form of a virtual machine, which includes all datasets, tools and algorithms presented here. The virtual machine easily allows one to add, replace and update genomes, SV callers and post-processing routines and therefore provides an easy, out-of-the-box environment for complex SV discovery tasks. SV-AUTOPILOT was used to make a direct comparison between 7 popular SV tools on the Arabidopsis thaliana genome using the Landsberg (Ler) ecotype as a standardized dataset. Recall and precision measurements suggest that Pindel and Clever were the most adaptable to this dataset across all size ranges while Delly performed well for SVs larger than 250 nucleotides. A novel, statistically-sound merging process, which can control the false discovery rate, reduced the false positive rate on the Arabidopsis benchmark dataset used here by >60%. SV-AUTOPILOT provides a meta-tool platform for future SV tool development and the benchmarking of tools on other genomes using a standardized pipeline. It optimizes detection of SVs in non-human genomes using statistically robust merging. The benchmarking in this study has demonstrated the power of 7 different SV tools for analyzing different size classes and types of structural variants. The optional merge

  4. Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab.

    PubMed

    Muthumani, Kar; Flingai, Seleeke; Wise, Megan; Tingey, Colleen; Ugen, Kenneth E; Weiner, David B

    2013-10-01

    Monoclonal antibody preparations have demonstrated considerable clinical utility in the treatment of specific malignancies, as well as inflammatory and infectious diseases. Antibodies are conventionally delivered by passive administration, typically requiring costly large-scale laboratory development and production. Additional limitations include the necessity for repeat administrations, and the length of in vivo potency. Therefore, the development of methods to generate therapeutic antibodies and antibody like molecules in vivo, distinct from an active antigen-based immunization strategy, would have considerable clinical utility. In fact, adeno-associated viral (AAV) vector mediated delivery of immunoglobulin genes with subsequent generation of functional antibodies has recently been developed. As well, anon-viral vector mediated nucleic acid based delivery technology could permit the generation of therapeutic/prophylactic antibodies in vivo, obviating potential safety issues associated with viral vector based gene delivery. This delivery strategy has limitations as well, mainly due to very low in vivo production and expression of protein from the delivered gene. In the study reported here we have constructed an "enhanced and optimized" DNA plasmid technology to generate immunoglobulin heavy and light chains (i.e., Fab fragments) from an established neutralizing anti-HIV envelope glycoprotein monoclonal antibody (VRC01). This "enhanced" DNA (E-DNA) plasmid technology includes codon/RNA optimization, leader sequence utilization, as well as targeted potentiation of delivery and expression of the Fab immunoglobulin genes through use of "adaptive" in vivo electroporation. The results demonstrate that delivery by this method of a single administration of the optimized Fab expressing constructs resulted in generation of Fab molecules in mouse sera possessing high antigen specific binding and HIV neutralization activity for at least 7 d after injection, against diverse

  5. A Pipeline for Constructing Optimized N-Body Models of Interacting Galaxies

    NASA Astrophysics Data System (ADS)

    Harvey, Allen S., Jr.

    friction and determines initial conditions to use for evolution of in an N-Body simulation. These initial conditions are used to create, scale, and reposition unit galaxy models for use in an N-Body simulation of the users choice, and creates the necessary input deck for it. For each simulation, a scoring metric is calculated to determine the quality of fit that the N-Body simulation has in regards to the original SPAM simulation. The scores from each simulation are used in a second order Newton-Raphson optimization step to iterate on values of dynamical friction. This dissertation demonstrates the use of the pipeline to model 54 pairs of interacting galaxies. These models in most cases greatly improve upon the accuracy of faster running models in identifying a set of parameters to define each interacting galaxy with relatively small computational investment. The resulting parameters can be used by higher resolution simulations with more complete sets of physics, such as gas dynamics and star formation, to more readily compare to observational data.

  6. Optimism

    PubMed Central

    Carver, Charles S.; Scheier, Michael F.; Segerstrom, Suzanne C.

    2010-01-01

    Optimism is an individual difference variable that reflects the extent to which people hold generalized favorable expectancies for their future. Higher levels of optimism have been related prospectively to better subjective well-being in times of adversity or difficulty (i.e., controlling for previous well-being). Consistent with such findings, optimism has been linked to higher levels of engagement coping and lower levels of avoidance, or disengagement, coping. There is evidence that optimism is associated with taking proactive steps to protect one's health, whereas pessimism is associated with health-damaging behaviors. Consistent with such findings, optimism is also related to indicators of better physical health. The energetic, task-focused approach that optimists take to goals also relates to benefits in the socioeconomic world. Some evidence suggests that optimism relates to more persistence in educational efforts and to higher later income. Optimists also appear to fare better than pessimists in relationships. Although there are instances in which optimism fails to convey an advantage, and instances in which it may convey a disadvantage, those instances are relatively rare. In sum, the behavioral patterns of optimists appear to provide models of living for others to learn from. PMID:20170998

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

    PubMed

    Smith, Colin A; Kortemme, Tanja

    2011-01-01

    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.

  8. Identification of systems containing nonlinear stiffnesses using backbone curves

    NASA Astrophysics Data System (ADS)

    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.

  9. Removal of antibiotics and antibiotic resistance genes from domestic sewage by constructed wetlands: Optimization of wetland substrates and hydraulic loading.

    PubMed

    Chen, Jun; Wei, Xiao-Dong; Liu, You-Sheng; Ying, Guang-Guo; Liu, Shuang-Shuang; He, Liang-Ying; Su, Hao-Chang; Hu, Li-Xin; Chen, Fan-Rong; Yang, Yong-Qiang

    2016-09-15

    This study aimed to assess removal potential of antibiotics and antibiotic resistance genes (ARGs) in raw domestic wastewater by various mesocosm-scale horizontal subsurface-flow constructed wetlands (CWs) planted Cyperus alternifolius L. with different design parameters. Twelve CWs with three hydraulic loading rates (HLR 10, 20 and 30cm/day) and four substrates (oyster shell, zeolite, medical stone and ceramic) were set up in order to select the best optimized wetland. The result showed that 7 target antibiotics compounds including erythromycin-H2O, lincomycin, monensin, ofloxacin, sulfamerazine, sulfamethazine and novobiocin were detected, and all selected 18 genes (three sulfonamide resistance genes (sul1, sul2 and sul3), four tetracycline resistance genes (tetG, tetM, tetO and tetX), two macrolide resistance genes (ermB and ermC), three quinolone resistance genes (qnrB, qnrD and qnrS) and four chloramphenicol resistance genes (cmlA, fexA, fexB and floR)) and two integrase genes (int1 and int2) were positively detected in the domestic wastewaters. The aqueous removal rates of the total antibiotics ranged from17.9 to 98.5%, while those for the total ARGs varied between 50.0 and 85.8% by the mesocosm-scale CWs. After considering their aqueous removal rates in combination with their mass removals, the CW with zeolite as the substrate and HLR of 20cm/day was selected as the best choice. Combined chemical and biological analyses indicate that both microbial degradation and physical sorption processes were responsible for the fate of antibiotics and ARGs in the wetlands. The findings from this study suggest constructed wetlands could be a promising technology for the removal of emerging contaminants such as antibiotics and ARGs in domestic wastewater. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Hydrophobic core packing and backbone flexibility in coiled coils

    NASA Astrophysics Data System (ADS)

    Plecs, Joseph John

    1999-11-01

    An understanding of the structure and function of protein molecules requires an understanding of how their hydrophobic cores are assembled, including how the peptide backbone can adjust to accommodate different packing arrangements. Using coiled-coil molecules as a model of protein structures, we studied several cases in which the arrangement of packing groups in the hydrophobic core controls the structure of a folded molecule. First, we consider an example of a prosthetic packing group, where the addition of a hydrophobic ligand permits a new packing arrangement that incorporates the ligand, leading to a new overall structure. Second, the crystal structures of two peptides designed to adopt a novel fold, the right-handed coiled coils, reveal how a small change in core packing can discriminate between two different folds. And last, the design of heterodimers based on core-packing complementarity establishes that core packing can convey specificity of association between different molecules, as well as determining the molecular structure. The heterodimer designs also demonstrate the importance of a combination of backbone freedom and restriction in predicting the energetics of folded molecules. In this case, a parametrized coiled- coil backbone with appropriate parameters and restrictions was required to predict stabilities. We conclude that core packing can exert a great deal of control over the structure of proteins, and that many of its effects can be accurately predicted by modeling the molecular interactions in the context of a flexible overall structure.

  11. Geometry motivated alternative view on local protein backbone structures.

    PubMed

    Zacharias, Jan; Knapp, Ernst Walter

    2013-11-01

    We present an alternative to the classical Ramachandran plot (R-plot) to display local protein backbone structure. Instead of the (φ, ψ)-backbone angles relating to the chemical architecture of polypeptides generic helical parameters are used. These are the rotation or twist angle ϑ and the helical rise parameter d. Plots with these parameters provide a different view on the nature of local protein backbone structures. It allows to display the local structures in polar (d, ϑ)-coordinates, which is not possible for an R-plot, where structural regimes connected by periodicity appear disconnected. But there are other advantages, like a clear discrimination of the handedness of a local structure, a larger spread of the different local structure domains--the latter can yield a better separation of different local secondary structure motives--and many more. Compared to the R-plot we are not aware of any major disadvantage to classify local polypeptide structures with the (d, ϑ)-plot, except that it requires some elementary computations. To facilitate usage of the new (d, ϑ)-plot for protein structures we provide a web application (http://agknapp.chemie.fu-berlin.de/secsass), which shows the (d, ϑ)-plot side-by-side with the R-plot.

  12. Side-chain and backbone ordering in homopolymers.

    PubMed

    Wei, Yanjie; Nadler, Walter; Hansmann, Ulrich H E

    2007-04-26

    In order to study the relation between backbone and side-chain ordering in proteins, we have performed multicanonical simulations of deka-peptide chains with various side groups. Glu(10), Gln(10), Asp(10), Asn(10), and Lys(10) were selected to cover a wide variety of possible interactions between the side chains of the monomers. All homopolymers undergo helix-coil transitions. We found that peptides with long side chains that are capable of hydrogen bonding, i.e., Glu(10), and Gln(10), exhibit a second transition at lower temperatures connected with side-chain ordering. This occurs in the gas phase as well as in solvent, although the character of the side-chain structure is different in each case. However, in polymers with short side chains capable of hydrogen bonding, i.e., Asp(10) and Asn(10), side-chain ordering takes place over a wide temperature range and exhibits no phase transition-like character. Moreover, non-backbone hydrogen bonds show enhanced formation and fluctuations already at the helix-coil transition temperature, indicating competition between side-chain and backbone hydrogen bond formation. Again, these results are qualitatively independent of the environment. Side-chain ordering in Lys(10), whose side groups are long and polar, also takes place over a wide temperature range and exhibits no phase transition-like character in both environments. Reasons for the observed chain length threshold and consequences from these results for protein folding are discussed.

  13. Optimal Use of Data in Parallel Tempering Simulations for the Construction of Discrete-State Markov Models of Biomolecular Dynamics

    SciTech Connect

    Prinz, Jan-Hendrik; Chondera, John D; Pande, Vijay S; Swope, William C; Smith, Jeremy C; Noe, F

    2011-01-01

    Parallel tempering (PT) molecular dynamics simulations have been extensively investigated as a means of efficient sampling of the configurations of biomolecular systems. Recent work has demonstrated how the short physical trajectories generated in PT simulations of biomolecules can be used to construct the Markov models describing biomolecular dynamics at each simulated temperature. While this approach describes the temperature-dependent kinetics, it does not make optimal use of all available PT data, instead estimating the rates at a given temperature using only data from that temperature. This can be problematic, as some relevant transitions or states may not be sufficiently sampled at the temperature of interest, but might be readily sampled at nearby temperatures. Further, the comparison of temperature-dependent properties can suffer from the false assumption that data collected from different temperatures are uncorrelated. We propose here a strategy in which, by a simple modification of the PT protocol, the harvested trajectories can be reweighted, permitting data from all temperatures to contribute to the estimated kinetic model. The method reduces the statistical uncertainty in the kinetic model relative to the single temperature approach and provides estimates of transition probabilities even for transitions not observed at the temperature of interest. Further, the method allows the kinetics to be estimated at temperatures other than those at which simulations were run. We illustrate this method by applying it to the generation of a Markov model of the conformational dynamics of the solvated terminally blocked alanine peptide.

  14. Ant mound as an optimal shape in constructal design: solar irradiation and circadian brood/fungi-warming sorties.

    PubMed

    Kasimova, R G; Tishin, D; Obnosov, Yu V; Dlussky, G M; Baksht, F B; Kacimov, A R

    2014-08-21

    Sizes, shapes, ambient and in-dome temperature, incoming solar radiation and illumination are measured on a Formica rufa anthill in a mixed forest of the Volga-Kama National Reserve in Russia. These data are used in a conceptual model of insolation of a right conical surface by direct-beam, descending atmospheric and ascending ground-reflected radiation. Unlike a standard calculation of the energy flux intercepted by a solar panel, the anthill is a 3-D structure and double-integration of the cosine of the angle between the solar beams and normal to the surface is carried out for a "cozy trapezium", where the insects expose themselves and the brood to "morning" sunbathing pulses (Jones and Oldroyd, 2007). Several constructal design problems are formulated with the criteria involving either a pure solar energy gained by the dome or this energy, as a mathematical criterion, penalized by additive terms of mechanical energy (potential and friction) lost by the ants in their diurnal forays from a "heartland" of the nest to the sun-basking zone on the surface. The unique and global optima are analytically found, with the optimal tilt angle of the cone explicitly expressed through the zenith angle of the Sun and meteorological constants for the isotropic sky model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A Conceptual Framework for Procurement Decision Making Model to Optimize Supplier Selection: The Case of Malaysian Construction Industry

    NASA Astrophysics Data System (ADS)

    Chuan, Ngam Min; Thiruchelvam, Sivadass; Nasharuddin Mustapha, Kamal; Che Muda, Zakaria; Mat Husin, Norhayati; Yong, Lee Choon; Ghazali, Azrul; Ezanee Rusli, Mohd; Itam, Zarina Binti; Beddu, Salmia; Liyana Mohd Kamal, Nur

    2016-03-01

    This paper intends to fathom the current state of procurement system in Malaysia specifically in the construction industry in the aspect of supplier selection. This paper propose a comprehensive study on the supplier selection metrics for infrastructure building, weight the importance of each metrics assigned and to find the relationship between the metrics among initiators, decision makers, buyers and users. With the metrics hierarchy of criteria importance, a supplier selection process can be defined, repeated and audited with lesser complications or difficulties. This will help the field of procurement to improve as this research is able to develop and redefine policies and procedures that have been set in supplier selection. Developing this systematic process will enable optimization of supplier selection and thus increasing the value for every stakeholders as the process of selection is greatly simplified. With a new redefined policy and procedure, it does not only increase the company’s effectiveness and profit, but also make it available for the company to reach greater heights in the advancement of procurement in Malaysia.

  16. Performance evaluation of wastewater treatment using horizontal subsurface flow constructed wetlands optimized by micro-aeration and substrate selection.

    PubMed

    Zhong, Fei; Wu, Juan; Dai, Yanran; Xiang, Dongfang; Cheng, Shuiping; Ji, Hongjiu

    2015-01-01

    The effects of micro-aeration and substrate selection on domestic sewage treatment performance were explored using three pairs (with or without micro-aeration) of horizontal subsurface flow (HSSF) constructed wetlands (CWs) filled with zeolite, ceramsite or quartz granules. The individual and combined effects of micro-aeration and substrate selection on the purification performance of the experimental-scale HSSF CWs were evaluated. The results showed that micro-aeration significantly increased the treatment efficiencies for chemical oxygen demand, total nitrogen, total phosphorus (TP), ortho-phosphate (PO4(3-)-P) and ammonium nitrogen (NH4+-N) using HSSF CWs, while the substrate selection significantly affected the TP, PO4(3-)-P and NH4+-N removal efficiencies (p<0.05). A two-way analysis of variance (ANOVA) indicated that there was a significant interaction term (i.e. micro-aeration×substrate selection) for NH4+-N removal (p<0.05). Among the three substrates, ceramsite was the best substrate for the treatment of domestic sewage using HSSF CWs. Therefore, the results of this study suggest that a ceramsite-filled HSSF CW with micro-aeration could be the optimal configuration for decentralized domestic sewage treatment.

  17. Induced helical backbone conformations of self-organizable dendronized polymers.

    PubMed

    Rudick, Jonathan G; Percec, Virgil

    2008-12-01

    Control of function through the primary structure of a molecule presents a significant challenge with valuable rewards for nanoscience. Dendritic building blocks encoded with information that defines their three-dimensional shape (e.g., flat-tapered or conical) and how they associate with each other are referred to as self-assembling dendrons. Self-organizable dendronized polymers possess a flat-tapered or conical self-assembling dendritic side chain on each repeat unit of a linear polymer backbone. When appended to a covalent polymer, the self-assembling dendrons direct a folding process (i.e., intramolecular self-assembly). Alternatively, intermolecular self-assembly of dendrons mediated by noncovalent interactions between apex groups can generate a supramolecular polymer backbone. Self-organization, as we refer to it, is the spontaneous formation of periodic and quasiperiodic arrays from supramolecular elements. Covalent and supramolecular polymers jacketed with self-assembling dendrons self-organize. The arrays are most often comprised of cylindrical or spherical objects. The shape of the object is determined by the primary structure of the dendronized polymer: the structure of the self-assembling dendron and the length of the polymer backbone. It is therefore possible to predictably generate building blocks for single-molecule nanotechnologies or arrays of supramolecules for bottom-up self-assembly. We exploit the self-organization of polymers jacketed with self-assembling dendrons to elucidate how primary structure determines the adopted conformation and fold (i.e., secondary and tertiary structure), how the supramolecules associate (i.e., quaternary structure), and their resulting functions. A combination of experimental techniques is employed to interrogate the primary, secondary, tertiary, and quaternary structure of the self-organizable dendronized polymers. We refer to the process by which we interpolate between the various levels of structural

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

    NASA Technical Reports Server (NTRS)

    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.

  19. Antibacterial Studies of Cationic Polymers with Alternating, Random and Uniform Backbones

    PubMed Central

    Song, Airong; Walker, Stephen G.; Parker, Kathlyn A.; Sampson, Nicole S.

    2011-01-01

    Antibacterial polymers have potential as pharmaceuticals and as coatings for implantation devices. The design of these materials will be optimized when we have a complete understanding of the structural features that impart activity toward target organisms and those that are benign with respect to the mammalian host. In this work, four series of polymers in which cationic and hydrophobic groups were distributed along the backbone were tested against six different bacterial species (both Gram positive and Gram negative) and for host cytotoxicities (red blood cell lysis). The most effective of the polymers studied are regularly spaced, featuring a 6–8 carbon stretch along the backbone between side chains that present positively charged groups. They cause potassium efflux, disorder the bacterial cytoplasmic membrane, and disrupt the membrane potential. These polymers, available from alternating ring opening metathesis polymerization (AROMP), offer proof of principle for the importance of regular spacing in antibacterial polymers and for the synthesis of additional functional materials based on regularly spaced scaffolds. PMID:21370918

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

    PubMed

    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.

  1. Acceleration of protein backbone NMR assignment by combinatorial labeling: Application to a small molecule binding study.

    PubMed

    Hein, Christopher; Löhr, Frank; Schwarz, Daniel; Dötsch, Volker

    2017-05-01

    Selective labeling with stable isotopes has long been recognized as a valuable tool in protein NMR to alleviate signal overlap and sensitivity limitations. In this study, combinatorial (15) N-, (13) C(α) -, and (13) C'-selective labeling has been used during the backbone assignment of human cyclophilin D to explore binding of an inhibitor molecule. Using a cell-free expression system, a scheme that involves (15) N, 1-(13) C, 2-(13) C, fully (15) N/(13) C, and unlabeled amino acids was optimized to gain a maximum of assignment information from three samples. This scheme was combined with time-shared triple-resonance NMR experiments, which allows a fast and efficient backbone assignment by giving the unambiguous assignment of unique amino acid pairs in the protein, the identity of ambiguous pairs and information about all 19 non-proline amino acid types. It is therefore well suited for binding studies where de novo assignments of amide (1) H and (15) N resonances need to be obtained, even in cases where sensitivity is the limiting factor. © 2016 Wiley Periodicals, Inc.

  2. Retrieving Backbone String Neighbors Provides Insights Into Structural Modeling of Membrane Proteins*

    PubMed Central

    Sun, Jiang-Ming; Li, Tong-Hua; Cong, Pei-Sheng; Tang, Sheng-Nan; Xiong, Wen-Wei

    2012-01-01

    Identification of protein structural neighbors to a query is fundamental in structure and function prediction. Here we present BS-align, a systematic method to retrieve backbone string neighbors from primary sequences as templates for protein modeling. The backbone conformation of a protein is represented by the backbone string, as defined in Ramachandran space. The backbone string of a query can be accurately predicted by two innovative technologies: a knowledge-driven sequence alignment and encoding of a backbone string element profile. Then, the predicted backbone string is employed to align against a backbone string database and retrieve a set of backbone string neighbors. The backbone string neighbors were shown to be close to native structures of query proteins. BS-align was successfully employed to predict models of 10 membrane proteins with lengths ranging between 229 and 595 residues, and whose high-resolution structural determinations were difficult to elucidate both by experiment and prediction. The obtained TM-scores and root mean square deviations of the models confirmed that the models based on the backbone string neighbors retrieved by the BS-align were very close to the native membrane structures although the query and the neighbor shared a very low sequence identity. The backbone string system represents a new road for the prediction of protein structure from sequence, and suggests that the similarity of the backbone string would be more informative than describing a protein as belonging to a fold. PMID:22415040

  3. Photocaged G-Quadruplex DNAzyme and Aptamer by Post-Synthetic Modification on Phosphodiester Backbone.

    PubMed

    Feng, Mengli; Ruan, Zhiyuan; Shang, Jiachen; Xiao, Lu; Tong, Aijun; Xiang, Yu

    2017-02-15

    G-quadruplex-containing DNAzymes and aptamers are widely applied in many research fields because of their high stability and prominent activities versus the protein counterparts. In this work, G-quadruplex DNAs were equipped with photolabile groups to construct photocaged DNAzymes and aptamers. We incorporated TEEP-OH (thioether-enol phosphate, phenol substituted) into phosphodiester backbone of G-quadruplex DNA by a facile post-synthetic method to achieve efficient photocaging of their activities. Upon light irradiation, the peroxidase-mimicking activity of the caged G-quadruplex DNAzyme was activated, through the transformation of TEEP-OH into a native DNA phosphodiester without any artificial scar. Similarly, the caged G-quadruplex thrombin-binding aptamer also showed light-induced activation of thrombin inhibition activity. This method could serve as a general strategy to prepare photocaged G-quadruplex DNA with other activities for noninvasive control of their functions.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Construction of anthropomorphic hybrid, dual-lattice voxel models for optimizing image quality and dose in radiography

    NASA Astrophysics Data System (ADS)

    Petoussi-Henss, Nina; Becker, Janine; Greiter, Matthias; Schlattl, Helmut; Zankl, Maria; Hoeschen, Christoph

    2014-03-01

    In radiography there is generally a conflict between the best image quality and the lowest possible patient dose. A proven method of dosimetry is the simulation of radiation transport in virtual human models (i.e. phantoms). However, while the resolution of these voxel models is adequate for most dosimetric purposes, they cannot provide the required organ fine structures necessary for the assessment of the imaging quality. The aim of this work is to develop hybrid/dual-lattice voxel models (called also phantoms) as well as simulation methods by which patient dose and image quality for typical radiographic procedures can be determined. The results will provide a basis to investigate by means of simulations the relationships between patient dose and image quality for various imaging parameters and develop methods for their optimization. A hybrid model, based on NURBS (Non Linear Uniform Rational B-Spline) and PM (Polygon Mesh) surfaces, was constructed from an existing voxel model of a female patient. The organs of the hybrid model can be then scaled and deformed in a non-uniform way i.e. organ by organ; they can be, thus, adapted to patient characteristics without losing their anatomical realism. Furthermore, the left lobe of the lung was substituted by a high resolution lung voxel model, resulting in a dual-lattice geometry model. "Dual lattice" means in this context the combination of voxel models with different resolution. Monte Carlo simulations of radiographic imaging were performed with the code EGS4nrc, modified such as to perform dual lattice transport. Results are presented for a thorax examination.

  6. Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation.

    PubMed

    Yu, Weilin; Sun, Tuan-Wei; Qi, Chao; Ding, Zhenyu; Zhao, Huakun; Zhao, Shichang; Shi, Zhongmin; Zhu, Ying-Jie; Chen, Daoyun; He, Yaohua

    2017-01-01

    Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100-300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration.

  7. Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation

    PubMed Central

    Yu, Weilin; Sun, Tuan-Wei; Qi, Chao; Ding, Zhenyu; Zhao, Huakun; Zhao, Shichang; Shi, Zhongmin; Zhu, Ying-Jie; Chen, Daoyun; He, Yaohua

    2017-01-01

    Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100–300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration. PMID:28392688

  8. Using halogen bonds to address the protein backbone: a systematic evaluation.

    PubMed

    Wilcken, Rainer; Zimmermann, Markus O; Lange, Andreas; Zahn, Stefan; Boeckler, Frank M

    2012-08-01

    Halogen bonds are specific embodiments of the sigma hole bonding paradigm. They represent directional interactions between the halogens chlorine, bromine, or iodine and an electron donor as binding partner. Using quantum chemical calculations at the MP2 level, we systematically explore how they can be used in molecular design to address the omnipresent carbonyls of the protein backbone. We characterize energetics and directionality and elucidate their spatial variability in sub-optimal geometries that are expected to occur in protein-ligand complexes featuring a multitude of concomitant interactions. By deriving simple rules, we aid medicinal chemists and chemical biologists in easily exploiting them for scaffold decoration and design. Our work shows that carbonyl-halogen bonds may be used to expand the patentable medicinal chemistry space, redefining halogens as key features. Furthermore, this data will be useful for implementing halogen bonds into pharmacophore models or scoring functions making the QM information available for automatic molecular recognition in virtual high throughput screening.

  9. Facile backbone structure determination of human membrane proteins by NMR spectroscopy

    PubMed Central

    Klammt, Christian; Maslennikov, Innokentiy; Bayrhuber, Monika; Eichmann, Cédric; Vajpai, Navratna; Chiu, Ellis Jeremy Chua; Blain, Katherine Y; Esquivies, Luis; Kwon, June Hyun Jung; Balana, Bartosz; Pieper, Ursula; Sali, Andrej; Slesinger, Paul A; Kwiatkowski, Witek; Riek, Roland; Choe, Senyon

    2013-01-01

    Although nearly half of today’s major pharmaceutical drugs target human integral membrane proteins (hIMPs), only 30 hIMP structures are currently available in the Protein Data Bank, largely owing to inefficiencies in protein production. Here we describe a strategy for the rapid structure determination of hIMPs, using solution NMR spectroscopy with systematically labeled proteins produced via cell-free expression. We report new backbone structures of six hIMPs, solved in only 18 months from 15 initial targets. Application of our protocols to an additional 135 hIMPs with molecular weight <30 kDa yielded 38 hIMPs suitable for structural characterization by solution NMR spectroscopy without additional optimization. PMID:22609626

  10. Flexibility of backbone fibrils in α-chitin crystals with different degree of acetylation.

    PubMed

    Yu, Zechuan; Lau, Denvid

    2017-10-15

    Acetyl groups are backbone outreaches that enhance inter-fibril connection in chitin and chitosan fibril bundle. Removal of acetyl groups affects flexibility of chitosan fibril bundle, thereby affecting mechanical strength of chitosan-based products. Understandings of relationship between degree of acetylation and flexibility of chitin fibril bundle conduce to optimization of synthetic chitin materials. Here, the relationship is examined by performing molecular dynamics simulations. Coiling of chitin and chitosan fibril bundle with different degree of acetylation is observed and flexibility of fibrils is measured. Number and alignment of acetyl groups are found to be important factors determining the flexibility of chitin and chitosan fibril bundle. Structural instability can be caused by incompatible alignment of acetyl groups. Our findings on synthetic chitin-based materials indicate that adding a small amount of acetyl groups to chitosan can significantly enhance the integrity of fibril bundle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Using halogen bonds to address the protein backbone: a systematic evaluation

    NASA Astrophysics Data System (ADS)

    Wilcken, Rainer; Zimmermann, Markus O.; Lange, Andreas; Zahn, Stefan; Boeckler, Frank M.

    2012-08-01

    Halogen bonds are specific embodiments of the sigma hole bonding paradigm. They represent directional interactions between the halogens chlorine, bromine, or iodine and an electron donor as binding partner. Using quantum chemical calculations at the MP2 level, we systematically explore how they can be used in molecular design to address the omnipresent carbonyls of the protein backbone. We characterize energetics and directionality and elucidate their spatial variability in sub-optimal geometries that are expected to occur in protein-ligand complexes featuring a multitude of concomitant interactions. By deriving simple rules, we aid medicinal chemists and chemical biologists in easily exploiting them for scaffold decoration and design. Our work shows that carbonyl-halogen bonds may be used to expand the patentable medicinal chemistry space, redefining halogens as key features. Furthermore, this data will be useful for implementing halogen bonds into pharmacophore models or scoring functions making the QM information available for automatic molecular recognition in virtual high throughput screening.

  12. "Chameleonic" backbone hydrogen bonds in protein binding and as drug targets.

    PubMed

    Menéndez, C A; Accordino, S R; Gerbino, D C; Appignanesi, G A

    2015-10-01

    We carry out a time-averaged contact matrix study to reveal the existence of protein backbone hydrogen bonds (BHBs) whose net persistence in time differs markedly form their corresponding PDB-reported state. We term such interactions as "chameleonic" BHBs, CBHBs, precisely to account for their tendency to change the structural prescription of the PDB for the opposite bonding propensity in solution. We also find a significant enrichment of protein binding sites in CBHBs, relate them to local water exposure and analyze their behavior as ligand/drug targets. Thus, the dynamic analysis of hydrogen bond propensity might lay the foundations for new tools of interest in protein binding-site prediction and in lead optimization for drug design.

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

    PubMed

    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... .

  14. Robust identification of backbone curves using control-based continuation

    NASA Astrophysics Data System (ADS)

    Renson, L.; Gonzalez-Buelga, A.; Barton, D. A. W.; Neild, S. A.

    2016-04-01

    Control-based continuation is a recently developed approach for testing nonlinear dynamic systems in a controlled manner and exploring their dynamic features as system parameters are varied. In this paper, control-based continuation is adapted to follow the locus where system response and excitation are in quadrature, extracting the backbone curve of the underlying conservative system. The method is applied to a single-degree-of-freedom oscillator under base excitation, and the results are compared with the standard resonant-decay method.

  15. Long-term forecasting of internet backbone traffic.

    PubMed

    Papagiannaki, Konstantina; Taft, Nina; Zhang, Zhi-Li; Diot, Christophe

    2005-09-01

    We introduce a methodology to predict when and where link additions/upgrades have to take place in an Internet protocol (IP) backbone network. Using simple network management protocol (SNMP) statistics, collected continuously since 1999, we compute aggregate demand between any two adjacent points of presence (PoPs) and look at its evolution at time scales larger than 1 h. We show that IP backbone traffic exhibits visible long term trends, strong periodicities, and variability at multiple time scales. Our methodology relies on the wavelet multiresolution analysis (MRA) and linear time series models. Using wavelet MRA, we smooth the collected measurements until we identify the overall long-term trend. The fluctuations around the obtained trend are further analyzed at multiple time scales. We show that the largest amount of variability in the original signal is due to its fluctuations at the 12-h time scale. We model inter-PoP aggregate demand as a multiple linear regression model, consisting of the two identified components. We show that this model accounts for 98% of the total energy in the original signal, while explaining 90% of its variance. Weekly approximations of those components can be accurately modeled with low-order autoregressive integrated moving average (ARIMA) models. We show that forecasting the long term trend and the fluctuations of the traffic at the 12-h time scale yields accurate estimates for at least 6 months in the future.

  16. A phylogenetic backbone for Bivalvia: an RNA-seq approach

    PubMed Central

    González, Vanessa L.; Andrade, Sónia C. S.; Bieler, Rüdiger; Collins, Timothy M.; Dunn, Casey W.; Mikkelsen, Paula M.; Taylor, John D.; Giribet, Gonzalo

    2015-01-01

    Bivalves are an ancient and ubiquitous group of aquatic invertebrates with an estimated 10 000–20 000 living species. They are economically significant as a human food source, and ecologically important given their biomass and effects on communities. Their phylogenetic relationships have been studied for decades, and their unparalleled fossil record extends from the Cambrian to the Recent. Nevertheless, a robustly supported phylogeny of the deepest nodes, needed to fully exploit the bivalves as a model for testing macroevolutionary theories, is lacking. Here, we present the first phylogenomic approach for this important group of molluscs, including novel transcriptomic data for 31 bivalves obtained through an RNA-seq approach, and analyse these data with published genomes and transcriptomes of other bivalves plus outgroups. Our results provide a well-resolved, robust phylogenetic backbone for Bivalvia with all major lineages delineated, addressing long-standing questions about the monophyly of Protobranchia and Heterodonta, and resolving the position of particular groups such as Palaeoheterodonta, Archiheterodonta and Anomalodesmata. This now fully resolved backbone demonstrates that genomic approaches using hundreds of genes are feasible for resolving phylogenetic questions in bivalves and other animals. PMID:25589608

  17. A phylogenetic backbone for Bivalvia: an RNA-seq approach.

    PubMed

    González, Vanessa L; Andrade, Sónia C S; Bieler, Rüdiger; Collins, Timothy M; Dunn, Casey W; Mikkelsen, Paula M; Taylor, John D; Giribet, Gonzalo

    2015-02-22

    Bivalves are an ancient and ubiquitous group of aquatic invertebrates with an estimated 10 000-20 000 living species. They are economically significant as a human food source, and ecologically important given their biomass and effects on communities. Their phylogenetic relationships have been studied for decades, and their unparalleled fossil record extends from the Cambrian to the Recent. Nevertheless, a robustly supported phylogeny of the deepest nodes, needed to fully exploit the bivalves as a model for testing macroevolutionary theories, is lacking. Here, we present the first phylogenomic approach for this important group of molluscs, including novel transcriptomic data for 31 bivalves obtained through an RNA-seq approach, and analyse these data with published genomes and transcriptomes of other bivalves plus outgroups. Our results provide a well-resolved, robust phylogenetic backbone for Bivalvia with all major lineages delineated, addressing long-standing questions about the monophyly of Protobranchia and Heterodonta, and resolving the position of particular groups such as Palaeoheterodonta, Archiheterodonta and Anomalodesmata. This now fully resolved backbone demonstrates that genomic approaches using hundreds of genes are feasible for resolving phylogenetic questions in bivalves and other animals.

  18. Carbon and amide detect backbone assignment methods of a novel repeat protein from the staphylocoagulase in S. aureus.

    PubMed

    Voehler, Markus; Ashoka, Maddur Appajaiah; Meiler, Jens; Bock, Paul E

    2017-08-17

    The C-terminal repeat domain of staphylocoagulase that is secreted by the S. aureus is believed to play an important role interacting with fibrinogen and promotes blood clotting. To study this interaction by NMR, full assignment of each amide residue in the HSQC spectrum was required. Despite of the short sequence of the repeat construct, the HSQC spectrum contained a substantial amount of overlapped and exchange broadened resonances, indicating little secondary or tertiary structure. This caused severe problems while using the conventional, amide based NMR method for the backbone assignment. With the growing interest in small apparently disordered proteins, these issues are being faced more frequently. An alternative strategy to improve the backbone assignment capability involved carbon direct detection methods. Circumventing the amide proton detection offers a larger signal dispersion and more uniform signal intensity. For peptides with higher concentrations and in combination with the cold carbon channels of new cryoprobes, higher fields, and sufficiently long relaxation times, the disadvantage of the lower sensitivity of the (13)C nucleus can be overcome. Another advantage of this method is the assignment of the proline backbone residues. Complete assignment with the carbon-detected strategy was achieved with a set of only two 3D, one 2D, and a HNCO measurement, which was necessary to translate the information to the HSQC spectrum.

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

    PubMed Central

    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

  20. Optimal flux patterns in cellular metabolic networks.

    PubMed

    Almaas, Eivind

    2007-06-01

    The availability of whole-cell-level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate the metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations has relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reactions are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central carbon metabolic pathways for the sample of random environments.

  1. Optimal flux patterns in cellular metabolic networks

    SciTech Connect

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

  2. Optimal flux patterns in cellular metabolic networks

    NASA Astrophysics Data System (ADS)

    Almaas, Eivind

    2007-06-01

    The availability of whole-cell-level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate the metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30 000 random cellular environments. The distribution of reaction fluxes is heavy tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations has relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reactions are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central carbon metabolic pathways for the sample of random environments.

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

    PubMed

    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.

  4. Refined solution structure and backbone dynamics of HIV-1 Nef.

    PubMed Central

    Grzesiek, S.; Bax, A.; Hu, J. S.; Kaufman, J.; Palmer, I.; Stahl, S. J.; Tjandra, N.; Wingfield, P. T.

    1997-01-01

    The tendency of HIV-1 Nef to form aggregates in solution, particularly at pH values below 8, together with its large fraction of highly mobile residues seriously complicated determination of its three-dimensional structure, both for heteronuclear solution NMR (Grzesiek et al., 1996a, Nat Struct Biol 3:340-345) and for X-ray crystallography (Lee et al., 1996, Cell 85:931-942). Methods used to determine the Nef structure by NMR at pH 8 and 0.6 mM concentration are presented, together with a detailed description of Nef's secondary and tertiary structure. The described techniques have general applicability for the NMR structure determination of proteins that are aggregating and/or have limited stability at low pH values. Extensive chemical shift assignments are reported for backbone and side chain 1H, 13C, and 15N resonances of the HIV-1 Nef deletion mutants NEF delta 2-39, NEF delta 2-39, delta 159-173, and of NEF delta 2-39, delta 159-173 in complex with the SH3 domain of the Hck tyrosine protein kinase. Besides a type II polyproline helix, Nef's structure consists of three alpha-helices, a 3(10) helix, and a five-stranded anti-parallel beta-sheet. The analysis of 15N relaxation parameters of the backbone amide sites reveals that all the secondary structure elements are non-mobile on the picosecond to nanosecond and on the millisecond time scale. A large number of slowly exchanging amide protons provides evidence for the stability of the Nef core even on the time scale of hours. Significant internal motions on the ps to ns time scale are detected for residues 60 to 71 and for residues 149 to 180, which form solvent-exposed loops. The residues of the HIV-1 protease cleavage site (W57/L58) do not exhibit large amplitude motions on the sub-nanosecond time scale, and their side chains insert themselves into a hydrophobic crevice formed between the C-terminus of helix 1 and the N-terminus of helix 2. A refined structure has been determined based on additional constraints

  5. Protein side-chain resonance assignment and NOE assignment using RDC-defined backbones without TOCSY data.

    PubMed

    Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

    2011-08-01

    One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA: (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA: extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA: assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA: have backbone

  6. A Native to Amyloidogenic Transition Regulated by a Backbone Trigger

    SciTech Connect

    Eakin,C.; Berman, A.; Miranker, A.

    2006-01-01

    Many polypeptides can self-associate into linear, aggregated assemblies termed amyloid fibers. High-resolution structural insights into the mechanism of fibrillogenesis are elusive owing to the transient and mixed oligomeric nature of assembly intermediates. Here, we report the conformational changes that initiate fiber formation by beta-2-microglobulin (beta2m) in dialysis-related amyloidosis. Access of beta2m to amyloidogenic conformations is catalyzed by selective binding of divalent cations. The chemical basis of this process was determined to be backbone isomerization of a conserved proline. On the basis of this finding, we designed a beta2m variant that closely adopts this intermediate state. The variant has kinetic, thermodynamic and catalytic properties consistent with its being a fibrillogenic intermediate of wild-type beta2m. Furthermore, it is stable and folded, enabling us to unambiguously determine the initiating conformational changes for amyloid assembly at atomic resolution.

  7. Bioactivities of fish protein hydrolysates from defatted salmon backbones.

    PubMed

    Slizyte, Rasa; Rommi, Katariina; Mozuraityte, Revilija; Eck, Peter; Five, Kathrine; Rustad, Turid

    2016-09-01

    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.

  8. Reconstruction of the Sunspot Group Number: The Backbone Method

    NASA Astrophysics Data System (ADS)

    Svalgaard, Leif; Schatten, Kenneth H.

    2016-11-01

    We have reconstructed the sunspot-group count, not by comparisons with other reconstructions and correcting those where they were deemed to be deficient, but by a re-assessment of original sources. The resulting series is a pure solar index and does not rely on input from other proxies, e.g. radionuclides, auroral sightings, or geomagnetic records. "Backboning" the data sets, our chosen method, provides substance and rigidity by using long-time observers as a stiffness character. Solar activity, as defined by the Group Number, appears to reach and sustain for extended intervals of time the same level in each of the last three centuries since 1700 and the past several decades do not seem to have been exceptionally active, contrary to what is often claimed.

  9. Chemical characteristics and antithrombotic effect of chondroitin sulfates from sturgeon skull and sturgeon backbone.

    PubMed

    Gui, Meng; Song, Juyi; Zhang, Lu; Wang, Shun; Wu, Ruiyun; Ma, Changwei; Li, Pinglan

    2015-06-05

    Chondroitin sulfates (CSs) were extracted from sturgeon skull and backbone, and their chemical composition, anticoagulant, anti-platelet and thrombolysis activities were evaluated. The average molecular weights of CS from sturgeon skull and backbone were 38.5kDa and 49.2kDa, respectively. Disaccharide analysis indicated that the sturgeon backbone CS was primarily composed of disaccharide monosulfated in position four of the GalNAc (37.8%) and disaccharide monosulfated in position six of the GalNAc (59.6%) while sturgeon skull CS was primarily composed of nonsulfated disaccharide (74.2%). Sturgeon backbone CS showed stronger antithrombotic effect than sturgeon skull CS. Sturgeon backbone CS could significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT), inhibited ADP-induced platelet aggregation and dissolved platelet plasma clots in vitro. The results suggested that sturgeon backbone CS can be explored as a functional food with antithrombotic function.

  10. Cost-effectiveness analysis of dolutegravir plus backbone compared with raltegravir plus backbone, darunavir+ritonavir plus backbone and efavirenz/tenofovir/emtricitabine in treatment naïve and experienced HIV-positive patients.

    PubMed

    Restelli, Umberto; Rizzardini, Giuliano; Antinori, Andrea; Lazzarin, Adriano; Bonfanti, Marzia; Bonfanti, Paolo; Croce, Davide

    2017-01-01

    In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER) of the use of DTG+backbone compared with raltegravir (RAL)+backbone, darunavir (DRV)+ritonavir(r)+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service's point of view. A published Monte Carlo Individual Simulation Model (ARAMIS-DTG model) was used to perform the analysis. Patients pass through mutually exclusive health states (defined in terms of diagnosis of HIV with or without opportunistic infections [OIs] and cardiovascular disease [CVD]) and successive lines of therapy. The model considers costs (2014) and quality of life per monthly cycle in a lifetime horizon. Costs and quality-adjusted life years (QALYs) are dependent on OI, CVD, AIDS events, adverse events and antiretroviral therapies. In treatment-naïve patients, DTG dominates RAL; compared with DRV/r, the ICER obtained is of 38,586 €/QALY (6,170 €/QALY in patients with high viral load) and over EFV/TDF/FTC, DTG generates an ICER of 33,664 €/QALY. In treatment-experienced patients, DTG compared to RAL leads to an ICER of 12,074 €/QALY. The use of DTG+backbone may be cost effective in treatment-naïve and treatment-experienced patients compared with RAL+backbone and in treatment-naïve patients compared with DRV/r+backbone and EFV/TDF/FTC considering a threshold of 40,000 €/QALY.

  11. Computational design of high-affinity epitope scaffolds by backbone grafting of a linear epitope.

    PubMed

    Azoitei, Mihai L; Ban, Yih-En Andrew; Julien, Jean-Philippe; Bryson, Steve; Schroeter, Alexandria; Kalyuzhniy, Oleksandr; Porter, Justin R; Adachi, Yumiko; Baker, David; Pai, Emil F; Schief, William R

    2012-01-06

    Computational grafting of functional motifs onto scaffold proteins is a promising way to engineer novel proteins with pre-specified functionalities. Typically, protein grafting involves the transplantation of protein side chains from a functional motif onto structurally homologous regions of scaffold proteins. Using this approach, we previously transplanted the human immunodeficiency virus 2F5 and 4E10 epitopes onto heterologous proteins to design novel "epitope-scaffold" antigens. However, side-chain grafting is limited by the availability of scaffolds with compatible backbone for a given epitope structure and offers no route to modify backbone structure to improve mimicry or binding affinity. To address this, we report here a new and more aggressive computational method-backbone grafting of linear motifs-that transplants the backbone and side chains of linear functional motifs onto scaffold proteins. To test this method, we first used side-chain grafting to design new 2F5 epitope scaffolds with improved biophysical characteristics. We then independently transplanted the 2F5 epitope onto three of the same parent scaffolds using the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone grafting designs showed close agreement with both the computational models and the desired epitope structure. In two cases, backbone grafting scaffolds bound antibody 2F5 with 30- and 9-fold higher affinity than corresponding side-chain grafting designs. These results demonstrate that flexible backbone methods for epitope grafting can significantly improve binding affinities over those achieved by fixed backbone methods alone. Backbone grafting of linear motifs is a general method to transplant functional motifs when backbone remodeling of the target scaffold is necessary.

  12. Optimism Reborn. Nicaragua's Participative Education Revolution, the Citizen Power Development Model and the Construction of "21st Century Socialism"

    ERIC Educational Resources Information Center

    Muhr, Thomas

    2013-01-01

    This paper explores Nicaragua's Participative Education Revolution and the Citizen Power national development model in the construction of socialism in the 21st century in Latin America and the Caribbean through the Bolivarian Alliance for the Peoples of Our America--Peoples' Trade Agreement. Centred around the notion of "revolutionary…

  13. Optimism Reborn. Nicaragua's Participative Education Revolution, the Citizen Power Development Model and the Construction of "21st Century Socialism"

    ERIC Educational Resources Information Center

    Muhr, Thomas

    2013-01-01

    This paper explores Nicaragua's Participative Education Revolution and the Citizen Power national development model in the construction of socialism in the 21st century in Latin America and the Caribbean through the Bolivarian Alliance for the Peoples of Our America--Peoples' Trade Agreement. Centred around the notion of "revolutionary…

  14. Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs

    PubMed Central

    Sonnaert, Maarten; Kerckhofs, Greet; Papantoniou, Ioannis; Van Vlierberghe, Sandra; Boterberg, Veerle; Dubruel, Peter; Luyten, Frank P.; Schrooten, Jan; Geris, Liesbet

    2015-01-01

    To progress the fields of tissue engineering (TE) and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds) becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells) in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial ‘design of experiments’ approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid) and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology. PMID:26076131

  15. Pendant Dynamics of Ethylene-Oxide Containing Polymers with Diverse Backbones

    NASA Astrophysics Data System (ADS)

    Bartels, Joshua; Wang, Jing-Han Helen; Chen, Quan; Runt, James; Colby, Ralph

    In the last twenty years, a wide variety of ion conducting polymers have used ether oxygens to facilitate ion conduction, and it is therefore important to understand the dynamics of ether oxygens (EOs) when attached to different polymer backbones. Four different EO-containing polymer architectures are studied by dielectric spectroscopy to understand the backbone effect on the EO dipoles. Polysiloxanes, polyphosphazenes, polymethylmethacrylates, and a polyester ether are compared, with different EO pendant lengths for the siloxane and methylmethacrylate backbones. The flexible polysiloxanes and polyphosphazene backbones impart superior segmental mobility with a glass transition temperature 15 K lower than that of the organic backbone polymers. Short EO pendants are found to impart a lower static dielectric constant at comparable EO content as compared to longer EO pendants of either inorganic or organic backbones. The long-pendant polymethylmethacrylate polymers show two relaxations corresponding to fast EOs near the pendant tail end and slow EOs close to the slower backbone, whereas the long-pendant polysiloxane shows a single relaxation due to the siloxane backbone relaxing faster than the EO pendant. Supported by the NSF Division of Materials Research Polymers Program through Grants DMR-1404586 (RHC) and DMR-1505953 (JR).

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

    PubMed

    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.

  17. Thermogelling Biodegradable Polymers with Hydrophilic Backbones: PEG-g-PLGA

    SciTech Connect

    Jeong, Byeongmoon; Kibbey, Merinda R.; Birnbaum, Jerome C.; Won, You-Yeong; Gutowska, Anna

    2000-10-31

    The aqueous solutions of poly(ethylene glycol)grafted with poly(lactic acid-co-glycolic acid) flow freely at room temperature but form gels at higher temperature. The existence of micelles in water at low polymer concentration was confirmed by Cro-transmission electron microscopy and dye solubilization studies. The micellar diameter and critical micelle concentration are about 9 nm and 0.47 wt.% respectively. The critical gel concentration, above which a gel phase appears was 16 wt.% and sol-to-gel transition temperature was slightly affected by the concentration in the range of 16 {approx} 25 wt.%. At sol-to-gel transition, viscosity increased abruptly and C-NMR showed molecular motion of hydrophilic poly(lactic acid-co-glycolic acid) side-chains increased. The hydrogel of PEG-g-PLGA with hydrophilic backbones was transparent during degradation and remained a gel for one week, suggesting a promising material for short-term drug delivery.

  18. A New Secondary Structure Assignment Algorithm Using Cα Backbone Fragments.

    PubMed

    Cao, Chen; Wang, Guishen; Liu, An; Xu, Shutan; Wang, Lincong; Zou, Shuxue

    2016-03-11

    The assignment of secondary structure elements in proteins is a key step in the analysis of their structures and functions. We have developed an algorithm, SACF (secondary structure assignment based on Cα fragments), for secondary structure element (SSE) assignment based on the alignment of Cα backbone fragments with central poses derived by clustering known SSE fragments. The assignment algorithm consists of three steps: First, the outlier fragments on known SSEs are detected. Next, the remaining fragments are clustered to obtain the central fragments for each cluster. Finally, the central fragments are used as a template to make assignments. Following a large-scale comparison of 11 secondary structure assignment methods, SACF, KAKSI and PROSS are found to have similar agreement with DSSP, while PCASSO agrees with DSSP best. SACF and PCASSO show preference to reducing residues in N and C cap regions, whereas KAKSI, P-SEA and SEGNO tend to add residues to the terminals when DSSP assignment is taken as standard. Moreover, our algorithm is able to assign subtle helices (310-helix, π-helix and left-handed helix) and make uniform assignments, as well as to detect rare SSEs in β-sheets or long helices as outlier fragments from other programs. The structural uniformity should be useful for protein structure classification and prediction, while outlier fragments underlie the structure-function relationship.

  19. A New Secondary Structure Assignment Algorithm Using Cα Backbone Fragments

    PubMed Central

    Cao, Chen; Wang, Guishen; Liu, An; Xu, Shutan; Wang, Lincong; Zou, Shuxue

    2016-01-01

    The assignment of secondary structure elements in proteins is a key step in the analysis of their structures and functions. We have developed an algorithm, SACF (secondary structure assignment based on Cα fragments), for secondary structure element (SSE) assignment based on the alignment of Cα backbone fragments with central poses derived by clustering known SSE fragments. The assignment algorithm consists of three steps: First, the outlier fragments on known SSEs are detected. Next, the remaining fragments are clustered to obtain the central fragments for each cluster. Finally, the central fragments are used as a template to make assignments. Following a large-scale comparison of 11 secondary structure assignment methods, SACF, KAKSI and PROSS are found to have similar agreement with DSSP, while PCASSO agrees with DSSP best. SACF and PCASSO show preference to reducing residues in N and C cap regions, whereas KAKSI, P-SEA and SEGNO tend to add residues to the terminals when DSSP assignment is taken as standard. Moreover, our algorithm is able to assign subtle helices (310-helix, π-helix and left-handed helix) and make uniform assignments, as well as to detect rare SSEs in β-sheets or long helices as outlier fragments from other programs. The structural uniformity should be useful for protein structure classification and prediction, while outlier fragments underlie the structure–function relationship. PMID:26978354

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Data Acquisition Backbone Core DABC release v1.0

    NASA Astrophysics Data System (ADS)

    Adamczewski-Musch, J.; Essel, H. G.; Kurz, N.; Linev, S.

    2010-04-01

    The Data Acquisition Backbone Core (DABC) is a general purpose software framework designed for the implementation of a wide-range of data acquisition systems - from various small detector test beds to high performance systems. DABC consists of a compact data-flow kernel and a number of plug-ins for various functional components like data inputs, device drivers, user functional modules and applications. DABC provides configurable components for implementing event building over fast networks like InfiniBand or Gigabit Ethernet. A generic Java GUI provides the dynamic control and visualization of control parameters and commands, provided by DIM servers. A first set of application plug-ins has been implemented to use DABC as event builder for the front-end components of the GSI standard DAQ system MBS (Multi Branch System). Another application covers the connection to DAQ readout chains from detector front-end boards (N-XYTER) linked to read-out controller boards (ROC) over UDP into DABC for event building, archiving and data serving. This was applied for data taking in the September 2008 test beamtime for the CBM experiment at GSI. DABC version 1.0 is released and available from the website.

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

    PubMed

    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.

  3. Backbone Assignment of the MALT1 Paracaspase by Solution NMR

    PubMed Central

    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 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. PMID:26788853

  4. Construct optimization for studying protein complexes: obtaining diffraction-quality crystals of the pseudosymmetric PSPC1-NONO heterodimer.

    PubMed

    Lee, Mihwa; Passon, Daniel M; Hennig, Sven; Fox, Archa H; Bond, Charles S

    2011-11-01

    The methodology of protein crystallography provides a number of potential bottlenecks. Here, an approach to successful structure solution of a difficult heterodimeric complex of two human proteins, paraspeckle component 1 (PSPC1) and non-POU domain-containing octamer-binding protein (NONO), that are involved in gene regulation and the structural integrity of nuclear bodies termed paraspeckles is described. With the aid of bioinformatic predictions and systematic screening of a panel of constructs, bottlenecks of protein solubility, crystallization, crystal quality and crystallographic pseudosymmetry were overcome in order to produce crystals that ultimately revealed the structure.

  5. Design and Synthesis of Efficient Fluorescent Dyes for Incorporation into DNA Backbone and Biomolecule Detection

    PubMed Central

    Wang, Wei; Li, Alexander D. Q.

    2008-01-01

    We report here the design and synthesis of a series of π-conjugated fluorescent dyes with D-A-D (D: donor; A: Acceptor), D-π-D, A-π-A, and D-π-A for applications as the signaling motif in biological-synthetic hybrid foldamers for DNA detection. Horner-Wadsworth-Emmons (HWE) reaction and Knoevenagel condensation were demonstrated as the optimum ways for construction of long π-conjugated systems. Such rod-like chromophores have distinct advantages, as their fluorescence properties are not quenched by the presence of DNA. To be incorporated into the backbone of DNA, the chromophores need to be reasonably soluble in organic solvent for solid-phase synthesis, and therefore a strategy of using flexible tetra(ethylene glycol) (TEG) linkers at either end of these rod-like dyes were developed. The presence of TEG facilitates the protection of the chain-growing hydroxyl group with DMTrCl (dimethoxy trityl chloride) as well as the activation of the coupling step with phosphoramidite chemistry on an automated DNA synthesizer. To form fluorescence resonance energy transfer (FRET) pairs, six synthetic chromophores with blue to red fluorescence have been developed and those with orthogonal fluorescent emission were chosen for incorporation into DNA-chromophore hybrid foldamers. PMID:17508711

  6. Side-chain to backbone interactions dictate the conformational preferences of a cyclopentane arginine analogue

    PubMed Central

    Revilla-López, Guillem; Torras, Juan; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

    2009-01-01

    The intrinsic conformational preferences of the non-proteinogenic amino acids constructed by incorporating the arginine side chain in the β position of 1-aminocyclopentane-1-carboxylic acid (either in a cis or a trans orientation relative to the amino group) have been investigated using computational methods. These compounds may be considered as constrained analogues of arginine (denoted as c5Arg) in which the orientation of the side chain is fixed by the cyclopentane moiety. Specifically, the N-acetyl-N′-methylamide derivatives of cis and trans-c5Arg have been examined in the gas phase and in solution using B3LYP/6-311+G(d,p) calculations and Molecular Dynamics simulations. Results indicate that the conformational space available to these compounds is highly restricted, their conformational preferences being dictated by the ability of the guanidinium group in the side chain to establish hydrogen-bond interactions with the backbone. A comparison with the behavior previously described for the analogous phenylalanine derivatives is presented. PMID:19236034

  7. [Obtaining marker-free transgenic soybean plants with optimal frequency by constructing three T-DNAs binary vector].

    PubMed

    Ye, Xing-Guo; Qin, Hua

    2007-01-01

    Obtaining marker-free plants with high efficiency will benefit the environmental release of transgenic crops. To achieve this point, a binary vector pNB35SVIP1 with three T-DNAs was constructed by using several mediate plasmids, in which one copy of bar gene expression cassette and two copies of VIP1 gene expression cassette were included. EHA101 Agrobacterium strain harboring the final construct was applied to transform soybean (Glycine max) cotyledon nodes. Through 2 - 3 months regeneration and selection on 3 - 5mg/L glufosinate containing medium, transgenic soybean plants were confirmed to be obtained at 0.83% - 3.16%, and co-transformation efficiency of both gene in the same individual reached up to 86.4%, based on southern blot test. By the analysis of PCR, southern blot and northern blot combining with leaf painting of herbicide in T1 progenies, 41 plants were confirmed to be eliminated of bar gene with the frequency of 7.6% . Among the T1 populations tested, the loss of the alien genes happened in 22.7% lines, the silence of bar gene took place in 27.3% lines, and VIP1 gene silence existed in 37.1% marker-free plants. The result also suggested that the plasmid with three T-DNAs might be an ideal vector to generate maker-free genetic modified organism.

  8. Geological aspects of model construction for well placement optimization in a mixed fluvio-aeolian reservoir, UKCS

    SciTech Connect

    Hern, C.Y.; Lewis, J.J.M.; Seifert, D.; Steel, N.C.T.

    1996-12-31

    The cost-effective development of small fields requires a thorough description of the reservoir with a strong focus on the estimation of uncertainty. In this example, 3-D reservoir models are used to define and risk optimum well trajectories in a complex, mixed fluvio-aeolian gas reservoir. Emphasis is placed on the definition and quantification of those geological factors that affect the integrity of the hybrid stochastic-deterministic reservoir model. Sequential Indicator Simulation (SIS) models conditioned to well data were constructed for target zones. Construction of geologically realistic models required identification of genetic units, an understanding of their spatial distribution and assignation of appropriate dimensions. These objectives were achieved by an integration of probe-permeametry and sedimentology data on reservoir core, and the derivation of relevant genetic unit architectures from analogous sequences at outcrop. Assignation of appropriate sizes depends on the similarity between the outcrop analogue and the subsurface reservoir. Similarity was assessed by comparison of facies types, their proportions, the vertical association of facies, types of fluvio-aeolian interaction, the size of depositional systems and general depositional environment. Outcrop data were compared to reservoir observations and sub-sampled to eliminate unrepresentative elements. The SIS models generated with this data were {open_quote}pin-cushioned{close_quote} with over 100,000 numerical {open_quotes}wells{close_quotes} of varying azimuth, length, inclination and elevation. Much improved decision support was provided through a statistical definition of the {open_quote}optimum{close_quote} well trajectory.

  9. Geological aspects of model construction for well placement optimization in a mixed fluvio-aeolian reservoir, UKCS

    SciTech Connect

    Hern, C.Y.; Lewis, J.J.M.; Seifert, D. ); Steel, N.C.T. )

    1996-01-01

    The cost-effective development of small fields requires a thorough description of the reservoir with a strong focus on the estimation of uncertainty. In this example, 3-D reservoir models are used to define and risk optimum well trajectories in a complex, mixed fluvio-aeolian gas reservoir. Emphasis is placed on the definition and quantification of those geological factors that affect the integrity of the hybrid stochastic-deterministic reservoir model. Sequential Indicator Simulation (SIS) models conditioned to well data were constructed for target zones. Construction of geologically realistic models required identification of genetic units, an understanding of their spatial distribution and assignation of appropriate dimensions. These objectives were achieved by an integration of probe-permeametry and sedimentology data on reservoir core, and the derivation of relevant genetic unit architectures from analogous sequences at outcrop. Assignation of appropriate sizes depends on the similarity between the outcrop analogue and the subsurface reservoir. Similarity was assessed by comparison of facies types, their proportions, the vertical association of facies, types of fluvio-aeolian interaction, the size of depositional systems and general depositional environment. Outcrop data were compared to reservoir observations and sub-sampled to eliminate unrepresentative elements. The SIS models generated with this data were [open quote]pin-cushioned[close quote] with over 100,000 numerical [open quotes]wells[close quotes] of varying azimuth, length, inclination and elevation. Much improved decision support was provided through a statistical definition of the [open quote]optimum[close quote] well trajectory.

  10. [Optimization of nitrogen and phosphorus removal in vertical subsurface flow constructed wetlands by using polypropylene pellet as part of substrate].

    PubMed

    Tang, Xian-Qiang; Li, Jin-Zhong; Li, Xue-Ju; Liu, Xue-Gong; Huang, Sui-Liang

    2008-05-01

    Constructed wetlands experiments were conducted by using shale and Typha latifolia L. as vertical subsurface flow constructed wetland substrate and plant for eutrophic Jin River water treatment, and part of shale with polypropylene pellet was replaced to investigate its effect on nitrogen and phosphorus removal. In this study, hydraulic loading rate was equal to 800 mm/d, theoretic residence time was equal to 12 h. During the entire running period, maximal monthly mean ammonia-nitrogen (NH(4+) -N), total nitrogen (TN), soluble reactive phosphorus (SRP) and total phosphorus (TP) removal rates were observed in August 2006. In contrast to the full shale used wetland, polypropylene pellet enhanced ammonia-nitrogen, total nitrogen, soluble reactive phosphorus and total phosphorus removal by 13.38%, 8.9%, 9.29% and 8.25% respectively. After finishing the experiment, aboveground plant biomass (stems and leaves) of Typha latifolia L. was harvested, and its weight and nutrient content (total nitrogen and total phosphorus) were measured. Analysis of aboveground plant biomass indicated that polypropylene pellet restrained the increase in biomass but stimulated assimilation of nitrogen and phosphorus into stems and leaves. The subsequent harvesting of the plants resulted in the additional removal of total nitrogen and phosphorus of about 29.382 g x m(-2) and 13.469 g x m(-2), respectively.

  11. Proteins of well-defined structures can be designed without backbone readjustment by a statistical model.

    PubMed

    Zhou, Xiaoqun; Xiong, Peng; Wang, Meng; Ma, Rongsheng; Zhang, Jiahai; Chen, Quan; Liu, Haiyan

    2016-12-01

    We report that using mainly a statistical energy model, protein sequence design for designable backbones can be carried out with high confidence without considering backbone relaxation. A recently-developed statistical energy function for backbone-based protein sequence design has been rationally revised to improve its accuracy. As a demonstrative example, this revised model is applied to design a de novo protein for a target backbone for which the previous model had relied on after-design directed evolution to produce a well-folded protein. The actual backbone structure of the newly designed protein agrees excellently with the corresponding target. Besides presenting a new protein design protocol with experimentally verifications on different backbone types, our study implies that with an energy model of an appropriate resolution, proteins of well-defined structures instead of molten globules can be designed without the explicit consideration of backbone variations due to side chain changes, even if the side chain changes correspond to complete sequence redesigns.

  12. Influence of backbone on the charge transport properties of G4-DNA molecules: a model-based calculation.

    PubMed

    Guo, Ai-Min; Yang, Zhi; Zhu, Hong-Jun; Xiong, Shi-Jie

    2010-02-17

    We put forward a model Hamiltonian to describe the influence of backbone energetics on charge transport through guanine-quadruplex DNA (G4-DNA) molecules. Our analytical results show that an energy gap can be produced in the energy spectrum of G4-DNA by hybridization effects between the backbone and the base and by on-site energy difference of the backbone from the base. The environmental effects are investigated by introducing different types of disorder into the backbone sites. Our numerical results suggest that the localization length of G4-DNA can be significantly enhanced by increasing the backbone disorder degree when the environment-induced disorder is sufficiently large. There exists a backbone disorder-induced semiconducting-metallic transition in short G4-DNA molecules, where G4-DNA behaves as a semiconductor if the backbone disorder is weak and behaves as a conductor if the backbone disorder degree surpasses a critical value.

  13. Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold

    SciTech Connect

    Azoitei, Mihai L.; Correia, Bruno E.; Ban, Yih-En Andrew; Carrico, Chris; Kalyuzhniy, Oleksandr; Chen, Lei; Schroeter, Alexandria; Huang, Po-Ssu; McLellan, Jason S.; Kwong, Peter D.; Baker, David; Strong, Roland K.; Schief, William R.

    2012-02-07

    The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.

  14. Uganda's National Transmission Backbone Infrastructure Project: Technical Challenges and the Way Forward

    NASA Astrophysics Data System (ADS)

    Bulega, T.; Kyeyune, A.; Onek, P.; Sseguya, R.; Mbabazi, D.; Katwiremu, E.

    2011-10-01

    Several publications have identified technical challenges facing Uganda's National Transmission Backbone Infrastructure project. This research addresses the technical limitations of the National Transmission Backbone Infrastructure project, evaluates the goals of the project, and compares the results against the technical capability of the backbone. The findings of the study indicate a bandwidth deficit, which will be addressed by using dense wave division multiplexing repeaters, leasing bandwidth from private companies. Microwave links for redundancy, a Network Operation Center for operation and maintenance, and deployment of wireless interoperability for microwave access as a last-mile solution are also suggested.

  15. Predicting backbone Cα angles and dihedrals from protein sequences by stacked sparse auto-encoder deep neural network.

    PubMed

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

    2014-10-30

    Because a nearly constant distance between two neighbouring Cα atoms, local backbone structure of proteins can be represented accurately by the angle between C(αi-1)-C(αi)-C(αi+1) (θ) and a dihedral angle rotated about the C(αi)-C(αi+1) bond (τ). θ and τ angles, as the representative of structural properties of three to four amino-acid residues, offer a description of backbone conformations that is complementary to φ and ψ angles (single residue) and secondary structures (>3 residues). Here, we report the first machine-learning technique for sequence-based prediction of θ and τ angles. Predicted angles based on an independent test have a mean absolute error of 9° for θ and 34° for τ with a distribution on the θ-τ plane close to that of native values. The average root-mean-square distance of 10-residue fragment structures constructed from predicted θ and τ angles is only 1.9Å from their corresponding native structures. Predicted θ and τ angles are expected to be complementary to predicted ϕ and ψ angles and secondary structures for using in model validation and template-based as well as template-free structure prediction. The deep neural network learning technique is available as an on-line server called Structural Property prediction with Integrated DEep neuRal network (SPIDER) at http://sparks-lab.org.

  16. Catalytic mechanism of DNA backbone cleavage by the restriction enzyme EcoRV: a quantum mechanical/molecular mechanical analysis.

    PubMed

    Imhof, Petra; Fischer, Stefan; Smith, Jeremy C

    2009-09-29

    Endonucleases, such as the restriction enzyme EcoRV, cleave the DNA backbone at a specific recognition sequence. We have investigated the catalytic mechanism of backbone phosphodiester hydrolysis by the restriction enzyme EcoRV by means of hybrid quantum mechanical/molecular mechanical calculations. An exhaustive computation of different reaction pathways is performed, thus generating a network of pathways. Comparison of the computed (AM1d/MM) enzymatic reaction pathways with an analogous mechanism for small-molecule model systems [AM1/d and B3LYP/6-31++G(d,p)] reveals that the transition barriers for associative hydrolysis, which is more probable in the model systems, are not lowered by the enzyme. Instead, a reaction mechanism which has mostly dissociative character is more likely. The protein environment is tuned to significantly electrostatically stabilize the transition state structures. The direct catalytic impact of essential residues is determined: The magnesium metal ion activates a water molecule, thus facilitating protonation of the leaving group. A reduction of the coordination number of the magnesium metal ion from six to four upon the positioning of the attacking water molecule explains why larger metal ions, such as calcium, are not catalytically active. The nucleophile is generated by the transfer of a proton from the attacking water molecule to a carboxylic oxygen atom of aspartate 90. The catalytic effect of lysine 92 involves proper positioning of the scissile phosphate group and, more importantly, stabilization of the metaphosphate intermediate in an orientation optimal for attack of the nucleophile.

  17. Multi-source micro-friction identification for a class of cable-driven robots with passive backbone

    NASA Astrophysics Data System (ADS)

    Tjahjowidodo, Tegoeh; Zhu, Ke; Dailey, Wayne; Burdet, Etienne; Campolo, Domenico

    2016-12-01

    This paper analyses the dynamics of cable-driven robots with a passive backbone and develops techniques for their dynamic identification, which are tested on the H-Man, a planar cabled differential transmission robot for haptic interaction. The mechanism is optimized for human-robot interaction by accounting for the cost-benefit-ratio of the system, specifically by eliminating the necessity of an external force sensor to reduce the overall cost. As a consequence, this requires an effective dynamic model for accurate force feedback applications which include friction behavior in the system. We first consider the significance of friction in both the actuator and backbone spaces. Subsequently, we study the required complexity of the stiction model for the application. Different models representing different levels of complexity are investigated, ranging from the conventional approach of Coulomb to an advanced model which includes hysteresis. The results demonstrate each model's ability to capture the dynamic behavior of the system. In general, it is concluded that there is a trade-off between model accuracy and the model cost.

  18. Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid.

    PubMed

    Babbitt, Gregory A; Alawad, Mohammed A; Schulze, Katharina V; Hudson, André O

    2014-01-01

    While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (≈GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an 'accessory' during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context.

  19. Synonymous codon bias and functional constraint on GC3-related DNA backbone dynamics in the prokaryotic nucleoid

    PubMed Central

    Babbitt, Gregory A.; Alawad, Mohammed A.; Schulze, Katharina V.; Hudson, André O.

    2014-01-01

    While mRNA stability has been demonstrated to control rates of translation, generating both global and local synonymous codon biases in many unicellular organisms, this explanation cannot adequately explain why codon bias strongly tracks neighboring intergene GC content; suggesting that structural dynamics of DNA might also influence codon choice. Because minor groove width is highly governed by 3-base periodicity in GC, the existence of triplet-based codons might imply a functional role for the optimization of local DNA molecular dynamics via GC content at synonymous sites (≈GC3). We confirm a strong association between GC3-related intrinsic DNA flexibility and codon bias across 24 different prokaryotic multiple whole-genome alignments. We develop a novel test of natural selection targeting synonymous sites and demonstrate that GC3-related DNA backbone dynamics have been subject to moderate selective pressure, perhaps contributing to our observation that many genes possess extreme DNA backbone dynamics for their given protein space. This dual function of codons may impose universal functional constraints affecting the evolution of synonymous and non-synonymous sites. We propose that synonymous sites may have evolved as an ‘accessory’ during an early expansion of a primordial genetic code, allowing for multiplexed protein coding and structural dynamic information within the same molecular context. PMID:25200075

  20. [Generation of vector backbone-free and selectable marker-free transgenic maize (Zea mays L.) via ovary-drip method].

    PubMed

    Yang, Ai-Fu; Su, Qiao; An, Li-Jia

    2009-01-01

    The presence of vector backbone sequences and selectable marker genes in transgenic plants has been the key concern for biosafety. A direct solution is to totally avoid the use of vector backbone sequences and selectable marker genes from the beginning of transgenic plant generation. In this study, the ovary-drip method was established and optimized. The key features of this method focused on the complete removal of the whole styles, and the subsequent application of a DNA solution directly to the ovaries. A vector backbone-free and selectable marker-free linear GFP cassette (Ubi-GFP -nos) was transformed into maize via the ovary-drip method. PCR analysis showed that suitable maize variety was 9818 and optimal transformation time was 18-20 h after pollination, which produced the highest PCR positive frequency (3.01%). Southern blotting analysis showed that the transgenic plants had simple integration patterns (1-2 bands). GFP transcription was de-tected by RT-PCR analysis. Green fluorescence was observed in roots and immature embryos of transgenic plants by a fluorescence microscopy.

  1. Protein structure refinement by optimization.

    PubMed

    Carlsen, Martin; Røgen, Peter

    2015-09-01

    Knowledge-based protein potentials are simplified potentials designed to improve the quality of protein models, which is important as more accurate models are more useful for biological and pharmaceutical studies. Consequently, knowledge-based potentials often are designed to be efficient in ordering a given set of deformed structures denoted decoys according to how close they are to the relevant native protein structure. This, however, does not necessarily imply that energy minimization of this potential will bring the decoys closer to the native structure. In this study, we introduce an iterative strategy to improve the convergence of decoy structures. It works by adding energy optimized decoys to the pool of decoys used to construct the next and improved knowledge-based potential. We demonstrate that this strategy results in significantly improved decoy convergence on Titan high resolution decoys and refinement targets from Critical Assessment of protein Structure Prediction competitions. Our potential is formulated in Cartesian coordinates and has a fixed backbone potential to restricts motions to be close to those of a dihedral model, a fixed hydrogen-bonding potential and a variable coarse grained carbon alpha potential consisting of a pair potential and a novel solvent potential that are b-spline based as we use explicit gradient and Hessian for efficient energy optimization. © 2015 Wiley Periodicals, Inc.

  2. Protein Side-Chain Resonance Assignment and NOE Assignment Using RDC-Defined Backbones without TOCSY Data3

    PubMed Central

    Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

    2011-01-01

    One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA have backbone RMSD 0

  3. Optimization of the bamboo guadua angustifolia kunth in the elaboration of glued laminated elements for constructive use

    NASA Astrophysics Data System (ADS)

    Díaz, G. A.; Cruz, R. A.; Chávez, A. M.

    2013-11-01

    Bamboo is considered one of the best timber resources in the world because for its mechanical properties and high sustainability; this research aims to improve the mechanical properties of the laminated glued bamboo Guadua Angustifolia Kunth (GAK) for use as structural elements, starting from de very manufacture process; this is important because it is possible to observe variations in the flexural strength and the elastic modulus in GAK samples taken from different heights and thickness of the culm. In order to analyze the influence of these final mechanical properties variations in the laminated, the height of the culm where samples are extracted (cepa, basa and sobrebasa) it is taken as a variable from where different types of laminated were manufactured, seeking to make optimal the configuration based in the transversal section area and the material strength. Three assemblies were designed varying the overlap of the adhesion lines and it concluded that the highest strength average values were obtained in the laminated composites manufactured with samples taken from the bottom of the culm (basa), which is possible because in these elements there are less adhesion lines than the other ones (middle, top and mixed) or the better matching of themselves.

  4. Construction of high-resolution stochastic geological models and optimal upscaling to a simplified layer-type hydrogeological model

    NASA Astrophysics Data System (ADS)

    Quental, Paulo; Almeida, José António; Simões, Manuela

    2012-04-01

    Despite inequalities in spatial resolution between stochastic geological models and flow simulator models, geostatistical algorithms are used for the characterisation of groundwater systems. From available data to grid-block hydraulic parameters, workflows basically utilise the development of a detailed geostatistical model (morphology and properties) followed by upscaling. This work aims to design and test a two-step methodology encompassing the generation of a high-resolution 3D stochastic geological model and simplification into a low-resolution groundwater layer-type model. First, a high-resolution 3D stochastic model of rock types or hydrofacies (sets of rock types with similar hydraulic characteristics) is generated using an enhanced version of the sequential indicator simulation (SIS) with corrections for local probabilities and for two- and three-point template statistics. In a second step, the high-resolution geological model provided by SIS is optimally simplified into a small set of layers according to a supervised simulated annealing (SA) optimisation procedure and at the end equivalent hydraulic properties are upscaled. Two outcomes are provided by this methodology: (1) a regular 2D mesh of the top and bottom limits of each hydrogeological unit or layer from a conceptual model and (2), for each layer, a 2D grid-block of equivalent hydraulic parameters prepared to be inputted into an aquifer simulator. This methodology was tested for the upper aquifer area of SPEL (Sociedade Portuguesa de Explosivos), an explosives deactivation plant in Seixal municipality, Portugal.

  5. Optimal construction of a fast and accurate polarisable water potential based on multipole moments trained by machine learning.

    PubMed

    Handley, Chris M; Hawe, Glenn I; Kell, Douglas B; Popelier, Paul L A

    2009-08-14

    To model liquid water correctly and to reproduce its structural, dynamic and thermodynamic properties warrants models that account accurately for electronic polarisation. We have previously demonstrated that polarisation can be represented by fluctuating multipole moments (derived by quantum chemical topology) predicted by multilayer perceptrons (MLPs) in response to the local structure of the cluster. Here we further develop this methodology of modeling polarisation enabling control of the balance between accuracy, in terms of errors in Coulomb energy and computing time. First, the predictive ability and speed of two additional machine learning methods, radial basis function neural networks (RBFNN) and Kriging, are assessed with respect to our previous MLP based polarisable water models, for water dimer, trimer, tetramer, pentamer and hexamer clusters. Compared to MLPs, we find that RBFNNs achieve a 14-26% decrease in median Coulomb energy error, with a factor 2.5-3 slowdown in speed, whilst Kriging achieves a 40-67% decrease in median energy error with a 6.5-8.5 factor slowdown in speed. Then, these compromises between accuracy and speed are improved upon through a simple multi-objective optimisation to identify Pareto-optimal combinations. Compared to the Kriging results, combinations are found that are no less accurate (at the 90th energy error percentile), yet are 58% faster for the dimer, and 26% faster for the pentamer.

  6. Modeling 15N NMR chemical shift changes in protein backbone with pressure

    NASA Astrophysics Data System (ADS)

    La Penna, Giovanni; Mori, Yoshiharu; Kitahara, Ryo; Akasaka, Kazuyuki; Okamoto, Yuko

    2016-08-01

    Nitrogen chemical shift is a useful parameter for determining the backbone three-dimensional structure of proteins. Empirical models for fast calculation of N chemical shift are improving their reliability, but there are subtle effects that cannot be easily interpreted. Among these, the effects of slight changes in hydrogen bonds, both intramolecular and with water molecules in the solvent, are particularly difficult to predict. On the other hand, these hydrogen bonds are sensitive to changes in protein environment. In this work, the change of N chemical shift with pressure for backbone segments in the protein ubiquitin is correlated with the change in the population of hydrogen bonds involving the backbone amide group. The different extent of interaction of protein backbone with the water molecules in the solvent is put in evidence.

  7. The radical cationic repair pathway of cyclobutane pyrimidine dimer: the effect of sugar-phosphate backbone.

    PubMed

    Ebrahimi, Ali; Habibi-Khorassani, Mostafa; Shahraki, Asiyeh

    2013-01-01

    Radical cationic repair process of cis-syn thymine dimer has been investigated when (1) sugar-phosphate backbones were substituted by hydrogen atoms, (2) phosphate group was substituted by two hydrogen atoms each on a sugar ring and (3) sugar-phosphate backbone was taken into account. The effect of the interactions between N1 and N1' lone pairs and the C6-C6' antibonding orbital are the most important evidences for the cleavage of the C6-C6' bond in the first step of radical cationic repair mechanism in the absence of the sugar-phosphate backbone. The impact of the N1 and N1' lone pairs on the C6-C6' bond cleavage decreases and the energy barrier of the cleavage of that bond significantly increases in the presence of the deoxynucleoside sugars and the sugar-phosphate backbone. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  8. A comprehensive library of blocked dipeptides reveals intrinsic backbone conformational propensities of unfolded proteins.

    PubMed

    Oh, Kwang-Im; Lee, Kyung-Koo; Park, Eun-Kyung; Jung, Youngae; Hwang, Geum-Sook; Cho, Minhaeng

    2012-04-01

    Despite prolonged scientific efforts to elucidate the intrinsic peptide backbone preferences of amino-acids based on understanding of intermolecular forces, many open questions remain, particularly concerning neighboring peptide interaction effects on the backbone conformational distribution of short peptides and unfolded proteins. Here, we show that spectroscopic studies of a complete library of 400 dipeptides reveal that, irrespective of side-chain properties, the backbone conformation distribution is narrow and they adopt polyproline II and β-strand, indicating the importance of backbone peptide solvation and electronic effects. By directly comparing the dipeptide circular dichroism and NMR results with those of unfolded proteins, the comprehensive dipeptides form a complete set of structural motifs of unfolded proteins. We thus anticipate that the present dipeptide library with spectroscopic data can serve as a useful database for understanding the nature of unfolded protein structures and for further refinements of molecular mechanical parameters. Copyright © 2011 Wiley Periodicals, Inc.

  9. Increasing Sequence Diversity with Flexible Backbone Protein Design: The Complete Redesign of a Protein Hydrophobic Core

    SciTech Connect

    Murphy, Grant S.; Mills, Jeffrey L.; Miley, Michael J.; Machius, Mischa; Szyperski, Thomas; Kuhlman, Brian

    2015-10-15

    Protein design tests our understanding of protein stability and structure. Successful design methods should allow the exploration of sequence space not found in nature. However, when redesigning naturally occurring protein structures, most fixed backbone design algorithms return amino acid sequences that share strong sequence identity with wild-type sequences, especially in the protein core. This behavior places a restriction on functional space that can be explored and is not consistent with observations from nature, where sequences of low identity have similar structures. Here, we allow backbone flexibility during design to mutate every position in the core (38 residues) of a four-helix bundle protein. Only small perturbations to the backbone, 12 {angstrom}, were needed to entirely mutate the core. The redesigned protein, DRNN, is exceptionally stable (melting point >140C). An NMR and X-ray crystal structure show that the side chains and backbone were accurately modeled (all-atom RMSD = 1.3 {angstrom}).

  10. Modeling (15)N NMR chemical shift changes in protein backbone with pressure.

    PubMed

    La Penna, Giovanni; Mori, Yoshiharu; Kitahara, Ryo; Akasaka, Kazuyuki; Okamoto, Yuko

    2016-08-28

    Nitrogen chemical shift is a useful parameter for determining the backbone three-dimensional structure of proteins. Empirical models for fast calculation of N chemical shift are improving their reliability, but there are subtle effects that cannot be easily interpreted. Among these, the effects of slight changes in hydrogen bonds, both intramolecular and with water molecules in the solvent, are particularly difficult to predict. On the other hand, these hydrogen bonds are sensitive to changes in protein environment. In this work, the change of N chemical shift with pressure for backbone segments in the protein ubiquitin is correlated with the change in the population of hydrogen bonds involving the backbone amide group. The different extent of interaction of protein backbone with the water molecules in the solvent is put in evidence.

  11. Combining dehydration, construct optimization and improved data collection to solve the crystal structure of a CRM1-RanGTP-SPN1-Nup214 quaternary nuclear export complex.

    PubMed

    Monecke, Thomas; Dickmanns, Achim; Weiss, Manfred S; Port, Sarah A; Kehlenbach, Ralph H; Ficner, Ralf

    2015-12-01

    High conformational flexibility is an intrinsic and indispensable property of nuclear transport receptors, which makes crystallization and structure determination of macromolecular complexes containing exportins or importins particularly challenging. Here, the crystallization and structure determination of a quaternary nuclear export complex consisting of the exportin CRM1, the small GTPase Ran in its GTP-bound form, the export cargo SPN1 and an FG repeat-containing fragment of the nuclear pore complex component nucleoporin Nup214 fused to maltose-binding protein is reported. Optimization of constructs, seeding and the development of a sophisticated protocol including successive PEG-mediated crystal dehydration as well as additional post-mounting steps were essential to obtain well diffracting crystals.

  12. An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h)

    PubMed Central

    2017-01-01

    The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom—the backbone dihedral angles φ and ψ (Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide’s conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ =  − 100°  left-handed or right-handed?). This report provides a new metric for backbone handedness (h) based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone’s internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θ)d∕|d|, with range [−1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0°) and trans (ω = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ, ψ) space. These maps fill in the ‘dead space’ within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including cis

  13. A simple model of backbone flexibility improves modeling of side-chain conformational variability.

    PubMed

    Friedland, Gregory D; Linares, Anthony J; Smith, Colin A; Kortemme, Tanja

    2008-07-18

    The considerable flexibility of side-chains in folded proteins is important for protein stability and function, and may have a role in mediating allosteric interactions. While sampling side-chain degrees of freedom has been an integral part of several successful computational protein design methods, the predictions of these approaches have not been directly compared to experimental measurements of side-chain motional amplitudes. In addition, protein design methods frequently keep the backbone fixed, an approximation that may substantially limit the ability to accurately model side-chain flexibility. Here, we describe a Monte Carlo approach to modeling side-chain conformational variability and validate our method against a large dataset of methyl relaxation order parameters derived from nuclear magnetic resonance (NMR) experiments (17 proteins and a total of 530 data points). We also evaluate a model of backbone flexibility based on Backrub motions, a type of conformational change frequently observed in ultra-high-resolution X-ray structures that accounts for correlated side-chain backbone movements. The fixed-backbone model performs reasonably well with an overall rmsd between computed and predicted side-chain order parameters of 0.26. Notably, including backbone flexibility leads to significant improvements in modeling side-chain order parameters for ten of the 17 proteins in the set. Greater accuracy of the flexible backbone model results from both increases and decreases in side-chain flexibility relative to the fixed-backbone model. This simple flexible-backbone model should be useful for a variety of protein design applications, including improved modeling of protein-protein interactions, design of proteins with desired flexibility or rigidity, and prediction of correlated motions within proteins.

  14. Evaluating the performance of CMIP5 GCMs in Northern Eurasia and constructing optimal ensemble projection: analysis of regional precipitation patterns (Invited)

    NASA Astrophysics Data System (ADS)

    Kokorev, V.; Anisimov, O. A.

    2013-12-01

    Despite significant improvements in the complexity and quality of the global climate models, even the most recent CMIP-5 GCMs differ in results at regional scale. Several studies have tried to assess and quantify the uncertainties of temperature and atmospheric pressure parameters, while the evaluation of precipitation parameters at regional scale is yet to be done. The goal of this study is to perform comprehensive analysis of precipitation uncertainty for Northern Eurasia. To accomplish this goal we contrast selected precipitation parameters from two generations of CMIP5 and CMIP3 GCMs with observations at regional level and suggest the methodology for constructing the optimal ensemble projection. We used data from 744 Russian weather stations to identify 14 regions in Northern Eurasia characterized by coherent changes of temperature characteristics and precipitation. In each region we identified the tipping point, which divide timeseries into baseline period and period of contemporary climate change, and tested the ability of GCMs to simulate precipitation patterns and trends in each region. Ultimately, we ranked GCMs according to their performance in representing regional precipitation parameters. We used this ranking to construct several regional ensembles consisting of different number of high-ranked models and compared results from these optimized ensembles with observations and with the ensemble of all models. The ultimate conclusion of our study is that the methodology based on pre-selection of top ranked models allows narrowing the range of uncertainty in climate projection at regional level. With latest generation of GCMs this methodology could be applied not only to air temperature but also to precipitation parameters. We also found that models from CMIP5 generation demonstrate much higher performance than CMIP3 models in replicating precipitation parameters in the period of contemporary climate change. Acknowledgement. This study is supported by the

  15. Construction of nested genetic core collections to optimize the exploitation of natural diversity in Vitis vinifera L. subsp. sativa

    PubMed Central

    Le Cunff, Loïc; Fournier-Level, Alexandre; Laucou, Valérie; Vezzulli, Silvia; Lacombe, Thierry; Adam-Blondon, Anne-Françoise; Boursiquot, Jean-Michel; This, Patrice

    2008-01-01

    Background The first high quality draft of the grape genome sequence has just been published. This is a critical step in accessing all the genes of this species and increases the chances of exploiting the natural genetic diversity through association genetics. However, our basic knowledge of the extent of allelic variation within the species is still not sufficient. Towards this goal, we constructed nested genetic core collections (G-cores) to capture the simple sequence repeat (SSR) diversity of the grape cultivated compartment (Vitis vinifera L. subsp. sativa) from the world's largest germplasm collection (Domaine de Vassal, INRA Hérault, France), containing 2262 unique genotypes. Results Sub-samples of 12, 24, 48 and 92 varieties of V. vinifera L. were selected based on their genotypes for 20 SSR markers using the M-strategy. They represent respectively 58%, 73%, 83% and 100% of total SSR diversity. The capture of allelic diversity was analyzed by sequencing three genes scattered throughout the genome on 233 individuals: 41 single nucleotide polymorphisms (SNPs) were identified using the G-92 core (one SNP for every 49 nucleotides) while only 25 were observed using a larger sample of 141 individuals selected on the basis of 50 morphological traits, thus demonstrating the reliability of the approach. Conclusion The G-12 and G-24 core-collections displayed respectively 78% and 88% of the SNPs respectively, and are therefore of great interest for SNP discovery studies. Furthermore, the nested genetic core collections satisfactorily reflected the geographic and the genetic diversity of grape, which are also of great interest for the study of gene evolution in this species. PMID:18384667

  16. Construction of Core Collections Suitable for Association Mapping to Optimize Use of Mediterranean Olive (Olea europaea L.) Genetic Resources

    PubMed Central

    El Bakkali, Ahmed; Haouane, Hicham; Moukhli, Abdelmajid; Costes, Evelyne; Van Damme, Patrick; Khadari, Bouchaib

    2013-01-01

    Phenotypic characterisation of germplasm collections is a decisive step towards association mapping analyses, but it is particularly expensive and tedious for woody perennial plant species. Characterisation could be more efficient if focused on a reasonably sized subset of accessions, or so-called core collection (CC), reflecting the geographic origin and variability of the germplasm. The questions that arise concern the sample size to use and genetic parameters that should be optimized in a core collection to make it suitable for association mapping. Here we investigated these questions in olive (Olea europaea L.), a perennial fruit species. By testing different sampling methods and sizes in a worldwide olive germplasm bank (OWGB Marrakech, Morocco) containing 502 unique genotypes characterized by nuclear and plastid loci, a two-step sampling method was proposed. The Shannon-Weaver diversity index was found to be the best criterion to be maximized in the first step using the Core Hunter program. A primary core collection of 50 entries (CC50) was defined that captured more than 80% of the diversity. This latter was subsequently used as a kernel with the Mstrat program to capture the remaining diversity. 200 core collections of 94 entries (CC94) were thus built for flexibility in the choice of varieties to be studied. Most entries of both core collections (CC50 and CC94) were revealed to be unrelated due to the low kinship coefficient, whereas a genetic structure spanning the eastern and western/central Mediterranean regions was noted. Linkage disequilibrium was observed in CC94 which was mainly explained by a genetic structure effect as noted for OWGB Marrakech. Since they reflect the geographic origin and diversity of olive germplasm and are of reasonable size, both core collections will be of major interest to develop long-term association studies and thus enhance genomic selection in olive species. PMID:23667437

  17. Construction of core collections suitable for association mapping to optimize use of Mediterranean olive (Olea europaea L.) genetic resources.

    PubMed

    El Bakkali, Ahmed; Haouane, Hicham; Moukhli, Abdelmajid; Costes, Evelyne; Van Damme, Patrick; Khadari, Bouchaib

    2013-01-01

    Phenotypic characterisation of germplasm collections is a decisive step towards association mapping analyses, but it is particularly expensive and tedious for woody perennial plant species. Characterisation could be more efficient if focused on a reasonably sized subset of accessions, or so-called core collection (CC), reflecting the geographic origin and variability of the germplasm. The questions that arise concern the sample size to use and genetic parameters that should be optimized in a core collection to make it suitable for association mapping. Here we investigated these questions in olive (Olea europaea L.), a perennial fruit species. By testing different sampling methods and sizes in a worldwide olive germplasm bank (OWGB Marrakech, Morocco) containing 502 unique genotypes characterized by nuclear and plastid loci, a two-step sampling method was proposed. The Shannon-Weaver diversity index was found to be the best criterion to be maximized in the first step using the Core Hunter program. A primary core collection of 50 entries (CC50) was defined that captured more than 80% of the diversity. This latter was subsequently used as a kernel with the Mstrat program to capture the remaining diversity. 200 core collections of 94 entries (CC94) were thus built for flexibility in the choice of varieties to be studied. Most entries of both core collections (CC50 and CC94) were revealed to be unrelated due to the low kinship coefficient, whereas a genetic structure spanning the eastern and western/central Mediterranean regions was noted. Linkage disequilibrium was observed in CC94 which was mainly explained by a genetic structure effect as noted for OWGB Marrakech. Since they reflect the geographic origin and diversity of olive germplasm and are of reasonable size, both core collections will be of major interest to develop long-term association studies and thus enhance genomic selection in olive species.

  18. Optimal sequence selection in proteins of known structure by simulated evolution.

    PubMed Central

    Hellinga, H W; Richards, F M

    1994-01-01

    Rational design of protein structure requires the identification of optimal sequences to carry out a particular function within a given backbone structure. A general solution to this problem requires that a potential function describing the energy of the system as a function of its atomic coordinates be minimized simultaneously over all available sequences and their three-dimensional atomic configurations. Here we present a method that explicitly minimizes a semiempirical potential function simultaneously in these two spaces, using a simulated annealing approach. The method takes the fixed three-dimensional coordinates of a protein backbone and stochastically generates possible sequences through the introduction of random mutations. The corresponding three-dimensional coordinates are constructed for each sequence by "redecorating" the backbone coordinates of the original structure with the corresponding side chains. These are then allowed to vary in their structure by random rotations around free torsional angles to generate a stochastic walk in configurational space. We have named this method protein simulated evolution, because, in loose analogy with natural selection, it randomly selects for allowed solutions in the sequence of a protein subject to the "selective pressure" of a potential function. Energies predicted by this method for sequences of a small group of residues in the hydrophobic core of the phage lambda cI repressor correlate well with experimentally determined biological activities. This "genetic selection by computer" approach has potential applications in protein engineering, rational protein design, and structure-based drug discovery. PMID:8016069

  19. Bio-cathode materials evaluation and configuration optimization for power output of vertical subsurface flow constructed wetland - microbial fuel cell systems.

    PubMed

    Liu, Shentan; Song, Hailiang; Wei, Size; Yang, Fei; Li, Xianning

    2014-08-01

    To optimize the performance of a vertical subsurface flow constructed wetland-microbial fuel cell (CW-MFC), studies of bio-cathode materials and reactor configurations were carried out. Three commonly used bio-cathode materials including stainless steel mesh (SSM), carbon cloth (CC) and granular activated carbon (GAC) were compared and evaluated. GAC-SSM bio-cathode achieved the highest maximum power density of 55.05 mWm(-2), and it was most suitable for CW-MFCs application because of its large surface area and helpful capillary water absorption. Two types of CW-MFCs with roots were constructed, one was placed in the anode and the other was placed in the cathode. Both planted CW-MFCs obtained higher power output than non-planted CW-MFC. Periodic voltage fluctuations of planted CW-MFCs were caused by light/dark cycles, and the influent substrate concentration significantly affected the amplitude of oscillation. The coulombic efficiencies of CW-MFCs decreased greatly with the increase of the influent substrate concentration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11.

    PubMed

    Fowler, Melissa L; McPhail, Jacob A; Jenkins, Meredith L; Masson, Glenn R; Rutaganira, Florentine U; Shokat, Kevan M; Williams, Roger L; Burke, John E

    2016-04-01

    The ability of proteins to bind and interact with protein partners plays fundamental roles in many cellular contexts. X-ray crystallography has been a powerful approach to understand protein-protein interactions; however, a challenge in the crystallization of proteins and their complexes is the presence of intrinsically disordered regions. In this article, we describe an application of hydrogen deuterium exchange mass spectrometry (HDX-MS) to identify dynamic regions within type III phosphatidylinositol 4 kinase beta (PI4KIIIβ) in complex with the GTPase Rab11. This information was then used to design deletions that allowed for the production of diffraction quality crystals. Importantly, we also used HDX-MS to verify that the new construct was properly folded, consistent with it being catalytically and functionally active. Structures of PI4KIIIβ in an Apo state and bound to the potent inhibitor BQR695 in complex with both GTPγS and GDP loaded Rab11 were determined. This hybrid HDX-MS/crystallographic strategy revealed novel aspects of the PI4KIIIβ-Rab11 complex, as well as the molecular mechanism of potency of a PI4K specific inhibitor (BQR695). This approach is widely applicable to protein-protein complexes, and is an excellent strategy to optimize constructs for high-resolution structural approaches.

  1. Optimization of construct design and fermentation strategy for the production of bioactive ATF-SAP, a saporin based anti-tumoral uPAR-targeted chimera.

    PubMed

    Errico Provenzano, Alfredo; Posteri, Riccardo; Giansanti, Francesco; Angelucci, Francesco; Flavell, Sopsamorn U; Flavell, David J; Fabbrini, Maria Serena; Porro, Danilo; Ippoliti, Rodolfo; Ceriotti, Aldo; Branduardi, Paola; Vago, Riccardo

    2016-11-14

    The big challenge in any anti-tumor therapeutic approach is represented by the development of drugs selectively acting on the target with limited side effects, that exploit the unique characteristics of malignant cells. The urokinase (urokinase-type plasminogen activator, uPA) and its receptor uPAR have been identified as preferential target candidates since they play a key role in the evolution of neoplasms and are associated with neoplasm aggressiveness and poor clinical outcome in several different tumor types. To selectively target uPAR over-expressing cancer cells, we prepared a set of chimeric proteins (ATF-SAP) formed by the human amino terminal fragments (ATF) of uPA and the plant ribosome inactivating protein saporin (SAP). Codon-usage optimization was used to increase the expression levels of the chimera in the methylotrophic yeast Pichia pastoris. We then moved the bioprocess to bioreactors and demonstrated that the fed-batch production of the recombinant protein can be successfully achieved, obtaining homogeneous discrete batches of the desired constructs. We also determined the cytotoxic activity of the obtained batch of ATF-SAP which was specifically cytotoxic for U937 leukemia cells, while another construct containing a catalytically inactive mutant form of SAP showed no activity. Our results demonstrate that the uPAR-targeted, saporin-based recombinant fusion ATF-SAP can be produced in a fed-batch fermentation with full retention of the molecules selective cytotoxicity and hence therapeutic potential.

  2. Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11

    PubMed Central

    Fowler, Melissa L.; McPhail, Jacob A.; Jenkins, Meredith L.; Masson, Glenn R.; Rutaganira, Florentine U.; Shokat, Kevan M.; Williams, Roger L.

    2016-01-01

    Abstract The ability of proteins to bind and interact with protein partners plays fundamental roles in many cellular contexts. X‐ray crystallography has been a powerful approach to understand protein‐protein interactions; however, a challenge in the crystallization of proteins and their complexes is the presence of intrinsically disordered regions. In this article, we describe an application of hydrogen deuterium exchange mass spectrometry (HDX‐MS) to identify dynamic regions within type III phosphatidylinositol 4 kinase beta (PI4KIIIβ) in complex with the GTPase Rab11. This information was then used to design deletions that allowed for the production of diffraction quality crystals. Importantly, we also used HDX‐MS to verify that the new construct was properly folded, consistent with it being catalytically and functionally active. Structures of PI4KIIIβ in an Apo state and bound to the potent inhibitor BQR695 in complex with both GTPγS and GDP loaded Rab11 were determined. This hybrid HDX‐MS/crystallographic strategy revealed novel aspects of the PI4KIIIβ‐Rab11 complex, as well as the molecular mechanism of potency of a PI4K specific inhibitor (BQR695). This approach is widely applicable to protein‐protein complexes, and is an excellent strategy to optimize constructs for high‐resolution structural approaches. PMID:26756197

  3. A quantitative experimental paradigm to optimize construction of rank order lists in the National Resident Matching Program: the ROSS-MOORE approach.

    PubMed

    Ross, David A; Moore, Edward Z

    2013-09-01

    As part of the National Resident Matching Program, programs must submit a rank order list of desired applicants. Despite the importance of this process and the numerous manifest limitations with traditional approaches, minimal research has been conducted to examine the accuracy of different ranking strategies. The authors developed the Moore Optimized Ordinal Rank Estimator (MOORE), a novel algorithm for ranking applicants that is based on college sports ranking systems. Because it is not possible to study the Match in vivo, the authors then designed the Recruitment Outcomes Simulation System (ROSS). This program was used to simulate a series of interview seasons and to compare MOORE and traditional approaches under different conditions. The accuracy of traditional ranking and the MOORE approach are equally and adversely affected with higher levels of intrarater variability. However, compared with traditional ranking methods, MOORE produces a more accurate rank order list as interrater variability increases. The present data demonstrate three key findings. First, they provide proof of concept that it is possible to scientifically test the accuracy of different rank methods used in the Match. Second, they show that small amounts of variability can have a significant adverse impact on the accuracy of rank order lists. Finally, they demonstrate that an ordinal approach may lead to a more accurate rank order list in the presence of interviewer bias. The ROSS-MOORE approach offers programs a novel way to optimize the recruitment process and, potentially, to construct a more accurate rank order list.

  4. The multiscale backbone of the human phenotype network based on biological pathways

    PubMed Central

    2014-01-01

    Background Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes. Results The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. We extract the multi-scale information backbone of the PHPN based on the local densities of the network and discarding weak connection. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present examples of expected clinical connections identified by PHPN as proof of principle. Conclusions We unveil a previously uncharacterized connection between phenotype modules and discuss potential mechanistic connections that are obvious only in retrospect. The PHPN shows tremendous potential to become a useful tool both in the unveiling of the diseases’ common biology, and in the elaboration of diagnosis and treatments. PMID:24460644

  5. An efficient randomized algorithm for contact-based NMR backbone resonance assignment.

    PubMed

    Kamisetty, Hetunandan; Bailey-Kellogg, Chris; Pandurangan, Gopal

    2006-01-15

    Backbone resonance assignment is a critical bottleneck in studies of protein structure, dynamics and interactions by nuclear magnetic resonance (NMR) spectroscopy. A minimalist approach to assignment, which we call 'contact-based', seeks to dramatically reduce experimental time and expense by replacing the standard suite of through-bond experiments with the through-space (nuclear Overhauser enhancement spectroscopy, NOESY) experiment. In the contact-based approach, spectral data are represented in a graph with vertices for putative residues (of unknown relation to the primary sequence) and edges for hypothesized NOESY interactions, such that observed spectral peaks could be explained if the residues were 'close enough'. Due to experimental ambiguity, several incorrect edges can be hypothesized for each spectral peak. An assignment is derived by identifying consistent patterns of edges (e.g. for alpha-helices and beta-sheets) within a graph and by mapping the vertices to the primary sequence. The key algorithmic challenge is to be able to uncover these patterns even when they are obscured by significant noise. This paper develops, analyzes and applies a novel algorithm for the identification of polytopes representing consistent patterns of edges in a corrupted NOESY graph. Our randomized algorithm aggregates simplices into polytopes and fixes inconsistencies with simple local modifications, called rotations, that maintain most of the structure already uncovered. In characterizing the effects of experimental noise, we employ an NMR-specific random graph model in proving that our algorithm gives optimal performance in expected polynomial time, even when the input graph is significantly corrupted. We confirm this analysis in simulation studies with graphs corrupted by up to 500% noise. Finally, we demonstrate the practical application of the algorithm on several experimental beta-sheet datasets. Our approach is able to eliminate a large majority of noise edges and to

  6. Quantitative 2D and 3D Gamma-HCP experiments for the determination of the angles alpha and zeta in the phosphodiester backbone of oligonucleotides.

    PubMed

    Nozinovic, Senada; Richter, Christian; Rinnenthal, Jörg; Fürtig, Boris; Duchardt-Ferner, Elke; Weigand, Julia E; Schwalbe, Harald

    2010-08-04

    The quantitative Gamma-(HCP) experiment, a novel heteronuclear NMR pulse sequence for the determination of the RNA backbone angles alpha(O3'(i-1)-P(i)-O5'(i)-C5'(i)) and zeta(C3'(i)-O3'(i)-P(i+1)-O5'(i+1)) in (13)C-labeled RNA, is introduced. The experiment relies on the interaction between the CH bond vector dipole and the (31)P chemical shift anisotropy (CSA), which affects the relaxation of the (13)C,(31)P double- and zero-quantum coherence and thus the intensity of the detectable magnetization. With the new pulse sequence, five different cross-correlated relaxation rates along the phosphodiester backbone can be measured in a quantitative manner, allowing projection-angle and torsion-angle restraints for the two backbone angles alpha and zeta to be extracted. Two versions of the pulse sequence optimized for the CH and CH(2) groups are introduced and demonstrated for a 14-mer cUUCGg tetraloop RNA model system and for a 27-mer RNA with a previously unknown structure. The restraints were incorporated into the calculation of a very high resolution structure of the RNA model system (Nozinovic, S.; et al. Nucleic Acids Res. 2010, 38, 683). Comparison with the X-ray structure of the cUUCGg tetraloop confirmed the high quality of the data, suggesting that the method can significantly improve the quality of RNA structure determination.

  7. 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.

    PubMed

    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.

  8. Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses.

    PubMed

    Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nantawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

    2012-02-14

    Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby canine kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 2(9) HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems.

  9. Cloned cDNA of A/swine/Iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza A viruses

    PubMed Central

    Lekcharoensuk, Porntippa; Wiriyarat, Witthawat; Petcharat, Nuntawan; Lekcharoensuk, Chalermpol; Auewarakul, Prasert; Richt, Juergen A

    2012-01-01

    Reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted A/Puerto Rico/8/34 (PR8) strain. This egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. In order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate (A/swine/Iowa/15/30 (H1N1) (rg1930) that was shown to give high yield in Madin-Darby Canine Kidney (MDCK) cells was used as the internal gene donor for reverse genetics plasmids. In this report, the internal genes from rg1930 were used for construction of reverse genetics viruses carrying a cleavage site-modified hemagglutinin (HA) gene and neuraminidase (NA) gene from a highly pathogenic H5N1 virus. The resulting virus (rg1930H5N1) was low pathogenic in vivo. Inactivated rg1930H5N1 vaccine completely protected chickens from morbidity and mortality after challenge with highly pathogenic H5N1. Protective immunity was obtained when chickens were immunized with an inactivated vaccine consisting of at least 29 HA units of the rg1930H5N1 virus. In comparison to the PR8-based reverse genetics viruses carrying the same HA and NA genes from an H5N1 virus, rg1930 based viruses yielded higher viral titers in MDCK and Vero cells. In addition, the reverse genetics derived H3N2 and H5N2 viruses with the rg1930 backbone replicated in MDCK cells better than the cognate viruses with the rgPR8 backbone. It is concluded that this newly established reverse genetics backbone system could serve as a candidate for a master donor strain for development of inactivated influenza vaccines in cell-based systems. PMID:22230579

  10. An exhaustive survey of regular peptide conformations using a new metric for backbone handedness ( h )

    DOE PAGES

    Mannige, Ranjan V.

    2017-05-16

    The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom—the backbone dihedral anglesφandψ(Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function ofφandψhas not been completely described for bothcisandtransbackbones. Additionally, little intuitive understanding is available about a peptide’s conformation simply from knowing theφandψvalues of a peptide (e.g., is the regular peptide defined byφ = ψ =  - 100°  left-handed or right-handed?). This report provides a new metric for backbone handednessmore » (h) based on interpreting a peptide backbone as a helix with axial displacementdand angular displacementθ, both of which are derived from a peptide backbone’s internal coordinates, especially dihedral anglesφ,ψandω. In particular,hequals sin(θ)d/d|, with range [-1, 1] and negative (or positive) values indicating left(or right)-handedness. The metrichis used to characterize the handedness of every region of the Ramachandran plot for bothcis(ω = 0°) and trans (ω = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ,ψ) space. These maps fill in the ‘dead space’ within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based ondandθthat serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone includingcisandtransbackbones. The intuitiveness

  11. Subgraph "backbone" analysis of dynamic brain networks during consciousness and anesthesia.

    PubMed

    Shin, Jeongkyu; Mashour, George A; Ku, Seungwoo; Kim, Seunghwan; Lee, Uncheol

    2013-01-01

    General anesthesia significantly alters brain network connectivity. Graph-theoretical analysis has been used extensively to study static brain networks but may be limited in the study of rapidly changing brain connectivity during induction of or recovery from general anesthesia. Here we introduce a novel method to study the temporal evolution of network modules in the brain. We recorded multichannel electroencephalograms (EEG) from 18 surgical patients who underwent general anesthesia with either propofol (n = 9) or sevoflurane (n = 9). Time series data were used to reconstruct networks; each electroencephalographic channel was defined as a node and correlated activity between the channels was defined as a link. We analyzed the frequency of subgraphs in the network with a defined number of links; subgraphs with a high probability of occurrence were deemed network "backbones." We analyzed the behavior of network backbones across consciousness, anesthetic induction, anesthetic maintenance, and two points of recovery. Constitutive, variable and state-specific backbones were identified across anesthetic state transitions. Brain networks derived from neurophysiologic data can be deconstructed into network backbones that change rapidly across states of consciousness. This technique enabled a granular description of network evolution over time. The concept of network backbones may facilitate graph-theoretical analysis of dynamically changing networks.

  12. Backbone dipoles generate positive potentials in all proteins: origins and implications of the effect.

    PubMed Central

    Gunner, M R; Saleh, M A; Cross, E; ud-Doula, A; Wise, M

    2000-01-01

    Asymmetry in packing the peptide amide dipole results in larger positive than negative regions in proteins of all folding motifs. The average side chain potential in 305 proteins is 109 +/- 30 mV (2. 5 +/- 0.7 kcal/mol/e). Because the backbone has zero net charge, the non-zero potential is unexpected. The larger oxygen at the negative and smaller proton at the positive end of the amide dipole yield positive potentials because: 1) at allowed phi and psi angles residues come off the backbone into the positive end of their own amide dipole, avoiding the large oxygen; and 2) amide dipoles with their carbonyl oxygen surface exposed and amine proton buried make the protein interior more positive. Twice as many amides have their oxygens exposed than their amine protons. The distribution of acidic and basic residues shows the importance of the bias toward positive backbone potentials. Thirty percent of the Asp, Glu, Lys, and Arg are buried. Sixty percent of buried residues are acids, only 40% bases. The positive backbone potential stabilizes ionization of 20% of the acids by >3 pH units (-4.1 kcal/mol). Only 6.5% of the bases are equivalently stabilized by negative regions. The backbone stabilizes bound anions such as phosphates and rarely stabilizes bound cations. PMID:10692303

  13. Vel-IO 3D: A tool for 3D velocity model construction, optimization and time-depth conversion in 3D geological modeling workflow

    NASA Astrophysics Data System (ADS)

    Maesano, Francesco E.; D'Ambrogi, Chiara

    2017-02-01

    We present Vel-IO 3D, a tool for 3D velocity model creation and time-depth conversion, as part of a workflow for 3D model building. The workflow addresses the management of large subsurface dataset, mainly seismic lines and well logs, and the construction of a 3D velocity model able to describe the variation of the velocity parameters related to strong facies and thickness variability and to high structural complexity. Although it is applicable in many geological contexts (e.g. foreland basins, large intermountain basins), it is particularly suitable in wide flat regions, where subsurface structures have no surface expression. The Vel-IO 3D tool is composed by three scripts, written in Python 2.7.11, that automate i) the 3D instantaneous velocity model building, ii) the velocity model optimization, iii) the time-depth conversion. They determine a 3D geological model that is consistent with the primary geological constraints (e.g. depth of the markers on wells). The proposed workflow and the Vel-IO 3D tool have been tested, during the EU funded Project GeoMol, by the construction of the 3D geological model of a flat region, 5700 km2 in area, located in the central part of the Po Plain. The final 3D model showed the efficiency of the workflow and Vel-IO 3D tool in the management of large amount of data both in time and depth domain. A 4 layer-cake velocity model has been applied to a several thousand (5000-13,000 m) thick succession, with 15 horizons from Triassic up to Pleistocene, complicated by a Mesozoic extensional tectonics and by buried thrusts related to Southern Alps and Northern Apennines.

  14. New reconstruction of the sunspot group numbers since 1739 using direct calibration and "backbone" methods

    NASA Astrophysics Data System (ADS)

    Chatzistergos, Theodosios; Usoskin, Ilya G.; Kovaltsov, Gennady A.; Krivova, Natalie A.; Solanki, Sami K.

    2017-06-01

    Context. The group sunspot number (GSN) series constitute the longest instrumental astronomical database providing information on solar activity. This database is a compilation of observations by many individual observers, and their inter-calibration has usually been performed using linear rescaling. There are multiple published series that show different long-term trends for solar activity. Aims: We aim at producing a GSN series, with a non-linear non-parametric calibration. The only underlying assumptions are that the differences between the various series are due to different acuity thresholds of the observers, and that the threshold of each observer remains constant throughout the observing period. Methods: We used a daisy chain process with backbone (BB) observers and calibrated all overlapping observers to them. We performed the calibration of each individual observer with a probability distribution function (PDF) matrix constructed considering all daily values for the overlapping period with the BB. The calibration of the BBs was carried out in a similar manner. The final series was constructed by merging different BB series. We modelled the propagation of errors straightforwardly with Monte Carlo simulations. A potential bias due to the selection of BBs was investigated and the effect was shown to lie within the 1σ interval of the produced series. The exact selection of the reference period was shown to have a rather small effect on our calibration as well. Results: The final series extends back to 1739 and includes data from 314 observers. This series suggests moderate activity during the 18th and 19th century, which is significantly lower than the high level of solar activity predicted by other recent reconstructions applying linear regressions. Conclusions: The new series provides a robust reconstruction, based on modern and non-parametric methods, of sunspot group numbers since 1739, and it confirms the existence of the modern grand maximum of solar

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Fast extraction of the backbone of projected bipartite networks to aid community detection

    NASA Astrophysics Data System (ADS)

    Liebig, J.; Rao, A.

    2016-01-01

    This paper introduces a computationally inexpensive method for extracting the backbone of one-mode networks projected from bipartite networks. We show that the edge weights in the one-mode projections are distributed according to a Poisson binomial distribution and that finding the expected weight distribution of a one-mode network projected from a random bipartite network only requires knowledge of the bipartite degree distributions. Being able to extract the backbone of a projection is highly beneficial in filtering out redundant information in large complex networks and narrowing down the information in the one-mode projection to the most relevant. We demonstrate that the backbone of a one-mode projection aids in the detection of communities.

  18. Improved Generation of Induced Cardiomyocytes Using a Polycistronic Construct Expressing Optimal Ratio of Gata4, Mef2c and Tbx5

    PubMed Central

    Wang, Li; Liu, Ziqing; Yin, Chaoying; Zhou, Yang; Liu, Jiandong; Qian, Li

    2017-01-01

    Direct conversion of cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) holds great potential for regenerative medicine by offering alternative strategies for treatment of heart disease. This conversion has been achieved by forced expression of defined factors such as Gata4 (G), Mef2c (M) and Tbx5 (T). Traditionally, iCMs are generated by a cocktail of viruses expressing these individual factors. However, reprogramming efficiency is relatively low and most of the in vitro G,M,T-transduced fibroblasts do not become fully reprogrammed, making it difficult to study the reprogramming mechanisms. We recently have shown that the stoichiometry of G,M,T is crucial for efficient iCM reprogramming. An optimal stoichiometry of G,M,T with relative high level of M and low levels of G and T achieved by using our polycistronic MGT vector (hereafter referred to as MGT) significantly increased reprogramming efficiency and improved iCM quality in vitro. Here we provide a detailed description of the methodology used to generate iCMs with MGT construct from cardiac fibroblasts. Isolation of cardiac fibroblasts, generation of virus for reprogramming and evaluation of the reprogramming process are also included to provide a platform for efficient and reproducible generation of iCMs. PMID:26649751

  19. Selecting Question-Specific Genes to Reduce Incongruence in Phylogenomics: A Case Study of Jawed Vertebrate Backbone Phylogeny.

    PubMed

    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. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Naphthodithiophene-Based Conjugated Polymer with Linear, Planar Backbone Conformation and Strong Intermolecular Packing for Efficient Organic Solar Cells.

    PubMed

    Lee, Jaewon; Ko, Hyomin; Song, Eunjoo; Kim, Heung Gyu; Cho, Kilwon

    2015-09-30

    Two donor-acceptor copolymers, PBDT and PNDT, containing 4,8-bis(2-ethylhexyloxy)benzo[1,2-b:3,4-b']dithiophene (BDT) and 4,9-bis(2-ethylhexyloxy)naphtho[1,2-b:5,6-b']dithiophene (NDT), respectively, as an electron-rich unit and 5,6-difluoro-2,1,3-benzothiadiazole (2FBT) as an electron-deficient unit, were synthesized and compared. The introduction of the NDT core into the conjugated backbone was found to effectively improve both light harvesting and the charge carrier mobility by enhancing chain planarity and backbone linearity; the NDT copolymer has stronger noncovalent interactions and smaller bond angles than those of the BDT-based polymer. Moreover, the introduction of the NDT core brings about a drastic change in the molecular orientation into the face-on motif and results in polymer:PCBM blend films with well-mixed interpenetrating nanofibrillar bulk-heterojunction networks with small-scale phase separation, which produce solar cells with higher short-circuit current density and fill factor values. A conventional optimized device structure containing PNDT:PC71BM was found to exhibit a maximum solar efficiency of 6.35%, an open-circuit voltage of 0.84 V, a short-circuit current density of 11.92 mA cm(-2), and a fill factor of 63.5% with thermal annealing, which demonstrates that the NDT and DT2FBT moieties are a promising electron-donor/acceptor combination for high-performance photovoltaics.

  1. Electric field induced localization phenomena in a ladder network with superlattice configuration: Effect of backbone environment

    SciTech Connect

    Dutta, Paramita; Karmakar, S. N.; Maiti, Santanu K.

    2014-09-15

    Electric field induced localization properties of a tight-binding ladder network in presence of backbone sites are investigated. Based on Green's function formalism we numerically calculate two-terminal transport together with density of states for different arrangements of atomic sites in the ladder and its backbone. Our results lead to a possibility of getting multiple mobility edges which essentially plays a switching action between a completely opaque to fully or partly conducting region upon the variation of system Fermi energy, and thus, support in fabricating mesoscopic or DNA-based switching devices.

  2. Solvation thermodynamics of amino acid side chains on a short peptide backbone

    SciTech Connect

    Hajari, Timir; Vegt, Nico F. A. van der

    2015-04-14

    The hydration process of side chain analogue molecules differs from that of the actual amino acid side chains in peptides and proteins owing to the effects of the peptide backbone on the aqueous solvent environment. A recent molecular simulation study has provided evidence that all nonpolar side chains, attached to a short peptide backbone, are considerably less hydrophobic than the free side chain analogue molecules. In contrast to this, the hydrophilicity of the polar side chains is hardly affected by the backbone. To analyze the origin of these observations, we here present a molecular simulation study on temperature dependent solvation free energies of nonpolar and polar side chains attached to a short peptide backbone. The estimated solvation entropies and enthalpies of the various amino acid side chains are compared with existing side chain analogue data. The solvation entropies and enthalpies of the polar side chains are negative, but in absolute magnitude smaller compared with the corresponding analogue data. The observed differences are large; however, owing to a nearly perfect enthalpy-entropy compensation, the solvation free energies of polar side chains remain largely unaffected by the peptide backbone. We find that a similar compensation does not apply to the nonpolar side chains; while the backbone greatly reduces the unfavorable solvation entropies, the solvation enthalpies are either more favorable or only marginally affected. This results in a very small unfavorable free energy cost, or even free energy gain, of solvating the nonpolar side chains in strong contrast to solvation of small hydrophobic or nonpolar molecules in bulk water. The solvation free energies of nonpolar side chains have been furthermore decomposed into a repulsive cavity formation contribution and an attractive dispersion free energy contribution. We find that cavity formation next to the peptide backbone is entropically favored over formation of similar sized nonpolar side

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Polyolefin backbone substitution in binders for low temperature powder injection moulding feedstocks.

    PubMed

    Hausnerova, Berenika; Kuritka, Ivo; Bleyan, Davit

    2014-02-27

    This paper reports the substitution of polyolefin backbone binder components with low melting temperature carnauba wax for powder injection moulding applications. The effect of various binder compositions of Al₂O₃ feedstock on thermal degradation parameters is investigated by thermogravimetric analysis. Within the experimental framework 29 original feedstock compositions were prepared and the superiority of carnauba wax over the polyethylene binder backbone was demonstrated in compositions containing polyethylene glycol as the initial opening agent and governing the proper mechanism of the degradation process. Moreover, the replacement of synthetic polymer by the natural wax contributes to an increase of environmental sustainability of modern industrial technologies.

  5. Ebolavirus VP35 Coats the Backbone of Double-Stranded RNA for Interferon Antagonism

    PubMed Central

    Bale, Shridhar; Julien, Jean-Philippe; Bornholdt, Zachary A.; Krois, Alexander S.; Wilson, Ian A.

    2013-01-01

    Recognition of viral double-stranded RNA (dsRNA) activates interferon production and immune signaling in host cells. Crystal structures of ebolavirus VP35 show that it caps dsRNA ends to prevent sensing by pattern recognition receptors such as RIG-I. In contrast, structures of marburgvirus VP35 show that it primarily coats the dsRNA backbone. Here, we demonstrate that ebolavirus VP35 also coats the dsRNA backbone in solution, although binding to the dsRNA ends probably constitutes the initial binding event. PMID:23824825

  6. Convenient and Scalable Synthesis of Fmoc-Protected Peptide Nucleic Acid Backbone

    PubMed Central

    Feagin, Trevor A.; Shah, Nirmal I.; Heemstra, Jennifer M.

    2012-01-01

    The peptide nucleic acid backbone Fmoc-AEG-OBn has been synthesized via a scalable and cost-effective route. Ethylenediamine is mono-Boc protected, then alkylated with benzyl bromoacetate. The Boc group is removed and replaced with an Fmoc group. The synthesis was performed starting with 50 g of Boc anhydride to give 31 g of product in 32% overall yield. The Fmoc-protected PNA backbone is a key intermediate in the synthesis of nucleobase-modified PNA monomers. Thus, improved access to this molecule is anticipated to facilitate future investigations into the chemical properties and applications of nucleobase-modified PNA. PMID:22848796

  7. Randomized controlled trials: still the backbone of vascular surgery?

    PubMed

    Naylor, A R

    Prior to the introduction of evidence-based medicine, decision-making was largely based upon 'intuitive reasoning', whereby senior clinicians dictated practice based upon personal dogma, personal experience and (often) biased observational studies. This era began to end (in vascular surgery) following completion of the landmark randomized trials in carotid disease, which recruited patients throughout the 1980s. Despite scepticism amongst some surgeons of the time these particular randomized trials have stood the test of time and remain the cornerstone of virtually every guideline of practice to this day. The carotid randomized trials became a beacon for using 'evidence' rather than 'intuitive reasoning' and randomized trials have now been used to determine optimal practice in a plethora of carotid surgery and stenting trials, lower limb revascularization and numerous aortic aneurysm based studies. The literature abounds with situations where practice (previously based on observational study data) was changed overnight following publication of a well-designed randomized trial. However, while observational studies are prone to selection bias, randomized trials bring their own unique limitations including problems with external validity, they take too long to complete, they are very expensive, they are notorious for problems with recruitment and they can frequently become obsolete. This has led to a (not unreasonable) call for more observational studies to be used in the development of practice guidelines. Unfortunately, the principle guideline bodies around the world, e.g. National Institute for Health and Care Excellence (NICE) and the American Heart Association (AHA), prioritize randomized trial evidence above all else. Until that changes, guideline makers will find it very difficult to deviate from using historical randomized trial evidence, even when high quality observational data suggest that 'real world' practice bears little comparison to that reported in the

  8. The Zurich Tradition: Backbone of the Wolf Number Series (Invited)

    NASA Astrophysics Data System (ADS)

    Friedli, T. K.

    2013-12-01

    The Wolf Series of Sunspot Relative Numbers is divided into a more recent part starting from 1849 up to present which is based on dedicated visual observations and into a reconstructed part reaching back to the mythological ages of Galileo, Harriot and Scheiner which is based solely on indirect countings made from drawings or texts from various archives. The Zurich tradition consists of a framework of rules and prerequisites concerning the quality and power of the instrumentation, the observation and counting techniques, the methods for calibration and preservation of scale and the construction of a long-term record. This framework guarantees the homogeneity of the series and the preservation of the original scale. In the modern part of the series up to 1980, the published Wolf numbers are based in over 90% of the days on calibrated visual observations of the original Fraunhofer refractor. The long term preservation of the original scale is thus mainly determined by the quality and validity of the calibration from one generation of standard observers to the next and on the internal consistency of the individual observing and counting methods of each standard observer. Since 1996 the historical standard refractor of Rudolf Wolf, in succession of the Zurich observers, has been used by the author for the daily determination of the sunspot relative number. With the aid of a small network of keen amateur astronomers of the Rudolf Wolf Gesellschaft these observations could be calibrated to the former Zurich scale. This results in an extension of the original Zurich series which is independent from the official one by SIDC or from the one by AAVSO. The main lesson learned from this exercise is that calibration functions reduce to simple proportionality factors as long as the calculations are made within a proper statistical regression framework over a sufficiently long evaluation period covering both maximum and minimum activity phases. Based on the original observations

  9. Effects of Protein Stabilizing Agents on Thermal Backbone Motions: A Disulfide Trapping Study†

    PubMed Central

    Butler, Scott L.; Falke, Joseph J.

    2010-01-01

    Chemical stabilizers are widely used to enhance protein stability, both in nature and in the laboratory. Here, the molecular mechanism of chemical stabilizers is studied using a disulfide trapping assay to measure the effects of stabilizers on thermal backbone dynamics in the Escherichia coli galactose/glucose binding protein. Two types of backbone fluctuations are examined: (a) relative movements of adjacent surface α-helices within the same domain and (b) interdomain twisting motions. Both types of fluctuations are significantly reduced by all six stabilizers tested (glycerol, sucrose, trehalose, l-glucose, d-glucose, and d-galactose), and in each case larger amplitude motions are inhibited more than smaller ones. Motional inhibition does not require a high-affinity stabilizer binding site, indicating that the effects of stabilizers are nonspecific. Overall, the results support the theory that effective stabilizing agents act by favoring the most compact structure of a protein, thereby reducing local backbone fluctuations away from the fully folded state. Such inhibition of protein backbone dynamics may be a general mechanism of protein stabilization in extreme thermal or chemical environments. PMID:8718847

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

    ERIC Educational Resources Information Center

    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…

  11. On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.

    PubMed

    Sharp, Kim A; O'Brien, Evan; Kasinath, Vignesh; Wand, A Joshua

    2015-05-01

    Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O(2) NH ) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O(2) NH  < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O(2) axis . A calibration curve for backbone entropy vs. O(2) NH is developed, which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O(2) NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, for example, upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O(2) axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. © 2015 Wiley Periodicals, Inc.

  12. On the relationship between NMR-derived amide order parameters and protein backbone entropy changes

    PubMed Central

    Sharp, Kim A.; O’Brien, Evan; Kasinath, Vignesh; Wand, A. Joshua

    2015-01-01

    Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O2NH) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O2NH < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O2axis. A calibration curve for backbone entropy vs. O2NH is developed which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O2NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, e.g. upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O2axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. PMID:25739366

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

    ERIC Educational Resources Information Center

    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…

  14. Residue-Specific Side-Chain Packing Determines the Backbone Dynamics of Transmembrane Model Helices

    PubMed Central

    Quint, Stefan; Widmaier, Simon; Minde, David; Hornburg, Daniel; Langosch, Dieter; Scharnagl, Christina

    2010-01-01

    The transmembrane domains (TMDs) of membrane-fusogenic proteins contain an overabundance of β-branched residues. In a previous effort to systematically study the relation among valine content, fusogenicity, and helix dynamics, we developed model TMDs that we termed LV-peptides. The content and position of valine in LV-peptides determine their fusogenicity and backbone dynamics, as shown experimentally. Here, we analyze their conformational dynamics and the underlying molecular forces using molecular-dynamics simulations. Our study reveals that backbone dynamics is correlated with the efficiency of side-chain to side-chain van der Waals packing between consecutive turns of the helix. Leu side chains rapidly interconvert between two rotameric states, thus favoring contacts to its i±3 and i±4 neighbors. Stereochemical restraints acting on valine side chains in the α-helix force both β-substituents into an orientation where i,i±3 interactions are less favorable than i,i±4 interactions, thus inducing a local packing deficiency at VV3 motifs. We provide a quantitative molecular model to explain the relationship among chain connectivity, side-chain mobility, and backbone flexibility. We expect that this mechanism also defines the backbone flexibility of natural TMDs. PMID:20959095

  15. Automated extraction of backbone deuteration levels from amide H/2H mass spectrometry experiments

    PubMed Central

    Hotchko, Matthew; Anand, Ganesh S.; Komives, Elizabeth A.; Ten Eyck, Lynn F.

    2006-01-01

    A Fourier deconvolution method has been developed to explicitly determine the amount of backbone amide deuterium incorporated into protein regions or segments by hydrogen/deuterium (H/D) exchange with high-resolution mass spectrometry. Determination and analysis of the level and number of backbone amide exchanging in solution provide more information about the solvent accessibility of the protein than do previous centroid methods, which only calculate the average deuterons exchanged. After exchange, a protein is digested into peptides as a way of determining the exchange within a local area of the protein. The mass of a peptide upon deuteration is a sum of the natural isotope abundance, fast exchanging side-chain hydrogens (present in MALDI-TOF H/2H data) and backbone amide exchange. Removal of the components of the isotopic distribution due to the natural isotope abundances and the fast exchanging side-chains allows for a precise quantification of the levels of backbone amide exchange, as is shown by an example from protein kinase A. The deconvoluted results are affected by overlapping peptides or inconsistent mass envelopes, and evaluation procedures for these cases are discussed. Finally, a method for determining the back exchange corrected populations is presented, and its effect on the data is discussed under various circumstances. PMID:16501228

  16. Insights on chiral, backbone modified peptide nucleic acids: Properties and biological activity

    PubMed Central

    Moccia, Maria; Adamo, Mauro F A; Saviano, Michele

    2014-01-01

    PNAs are emerging as useful synthetic devices targeting natural miRNAs. In particular 3 classes of structurally modified PNAs analogs are herein described, namely α, β and γ, which differ by their backbone modification. Their mode and binding affinity for natural nucleic acids and their use in medicinal chemistry as potential miRNA binders is discussed. PMID:26752710

  17. Oligonucleotides with conjugated dihydropyrroloindole tripeptides: base composition and backbone effects on hybridization.

    PubMed Central

    Kutyavin, I V; Lukhtanov, E A; Gamper, H B; Meyer, R B

    1997-01-01

    The ability of conjugated minor groove binding (MGB) residues to stabilize nucleic acid duplexes was investigated by synthesis of oligonucleotides bearing a tethered dihydropyrroloindole tripeptide (CDPI3). Duplexes bearing one or more of these conjugated MGBs were varied by base composition (AT- or GC-rich oligonucleotides), backbone modifications (phosphodiester DNA, 2'-O-methyl phosphodiester RNA or phosphorothioate DNA) and site of attachment of the MGB moiety (5'- or 3'-end of either duplex strand). Melting temperatures of the duplexes were determined. The conjugated CDPI3 residue enhanced the stability of virtually all duplexes studied. The extent of stabilization was backbone and sequence dependent and reached a maximum value of 40-49 degrees C for d(pT)8. d(pA)8. Duplexes with a phosphorothioate DNA backbone responded similarly on CDPI3 conjugation, although they were less stable than analogous phosphodiesters. Modest stabilization was obtained for duplexes with a 2'-O-methyl RNA backbone. The conjugated CDPI3 residue stabilized GC-rich DNA duplexes, albeit to a lesser extent than for AT-rich duplexes of the same length. PMID:9278496

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

    ERIC Educational Resources Information Center

    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…

  19. Increasing Sequence Diversity with Flexible Backbone Protein Design: The Complete Redesign of a Protein Hydrophobic Core

    PubMed Central

    Murphy, Grant S.; Mills, Jeffrey L.; Miley, Michael J.; Machius, Mischa; Szyperski, Thomas; Kuhlman, Brian

    2012-01-01

    Summary Protein design tests our understanding of protein stability and structure. Successful design methods should allow the exploration of sequence space not found in nature. However, when redesigning naturally occurring protein structures most fixed backbone design algorithms return amino acid sequences that share strong sequence identity with wild-type sequences, especially in the protein core. This behavior places a restriction on functional space that can be explored and is not consistent with observations from nature, where sequences of low identity have similar structures. Here, we allow backbone flexibility during design to mutate every position in the core (38 residues) of a four-helix bundle protein. Only small perturbations to the backbone, 1-2 Å, were needed to entirely mutate the core. The redesigned protein, DRNN, is exceptionally stable (melting point > 140 °C). An NMR and X-ray crystal structure show that the side chains and backbone were accurately modeled (all-atom RMSD = 1.3 Å). PMID:22632833

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

    ERIC Educational Resources Information Center

    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…

  1. Linear discrete diffraction and transverse localization of light in two-dimensional backbone lattices.

    PubMed

    Qi, Yiling; Zhang, Guoquan

    2010-09-13

    We study the linear discrete diffraction characteristics of light in two-dimensional backbone lattices. It is found that, as the refractive index modulation depth of the backbone lattice increases, high-order band gaps become open and broad in sequence, and the allowed band curves of the Floquet-Bloch modes become flat gradually. As a result, the diffraction pattern at the exit face converges gradually for both the on-site and off-site excitation cases. Particularly, when the refractive index modulation depth of the backbone lattice is high enough, for example, on the order of 0.01 for a square lattice, the light wave propagating in the backbone lattice will be localized in transverse dimension for both the on-site and off-site excitation cases. This is because only the first several allowed bands with nearly flat band curves are excited in the lattice, and the transverse expansion velocities of the Floquet-Bloch modes in these flat allowed bands approach to zero. Such a linear transverse localization of light may have potential applications in navigating light propagation dynamics and optical signal processing.

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

    PubMed

    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.

  3. Fc-optimized NKG2D-Fc constructs induce NK cell antibody-dependent cellular cytotoxicity against breast cancer cells independently of HER2/neu expression status.

    PubMed

    Raab, Stefanie; Steinbacher, Julia; Schmiedel, Benjamin J; Kousis, Philaretos C; Steinle, Alexander; Jung, Gundram; Grosse-Hovest, Ludger; Salih, Helmut R

    2014-10-15

    The ability of NK cells to mediate Ab-dependent cellular cytotoxicity (ADCC) largely contributes to the clinical success of antitumor Abs, including trastuzumab, which is approved for the treatment of breast cancer with HER2/neu overexpression. Notably, only ∼25% of breast cancer patients overexpress HER2/neu. Moreover, HER2/neu is expressed on healthy cells, and trastuzumab application is associated with side effects. In contrast, the ligands of the activating immunoreceptor NKG2D (NKG2DL) are selectively expressed on malignant cells. In this study, we took advantage of the tumor-associated expression of NKG2DL by using them as target Ags for NKG2D-IgG1 fusion proteins optimized by amino acid exchange S239D/I332E in their Fc part. Compared to constructs with wild-type Fc parts, fusion proteins carrying the S239D/I332E modification (NKG2D-Fc-ADCC) mediated highly enhanced degranulation, ADCC, and IFN-γ production of NK cells in response to breast cancer cells. NKG2D-Fc-ADCC substantially enhanced NK reactivity also against HER2/neu-low targets that were unaffected by trastuzumab, as both compounds mediated their immunostimulatory effects in strict dependence of target Ag expression levels. Thus, in line with the hierarchically organized potential of the various activating receptors governing NK reactivity and due to its highly increased affinity to CD16, NKG2D-Fc-ADCC potently enhances NK cell reactivity despite the inevitable reduction of activating signals upon binding to NKG2DL. Due to the tumor-restricted expression of NKG2DL, NKG2D-Fc-ADCC may constitute an attractive means for immunotherapy especially of HER2/neu-low or -negative breast cancer.

  4. Sparsity-optimized separation of body waves and ground-roll by constructing dictionaries using tunable Q-factor wavelet transforms with different Q-factors

    NASA Astrophysics Data System (ADS)

    Chen, Xin; Chen, Wenchao; Wang, Xiaokai; Wang, Wei

    2017-10-01

    Low-frequency oscillatory ground-roll is regarded as one of the main regular interference waves, which obscures primary reflections in land seismic data. Suppressing the ground-roll can reasonably improve the signal-to-noise ratio of seismic data. Conventional suppression methods, such as high-pass and various f-k filtering, usually cause waveform distortions and loss of body wave information because of their simple cut-off operation. In this study, a sparsity-optimized separation of body waves and ground-roll, which is based on morphological component analysis theory, is realized by constructing dictionaries using tunable Q-factor wavelet transforms with different Q-factors. Our separation model is grounded on the fact that the input seismic data are composed of low-oscillatory body waves and high-oscillatory ground-roll. Two different waveform dictionaries using a low Q-factor and a high Q-factor, respectively, are confirmed as able to sparsely represent each component based on their diverse morphologies. Thus, seismic data including body waves and ground-roll can be nonlinearly decomposed into low-oscillatory and high-oscillatory components. This is a new noise attenuation approach according to the oscillatory behaviour of the signal rather than the scale or frequency. We illustrate the method using both synthetic and field shot data. Compared with results from conventional high-pass and f-k filtering, the results of the proposed method prove this method to be effective and advantageous in preserving the waveform and bandwidth of reflections.

  5. Toward Improved Description of DNA Backbone: Revisiting Epsilon and Zeta Torsion Force Field Parameters

    PubMed Central

    Zgarbová, Marie; Luque, F. Javier; Šponer, Jiří; Cheatham, Thomas E.; Otyepka, Michal; Jurečka, Petr

    2013-01-01

    We present a refinement of the backbone torsion parameters ε and ζ of the Cornell et al. AMBER force field for DNA simulations. The new parameters, denoted as εζOL1, were derived from quantum-mechanical calculations with inclusion of conformation-dependent solvation effects according to the recently reported methodology (J. Chem. Theory Comput. 2012, 7(9), 2886-2902). The performance of the refined parameters was analyzed by means of extended molecular dynamics (MD) simulations for several representative systems. The results showed that the εζOL1 refinement improves the backbone description of B-DNA double helices and G-DNA stem. In B-DNA simulations, we observed an average increase of the helical twist and narrowing of the major groove, thus achieving better agreement with X-ray and solution NMR data. The balance between populations of BI and BII backbone substates was shifted towards the BII state, in better agreement with ensemble-refined solution experimental results. Furthermore, the refined parameters decreased the backbone RMS deviations in B-DNA MD simulations. In the antiparallel guanine quadruplex (G-DNA) the εζOL1 modification improved the description of non-canonical α/γ backbone substates, which were shown to be coupled to the ε/ζ torsion potential. Thus, the refinement is suggested as a possible alternative to the current ε/ζ torsion potential, which may enable more accurate modeling of nucleic acids. However, long-term testing is recommended before its routine application in DNA simulations. PMID:24058302

  6. A backbone design principle for covalent organic frameworks: the impact of weakly interacting units on CO2 adsorption.

    PubMed

    Zhai, Lipeng; Huang, Ning; Xu, Hong; Chen, Qiuhong; Jiang, Donglin

    2017-03-31

    Covalent organic frameworks are designed to have backbones with different yet discrete contents of triarylamine units that interact weakly with CO2. Adsorption experiments indicate that the triarylamine units dominate the CO2 adsorption process and the CO2 uptake increases monotonically with the triarylamine content. These profound collective effects reveal a principle for designing backbones targeting for CO2 capture and separation.

  7. Backbone chemical shift assignments for Xanthomonas campestris peroxiredoxin Q in the reduced and oxidized states: a dramatic change in backbone dynamics.

    PubMed

    Buchko, Garry W; Perkins, Arden; Parsonage, Derek; Poole, Leslie B; Karplus, P Andrew

    2016-04-01

    Peroxiredoxins (Prx) are ubiquitous enzymes that reduce peroxides as part of antioxidant defenses and redox signaling. While Prx catalytic activity and sensitivity to hyperoxidative inactivation depend on their dynamic properties, there are few examples where their dynamics has been characterized by NMR spectroscopy. Here, we provide a foundation for studies of the solution properties of peroxiredoxin Q from the plant pathogen Xanthomonas campestris (XcPrxQ) by assigning the observable (1)H(N), (15)N, (13)C(α), (13)C(β), and (13)C' chemical shifts for both the reduced (dithiol) and oxidized (disulfide) states. In the reduced state, most of the backbone amide resonances (149/152, 98 %) can be assigned in the XcPrxQ (1)H-(15)N HSQC spectrum. In contrast, a remarkable 51 % (77) of these amide resonances are not visible in the (1)H-(15)N HSQC spectrum of the disulfide state of the enzyme, indicating a substantial change in backbone dynamics associated with the formation of an intramolecular C48-C84 disulfide bond.

  8. Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Dinesh, Bhimareddy; Squillaci, Marco A.; Ménard-Moyon, Cécilia; Samorì, Paolo; Bianco, Alberto

    2015-09-01

    The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to transform the nanofibers into spherical structures. Moreover, the co-assembly of β and γ peptides with carbon nanotubes covalently functionalized with the same peptide generated unique dendritic assemblies. This comparative study on self-assembly using diphenylalanine backbone homologues and of the co-assembly with CNT covalent conjugates is the first example exploring the capacity of β and γ peptides to adopt precise nanostructures, particularly in combination with carbon nanotubes. The dendritic organization obtained by mixing carbon nanotubes and peptides might find interesting applications in tissue engineering and neuronal interfacing.The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to

  9. Backbone dynamics measurements on leukemia inhibitory factor, a rigid four-helical bundle cytokine.

    PubMed Central

    Yao, S.; Smith, D. K.; Hinds, M. G.; Zhang, J. G.; Nicola, N. A.; Norton, R. S.

    2000-01-01

    The backbone dynamics of the four-helical bundle cytokine leukemia inhibitory factor (LIF) have been investigated using 15N NMR relaxation and amide proton exchange measurements on a murine-human chimera, MH35-LIF. For rapid backbone motions (on a time scale of 10 ps to 100 ns), as probed by 15N relaxation measurements, the dynamics parameters were calculated using the model-free formalism incorporating the model selection approach. The principal components of the inertia tensor of MH35-LIF, as calculated from its NMR structure, were 1:0.98:0.38. The global rotational motion of the molecule was, therefore, assumed to be axially symmetric in the analysis of its relaxation data. This yielded a diffusion anisotropy D(parallel)/D(perpendicular) of 1.31 and an effective correlation time (4D(perpendicular) + 2D(parallel))(-1) of 8.9 ns. The average values of the order parameters (S2) for the four helices, the long interhelical loops, and the N-terminus were 0.91, 0.84, and 0.65, respectively, indicating that LIF is fairly rigid in solution, except at the N-terminus. The S2 values for the long interhelical loops of MH35-LIF were higher than those of their counterparts in short-chain members of the four-helical bundle cytokine family. Residues involved in LIF receptor binding showed no consistent pattern of backbone mobilities, with S2 values ranging from 0.71 to 0.95, but residues contributing to receptor binding site III had relatively lower S2 values, implying higher amplitude motions than for the backbone of sites I and II. In the relatively slow motion regime, backbone amide exchange measurements showed that a number of amides from the helical bundle exchanged extremely slowly, persisting for several months in 2H2O at 37 degrees C. Evidence for local unfolding was considered, and correlations among various structure-related parameters and the backbone amide exchange rates were examined. Both sets of data concur in showing that LIF is one of the most rigid four

  10. Increasing plasmid-based DNA vaccine construct (16 kb pSVK-HBVA) production in Escherichia coli XL10-Gold through optimization of media component.

    PubMed

    Wang, Yu; Zhang, Liang; Zhang, Wei; Wu, Hao; Zhu, Xiao Ming; Xu, Yuan Ji; Yan, Jin Qi; Yu, Ji Yun

    2015-01-02

    At present, there are production processes to produce protein by Escherichia coli (E. coli) fermentation. Research on the design and optimization of the plasmid fermentation medium, however, is less advanced. The fermentation medium that is optimized for plasmid DNA production is different from the medium that is optimized for protein production. So, establishing a scientific and rational method to optimize the fermentation medium used for plasmid production is very important. Previously, our laboratory developed a novel therapeutic DNA vaccine (named pSVK-HBVA) for hepatitis B based on the alphavirus replicon, and found that E. coli XL10-Gold was the optimal host strain for the production of plasmid pSVK-HBVA. The aim of this study was to establish a scientific and rational method to optimize the fermentation medium used for plasmid production, and investigate the effect of growth medium composition on the production of plasmid pSVK-HBVA harboured in E. coli XL10-Gold, as well as to optimize the medium composition. The one-factor-at-a-time experiments demonstrated that Luria-Bertani (LB) was the optimal basic medium. The optimal carbon source and nitrogen source were glycerol and home-made proteose peptone, respectively. Based on the Plackett-Burman (PB) design, proteose peptone, glycerol and NH4Cl were identified as the significant variables, which were further optimized by the steepest ascent (descent) method and central composite design. Growth medium optimization in 500-mL shake flasks by response surface methodology resulted in a maximum volumetric yield of 13.61 mg/L, which was approximately 2.5 times higher than that obtained from the basic medium (LB).

  11. SABBAC: online Structural Alphabet-based protein BackBone reconstruction from Alpha-Carbon trace

    PubMed Central

    Maupetit, Julien; Gautier, R.; Tufféry, Pierre

    2006-01-01

    SABBAC is an on-line service devoted to protein backbone reconstruction from alpha-carbon trace. It is based on the assembly of fragments taken from a library of reduced size, selected from the encoding of the protein trace in a hidden Markov model-derived structural alphabet. The assembly of the fragments is achieved by a greedy algorithm, using an energy-based scoring. Alpha-carbon coordinates remain unaffected. SABBAC simply positions the missing backbone atoms, no further refinement is performed. From our tests, SABBAC performs equal or better than other similar on-line approach and is robust to deviations on the alpha-carbon coordinates. It can be accessed at . PMID:16844979

  12. How Sensitive Is the Amide I Vibration of the Polypeptide Backbone to Electric Field?

    PubMed Central

    Oh, Kwang-Im; Fiorin, Giacomo

    2015-01-01

    Site-selective isotopic labelling of amide carbonyls offers a non-perturbative means to introduce a localized infrared probe into proteins. While this strategy has been widely used to investigate various biological questions, the dependence of the underlying amide I vibrational frequency on electric field (or Stark tuning rate) has not been fully determined, which prevents it from being used in a quantitative manner in certain applications. Herein, through the use of experiments and molecular dynamics simulations, the Stark tuning rate of the amide I vibration of an isotopically labeled backbone carbonyl in a transmembrane α-helix is determined to be approximately 1.4 cm−1/(MV/cm). This result provides a quantitative basis for using this vibrational model to assess local electric fields in proteins, among other applications. For instance, using this value, we are able to show that the backbone region of a dipeptide has a surprisingly low dielectric constant. PMID:26419214

  13. Non-Enzymatic RNA Backbone Proofreading through Energy-Dissipative Recycling.

    PubMed

    Mariani, Angelica; Sutherland, John D

    2017-06-01

    Non-enzymatic oligomerization of activated ribonucleotides leads to ribonucleic acids that contain a mixture of 2',5'- and 3',5'-linkages, and overcoming this backbone heterogeneity has long been considered a major limitation to the prebiotic emergence of RNA. Herein, we demonstrate non-enzymatic chemistry that progressively converts 2',5'-linkages into 3',5'-linkages through iterative degradation and repair. The energetic costs of this proofreading are met by the hydrolytic turnover of a phosphate activating agent and an acylating agent. With multiple rounds of this energy-dissipative recycling, we show that all-3',5'-linked duplex RNA can emerge from a backbone heterogeneous mixture, thereby delineating a route that could have driven RNA evolution on the early earth. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Backbone and side chain chemical shift assignments of apolipophorin III from Galleria mellonella.

    PubMed

    Crowhurst, Karin A; Horn, James V C; Weers, Paul M M

    2016-04-01

    Apolipophorin III, a 163 residue monomeric protein from the greater wax moth Galleria mellonella (abbreviated as apoLp-IIIGM), has roles in upregulating expression of antimicrobial proteins as well as binding and deforming bacterial membranes. Due to its similarity to vertebrate apolipoproteins there is interest in performing atomic resolution analysis of apoLp-IIIGM as part of an effort to better understand its mechanism of action in innate immunity. In the first step towards structural characterization of apoLp-IIIGM, 99 % of backbone and 88 % of side chain (1)H, (13)C and (15)N chemical shifts were assigned. TALOS+ analysis of the backbone resonances has predicted that the protein is composed of five long helices, which is consistent with the reported structures of apolipophorins from other insect species. The next stage in the characterization of apoLp-III from G. mellonella will be to utilize these resonance assignments in solving the solution structure of this protein.

  15. Protein backbone and sidechain torsion angles predicted from NMR chemical shifts using artificial neural networks

    PubMed Central

    Shen, Yang; Bax, Ad

    2013-01-01

    A new program, TALOS-N, is introduced for predicting protein backbone torsion angles from NMR chemical shifts. The program relies far more extensively on the use of trained artificial neural networks than its predecessor, TALOS+. Validation on an independent set of proteins indicates that backbone torsion angles can be predicted for a larger, ≥ 90% fraction of the residues, with an error rate smaller than ca 3.5%, using an acceptance criterion that is nearly two-fold tighter than that used previously, and a root mean square difference between predicted and crystallographically observed (φ,ψ) torsion angles of ca 12°. TALOS-N also reports sidechain χ1 rotameric states for about 50% of the residues, and a consistency with reference structures of 89%. The program includes a neural network trained to identify secondary structure from residue sequence and chemical shifts. PMID:23728592

  16. Design of an all-fiber erbium-doped laser system for simulating power load in backbone networks

    NASA Astrophysics Data System (ADS)

    Pobořil, Radek; Bednárek, Lukáš; Vanderka, Aleš; Hájek, Lukáš; Zbořil, Ondřej; Vašinek, Vladimír

    2016-12-01

    This article is focused on the design of an all-fiber laser that was supposed to be used for simulating power load similar to the power load in backbone networks. The first part of the article is a brief introduction to the topic of lasers and erbium doped fiber amplifiers. The following parts present design of a fiber laser with ring cavity, and measuring the ideal length of a doped fiber and the split ratio of the output coupler. After proposing the first stage -a laser- we focused on the construction of the two following stages -EDFA preamplifier and EDFA amplifier. There were used fibers with various levels of erbium ion density, namely ISO-GAIN I6, and Liekki ER110-4/125. The resulting output power of the whole system was 320 mW. This value is sufficient when we take into account that we used only single-mode fibers with energy pumped directly to the fiber core. The output wavelength of the whole laser system was 1559 nm.

  17. High Triplet Energy Level Achieved by Tuning the Arrangement of Building Blocks in Phosphorescent Polymer Backbones for Furnishing High Electroluminescent Performances in Both Blue and White Organic Light-Emitting Devices.

    PubMed

    Liu, Boao; Dang, Feifan; Tian, Zhuanzhuan; Feng, Zhao; Jin, Deyuan; Dang, Wanping; Yang, Xiaolong; Zhou, Guijiang; Wu, Zhaoxin

    2017-05-17

    A high triplet energy level (ET) of ca. 2.83 eV has been achieved in a novel polymer backbone through tuning the arrangement of two kinds of building blocks, showing enhanced hole injection/transporting capacity. Based on this new polymer backbone with high ET, both blue and white phosphorescent polymers were successfully developed with a trade-off between high ET and enhanced charge-carrier transporting ability. In addition, their photophysical features, electrochemical behaviors, and electroluminescent (EL) properties have been characterized in detail. Benefitting from the advantages associated with the novel polymer backbone, the blue phosphorescent polymers show top-ranking EL performances with a maximum luminance efficiency (ηL) of 15.22 cd A(-1), corresponding to a power efficiency (ηP) of 12.64 lm W(-1), and external quantum efficiency (ηext) of 6.22% and the stable Commission Internationale de L'Eclairage (CIE) coordinates of (0.19, 0.38). Furthermore, blue-orange (B-O) complementary-colored white phosphorescent polymers based on this novel polymer backbone were also obtained showing encouraging EL efficiencies of 12.34 cd A(-1), 9.59 lm W(-1), and 4.10% in the optimized WOLED together with exceptionally stable CIE coordinates of (Δx = 0.014, Δy = 0.010) in a wide driving voltage range from 4 to 16 V. All of these attractive EL results achieved by these novel phosphorescent polymers show the great potential of this new polymer backbone in developing highly efficient phosphorescent polymers.

  18. Improving the accuracy of protein stability predictions with multistate design using a variety of backbone ensembles.

    PubMed

    Davey, James A; Chica, Roberto A

    2014-05-01

    Multistate computational protein design (MSD) with backbone ensembles approximating conformational flexibility can predict higher quality sequences than single-state design with a single fixed backbone. However, it is currently unclear what characteristics of backbone ensembles are required for the accurate prediction of protein sequence stability. In this study, we aimed to improve the accuracy of protein stability predictions made with MSD by using a variety of backbone ensembles to recapitulate the experimentally measured stability of 85 Streptococcal protein G domain β1 sequences. Ensembles tested here include an NMR ensemble as well as those generated by molecular dynamics (MD) simulations, by Backrub motions, and by PertMin, a new method that we developed involving the perturbation of atomic coordinates followed by energy minimization. MSD with the PertMin ensembles resulted in the most accurate predictions by providing the highest number of stable sequences in the top 25, and by correctly binning sequences as stable or unstable with the highest success rate (≈90%) and the lowest number of false positives. The performance of PertMin ensembles is due to the fact that their members closely resemble the input crystal structure and have low potential energy. Conversely, the NMR ensemble as well as those generated by MD simulations at 500 or 1000 K reduced prediction accuracy due to their low structural similarity to the crystal structure. The ensembles tested herein thus represent on- or off-target models of the native protein fold and could be used in future studies to design for desired properties other than stability.

  19. Small molecule-mediated duplex formation of nucleic acids with 'incompatible' backbones.

    PubMed

    Cafferty, Brian J; Musetti, Caterina; Kim, Keunsoo; Horowitz, Eric D; Krishnamurthy, Ramanarayanan; Hud, Nicholas V

    2016-04-07

    Proflavine, a known intercalator of DNA and RNA, promotes duplex formation by nucleic acids with natural and non-natural backbones that otherwise form duplexes with low thermal stability, and even some that show no sign of duplex formation in the absence of proflavine. These findings demonstrate the potential for intercalators to be used as cofactors for the assembly of rationally designed nucleic acid structures, and could provide fundamental insights regarding intercalation of natural nucleic acid duplexes.

  20. Tritium containing polymers having a polymer backbone substantially void of tritium

    DOEpatents

    Jensen, G.A.; Nelson, D.A.; Molton, P.M.

    1992-03-31

    A radioluminescent light source comprises a solid mixture of a phosphorescent substance and a tritiated polymer. The solid mixture forms a solid mass having length, width, and thickness dimensions, and is capable of self-support. In one aspect of the invention, the phosphorescent substance comprises solid phosphor particles supported or surrounded within a solid matrix by a tritium containing polymer. The tritium containing polymer comprises a polymer backbone which is essentially void of tritium. 2 figs.

  1. Tritium containing polymers having a polymer backbone substantially void of tritium

    DOEpatents

    Jensen, George A.; Nelson, David A.; Molton, Peter M.

    1992-01-01

    A radioluminescent light source comprises a solid mixture of a phosphorescent substance and a tritiated polymer. The solid mixture forms a solid mass having length, width, and thickness dimensions, and is capable of self-support. In one aspect of the invention, the phosphorescent substance comprises solid phosphor particles supported or surrounded within a solid matrix by a tritium containing polymer. The tritium containing polymer comprises a polymer backbone which is essentially void of tritium.

  2. Hash: a Program to Accurately Predict Protein Hα Shifts from Neighboring Backbone Shifts3

    PubMed Central

    Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

    2012-01-01

    Chemical shifts provide not only peak identities for analyzing NMR data, but also an important source of conformational information for studying protein structures. Current structural studies requiring Hα chemical shifts suffer from the following limitations. (1) For large proteins, the Hα chemical shifts can be difficult to assign using conventional NMR triple-resonance experiments, mainly due to the fast transverse relaxation rate of Cα that restricts the signal sensitivity. (2) Previous chemical shift prediction approaches either require homologous models with high sequence similarity or rely heavily on accurate backbone and side-chain structural coordinates. When neither sequence homologues nor structural coordinates are available, we must resort to other information to predict Hα chemical shifts. Predicting accurate Hα chemical shifts using other obtainable information, such as the chemical shifts of nearby backbone atoms (i.e., adjacent atoms in the sequence), can remedy the above dilemmas, and hence advance NMR-based structural studies of proteins. By specifically exploiting the dependencies on chemical shifts of nearby backbone atoms, we propose a novel machine learning algorithm, called Hash, to predict Hα chemical shifts. Hash combines a new fragment-based chemical shift search approach with a non-parametric regression model, called the generalized additive model, to effectively solve the prediction problem. We demonstrate that the chemical shifts of nearby backbone atoms provide a reliable source of information for predicting accurate Hα chemical shifts. Our testing results on different possible combinations of input data indicate that Hash has a wide rage of potential NMR applications in structural and biological studies of proteins. PMID:23242797

  3. Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor.

    PubMed

    Schmidt, Karsten; Prakash, Thazha P; Donner, Aaron J; Kinberger, Garth A; Gaus, Hans J; Low, Audrey; Østergaard, Michael E; Bell, Melanie; Swayze, Eric E; Seth, Punit P

    2017-03-17

    Targeted delivery of antisense oligonucleotides (ASO) to hepatocytes via the asialoglycoprotein receptor (ASGR) has improved the potency of ASO drugs ∼30-fold in the clinic (1). In order to fully characterize the effect of GalNAc valency, oligonucleotide length, flexibility and chemical composition on ASGR binding, we tested and validated a fluorescence polarization competition binding assay. The ASGR binding, and in vitro and in vivo activities of 1, 2 and 3 GalNAc conjugated single stranded and duplexed ASOs were studied. Two and three GalNAc conjugated single stranded ASOs bind the ASGR with the strongest affinity and display optimal in vitro and in vivo activities. 1 GalNAc conjugated ASOs showed 10-fold reduced ASGR binding affinity relative to three GalNAc ASOs but only 2-fold reduced activity in mice. An unexpected observation was that the ASGR also appears to play a role in the uptake of unconjugated phosphorothioate modified ASOs in the liver as evidenced by the loss of activity of GalNAc conjugated and unconjugated ASOs in ASGR knockout mice. Our results provide insights into how backbone charge and chemical composition assist in the binding and internalization of highly polar anionic single stranded oligonucleotides into cells and tissues. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor

    PubMed Central

    Schmidt, Karsten; Prakash, Thazha P.; Donner, Aaron J.; Kinberger, Garth A.; Gaus, Hans J.; Low, Audrey; Østergaard, Michael E.; Bell, Melanie; Swayze, Eric E.

    2017-01-01

    Abstract Targeted delivery of antisense oligonucleotides (ASO) to hepatocytes via the asialoglycoprotein receptor (ASGR) has improved the potency of ASO drugs ∼30-fold in the clinic (1). In order to fully characterize the effect of GalNAc valency, oligonucleotide length, flexibility and chemical composition on ASGR binding, we tested and validated a fluorescence polarization competition binding assay. The ASGR binding, and in vitro and in vivo activities of 1, 2 and 3 GalNAc conjugated single stranded and duplexed ASOs were studied. Two and three GalNAc conjugated single stranded ASOs bind the ASGR with the strongest affinity and display optimal in vitro and in vivo activities. 1 GalNAc conjugated ASOs showed 10-fold reduced ASGR binding affinity relative to three GalNAc ASOs but only 2-fold reduced activity in mice. An unexpected observation was that the ASGR also appears to play a role in the uptake of unconjugated phosphorothioate modified ASOs in the liver as evidenced by the loss of activity of GalNAc conjugated and unconjugated ASOs in ASGR knockout mice. Our results provide insights into how backbone charge and chemical composition assist in the binding and internalization of highly polar anionic single stranded oligonucleotides into cells and tissues. PMID:28158620

  5. Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes.

    PubMed

    Dinesh, Bhimareddy; Squillaci, Marco A; Ménard-Moyon, Cécilia; Samorì, Paolo; Bianco, Alberto

    2015-10-14

    The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of β and γ homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, β and γ peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to transform the nanofibers into spherical structures. Moreover, the co-assembly of β and γ peptides with carbon nanotubes covalently functionalized with the same peptide generated unique dendritic assemblies. This comparative study on self-assembly using diphenylalanine backbone homologues and of the co-assembly with CNT covalent conjugates is the first example exploring the capacity of β and γ peptides to adopt precise nanostructures, particularly in combination with carbon nanotubes. The dendritic organization obtained by mixing carbon nanotubes and peptides might find interesting applications in tissue engineering and neuronal interfacing.

  6. Androgen deprivation therapy as backbone therapy in the management of prostate cancer

    PubMed Central

    Merseburger, Axel S; Alcaraz, Antonio; von Klot, Christoph A

    2016-01-01

    Androgen deprivation therapy (ADT) is well established as a backbone therapy for metastatic prostate cancer (mPCa), and both European and American guidelines emphasize the importance of maintaining ADT after progression to metastatic castration-resistant prostate cancer (CRPC). However, the use of ADT varies widely in clinical practice despite these recommendations. Both research and development of increasingly precise assay technologies have improved our understanding of androgen production and signaling, and the recent data have suggested that a new serum testosterone cutoff value of <0.7 nmol/L should be employed. Most clinical trials to date have used the historical 1.7 nmol/L cutoff, but the <0.7 nmol/L cutoff has been associated with improved patient outcomes. Combining agents with different mechanisms of action to achieve intense androgen blockade may improve survival both before and after progression to CRPC. Data suggest that this intensive approach to androgen deprivation could delay the transition to CPRC and hence improve survival dramatically. Various combinations of backbone ADT with chemotherapy or radiotherapy are under investigation. Administration of ADT is established in patients with intermediate or high-risk localized prostate cancer (PCa) receiving radiotherapy with curative intent. This article reviews the current and potential role of ADT as backbone therapy in both hormone-sensitive PCa and CRPC with a focus on mPCa. PMID:27942220

  7. Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar

    DOE PAGES

    Kim, Kwang Ho; Dutta, Tanmoy; Ralph, John; ...

    2017-04-20

    Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). Themore » strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process.« less

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

    PubMed

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

    2016-10-28

    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+d_{B}/2≈1.822 for backbone holes, where d_{B} is the backbone dimension. On the other hand, a model of simple holes within a percolation cluster yields τ=1+d_{f}/2=187/96≈1.948, where d_{f} 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 p_{c}, signifying explosive percolation behavior.

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Effect of protein backbone folding on the stability of protein-ligand complexes.

    PubMed

    Estrada, Ernesto; Uriarte, Eugenio; Vilar, Santiago

    2006-01-01

    The role played by the degree of folding of protein backbones in explaining the binding energetics of protein-ligand interactions has been studied. We analyzed the protein/peptide interactions in the RNase-S system in which amino acids at two positions of the peptide S have been mutated. The global degree of folding of the protein S correlates in a significant way with the free energy and enthalpy of the protein-peptide interactions. A much better correlation is found with the local contribution to the degree of folding of one amino acid residue: Thr36. This residue is shown to have a destabilizing interaction with Lys41, which interacts directly with peptide S. Another system, consisting of the interactions of small organic molecules with HIV-1 protease was also studied. In this case, the global change in the degree of folding of the protease backbone does not explain the binding energetics of protein-ligand interactions. However, a significant correlation is observed between the free energy of binding and the contribution of two amino acid residues in the HVI-1 protease: Gly49 and Ile66. In general, it was observed that the changes in the degree of folding are not restricted to the binding site of the protein chain but are distributed along the whole protein backbone. This study provides a basis for further consideration of the degree of folding as a parameter for empirical structural parametrizations of the binding energetics of protein folding and binding.

  11. Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase

    PubMed Central

    Harris, Karen S.; Durek, Thomas; Kaas, Quentin; Poth, Aaron G.; Gilding, Edward K.; Conlan, Brendon F.; Saska, Ivana; Daly, Norelle L.; van der Weerden, Nicole L.; Craik, David J.; Anderson, Marilyn A.

    2015-01-01

    Cyclotides are diverse plant backbone cyclized peptides that have attracted interest as pharmaceutical scaffolds, but fundamentals of their biosynthetic origin remain elusive. Backbone cyclization is a key enzyme-mediated step of cyclotide biosynthesis and confers a measure of stability on the resultant cyclotide. Furthermore, cyclization would be desirable for engineered peptides. Here we report the identification of four asparaginyl endopeptidases (AEPs), proteases implicated in cyclization, from the cyclotide-producing plant Oldenlandia affinis. We recombinantly express OaAEP1b and find it functions preferably as a cyclase by coupling C-terminal cleavage of propeptide substrates with backbone cyclization. Interestingly, OaAEP1b cannot cleave at the N-terminal site of O. affinis cyclotide precursors, implicating additional proteases in cyclotide biosynthesis. Finally, we demonstrate the broad utility of this enzyme by cyclization of peptides unrelated to cyclotides. We propose that recombinant OaAEP1b is a powerful tool for use in peptide engineering applications where increased stability of peptide products is desired. PMID:26680698

  12. Evolution of functional nucleic acids in the presence of nonheritable backbone heterogeneity.

    PubMed

    Trevino, Simon G; Zhang, Na; Elenko, Mark P; Lupták, Andrej; Szostak, Jack W

    2011-08-16

    Multiple lines of evidence support the hypothesis that the early evolution of life was dominated by RNA, which can both transfer information from generation to generation through replication directed by base-pairing, and carry out biochemical activities by folding into functional structures. To understand how life emerged from prebiotic chemistry we must therefore explain the steps that led to the emergence of the RNA world, and in particular, the synthesis of RNA. The generation of pools of highly pure ribonucleotides on the early Earth seems unlikely, but the presence of alternative nucleotides would support the assembly of nucleic acid polymers containing nonheritable backbone heterogeneity. We suggest that homogeneous monomers might not have been necessary if populations of heterogeneous nucleic acid molecules could evolve reproducible function. For such evolution to be possible, function would have to be maintained despite the repeated scrambling of backbone chemistry from generation to generation. We have tested this possibility in a simplified model system, by using a T7 RNA polymerase variant capable of transcribing nucleic acids that contain an approximately 11 mixture of deoxy- and ribonucleotides. We readily isolated nucleotide-binding aptamers by utilizing an in vitro selection process that shuffles the order of deoxy- and ribonucleotides in each round. We describe two such RNA/DNA mosaic nucleic acid aptamers that specifically bind ATP and GTP, respectively. We conclude that nonheritable variations in nucleic acid backbone structure may not have posed an insurmountable barrier to the emergence of functionality in early nucleic acids.

  13. On the mechanism of RNA phosphodiester backbone cleavage in the absence of solvent

    PubMed Central

    Riml, Christian; Glasner, Heidelinde; Rodgers, M. T.; Micura, Ronald; Breuker, Kathrin

    2015-01-01

    Ribonucleic acid (RNA) modifications play an important role in the regulation of gene expression and the development of RNA-based therapeutics, but their identification, localization and relative quantitation by conventional biochemical methods can be quite challenging. As a promising alternative, mass spectrometry (MS) based approaches that involve RNA dissociation in ‘top-down’ strategies are currently being developed. For this purpose, it is essential to understand the dissociation mechanisms of unmodified and posttranscriptionally or synthetically modified RNA. Here, we have studied the effect of select nucleobase, ribose and backbone modifications on phosphodiester bond cleavage in collisionally activated dissociation (CAD) of positively and negatively charged RNA. We found that CAD of RNA is a stepwise reaction that is facilitated by, but does not require, the presence of positive charge. Preferred backbone cleavage next to adenosine and guanosine in CAD of (M+nH)n+ and (M−nH)n− ions, respectively, is based on hydrogen bonding between nucleobase and phosphodiester moieties. Moreover, CAD of RNA involves an intermediate that is sufficiently stable to survive extension of the RNA structure and intramolecular proton redistribution according to simple Coulombic repulsion prior to backbone cleavage into c and y ions from phosphodiester bond cleavage. PMID:25904631

  14. Dispositional optimism.

    PubMed

    Carver, Charles S; Scheier, Michael F

    2014-06-01

    Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Dispositional Optimism

    PubMed Central

    Carver, Charles S.; Scheier, Michael F.

    2014-01-01

    Optimism is a cognitive construct (expectancies regarding future outcomes) that also relates to motivation: optimistic people exert effort, whereas pessimistic people disengage from effort. Study of optimism began largely in health contexts, finding positive associations between optimism and markers of better psychological and physical health. Physical health effects likely occur through differences in both health-promoting behaviors and physiological concomitants of coping. Recently, the scientific study of optimism has extended to the realm of social relations: new evidence indicates that optimists have better social connections, partly because they work harder at them. In this review, we examine the myriad ways this trait can benefit an individual, and our current understanding of the biological basis of optimism. PMID:24630971

  16. Synthesis and structural characterization of one- and two-dimensional coordination polymers based on platinum-silver metallic backbones.

    PubMed

    Liu, Fenghui; Chen, Wanzhi; Wang, Daqi

    2006-06-28

    Seven Pt-Ag coordination polymers [Pt(NH3)2(NHCO(t)Bu)2Ag(H2O)](ClO4) (1), [Pt2(dap)2(NHCO(t)Bu)4Ag2(NO3)(ClO4)] (dap = 1,2-diaminopropane, 2), [Pt2(en)2(NHCO(t)Bu)4Ag2(m-C6H4(CO2)2)].3H2O (en = ethylenediamine, 3), [Pt2(NH3)2(NHCO(t)Bu)2Ag2(p-C6H4(CO2)2)].2H2O (4), [Pt3(en)3(NHCO(t)Bu)6Ag2(p-C6H4(CO2)2)(1.5)].6H2O (5), [Pt(NH3)2(NHCO(t)Bu)4Ag(4-C5H4NCO2)2].10H2O (6), and [Pt2(en)2(NHCO(t)Bu)4Ag2(4-C5H4NCO2)](ClO4) (7) were synthesized from the corresponding [Pt(RNH2)2(NHCO(t)Bu)2] and Ag salts, respectively, and their structures were determined by X-ray crystallography. The Pt and Ag units aggregate into one-dimensional chains based on Pt-Ag backbones. Compounds 1, 2, and 6 possess an extended zigzag Pt-Ag chain motif, and the metallic chains arrange in a parallel fashion into layered structures. Compounds 3-5, and 7 form 2-D brick wall sheets due to the coordination of the bifunctional anions to the Ag+ ions of the neighboring chains. These polymers are constructed based on the Pt-Ag interactions and the coordination of amidate oxygen atoms to Ag ions. There are three kinds of short Pt-Ag bonds observed in the structures of these compounds. The Pt-Ag metallic backbone is formed by the stacking unsupported Pt-Ag bonds, the amidate doubly bridged Pt-Ag bonds, and the amidate singly bridged Pt-Ag bonds. In the chains, the Pt-Ag bond distances are quite short, and appear in the range of 2.78-2.97 A, which are comparable to known Pt-Ag dative bonds.

  17. Broadly Neutralizing Anti-Influenza Virus Antibodies: Enhancement of Neutralizing Potency in Polyclonal Mixtures and IgA Backbones

    PubMed Central

    He, Wenqian; Mullarkey, Caitlin E.; Duty, J. Andrew; Moran, Thomas M.; Palese, Peter

    2015-01-01

    ABSTRACT Current influenza virus vaccines rely upon the accurate prediction of circulating virus strains months in advance of the actual influenza season in order to allow time for vaccine manufacture. Unfortunately, mismatches occur frequently, and even when perfect matches are achieved, suboptimal vaccine efficacy leaves several high-risk populations vulnerable to infection. However, the recent discovery of broadly neutralizing antibodies that target the hemagglutinin (HA) stalk domain has renewed hope that the development of “universal” influenza virus vaccines may be within reach. Here, we examine the functions of influenza A virus hemagglutinin stalk-binding antibodies in an endogenous setting, i.e., as polyclonal preparations isolated from human sera. Relative to monoclonal antibodies that bind to the HA head domain, the neutralization potency of monoclonal stalk-binding antibodies was vastly inferior in vitro but was enhanced by several orders of magnitude in the polyclonal context. Furthermore, we demonstrated a surprising enhancement in IgA-mediated HA stalk neutralization relative to that achieved by antibodies of IgG isotypes. Mechanistically, this could be explained in two ways. Identical variable regions consistently neutralized virus more potently when in an IgA backbone compared to an IgG backbone. In addition, HA-specific memory B cells isolated from human peripheral blood were more likely to be stalk specific when secreting antibodies of IgA isotypes compared to those secreting IgG. Taken together, our data provide strong evidence that HA stalk-binding antibodies perform optimally when in a polyclonal context and that the targeted elicitation of HA stalk-specific IgA should be an important consideration during “universal” influenza virus vaccine design. IMPORTANCE Influenza viruses remain one of the most worrisome global public health threats due to their capacity to cause pandemics. While seasonal vaccines fail to protect against the

  18. Construction of high-resolution trace element time-series in slow growth speleothems by LA-ICP-MS: Importance of parameter optimization and oriented band fabric imagery

    NASA Astrophysics Data System (ADS)

    Miller, N. R.; Griffiths, R. E.; Banner, J. L.

    2012-12-01

    slit apertures, offer substantially improved spatial resolution over spot apertures. The addition of nitrogen (5 mL/min) to the carrier gas following the ablation cell generates a three- to five-fold increase in sensitivity for Mg, Sr and Ba. The technique involves establishing a grid of laser spots over prospective sample areas in order to provide precise correlation points for overlaying of UV-fluorescence imagery. The georeferenced imagery, which reveals the banded growth fabric, is then used to orient line scans so that the long-axis of the slit aperture is held parallel to banding throughout the length of the scan. For optimization of ablation and ionization parameters, the grid is rotated 90° so that line scans are performed parallel to banding (for which natural lateral heterogeneity can also be evaluated). Through the application of these techniques we are able to construct trace element signals that closely mimic the UV-fluorescence band spacing and are consistent with U-series growth-rate predictions, suggesting the possibility of subannual resolution at growth rates as slow as 23 μm/yr.

  19. Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids

    PubMed Central

    2016-01-01

    Diffusion models are important in tissue engineering as they enable an understanding of gas, nutrient, and signaling molecule delivery to cells in cell cultures and tissue constructs. As three-dimensional (3D) tissue constructs become larger, more intricate, and more clinically applicable, it will be essential to understand internal dynamics and signaling molecule concentrations throughout the tissue and whether cells are receiving appropriate nutrient delivery. Diffusion characteristics present a significant limitation in many engineered tissues, particularly for avascular tissues and for cells whose viability, differentiation, or function are affected by concentrations of oxygen and nutrients. This article seeks to provide novel analytic solutions for certain cases of steady-state and nonsteady-state diffusion and metabolism in basic 3D construct designs (planar, cylindrical, and spherical forms), solutions that would otherwise require mathematical approximations achieved through numerical methods. This model is applied to cerebral organoids, where it is shown that limitations in diffusion and organoid size can be partially overcome by localizing metabolically active cells to an outer layer in a sphere, a regionalization process that is known to occur through neuroglial precursor migration both in organoids and in early brain development. The given prototypical solutions include a review of metabolic information for many cell types and can be broadly applied to many forms of tissue constructs. This work enables researchers to model oxygen and nutrient delivery to cells, predict cell viability, study dynamics of mass transport in 3D tissue constructs, design constructs with improved diffusion capabilities, and accurately control molecular concentrations in tissue constructs that may be used in studying models of development and disease or for conditioning cells to enhance survival after insults like ischemia or implantation into the body, thereby providing a

  20. Inorganic backbone ionomers: Design and dielectric response of single-ion conducting polymers

    NASA Astrophysics Data System (ADS)

    Bartels, Joshua

    Ion-conducting polymers were studied primarily through the use of dielectric spectroscopy. The conclusions drawn from ion conduction models of the dielectric data are corroborated by additional independent experiments, including x-ray scattering, calorimetry, prism coupling, and DFT calculations. The broad concern of this dissertation is to understand and clarify a path forward in ion conducting polymer research. This is achieved by considering low-Tg ionomers and the advantages imparted by siloxane and phosphazene backbones. The most successful dielectric spectroscopy model for the materials studied is the electrode polarization model (EP), whereas other models, such as the Dyre random barrier model, fail to describe the experimental results. Seven nonionic ether oxygen (EO) containing polymers were studied in order to observe the effect that backbone chemistry has on dipole motion. Conventional carboncarbon backbone EO-containing polymers show no distinct advantage over similar EO-pendant polysiloxane or polyphosphazene systems. The mobility and effective backbone Tg imparted by the inorganic backbones are comparable. A short EO pendant results in a lower static dielectric constant due to restricted motion of dipoles close to the chain. The flexibility and chemical versatility of inorganic backbone polymers motivates further study of two ionomer systems. A polypohosphazene iodide conducting system was characterized by dielectric spectroscopy and x-ray scattering. Two end "tail" functionalization of the ammonium ion were used, a tail with two EOs and an alkyl tail of six carbons. This functional group plays an important role in ion dynamics and can wrap around the ion and self-solvate when EOs are present. The iodide-ammonium ionomers are observed to have unusually large high-frequency dielectric constants due to atomic polarization of ions. The strength of the atomic polarization scales with ion content. The aggregation state of ions is able to be determined from

  1. Chiral counteranion synergistic organocatalysis under high temperature: efficient construction of optically pure spiro[cyclohexanone-oxindole] backbone.

    PubMed

    Lan, Yu-Bao; Zhao, Hua; Liu, Zhao-Min; Liu, Guo-Gui; Tao, Jing-Chao; Wang, Xing-Wang

    2011-09-16

    The combination of a cinchona-based chiral primary amine and a BINOL-phosphoric acid has been demonstrated as a powerful and synergistic catalyst system for the double Michael addition of isatylidene malononitriles with α,β-unsaturated ketones, to provide the novel chiral spiro [cyclohexane-1,3'-indoline]-2',3-diones in high yields (88-99%) with excellent diastereo- and enantioselectivities (94:6-99:1 dr's, 95-99% ee's).

  2. Dead-End Elimination with Perturbations (“DEEPer”): A provable protein design algorithm with continuous sidechain and backbone flexibility

    PubMed Central

    Hallen, Mark A.; Keedy, Daniel A.; Donald, Bruce R.

    2012-01-01

    Computational protein and drug design generally require accurate modeling of protein conformations. This modeling typically starts with an experimentally-determined protein structure and considers possible conformational changes due to mutations or new ligands. The DEE/A* algorithm provably finds the GMEC (global minimum-energy conformation) of a protein assuming the backbone does not move and the sidechains take on conformations from a set of discrete, experimentally-observed conformations called rotamers. DEE/A* can efficiently find the overall GMEC for exponentially many mutant sequences. Previous improvements to DEE/A* include modeling ensembles of sidechain conformations and either continuous sidechain or backbone flexibility. We present a new algorithm, DEEPer (Dead-End Elimination with Perturbations), that combines these advantages and can also handle much more extensive backbone flexibility and backbone ensembles. DEEPer provably finds the GMEC or, if desired by the user, all conformations and sequences within a specified energy window of the GMEC. It includes the new abilities to handle arbitrarily large backbone perturbations and to generate ensembles of backbone conformations. It also incorporates the shear, an experimentally-observed local backbone motion never before used in design. Additionally, we derive a new method to accelerate DEE/A*-based calculations, indirect pruning, that is particularly useful for DEEPer. In 67 benchmark tests on 64 proteins, DEEPer consistently identified lower-energy conformations than previous methods did, indicating more accurate modeling. Additional tests demonstrated its ability to incorporate larger, experimentally-observed backbone conformational changes and to model realistic conformational ensembles. These capabilities provide significant advantages for modeling protein mutations and protein-ligand interactions. PMID:22821798

  3. Exposing hidden alternative backbone conformations in X-ray crystallography using qFit

    SciTech Connect

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

    2015-10-27

    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. Furthermore, 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.

  4. Exposing hidden alternative backbone conformations in X-ray crystallography using qFit

    DOE PAGES

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

    2015-10-27

    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 sidechainmore » 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. Furthermore, 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.« less

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

    PubMed Central

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

    2015-01-01

    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. PMID:26506617

  6. Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation.

    PubMed

    Qvit, Nir; Kornfeld, Opher S

    2016-01-26

    Protein-protein interactions (PPIs) are intimately involved in almost all biological processes and are linked to many human diseases. Therefore, there is a major effort to target PPIs in basic research and in the pharmaceutical industry. Protein-protein interfaces are usually large, flat, and often lack pockets, complicating the discovery of small molecules that target such sites. Alternative targeting approaches using antibodies have limitations due to poor oral bioavailability, low cell-permeability, and production inefficiency. Using peptides to target PPI interfaces has several advantages. Peptides have higher conformational flexibility, increased selectivity, and are generally inexpensive. However, peptides have their own limitations including poor stability and inefficiency crossing cell membranes. To overcome such limitations, peptide cyclization can be performed. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, predicting the bioactive conformation of a cyclic peptide is not trivial. To overcome this challenge, one attractive approach it to screen a focused library to screen in which all backbone cyclic peptides have the same primary sequence, but differ in parameters that influence their conformation, such as ring size and position. We describe a detailed protocol for synthesizing a library of backbone cyclic peptides targeting specific parasite PPIs. Using a rational design approach, we developed peptides derived from the scaffold protein Leishmania receptor for activated C-kinase (LACK). We hypothesized that sequences in LACK that are conserved in parasites, but not in the mammalian host homolog, may represent interaction sites for proteins that are critical for the parasites' viability. The cyclic peptides were synthesized using microwave irradiation to reduce reaction times and increase efficiency. Developing a library of backbone cyclic peptides with different ring sizes facilitates a

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Membrane Curvature Sensing by Amphipathic Helices Is Modulated by the Surrounding Protein Backbone

    PubMed Central

    Doucet, Christine M.; Esmery, Nina; de Saint-Jean, Maud; Antonny, Bruno

    2015-01-01

    Membrane curvature is involved in numerous biological pathways like vesicle trafficking, endocytosis or nuclear pore complex assembly. In addition to its topological role, membrane curvature is sensed by specific proteins, enabling the coordination of biological processes in space and time. Amongst membrane curvature sensors are the ALPS (Amphipathic Lipid Packing Sensors). ALPS motifs are short peptides with peculiar amphipathic properties. They are found in proteins targeted to distinct curved membranes, mostly in the early secretory pathway. For instance, the ALPS motif of the golgin GMAP210 binds trafficking vesicles, while the ALPS motif of Nup133 targets nuclear pores. It is not clear if, besides curvature sensitivity, ALPS motifs also provide target specificity, or if other domains in the surrounding protein backbone are involved. To elucidate this aspect, we studied the subcellular localization of ALPS motifs outside their natural protein context. The ALPS motifs of GMAP210 or Nup133 were grafted on artificial fluorescent probes. Importantly, ALPS motifs are held in different positions and these contrasting architectures were mimicked by the fluorescent probes. The resulting chimeras recapitulated the original proteins localization, indicating that ALPS motifs are sufficient to specifically localize proteins. Modulating the electrostatic or hydrophobic content of Nup133 ALPS motif modified its avidity for cellular membranes but did not change its organelle targeting properties. In contrast, the structure of the backbone surrounding the helix strongly influenced targeting. In particular, introducing an artificial coiled-coil between ALPS and the fluorescent protein increased membrane curvature sensitivity. This coiled-coil domain also provided membrane curvature sensitivity to the amphipathic helix of Sar1. The degree of curvature sensitivity within the coiled-coil context remains correlated to the natural curvature sensitivity of the helices. This suggests

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

    PubMed

    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.

  10. Membrane Curvature Sensing by Amphipathic Helices Is Modulated by the Surrounding Protein Backbone.

    PubMed

    Doucet, Christine M; Esmery, Nina; de Saint-Jean, Maud; Antonny, Bruno

    2015-01-01

    Membrane curvature is involved in numerous biological pathways like vesicle trafficking, endocytosis or nuclear pore complex assembly. In addition to its topological role, membrane curvature is sensed by specific proteins, enabling the coordination of biological processes in space and time. Amongst membrane curvature sensors are the ALPS (Amphipathic Lipid Packing Sensors). ALPS motifs are short peptides with peculiar amphipathic properties. They are found in proteins targeted to distinct curved membranes, mostly in the early secretory pathway. For instance, the ALPS motif of the golgin GMAP210 binds trafficking vesicles, while the ALPS motif of Nup133 targets nuclear pores. It is not clear if, besides curvature sensitivity, ALPS motifs also provide target specificity, or if other domains in the surrounding protein backbone are involved. To elucidate this aspect, we studied the subcellular localization of ALPS motifs outside their natural protein context. The ALPS motifs of GMAP210 or Nup133 were grafted on artificial fluorescent probes. Importantly, ALPS motifs are held in different positions and these contrasting architectures were mimicked by the fluorescent probes. The resulting chimeras recapitulated the original proteins localization, indicating that ALPS motifs are sufficient to specifically localize proteins. Modulating the electrostatic or hydrophobic content of Nup133 ALPS motif modified its avidity for cellular membranes but did not change its organelle targeting properties. In contrast, the structure of the backbone surrounding the helix strongly influenced targeting. In particular, introducing an artificial coiled-coil between ALPS and the fluorescent protein increased membrane curvature sensitivity. This coiled-coil domain also provided membrane curvature sensitivity to the amphipathic helix of Sar1. The degree of curvature sensitivity within the coiled-coil context remains correlated to the natural curvature sensitivity of the helices. This suggests

  11. Toward Atomistic Resolution Structure of Phosphatidylcholine Headgroup and Glycerol Backbone at Different Ambient Conditions†

    PubMed Central

    2015-01-01

    Phospholipids are essential building blocks of biological membranes. Despite a vast amount of very accurate experimental data, the atomistic resolution structures sampled by the glycerol backbone and choline headgroup in phoshatidylcholine bilayers are not known. Atomistic resolution molecular dynamics simulations have the potential to resolve the structures, and to give an arrestingly intuitive interpretation of the experimental data, but only if the simulations reproduce the data within experimental accuracy. In the present work, we simulated phosphatidylcholine (PC) lipid bilayers with 13 different atomistic models, and compared simulations with NMR experiments in terms of the highly structurally sensitive C–H bond vector order parameters. Focusing on the glycerol backbone and choline headgroups, we showed that the order parameter comparison can be used to judge the atomistic resolution structural accuracy of the models. Accurate models, in turn, allow molecular dynamics simulations to be used as an interpretation tool that translates these NMR data into a dynamic three-dimensional representation of biomolecules in biologically relevant conditions. In addition to lipid bilayers in fully hydrated conditions, we reviewed previous experimental data for dehydrated bilayers and cholesterol-containing bilayers, and interpreted them with simulations. Although none of the existing models reached experimental accuracy, by critically comparing them we were able to distill relevant chemical information: (1) increase of choline order parameters indicates the P–N vector tilting more parallel to the membrane, and (2) cholesterol induces only minor changes to the PC (glycerol backbone) structure. This work has been done as a fully open collaboration, using nmrlipids.blogspot.fi as a communication platform; all the scientific contributions were made publicly on this blog. During the open research process, the repository holding our simulation trajectories and files (https

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

    PubMed

    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.

  13. ngs_backbone: a pipeline for read cleaning, mapping and SNP calling using Next Generation Sequence

    PubMed Central

    2011-01-01

    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. PMID:21635747

  14. Backbone NMR assignments of tryparedoxin, the central protein in the hydroperoxide detoxification cascade of African trypanosomes, in the oxidized and reduced form.

    PubMed

    Wagner, Annika; Diehl, Erika; Krauth-Siegel, R Luise; Hellmich, Ute A

    2017-06-01

    Tryparedoxin (Tpx) is a pivotal protein in the redox-metabolism of trypanosomatid parasites. Tpx has previously been identified as a potential target for drug development in the fight against human African sleeping sickness caused by Trypanosoma brucei. Tpx belongs to the thioredoxin superfamily and acts as an oxidoreductase in the parasite's cytoplasm. It contains a WCPPC active site motif, which enables the protein to undergo thiol-disulfide exchange. To promote future protein-drug interaction analyses, we report the (1)H, (13)C and (15)N backbone chemical shift assignments for both the oxidized and reduced states of Tpx. The redox state of the protein has a significant impact on the chemical shifts of the residues at the active site of the protein, especially on the two redox active site cysteines. The NMR assignments presented here will be a prerequisite for investigating drug binding to Tpx in molecular detail and to drive further drug optimization.

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

    PubMed Central

    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

  16. Localization of strain in the RNA backbone and its functional implication

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel; Rabitz, Herschel

    1992-07-01

    It is known that an RNA molecule capable of self-splicing shares a common pattern of Watson-Crick base paris with other RNA species endowed with the same capability. The aim of this work is to introduce a minimal model Hamiltonian which determines a localized strain in the RNA backbone as the search for the molecular conformation is subject to the constraint imposed by the concensus secondary structure. The site where the strain is localized is shown to coincide with the splicing site of the molecule. As justified posteriori, the level of structural complexity of the model is sufficient to account for energy localization in a nontrivial fashion.

  17. Graphene-network-backboned architectures for high-performance lithium storage.

    PubMed

    Gong, Yongji; Yang, Shubin; Liu, Zheng; Ma, Lulu; Vajtai, Robert; Ajayan, Pulickel M

    2013-08-07

    An efficient hydrothermal approach is demonstrated to fabricate a series of graphene-network-backboned hybrid architectures such as MoS₂/graphene and FeOx/graphene, showing high specific surface area, porous structure, and continuous graphene networks. Such unique architectures exhibit a high reversible capacity (about 1100 mA h g⁻¹) for lithium ion batteries. High-rate capabilities of full charge to discharge in 25-45 s with a long cycle life (1500 cycles) are achieved at different rates.

  18. Sendai virus as a backbone for vaccines against RSV and other human paramyxoviruses.

    PubMed

    Russell, Charles J; Hurwitz, Julia L

    2016-01-01

    Human paramyxoviruses are the etiological agents for life-threatening respiratory virus infections of infants and young children. These viruses, including respiratory syncytial virus (RSV), the human parainfluenza viruses (hPIV1-4) and human metapneumovirus (hMPV), are responsible for millions of serious lower respiratory tract infections each year worldwide. There are currently no standard treatments and no licensed vaccines for any of these pathogens. Here we review research with which Sendai virus, a mouse parainfluenza virus type 1, is being advanced as a Jennerian vaccine for hPIV1 and as a backbone for RSV, hMPV and other hPIV vaccines for children.

  19. Synthesis and properties of carbohydrate-phosphate backbone-modified oligonucleotide analogues and nucleic acid mimetics

    NASA Astrophysics Data System (ADS)

    Abramova, Tatyana V.; Silnikov, Vladimir N.

    2011-05-01

    Advances in the synthesis of oligo(deoxy)ribonucleotide analogues and nucleic acid mimetics made in the last decade are summarized. Attention is focused on new methods for the synthesis of derivatives with a modified ribose-phosphate backbone (phosphorothioate, boranophosphate, and nucleoside phosphonate derivatives) and derivatives devoid of the phosphate group. Among nucleic acid mimetics, conformationally restricted modified peptide nucleic acids, including those bearing a negative or positive charge, and morpholino oligomers are considered. Advantages and drawbacks of the main types of analogues as regards the complexity of the synthesis and the possibility of their application as antisense agents or reagents for hybridization analysis are compared.

  20. Colloidal quantum dot lasers built on a passive two-dimensional photonic crystal backbone.

    PubMed

    Chang, Hojun; Min, Kyungtaek; Lee, Myungjae; Kang, Minsu; Park, Yeonsang; Cho, Kyung-Sang; Roh, Young-Geun; Hwang, Sung Woo; Jeon, Heonsu

    2016-03-28

    We report the room-temperature lasing action from two-dimensional photonic crystal (PC) structures composed of a passive Si3N4 backbone with an over-coat of CdSe/CdS/ZnS colloidal quantum dots (CQDs) for optical gain. When optically excited, devices lased in dual PC band-edge modes, with the modal dominance governed by the thickness of the CQD over-layer. The demonstrated laser platform should have an impact on future photonic integrated circuits as the on-chip coupling between active and passive components is readily achievable.

  1. An algorithm for converting a virtual-bond chain into a complete polypeptide backbone chain

    NASA Technical Reports Server (NTRS)

    Luo, N.; Shibata, M.; Rein, R.

    1991-01-01

    A systematic analysis is presented of the algorithm for converting a virtual-bond chain, defined by the coordinates of the alpha-carbons of a given protein, into a complete polypeptide backbone. An alternative algorithm, based upon the same set of geometric parameters used in the Purisima-Scheraga algorithm but with a different "linkage map" of the algorithmic procedures, is proposed. The global virtual-bond chain geometric constraints are more easily separable from the loal peptide geometric and energetic constraints derived from, for example, the Ramachandran criterion, within the framework of this approach.

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

    PubMed

    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. Toward Establishing the Validity of the Transformative Optimism Construct Measurement for Tsunami Preparedness: A Structural Equation Model for Visitors of the Pacific Northwest Coast

    ERIC Educational Resources Information Center

    Rios-Uribe, Carlos Andres

    2009-01-01

    Measurements of social constructs that evaluate natural hazard preparedness are important to decrease natural hazard vulnerability. Preparedness reduces natural hazard impacts and human vulnerability. Investment in education and education research contribute to human sustainable development and natural hazard preparedness. Faced with other needs,…

  4. Toward Establishing the Validity of the Transformative Optimism Construct Measurement for Tsunami Preparedness: A Structural Equation Model for Visitors of the Pacific Northwest Coast

    ERIC Educational Resources Information Center

    Rios-Uribe, Carlos Andres

    2009-01-01

    Measurements of social constructs that evaluate natural hazard preparedness are important to decrease natural hazard vulnerability. Preparedness reduces natural hazard impacts and human vulnerability. Investment in education and education research contribute to human sustainable development and natural hazard preparedness. Faced with other needs,…

  5. Discovery, adaptation and transcriptional activity of two tick promoters: Construction of a dual luciferase reporter system for optimization of RNA interference in Rhipicephalus (Boophilus) microplus cell lines

    USDA-ARS?s Scientific Manuscript database

    Dual luciferase reporter systems are valuable tools for functional genomic studies, but have not previously been developed for use in tick cell culture. We evaluated expression of available luciferase constructs in tick cell cultures derived from Rhipicephalus (Boophilus) microplus, an important vec...

  6. A semisynthetic strategy leads to alteration of the backbone amidate ligand in the NiSOD active site

    SciTech Connect

    Campeciño, Julius O.; Dudycz, Lech W.; Tumelty, David; Berg, Volker; Cabelli, Diane E.; Maroney, Michael J.

    2015-07-01

    Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategy that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. 14N-hyperfine is observed on gz

  7. Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development.

    PubMed

    Mott, Tiffany M; Vijayakumar, Sudhamathi; Sbrana, Elena; Endsley, Janice J; Torres, Alfredo G

    2015-01-01

    In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis. Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 10(4) CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001. Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis.

  8. A semisynthetic strategy leads to alteration of the backbone amidate ligand in the NiSOD active site

    DOE PAGES

    Campeciño, Julius O.; Dudycz, Lech W.; Tumelty, David; ...

    2015-07-01

    Computational investigations have implicated the amidate ligand in nickel superoxide dismutase (NiSOD) in stabilizing Ni-centered redox catalysis and in preventing cysteine thiolate ligand oxidation. To test these predictions, we have used an experimental approach utilizing a semisynthetic scheme that employs native chemical ligation of a pentapeptide (HCDLP) to recombinant S. coelicolor NiSOD lacking these N-terminal residues, NΔ5-NiSOD. Wild-type enzyme produced in this manner exhibits the characteristic spectral properties of recombinant WT-NiSOD and is as catalytically active. The semisynthetic scheme was also employed to construct a variant where the amidate ligand was converted to a secondary amine, H1*-NiSOD, a novel strategymore » that retains a backbone N-donor atom. The H1*-NiSOD variant was found to have only ~1% of the catalytic activity of the recombinant wild-type enzyme, and had altered spectroscopic properties. X-ray absorption spectroscopy reveals a four-coordinate planar site with N2S2-donor ligands, consistent with electronic absorption spectroscopic results indicating that the Ni center in H1*-NiSOD is mostly reduced in the as-isolated sample, as opposed to 50:50 Ni(II)/Ni(III) mixture that is typical for the recombinant wild-type enzyme. The EPR spectrum of as-isolated H1*-NiSOD accounts for ~11% of the Ni in the sample and is similar to WT-NiSOD, but more axial, with gz < gx,y. 14N-hyperfine is observed on gz« less

  9. Characterization of the Burkholderia mallei tonB Mutant and Its Potential as a Backbone Strain for Vaccine Development

    PubMed Central

    Mott, Tiffany M.; Vijayakumar, Sudhamathi; Sbrana, Elena; Endsley, Janice J.; Torres, Alfredo G.

    2015-01-01

    Background In this study, a Burkholderia mallei tonB mutant (TMM001) deficient in iron acquisition was constructed, characterized, and evaluated for its protective properties in acute inhalational infection models of murine glanders and melioidosis. Methodology/Principal Findings Compared to the wild-type, TMM001 exhibits slower growth kinetics, siderophore hyper-secretion and the inability to utilize heme-containing proteins as iron sources. A series of animal challenge studies showed an inverse correlation between the percentage of survival in BALB/c mice and iron-dependent TMM001 growth. Upon evaluation of TMM001 as a potential protective strain against infection, we found 100% survival following B. mallei CSM001 challenge of mice previously receiving 1.5 x 104 CFU of TMM001. At 21 days post-immunization, TMM001-treated animals showed significantly higher levels of B. mallei-specific IgG1, IgG2a and IgM when compared to PBS-treated controls. At 48 h post-challenge, PBS-treated controls exhibited higher levels of serum inflammatory cytokines and more severe pathological damage to target organs compared to animals receiving TMM001. In a cross-protection study of acute inhalational melioidosis with B. pseudomallei, TMM001-treated mice were significantly protected. While wild type was cleared in all B. mallei challenge studies, mice failed to clear TMM001. Conclusions/Significance Although further work is needed to prevent chronic infection by TMM001 while maintaining immunogenicity, our attenuated strain demonstrates great potential as a backbone strain for future vaccine development against both glanders and melioidosis. PMID:26114445

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Moisture-Resistant Polyimide Aerogels Containing Propylene Oxide Links in the Backbone.

    PubMed

    Meador, Mary Ann B; Agnello, Marika; McCorkle, Linda; Vivod, Stephanie L; Wilmoth, Nathan

    2016-10-12

    Polyimide aerogels made using anhydride-capped oligomers from 4,4'-oxydianiline (ODA) and 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA) cross-linked with 1,3,5-tri(aminophenoxy)benzene (TAB) have been reported with very good mechanical properties but poor resistance to moisture. Replacing 50 mol % of the ODA with poly(propylene glycol)bis(2-aminopropyl ether) (PPG) with an average molecular weight of 230 g/mol in the oligomer backbone gives aerogels with water contact angles of 80°. The aerogels also absorb very little moisture on soaking in water. The aerogels also shrink less with increasing PPG concentration and therefore have significantly lower density and higher porosity than those made without PPG. Mechanical properties of the aerogels increased with increasing density, regardless of the polymer backbone. Brunauer-Emmett-Teller (BET) surface area of the aerogels studied ranged from 300 to 400 m(2)/g, depending mainly on PPG concentration. The high moisture resistance makes them promising materials for substrates for lightweight antennas as well as insulation for a variety of applications.

  12. Low Molecular Weight Oligomers with Aromatic Backbone as Efficient Nonviral Gene Vectors.

    PubMed

    Luan, Chao-Ran; Liu, Yan-Hong; Zhang, Ji; Yu, Qing-Ying; Huang, Zheng; Wang, Bing; Yu, Xiao-Qi

    2016-05-04

    A series of oligomers were synthesized via ring-opening polymerization. Although the molecular weights of these oligomers are only ∼2.5 kDa, they could efficiently bind and condense DNA into nanoparticles. These oligomers gave comparable transfection efficiency (TE) to PEI 25 kDa, while their TE could even increase with the presence of serum, and up to 65 times higher TE than PEI was obtained. The excellent serum tolerance was also confirmed by TEM, flow cytometry, and BSA adsorption assay. Moreover, structure-activity relationship studies revealed some interesting factors. First, oligomers containing aromatic rings in the backbone showed better DNA binding ability. These materials could bring more DNA cargo into the cells, leading to much better TE. Second, the isomerism of the disubstituted phenyl group on the oligomer backbone has large effect on the transfection. The ortho-disubstituted ones gave at least 1 order of magnitude higher TE than meta- or para-disubstituted oligomers. Gel electrophoresis involving DNase and heparin indicated that the difficulty to release DNA might contribute to the lower TE of the latter. Such clues may help us to design novel nonviral gene vectors with high efficiency and biocompatibility.

  13. Osmolyte effects on protein stability and solubility: a balancing act between backbone and side-chains

    PubMed Central

    Auton, Matthew; Rösgen, Jörg; Sinev, Mikhail; Holthauzen, Luis Marcelo F.; Bolen, D. Wayne

    2011-01-01

    In adaptation biology the discovery of intracellular osmolyte molecules that in some cases reach molar levels, raises questions of how they influence protein thermodynamics. We’ve addressed such questions using the premise that from atomic coordinates, the transfer free energy of a native protein (ΔGtr,N) can be predicted by summing measured water-to-osmolyte transfer free energies of the protein’s solvent exposed side chain and backbone component parts. ΔGtr,D is predicted using a self avoiding random coil model for the protein, and ΔGtr,D − ΔGtr,N, predicts the m-value, a quantity that measures the osmolyte effect on the N ⇌ D transition. Using literature and newly measured m-values we show 1:1 correspondence between predicted and measured m-values covering a range of 12 kcal/mol/M in protein stability for 46 proteins and 9 different osmolytes. Osmolytes present a range of side chain and backbone effects on N and D solubility and protein stability key to their biological roles. PMID:21683504

  14. The Nanomechanical Properties of Lactococcus lactis Pili Are Conditioned by the Polymerized Backbone Pilin

    PubMed Central

    Castelain, Mickaël; Duviau, Marie-Pierre; Canette, Alexis; Schmitz, Philippe; Loubière, Pascal; Cocaign-Bousquet, Muriel; Piard, Jean-Christophe; Mercier-Bonin, Muriel

    2016-01-01

    Pili produced by Lactococcus lactis subsp. lactis are putative linear structures consisting of repetitive subunits of the major pilin PilB that forms the backbone, pilin PilA situated at the distal end of the pilus, and an anchoring pilin PilC that tethers the pilus to the peptidoglycan. We determined the nanomechanical properties of pili using optical-tweezers force spectroscopy. Single pili were exposed to optical forces that yielded force-versus-extension spectra fitted using the Worm-Like Chain model. Native pili subjected to a force of 0–200 pN exhibit an inextensible, but highly flexible ultrastructure, reflected by their short persistence length. We tested a panel of derived strains to understand the functional role of the different pilins. First, we found that both the major pilin PilB and sortase C organize the backbone into a full-length organelle and dictate the nanomechanical properties of the pili. Second, we found that both PilA tip pilin and PilC anchoring pilin were not essential for the nanomechanical properties of pili. However, PilC maintains the pilus on the bacterial surface and may play a crucial role in the adhesion- and biofilm-forming properties of L. lactis. PMID:27010408

  15. Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement

    DOE PAGES

    Moriarty, Nigel W.; Tronrud, Dale E.; Adams, Paul D.; ...

    2014-06-17

    Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common usage today have been designed based on the assumption that each type of bond or angle has a single ideal value independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL)more » of restraints for the protein backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this CDL into the Phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the conformation dependent library yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying the cdl=True option. This successful implementation paves the way for further aspects of the context-dependence of ideal geometry to be characterized and applied to improve experimental and predictive modelling accuracy.« less

  16. Backbone dynamics of the monomeric lambda repressor denatured state ensemble under nondenaturing conditions.

    PubMed

    Chugha, Preeti; Oas, Terrence G

    2007-02-06

    Oxidizing two native methionine residues predominantly populates the denatured state of monomeric lambda repressor (MetO-lambdaLS) under nondenaturing conditions. NMR was used to characterize the secondary structure and dynamics of MetO-lambdaLS in standard phosphate buffer. 13Calpha and 1Halpha chemical shift indices reveal a region of significant helicity between residues 9 and 29. This helical content is further supported by the observation of medium-range amide NOEs. The remaining residues do not exhibit significant helicity as determined by NMR. We determined 15N relaxation parameters for 64 of 85 residues at 600 and 800 MHz. There are two distinct regions of reduced flexibility, residues 8-32 in the N-terminal third and residues 50-83 in the C-terminal third. The middle third, residues 33-50, has greater flexibility. We have analyzed the amplitude of the backbone motions in terms of the physical properties of the amino acids and conclude that conformational restriction of the backbone MetO-lambdaLS is due to nascent helix formation in the region corresponding to native helix 1. The bulkiness of amino acid residues in the C-terminal third leads to the potential for hydrophobic interactions, which is suggested by chemical exchange detected by the difference in spectral density J(0) at the two static magnetic fields. The more flexible middle region is the result of a predominance of small side chains in this region.

  17. Cellulose nanofiber backboned Prussian blue nanoparticles as powerful adsorbents for the selective elimination of radioactive cesium

    NASA Astrophysics Data System (ADS)

    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.

  18. NMR Polypeptide Backbone Conformation of the E. coli Outer Membrane Protein W

    PubMed Central

    Horst, Reto; Stanczak, Pawel; Wüthrich, Kurt

    2014-01-01

    SUMMARY The outer membrane proteins (Omp) are key factors for bacterial survival and virulence. Among the Omps which have been structurally characterized either by X-ray crystallography or by NMR in solution, the crystal structure of OmpW stands out because three of its four extracellular loops are well defined, whereas long extracellular loops in other E. coli Omps are disordered in the crystals as well as in NMR structures. OmpW thus presented an opportunity for detailed comparison of the extracellular loops in a β-barrel membrane protein structure in crystals and in non-crystalline milieus. Here the polypeptide backbone conformation of OmpW in 30-Fos micelles was determined. Complete backbone NMR assignments were obtained and the loops were structurally characterized. In combination with the OmpW crystal structure, NMR line shape analyses and 15N{1H}-NOE data, these results showed that intact regular secondary structures in the loops undergo slow hinge motions at the detergent–solvent interface. PMID:25017731

  19. First-principles study of the effect of functional groups on polyaniline backbone

    PubMed Central

    Chen, X. P.; Jiang, J. K.; Liang, Q. H.; Yang, N.; Ye, H. Y.; Cai, M.; Shen, L.; Yang, D. G.; Ren, T. L.

    2015-01-01

    We present a first-principles density functional theory study focused on how the chemical and electronic properties of polyaniline are adjusted by introducing suitable substituents on a polymer backbone. Analyses of the obtained energy barriers, reaction energies and minimum energy paths indicate that the chemical reactivity of the polyaniline derivatives is significantly enhanced by protonic acid doping of the substituted materials. Further study of the density of states at the Fermi level, band gap, HOMO and LUMO shows that both the unprotonated and protonated states of these polyanilines are altered to different degrees depending on the functional group. We also note that changes in both the chemical and electronic properties are very sensitive to the polarity and size of the functional group. It is worth noting that these changes do not substantially alter the inherent chemical and electronic properties of polyaniline. Our results demonstrate that introducing different functional groups on a polymer backbone is an effective approach to obtain tailored conductive polymers with desirable properties while retaining their intrinsic properties, such as conductivity. PMID:26584671

  20. Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications

    PubMed Central

    Meade, Bryan R; Gogoi, Khirud; Hamil, Alexander S; Palm-Apergi, Caroline; van den Berg, Arjen; Hagopian, Jonathan C; Springer, Aaron D; Eguchi, Akiko; Kacsinta, Apollo D; Dowdy, Connor F; Presente, Asaf; Lönn, Peter; Kaulich, Manuel; Yoshioka, Naohisa; Gros, Edwige; Cui, Xian-Shu; Dowdy, Steven F

    2015-01-01

    RNA interference (RNAi) has great potential to treat human disease1–3. However, in vivo delivery of short interfering RNAs (siRNAs), which are negatively charged double-stranded RNA macromolecules, remains a major hurdle4–9. Current siRNA delivery has begun to move away from large lipid and synthetic nanoparticles to more defined molecular conjugates9. Here we address this issue by synthesis of short interfering ribonucleic neutrals (siRNNs) whose phosphate backbone contains neutral phosphotriester groups, allowing for delivery into cells. Once inside cells, siRNNs are converted by cytoplasmic thioesterases into native, charged phosphodiester-backbone siRNAs, which induce robust RNAi responses. siRNNs have favorable drug-like properties, including high synthetic yields, serum stability and absence of innate immune responses. Unlike siRNAs, siRNNs avidly bind serum albumin to positively influence pharmacokinetic properties. Systemic delivery of siRNNs conjugated to a hepatocyte-specific targeting domain induced extended dose-dependent in vivo RNAi responses in mice. We believe that siRNNs represent a technology that will open new avenues for development of RNAi therapeutics. PMID:25402614

  1. Cellulose nanofiber backboned Prussian blue nanoparticles as powerful adsorbents for the selective elimination of radioactive cesium

    PubMed Central

    Vipin, Adavan Kiliyankil; Fugetsu, Bunshi; Sakata, Ichiro; Isogai, Akira; Endo, Morinobu; Li, Mingda; Dresselhaus, Mildred S.

    2016-01-01

    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. PMID:27845441

  2. On contribution of known atomic partial charges of protein backbone in electrostatic potential density maps.

    PubMed

    Wang, Jimin

    2017-06-01

    Partial charges of atoms in a molecule and electrostatic potential (ESP) density for that molecule are known to bear a strong correlation. In order to generate a set of point-field force field parameters for molecular dynamics, Kollman and coworkers have extracted atomic partial charges for each of all 20 amino acids using restrained partial charge-fitting procedures from theoretical ESP density obtained from condensed-state quantum mechanics. The magnitude of atomic partial charges for neutral peptide backbone they have obtained is similar to that of partial atomic charges for ionized carboxylate side chain atoms. In this study, the effect of these known atomic partial charges on ESP is examined using computer simulations and compared with the experimental ESP density recently obtained for proteins using electron microscopy. It is found that the observed ESP density maps are most consistent with the simulations that include atomic partial charges of protein backbone. Therefore, atomic partial charges are integral part of atomic properties in protein molecules and should be included in model refinement. © 2017 The Protein Society.

  3. Impact of Backbone Tether Length and Structure on the Electrochemical Performance of Viologen Redox Active Polymers

    SciTech Connect

    Burgess, Mark; Chénard, Etienne; Hernández-Burgos, Kenneth; Nagarjuna, Gavvalapalli; Assary, Rajeev S.; Hui, Jingshu; Moore, Jeffrey S.; Rodríguez-López, Joaquín

    2016-10-25

    The design of chemically stable and electrochemically reversible redox active polymers (RAPs) is of great interest for energy storage technologies. Particularly, RAPs are new players for flow batteries relying on a size-exclusion based mechanism of electrolyte separation, but few studies have provided detailed molecular understanding of redox polymers in solution. Here, we use a systematic molecular design approach to investigate the impact of linker and redox-pendant electronic interactions on the performance of viologen RAPs. We used scanning electrochemical microscopy, cyclic voltammetry, bulk electrolysis, temperature-dependent absorbance, and spectroelectrochemistry to study the redox properties, charge transfer kinetics, and self-exchange of electrons through redox active dimers and their equivalent polymers. Stark contrast was observed between the electrochemical properties of viologen dimers and their corresponding polymers. Electron self-exchange kinetics in redox active dimers that only differ by their tether length and rigidity influences their charge transfer properties. Predictions from the Marcus Hush theory were consistent with observations in redox active dimers, but they failed to fully capture the behavior of macromolecular systems. For example, polymer bound viologen pendants, if too close in proximity, do not retain chemical reversibility. In contrast to polymer films, small modifications to the backbone structure decisively impact the bulk electrolysis of polymer solutions. This first comprehensive study highlights the careful balance between electronic interactions and backbone rigidity required to design RAPs with superior electrochemical performance.

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

    PubMed

    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.

  5. Conformation-dependent backbone geometry restraints set a new standard for protein crystallographic refinement

    SciTech Connect

    Moriarty, Nigel W.; Tronrud, Dale E.; Adams, Paul D.; Karplus, P. Andrew

    2014-06-17

    Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. The restraints in common usage today have been designed based on the assumption that each type of bond or angle has a single ideal value independent of context. However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL) of restraints for the protein backbone (Berkholz et al. 2009. Structure. 17, 1316). Here, we report the introduction of this CDL into the Phenix package and the results of test refinements of thousands of structures across a wide range of resolutions. These tests show that use of the conformation dependent library yields models that have substantially better agreement with ideal main-chain bond angles and lengths and, on average, a slightly enhanced fit to the X-ray data. No disadvantages of using the backbone CDL are apparent. In Phenix usage of the CDL can be selected by simply specifying the cdl=True option. This successful implementation paves the way for further aspects of the context-dependence of ideal geometry to be characterized and applied to improve experimental and predictive modelling accuracy.

  6. HIV-1 Phenotypic Reverse Transcriptase Inhibitor Drug Resistance Test Interpretation Is Not Dependent on the Subtype of the Virus Backbone

    PubMed Central

    Bronze, Michelle; Steegen, Kim; Wallis, Carole L.; De Wolf, Hans; Papathanasopoulos, Maria A.; Van Houtte, Margriet; Stevens, Wendy S.; de Wit, Tobias Rinke; Stuyver, Lieven J.

    2012-01-01

    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. PMID

  7. Constructed Wetlands

    EPA Pesticide Factsheets

    these systems can improve water quality, engineers and scientists construct systems that replicate the functions of natural wetlands. Constructed wetlands are treatment systems that use natural processes

  8. The Inherent Conformational Preferences of Glutamine-Containing Peptides: the Role for Side-Chain Backbone Hydrogen Bonds

    NASA Astrophysics Data System (ADS)

    Walsh, Patrick S.; McBurney, Carl; Gellman, Samuel H.; Zwier, Timothy S.

    2015-06-01

    Glutamine is widely known to be found in critical regions of peptides which readily fold into amyloid fibrils, the structures commonly associated with Alzheimer's disease and glutamine repeat diseases such as Huntington's disease. Building on previous single-conformation data on Gln-containing peptides containing an aromatic cap on the N-terminus (Z-Gln-OH and Z-Gln-NHMe), we present here single-conformation UV and IR spectra of Ac-Gln-NHBn and Ac-Ala-Gln-NHBn, with its C-terminal benzyl cap. These results point towards side-chain to backbone hydrogen bonds dominating the structures observed in the cold, isolated environment of a molecular beam. We have identified and assigned three main conformers for Ac-Gln-NHBn all involving primary side-chain to backbone interactions. Ac-Ala-Gln-NHBn extends the peptide chain by one amino acid, but affords an improvement in the conformational flexibility. Despite this increase in the flexibility, only a single conformation is observed in the gas-phase: a structure which makes use of both side-chain-to-backbone and backbone-to-backbone hydrogen bonds.

  9. Polarizable Simulations with Second order Interaction Model (POSSIM) force field: Developing parameters for alanine peptides and protein backbone

    PubMed Central

    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

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

    PubMed

    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.

  11. Automatised selection of load paths to construct reduced-order models in computational damage micromechanics: from dissipation-driven random selection to Bayesian optimization

    NASA Astrophysics Data System (ADS)

    Goury, Olivier; Amsallem, David; Bordas, Stéphane Pierre Alain; Liu, Wing Kam; Kerfriden, Pierre

    2016-08-01

    In this paper, we present new reliable model order reduction strategies for computational micromechanics. The difficulties rely mainly upon the high dimensionality of the parameter space represented by any load path applied onto the representative volume element. We take special care of the challenge of selecting an exhaustive snapshot set. This is treated by first using a random sampling of energy dissipating load paths and then in a more advanced way using Bayesian optimization associated with an interlocked division of the parameter space. Results show that we can insure the selection of an exhaustive snapshot set from which a reliable reduced-order model can be built.

  12. EMSCOPE - Electromagnetic Component of EarthScope Backbone and Transportable Array Experiments 2006-2008

    NASA Astrophysics Data System (ADS)

    Egbert, G.; Evans, R.; Ingate, S.; Livelybrooks, D.; Mickus, K.; Park, S.; Schultz, A.; Unsworth, M.; Wannamaker, P.

    2007-12-01

    USArray (http://www.iris.edu/USArray) in conjunction with EMSOC (Electromagnetic Studies of the Continents) (http://emsoc.ucr.edu/emsoc) is installing magnetotelluric (MT) stations as part of Earthscope. The MT component of Earthscope consists of permanent (Backbone) and transportable long period stations to record naturally occurring, time varying electric and magnetic fields to produce a regional lithospheric/asthensospheric electrical conductivity map of the United States. The recent arrival of 28 long period MT instruments allows for the final installation of the Backbone stations throughout the US and yearly transportable array studies. The Backbone MT survey consists of 7 stations spaced throughout the continental US with preliminary installation at Soap Creek, Oregon; Parkfield, California; Braden, Missouri and Socorro, New Mexico.Siting and permitting are underway or completed at stations in eastern Montana, northern Wisconsin and Virginia. These stations will be recording for at least five years to determine electrical conductivities at depths that extend into the mantle transition zone. The first transportable array experiment was performed in the summer and fall of 2006 in central and eastern Oregon (Oregon Pilot Project) using equipment loaned from EMSOC. Thirty-one long period MT stations were recorded with 14 to 21 day occupations. Preliminary 3D inverse models indicate several lithospheric electrical conductivity anomalies including a linear zone marked by low-high conductivity transition along the Klamath-Blue Mountain Lineament associated with a linear trend of gravity minima. High electrical conductivity values occur in the upper crust under the accreted terrains in the Blue Mountains region. The second transportable array experiment was performed in the summer and fall of 2007 and completes coverage of the Oregon, Washington, and western Idaho, targeting the Cascadia subduction zone, Precambrian boundaries, and sub-basalt lithologies. The 2008

  13. Optimization and comparison of different methods for RNA isolation for cDNA library construction from the reindeer lichen Cladonia rangiferina.

    PubMed

    Junttila, Sini; Lim, Kean-Jin; Rudd, Stephen

    2009-10-05

    The reindeer lichen is the product of a mutualistic relationship between a fungus and an algae. Lichen demonstrate a remarkable capacity to tolerate dehydration. This tolerance is driven by a variety of biochemical processes and the accumulation of specific secondary metabolites that may be of relevance to the pharmaceutical, biotechnology and agriculture industries. These protective metabolites hinder in vitro enzymatic reactions required in cDNA synthesis. Along with the low concentrations of RNA present within lichen tissues, the process of creating a cDNA library is technically challenging. An evaluation of existing commercial and published protocols for RNA extraction from plant or fungal tissues has been performed and experimental conditions have been optimised to balance the need for the highest quality total ribonucleotides and the constraints of budget, time and human resources. We present a protocol that balances inexpensive RNA extraction methods with commercial RNA clean-up kits to yield sufficient RNA for cDNA library construction. Evaluation of the protocol and the construction of, and sampling from, a cDNA library is used to demonstrate the suitability of the RNA extraction method for expressed sequence tag production.

  14. Optimization and comparison of different methods for RNA isolation for cDNA library construction from the reindeer lichen Cladonia rangiferina

    PubMed Central

    Junttila, Sini; Lim, Kean-Jin; Rudd, Stephen

    2009-01-01

    Background The reindeer lichen is the product of a mutualistic relationship between a fungus and an algae. Lichen demonstrate a remarkable capacity to tolerate dehydration. This tolerance is driven by a variety of biochemical processes and the accumulation of specific secondary metabolites that may be of relevance to the pharmaceutical, biotechnology and agriculture industries. These protective metabolites hinder in vitro enzymatic reactions required in cDNA synthesis. Along with the low concentrations of RNA present within lichen tissues, the process of creating a cDNA library is technically challenging. Findings An evaluation of existing commercial and published protocols for RNA extraction from plant or fungal tissues has been performed and experimental conditions have been optimised to balance the need for the highest quality total ribonucleotides and the constraints of budget, time and human resources. Conclusion We present a protocol that balances inexpensive RNA extraction methods with commercial RNA clean-up kits to yield sufficient RNA for cDNA library construction. Evaluation of the protocol and the construction of, and sampling from, a cDNA library is used to demonstrate the suitability of the RNA extraction method for expressed sequence tag production. PMID:19804636

  15. Optimal design of Ig 5' primers for construction of diverse phage antibody library established to select anti-HAb18GEF and anti-DOTA-Y Fabs for hepatoma pretargeting RIT.

    PubMed

    Zhang, Sihe; Xing, Jinliang; Zhang, Qing; Song, Fei; Li, Yu; Yang, Xiangmin; Chen, Zhinan

    2006-05-01

    Phage antibody library yields antibodies with higher affinity against different antigens, if diverse IgV gene repertoires can be amplified. As the currently available Fab primer sets cannot guarantee efficient amplification with high diversity, and because rare cloning sites can be found in certain Ig genes, here, we present an optimal set of Ig 5' primers, compatible with Fd 5' clone site replaced pComb3 vector, for diverse Fab phage display library construction. These novel Fab primes designed based on the newly classified IgV families, not only have best match and highest coverage for IgV family with minimized N-terminal amino acid changes, but also present good amplification diversity and efficiency of Ig gene from mice immunized with different forms of antigens (HAb18GEF, KLH-DOTA-Y, and HAb18G/pcDNA3). A high quality immune phage library with good diversity was constructed based on the mixed Ig repertoire, and five high affinity Fab antibodies were selected to specifically bind to HAb18GEF, DOTA-Y and an irrelevant antigen gamma-sm, respectively. This novel Fab primers set can be applied to the construction of diverse phage antibody library and the anti-HAb18GEF and anti-DOTA-Y Fab antibodies lay a solid foundation for radioimmunotherapy of hepatoma.

  16. Lunar base construction requirements

    NASA Technical Reports Server (NTRS)

    Jolly, Steve; Helleckson, Brent

    1990-01-01

    The following viewgraph presentation is a review of the Lunar Base Constructibility Study carried out in the spring and summer of 1990. The objective of the study was to develop a method for evaluating the constructibility of Phase A proposals to build facilities on orbit or on extraterrestrial surfaces. Space construction was broadly defined as all forms of assembly, disassembly, connection, disconnection, deployment, stowage, excavation, emplacement, activation, test, transportation, etc., required to create facilities in orbit and on the surfaces of other celestial bodies. It was discovered that decisions made in the face of stated and unstated assumptions early in the design process (commonly called Phase A) can lock in non-optimal construction methods. Often, in order to construct the design, alterations must be made to the design during much later phases of the project. Such 'fixes' can be very difficult, expensive, or perhaps impossible. Assessing constructibility should thus be a part of the iterative design process, starting with the Phase A studies and continuing through production. This study assumes that there exists a minimum set of key construction requirements (i.e., questions whose answers form the set of discriminators) that must be implied or specified in order to assess the constructibility of the design. This set of construction requirements constitutes a 'constructibility filter' which then becomes part of the iterative design process. Five inherently different, dichotomous design reference missions were used in the extraction of these requirements to assure the depth and breath of the list.

  17. Lunar base construction requirements

    NASA Technical Reports Server (NTRS)

    Jolly, Steve; Helleckson, Brent

    1990-01-01

    The following viewgraph presentation is a review of the Lunar Base Constructibility Study carried out in the spring and summer of 1990. The objective of the study was to develop a method for evaluating the constructibility of Phase A proposals to build facilities on orbit or on extraterrestrial surfaces. Space construction was broadly defined as all forms of assembly, disassembly, connection, disconnection, deployment, stowage, excavation, emplacement, activation, test, transportation, etc., required to create facilities in orbit and on the surfaces of other celestial bodies. It was discovered that decisions made in the face of stated and unstated assumptions early in the design process (commonly called Phase A) can lock in non-optimal construction methods. Often, in order to construct the design, alterations must be made to the design during much later phases of the project. Such 'fixes' can be very difficult, expensive, or perhaps impossible. Assessing constructibility should thus be a part of the iterative design process, starting with the Phase A studies and continuing through production. This study assumes that there exists a minimum set of key construction requirements (i.e., questions whose answers form the set of discriminators) that must be implied or specified in order to assess the constructibility of the design. This set of construction requirements constitutes a 'constructibility filter' which then becomes part of the iterative design process. Five inherently different, dichotomous design reference missions were used in the extraction of these requirements to assure the depth and breath of the list.

  18. Improved variation calling via an iterative backbone remapping and local assembly method for bacterial genomes

    PubMed Central

    Tae, Hongseok; Settlage, Robert E.; Shallom, Shamira; Bavarva, Jasmin H.; Preston, Dale; Hawkins, Gregory N.; Adams, L. Garry; Garner, Harold R.

    2012-01-01

    Sequencing data analysis remains limiting and problematic, especially for low complexity repeat sequences and transposon elements due to inherent sequencing errors and short sequence read lengths. We have developed a program, ReviSeq, which uses a hybrid method comprised of iterative remapping and local assembly upon a bacterial sequence backbone. Application of this method to six Brucella suis field isolates compared to the newly revised Brucella suis 1330 reference genome identified on average 13, 15, 19 and 9 more variants per sample than STAMPY/SAMtools, BWA/SAMtools, iCORN and BWA/PINDEL pipelines, and excluded on average 4, 2, 3 and 19 variants per sample, respectively. In total, using this iterative approach, we identified on average 87 variants including SNVs, short INDELs and long INDELs per strain when compared to the reference. Our program outperforms other methods especially for long INDEL calling. The program is available at http://reviseq.sourceforge.net. PMID:22967795

  19. X-shooter-backbone and UV-blue and visible spectrographs: final AIV and measured performances

    NASA Astrophysics Data System (ADS)

    Rasmussen, Per Kjærgaard; Zerbi, Filippo M.; Dekker, Hans; Vernet, Joel; Andersen, Jeppe J.; De Caprio, Vincenzo; Dimarcantonio, Paolo; D'Odorico, Sandro; Lizon, Jean-Louis; Lucuix, Christian; Michaelsen, Niels; Molinari, Emilio; Nørregaard, Preben; Riva, Alberto; Riva, Marco; Santin, Paolo; Sørensen, Anton N.; Spanò, Paolo; Wistisen, Dennis

    2008-07-01

    X-shooter is a wide band (U to K) intermediate resolution (4000-14000) single object three-arms spectrograph for the VLT. Currently in the last phase of integration, X-shooter will see the first light at ESO Paranal as the first of the VLT second generation instruments in the last quarter of 2008. We describe in this paper the final steps in the integration and testing phase of the central Backbone with its key functions (including the active flexure compensation mirrors) and of the two UV-Blue and Visible spectroscopic arms. We report on the stability results of the preslit optics and of the spectrographs and on the remarkable efficiency which is derived from the measurements of the optical components of the instrument.

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

    SciTech Connect

    Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J.

    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. Modification of Rifamycin Polyketide Backbone Leads to Improved Drug Activity against Rifampicin-resistant Mycobacterium tuberculosis*

    PubMed Central

    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

    2014-01-01

    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. PMID:24923585

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

    PubMed

    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.

  3. Sendai Virus as a Backbone for Vaccines against RSV and other Human Paramyxoviruses

    PubMed Central

    Russell, Charles J.; Hurwitz, Julia L.

    2016-01-01

    Summary Human paramyxoviruses are the etiological agents for life-threatening respiratory virus infections of infants and young children. These viruses – including respiratory syncytial virus (RSV), the human parainfluenza viruses (hPIV1-4), and human metapneumovirus (hMPV) – are responsible for millions of serious lower respiratory tract infections each year worldwide. There are currently no standard treatments and no licensed vaccines for any of these pathogens. Here we review research with which Sendai virus, a mouse parainfluenza virus type 1, is being advanced as a Jennerian vaccine for hPIV1 and as a backbone for RSV, hMPV, and other hPIV vaccines for children. PMID:26648515

  4. A gel-less isolation of untagged plasmid DNA insert from vector backbone in homogeneous format.

    PubMed

    Kalinichenko, Svetlana V; Shepelev, Mikhail V; Korobko, Igor V

    2017-03-15

    Agarose gel electrophoresis with subsequent DNA extraction from gel is routinely used for DNA fragment isolation after plasmid DNA digestion. We describe a gel-less method for DNA fragment isolation after plasmid DNA digestion which is based on in-solution negative selection through depletion of vector backbone bearing LoxP sites by sorption on solid phase-immobilized mutated Cre recombinase. The method might be especially useful in preparation of DNA fragments for transgenic animal generation where residual agarose presence is a concern, and DNA fragments are frequently large in size and thus might be mechanically damaged during purification with conventional affinity-based gel extraction methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Solid-phase synthesis of lidocaine and procainamide analogues using backbone amide linker (BAL) anchoring.

    PubMed

    Shannon, Simon K; Peacock, Mandy J; Kates, Steven A; Barany, George

    2003-01-01

    New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. NMR backbone resonance assignments of the prodomain variants of BDNF in the urea denatured state.

    PubMed

    Wang, Jing; Bains, Henrietta; Anastasia, Agustin; Bracken, Clay

    2017-09-20

    Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family of proteins which plays a central role in neuronal survival, growth, plasticity and memory. A single Val66Met variant has been identified in the prodomain of human BDNF that is associated with anxiety, depression and memory disorders. The structural differences within the full-length prodomain Val66 and Met66 isoforms could shed light on the mechanism of action of the Met66 and its impact on the development of neuropsychiatric-associated disorders. In the present study, we report the backbone (1)H, (13)C, and (15)N NMR assignments of both full-length Val66 and Met66 prodomains in the presence of 2 M urea. These conditions were utilized to suppress residual structure and aid subsequent native state structural investigations aimed at mapping and identifying variant-dependent conformational differences under native-state conditions.

  8. Optimization of RNA isolation from Brittle Leaf Disease affected date palm leaves and construction of a subtractive cDNA library.

    PubMed

    Saïdi, Mohammed Najib; Gargouri-Bouzid, Radhia; Rayanni, Mariem; Drira, Noureddine

    2009-01-01

    A simple and efficient method was described here for the isolation of high-quality RNA from date palm leaves affected with Brittle Leaf Disease (BLD) and containing high amount of phenolic compounds. The procedure was based on the use of a non-ionic detergent Nonidet-P40 (NP-40), Polyvinylpyrrolidone (PVP), and beta-mercaptoethanol in the extraction buffer in order to isolate cytoplasmic RNA and to prevent the oxidation of phenolic compounds. This method allowed the isolation of intact RNA, suitable for cDNA synthesis and library construction. Differential screening of the subtractive cDNA library from affected leaf RNA led to the identification of some BLD-induced genes.

  9. 1H, 13C, and 15N backbone assignment and secondary structure of the receptor-binding domain of vascular endothelial growth factor.

    PubMed Central

    Fairbrother, W. J.; Champe, M. A.; Christinger, H. W.; Keyt, B. A.; Starovasnik, M. A.

    1997-01-01

    Nearly complete sequence-specific 1H, 13C, and 15N resonance assignments are reported for the backbone atoms of the receptor-binding domain of vascular endothelial growth factor (VEGF), a 23-kDa homodimeric protein that is a major regulator of both normal and pathological angiogenesis. The assignment strategy relied on the use of seven 3D triple-resonance experiments [HN(CO)CA, HNCA, HNCO, (HCA)CONH, HN(COCA)HA, HN(CA)HA, and CBCA-(CO)NH] and a 3D 15N-TOCSY-HSQC experiment recorded on a 0.5 mM (12 mg/mL) sample at 500 MHz, pH 7.0, 45 degrees C. Under these conditions, 15N relaxation data show that the protein has a rotational correlation time of 15.0 ns. Despite this unusually long correlation time, assignments were obtained for 94 of the 99 residues; 8 residues lack amide 1H and 15N assignments, presumably due to rapid exchange of the amide 1H with solvent under the experimental conditions used. The secondary structure of the protein was deduced from the chemical shift indices of the 1H alpha, 13C alpha, 13C beta, and 13CO nuclei, and from analysis of backbone NOEs observed in a 3D 15N-NOESY-HSQC spectrum. Two helices and a significant amount of beta-sheet structure were identified, in general agreement with the secondary structure found in a recently determined crystal structure of a similar VEGF construct [Muller YA et al., 1997, Proc Natl Acad Sci USA 94:7192-7197]. PMID:9336848

  10. Remote consultation and diagnosis in medical imaging using a global PACS backbone network

    NASA Astrophysics Data System (ADS)

    Martinez, Ralph; Sutaria, Bijal N.; Kim, Jinman; Nam, Jiseung

    1993-10-01

    A Global PACS is a national network which interconnects several PACS networks at medical and hospital complexes using a national backbone network. A Global PACS environment enables new and beneficial operations between radiologists and physicians, when they are located in different geographical locations. One operation allows the radiologist to view the same image folder at both Local and Remote sites so that a diagnosis can be performed. The paper describes the user interface, database management, and network communication software which has been developed in the Computer Engineering Research Laboratory and Radiology Research Laboratory. Specifically, a design for a file management system in a distributed environment is presented. In the remote consultation and diagnosis operation, a set of images is requested from the database archive system and sent to the Local and Remote workstation sites on the Global PACS network. Viewing the same images, the radiologists use pointing overlay commands, or frames to point out features on the images. Each workstation transfers these frames, to the other workstation, so that an interactive session for diagnosis takes place. In this phase, we use fixed frames and variable size frames, used to outline an object. The data pockets for these frames traverses the national backbone in real-time. We accomplish this feature by using TCP/IP protocol sockets for communications. The remote consultation and diagnosis operation has been tested in real-time between the University Medical Center and the Bowman Gray School of Medicine at Wake Forest University, over the Internet. In this paper, we show the feasibility of the operation in a Global PACS environment. Future improvements to the system will include real-time voice and interactive compressed video scenarios.

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

    PubMed

    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.

  12. 40-Gbps optical backbone network deep packet inspection based on FPGA

    NASA Astrophysics Data System (ADS)

    Zuo, Yuan; Huang, Zhiping; Su, Shaojing

    2014-11-01

    In the era of information, the big data, which contains huge information, brings about some problems, such as high speed transmission, storage and real-time analysis and process. As the important media for data transmission, the Internet is the significant part for big data processing research. With the large-scale usage of the Internet, the data streaming of network is increasing rapidly. The speed level in the main fiber optic communication of the present has reached 40Gbps, even 100Gbps, therefore data on the optical backbone network shows some features of massive data. Generally, data services are provided via IP packets on the optical backbone network, which is constituted with SDH (Synchronous Digital Hierarchy). Hence this method that IP packets are directly mapped into SDH payload is named POS (Packet over SDH) technology. Aiming at the problems of real time process of high speed massive data, this paper designs a process system platform based on ATCA for 40Gbps POS signal data stream recognition and packet content capture, which employs the FPGA as the CPU. This platform offers pre-processing of clustering algorithms, service traffic identification and data mining for the following big data storage and analysis with high efficiency. Also, the operational procedure is proposed in this paper. Four channels of 10Gbps POS signal decomposed by the analysis module, which chooses FPGA as the kernel, are inputted to the flow classification module and the pattern matching component based on TCAM. Based on the properties of the length of payload and net flows, buffer management is added to the platform to keep the key flow information. According to data stream analysis, DPI (deep packet inspection) and flow balance distribute, the signal is transmitted to the backend machine through the giga Ethernet ports on back board. Practice shows that the proposed platform is superior to the traditional applications based on ASIC and NP.

  13. Statistical mechanics of protein allostery: Roles of backbone and side-chain structural fluctuations

    NASA Astrophysics Data System (ADS)

    Itoh, Kazuhito; Sasai, Masaki

    2011-03-01

    A statistical mechanical model of allosteric transition of proteins is developed by extending the structure-based model of protein folding to cases that a protein has two different native conformations. Partition function is calculated exactly within the model and free-energy surfaces associated with allostery are derived. In this paper, the model of allosteric transition proposed in a previous paper [Proc. Natl. Acad. Sci. U.S.A 134, 7775 (2010)] is reformulated to describe both fluctuation in side-chain configurations and that in backbone structures in a balanced way. The model is applied to example proteins, Ras, calmodulin, and CheY: Ras undergoes the allosteric transition between guanosine diphosphate (GDP)-bound and guanosine triphosphate (GTP)-bound forms, and the model results show that the GDP-bound form is stabilized enough to prevent unnecessary signal transmission, but the conformation in the GTP-bound state bears large fluctuation in side-chain configurations, which may help to bind multiple target proteins for multiple pathways of signaling. The calculated results of calmodulin show the scenario of sequential ordering in Ca2 + binding and the associated allosteric conformational change, which are realized though the sequential appearing of pre-existing structural fluctuations, i.e., fluctuations to show structures suitable to bind Ca2 + before its binding. Here, the pre-existing fluctuations to accept the second and third Ca2 + ions are dominated by the side-chain fluctuation. In CheY, the calculated side-chain fluctuation of Tyr106 is coordinated with the backbone structural change in the β4-α4 loop, which explains the pre-existing Y-T coupling process in this protein. Ability of the model to explain allosteric transitions of example proteins supports the view that the large entropic effects lower the free-energy barrier of allosteric transition.

  14. Enhanced biosynthetically directed fractional carbon-13 enrichment of proteins for backbone NMR Assignments

    PubMed Central

    Wenrich, Broc R.; Sonstrom, Reilly E.; Gupta, Riju A.; Rovnyak, David

    2015-01-01

    Routes to carbon-13 enrichment of bacterially expressed proteins include achieving uniform or positionally selective (e.g. ILV-Me, or 13C′, etc.) enrichment. We consider the potential for biosynthetically directed fractional enrichment (e.g. carbon-13 incorporation in the protein less than 100%) for performing routine n-(D)dimensional NMR spectroscopy of proteins. First, we demonstrate an approach to fractional isotope addition where the initial growth media containing natural abundance glucose is replenished at induction with a small amount (e.g. 10%w/w u-13C-glucose) of enriched nutrient. The approach considered here is to add 10% (e.g. 200 mg for a 2 g/L culture) u-13C-glucose at the induction time (OD600=0.8), resulting in a protein with enhanced 13C incorporation that gives almost the same NMR signal levels as an exact 20% 13C sample. Second, whereas fractional enrichment is used for obtaining stereospecific methyl assignments, we find that 13C incorporation levels no greater than 20%w/w yield 13C and 13C-13C spin pair incorporation sufficient to conduct typical 3D-bioNMR backbone experiments on moderate instrumentation (600 MHz, RT probe). Typical 3D-bioNMR experiments of a fractionally enriched protein yield expected backbone connectivities, and did not show amino acid biases in this work, with one exception. When adding 10% u-13C glucose to expression media at induction, there is poor preservation of 13Cα-13Cβ spin pairs in the amino acids ILV, leading to the absence of Cβ signals in HNCACB spectra for ILV, a potentially useful editing effect. Enhanced fractional carbon-13 enrichment provides lower-cost routes to high throughput protein NMR studies, and makes modern protein NMR more cost-accessible. PMID:26256059

  15. Backbone cyclization of analgesic conotoxin GeXIVA facilitates direct folding of the ribbon isomer.

    PubMed

    Wu, Xiaosa; Huang, Yen-Hua; Kaas, Quentin; Harvey, Peta J; Wang, Conan K; Tae, Han-Shen; Adams, David J; Craik, David J

    2017-08-28

    Conotoxin GeXIVA inhibits the α9α10 nicotinic acetylcholine receptor (nAChR) and is analgesic in animal models of pain. α-conotoxins have four cysteines, which can have three possible disulfide connectivities: globular (CysI-CysIII and CysII-CysIV); ribbon (CysI-CysIV and CysII-CysIII) or bead (CysI-CysII and CysIII-CysIV). Native α-conotoxins preferably adopt the globular connectivity, and previous studies of α-conotoxins have focused on the globular isomers as the ribbon and bead isomers typically have lower potency at nAChRs than the globular form. A recent report showed that the bead and ribbon isomers of GeXIVA are more potent than the globular isomer, with low nanomolar half maximal inhibitory concentrations (IC50s). Despite this high potency, the therapeutic potential of GeXIVA is limited because, like most peptides, it is susceptible to proteolytic degradation and is challenging to synthesize in high yield. Here we used backbone cyclization as a strategy to improve the folding yield as well as increase the serum stability of ribbon GeXIVA while preserving activity at the α9α10 nAChR. Specifically, cyclization of ribbon GeXIVA with a two-residue linker maintained the biological activity at the human α9α10 nAChR and improved stability in human serum. Short linkers led to selective formation of the ribbon disulfide isomer without requiring orthogonal protection. Overall, this study highlights the value of backbone cyclization in directing folding, improving yields and stabilizing conotoxins with therapeutic potential. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  16. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong

    2016-11-01

    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

  17. Backbone Dynamics of an Atypical Orphan Response Regulator Protein, Helicobacter pylori 1043

    PubMed Central

    Jeong, Ki-Woong; Ko, Hyunsook; Lee, Sung-Ah; Hong, Eunmi; Ko, Sunggeon; Cho, Hyun-Soo; Lee, Weontae; Kim, Yangmee

    2013-01-01

    An atypical orphan response regulator protein, HP1043 (HP-RR) in Helicobacter pylori, is proven to be essential for cell growth and does not require the well known phosphorelay scheme. HP-RR was identified as a symmetric dimer with two functional domains, an N-terminal regulatory domain (HP-RRr) and a C-terminal effector domain (HP-RRe). HP-RR is a new class of response regulator, as a phosphorylation-independent regulator. Previously, we have presented a detailed three-dimensional structure of HP-RR using NMR spectroscopy and X-ray crystallography. In this study, in order to understand the functional importance of flexibilities in HP-RRr and HP-RRe, T1, T2, heteronuclear NOE experiments have been performed and backbone dynamics of HP-RRr and HP-RRe were investigated. HP-RRr is a symmetric dimer and the interface region, α4-β5-α5 of dimer, showed high rigidity (high S2 values). Site of rearrangements associated with phosphorylation of HP-RRr (Ser75: Rex = 3.382, Ile95: Rex = 5.228) showed slow chemical exchanges. HP-RRe is composed of three α-helices flanked on two sides by anti-parallel β-sheets. Low order parameters as well as conformational exchanges in the centers of loop regions known as the DNA binding site and transcription site of HP-RRe suggested that flexibility of HP-RRe is essential for interaction with DNA. In conclusion, backbone dynamics information for HP-RR implies that structural flexibilities in HP-RRr are necessary for the phosphorylation site and the dynamic nature of HP-RRe is essential for the regulation of interaction between protein and DNA. PMID:23456337

  18. High-cost, high-capacity backbone for global brain communication.

    PubMed

    van den Heuvel, Martijn P; Kahn, René S; Goñi, Joaquín; Sporns, Olaf

    2012-07-10

    Network studies of human brain structural connectivity have identified a specific set of brain regions that are both highly connected and highly central. Recent analyses have shown that these putative hub regions are mutually and densely interconnected, forming a "rich club" within the human brain. Here we show that the set of pathways linking rich club regions forms a central high-cost, high-capacity backbone for global brain communication. Diffusion tensor imaging (DTI) data of two sets of 40 healthy subjects were used to map structural brain networks. The contributions to network cost and communication capacity of global cortico-cortical connections were assessed through measures of their topology and spatial embedding. Rich club connections were found to be more costly than predicted by their density alone and accounted for 40% of the total communication cost. Furthermore, 69% of all minimally short paths between node pairs were found to travel through the rich club and a large proportion of these communication paths consisted of ordered sequences of edges ("path motifs") that first fed into, then traversed, and finally exited the rich club, while passing through nodes of increasing and then decreasing degree. The prevalence of short paths that follow such ordered degree sequences suggests that neural communication might take advantage of strategies for dynamic routing of information between brain regions, with an important role for a highly central rich club. Taken together, our results show that rich club connections make an important contribution to interregional signal traffic, forming a central high-cost, high-capacity backbone for global brain communication.

  19. Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones.

    PubMed

    Suphaphiphat, Pirada; Whittaker, Lynne; De Souza, Ivna; Daniels, Rodney S; Dormitzer, Philip R; McCauley, John W; Settembre, Ethan C

    2016-07-12

    The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs). Improving the current process for making vaccine viruses can provide great value. We have previously established a synthetic approach for rapidly generating influenza viruses in a vaccine-approved Madin Darby canine kidney (MDCK) cell line using novel, high-growth backbones that increase virus rescue efficiency and antigen yield. This technology also has the potential to produce viruses that maintain antigenic similarity to the intended reference viruses, depending on the hemagglutinin (HA) and neuraminidase (NA) sequences used for gene synthesis. To demonstrate this utility, we generated a panel of synthetic viruses using HA and NA sequences from recent isolates and showed by hemagglutination inhibition (HI) tests that all synthetic viruses were antigenically-like their conventional egg- or cell-propagated reference strains and there was no impact of the novel backbones on antigenicity. This synthetic approach can be used for the efficient production of CVVs that may be more representative of circulating viruses and may be used for both egg- and cell-based vaccine manufacturing platforms. When combined with mammalian cell culture technology for antigen production, synthetic viruses generated using HA and NA sequences from a non-egg-adapted prototype can help to reduce the potential impact of antigenic differences between vaccine virus and circulating viruses on

  20. A computational study of radical initiated protein backbone homolytic dissociation on all natural amino acids.

    PubMed

    Uranga, Jon; Lakuntza, Oier; Ramos-Cordoba, Eloy; Matxain, Jon M; Mujika, Jon I

    2016-11-16

    Hydroxyl radical (˙OH) is known to be one of the most reactive species. In this work, the hydrogen abstraction by ˙OH from Cα and Cβ atoms of all amino acids is studied in the framework of density functional theory as this is the most favorable reaction mechanism when this kind of radical attacks a protein. From the myriad routes that the oxidation of a protein by a ˙OH radical may follow, fragmentation of the protein is one of the most damaging ones as it hampers the normal function of the protein. Therefore, cleavages of the Cα-C and Cα-N backbone bonds have been investigated as the second step of the mechanism. To the best of our knowledge, this is the first time that this reaction pathway has been systematically studied for all natural amino acids. The study includes the effects that the solvent dielectrics or the conformation of the peptide model employed has on the reaction. Interestingly, the results indicate that the nature of the side chain has little effect on the H abstraction reaction, and that for most of amino acids the attack at the Cα atom is favored over the attack at the Cβ atom. The origin of this preference relies on the larger capability of the formed radical intermediate to delocalize the unpaired electron, thus maximizing the captodative effect. Moreover, the reaction is more favorable when the reactant presents a β-sheet conformation, with a completely planar peptide backbone. With respect to the homolytic splitting of the Cα-C and Cα-N bonds, the former is favorable for almost all amino acids, whereas Ser and Thr are the only amino acids favoring the latter. These results agree with previous investigations but an accurate description of the electronic density analysis performed indicates that the origin of the different reaction pathway preferences relies on a large stabilization of the product rather than bond weakening at the radical intermediate.

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

    PubMed Central

    Trier, Nicole Hartwig; Dam, Catharina Essendrup; Olsen, Dorthe Tange; Hansen, Paul Robert; Houen, Gunnar

    2015-01-01

    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. PMID:26657009

  2. Aqueous self-assembly of hydrophobic macromolecules with adjustable rigidity of the backbone.

    PubMed

    Guan, Zhou; Liu, Dapeng; Lin, Jiaping; Wang, Xiaosong

    2017-08-02

    P(FpC3P) (Fp: CpFe(CO)2; C3P: propyl diphenyl phosphine) has a helical backbone, resulting from piano stool metal coordination geometry, which is rigid with intramolecular aromatic interaction of the phenyl groups. The macromolecule is hydrophobic, but the polarized CO groups can interact with water for aqueous self-assembly. The stiffness of P(FpC3P), which is adjustable by temperature, is an important factor influencing the morphologies of kinetically trapped assemblies. P(FpC3P)7 self-assembles in DMSO/water (10/90 by volume) into lamellae at 25 °C, vesicles at 40 °C and irregular aggregates at higher temperatures (60 and 70 °C). The colloidal stability decreases in the order of lamellae, vesicles and irregular aggregates. Dissipative particle dynamics (DPD) simulation reveals the same temperature-dependent self-assembled morphologies with an interior of hydrophobic aromatic groups covered with the metal coordination units. The rigid backbone at 25 °C accounts for the formation of the layered morphology, while the reduced rigidity of the same P(FpC3P)7 at 40 °C curves up the lamellae into vesicles. At a higher temperature (60 or 70 °C), P(FpC3P)7 behaves as a random coil without obvious amphiphilic segregation, resulting in irregular aggregates. The stiffness is, therefore, a crucial factor for the aqueous assembly of macromolecules without obvious amphiphilic segregation, which is reminiscent of the solution behavior observed for many hydrophobic biological macromolecules such as proteins.

  3. Hydrogen bonds between short polar side chains and peptide backbone: prevalence in proteins and effects on helix-forming propensities.

    PubMed

    Vijayakumar, M; Qian, H; Zhou, H X

    1999-03-01

    A survey of 322 proteins showed that the short polar (SP) side chains of four residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hydrogen bonds with neighboring backbone amides. Specifically, 32% of Thr, 29% of Ser, 26% of Asp, and 19% of Asn engage in such hydrogen bonds. When an SP residue caps the N terminal of a helix, the contribution to helix stability by a hydrogen bond with the amide of the N3 or N2 residue is well established. When an SP residue is in the middle of a helix, the side chain is unlikely to form hydrogen bonds with neighboring backbone amides for steric and geometric reasons. In essence the SP side chain competes with the backbone carbonyl for the same hydrogen-bonding partner (i.e., the backbone amide) and thus SP residues tend to break backbone carbonyl-amide hydrogen bonds. The proposition that this is the origin for the low propensities of SP residues in the middle of alpha helices (relative to those of nonpolar residues) was tested. The combined effects of restricting side-chain rotamer conformations (documented by Creamer and Rose, Proc Acad Sci USA, 1992;89:5937-5941; Proteins, 1994;19:85-97) and excluding side- chain to backbone hydrogen bonds by the helix were quantitatively analyzed. These were found to correlate strongly with four experimentally determined scales of helix-forming propensities. The correlation coefficients ranged from 0.72 to 0.87, which are comparable to those found for nonpolar residues (for which only the loss of side-chain conformational entropy needs to be considered).

  4. Solution structure and backbone dynamics of human epidermal-type fatty acid-binding protein (E-FABP).

    PubMed Central

    Gutiérrez-González, Luis H; Ludwig, Christian; Hohoff, Carsten; Rademacher, Martin; Hanhoff, Thorsten; Rüterjans, Heinz; Spener, Friedrich; Lücke, Christian

    2002-01-01

    Human epidermal-type fatty acid-binding protein (E-FABP) belongs to a family of intracellular 14-15 kDa lipid-binding proteins, whose functions have been associated with fatty acid signalling, cell growth, regulation and differentiation. As a contribution to understanding the structure-function relationship, we report in the present study features of its solution structure and backbone dynamics determined by NMR spectroscopy. Applying multi-dimensional high-resolution NMR techniques on unlabelled and 15N-enriched recombinant human E-FABP, the 1H and 15N resonance assignments were completed. On the basis of 2008 distance restraints, the three-dimensional solution structure of human E-FABP was subsequently obtained (backbone atom root-mean-square deviation of 0.92+/-0.11 A; where 1 A=0.1 nm), consisting mainly of 10 anti-parallel beta-strands that form a beta-barrel structure. 15N relaxation experiments (T1, T2 and heteronuclear nuclear Overhauser effects) at 500, 600 and 800 MHz provided information on the internal dynamics of the protein backbone. Nearly all non-terminal backbone amide groups showed order parameters S(2)>0.8, with an average value of 0.88+/-0.04, suggesting a uniformly low backbone mobility in the nanosecond-to-picosecond time range. Moreover, hydrogen/deuterium exchange experiments indicated a direct correlation between the stability of the hydrogen-bonding network in the beta-sheet structure and the conformational exchange in the millisecond-to-microsecond time range. The features of E-FABP backbone dynamics elaborated in the present study differ markedly from those of the phylogenetically closely related heart-type FABP and the more distantly related ileal lipid-binding protein, implying a strong interdependence with the overall protein stability and possibly also with the ligand-binding affinity for members of the lipid-binding protein family. PMID:12049637

  5. Optimization of the Small Glycan Presentation for Binding a Tumor-Associated Antibody: Application to the Construction of an Ultrasensitive Glycan Biosensor.

    PubMed

    Kveton, Filip; Blšáková, Anna; Hushegyi, Andras; Damborsky, Pavel; Blixt, Ola; Jansson, Bo; Tkac, Jan

    2017-03-21

    The main aim of the study was to optimize the interfacial presentation of a small antigen-a Tn antigen (N-acetylgalactosamine)-for binding to its analyte anti-Tn antibody. Three different methods for the interfacial display of a small glycan are compared here, including two methods based on the immobilization of the Tn antigen on a mixed self-assembled monolayer (SAM) (2D biosensor) and the third one utilizing a layer of a human serum albumin (HSA) for the immobilization of a glycan forming a 3D interface. Results showed that the 3D interface with the immobilized Tn antigen is the most effective bioreceptive surface for binding its analyte. The 3D impedimetric glycan biosensor exhibited a limit of detection of 1.4 aM, a wide linear range (6 orders of magnitude), and high assay reproducibility with an average relative standard deviation of 4%. The buildup of an interface was optimized using various techniques with the visualization of the glycans on the biosensor surface by atomic force microscopy. The study showed that the 3D biosensor is not only the most sensitive compared to other two biosensor platforms but that the Tn antigen on the 3D biosensor surface is more accessible for antibody binding with better kinetics of binding (t50% = 137 s, t50% = the time needed to attain 50% of a steady-state signal) compared to the 2D biosensor configuration with t50% = 354 s. The 3D glycan biosensor was finally applied for the analysis of a human serum sample spiked with an analyte.

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

    NASA Astrophysics Data System (ADS)

    Hamuro, Yoshitomo

    2017-01-01

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

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

    PubMed

    Hamuro, Yoshitomo

    2017-03-01

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

  8. The Effect of Different microRNA Backbones on Artificial miRNA Expression and Knockdown Activity Against HIV-1 Replication.

    PubMed

    Nejati, Ahmad; Soleimani, Masoud; Arefian, Ehsan; Marashi, Sayed M; Tabatabaie, Hamideh; Farahmand, Mohammad; Shoja, Zabihollah; Mahmoodi, Mahmood; Nategh, Rakhshandeh; Shahmahmoodi, Shohreh

    2016-01-01

    Artificial microRNAs (miRNAs) are designed to develop an RNAi-based gene therapy. Recently, it has been suggested that the flanking sequences and terminal loop structure play a critical role in RNAi biogenesis and target recognition, but no extensive study regarding the different miRNA backbone for artificial miRNAs optimization has been conducted. We tested three artificial miRNAs with human hsa-miR30a (common miRNA), hsa-miR150 (T cell specific miRNA), and hsa-miR122 (liver specific miRNA) backbones in HEK-293T and Jurkat cell lines. Artificial miRNA processing and knockdown efficiency were analyzed by stem-loop RT-PCR, qRT-PCR, luciferase assay and target challenging. We identified strikingly different RNAi activities among these different artificial miRNAs. Our results demonstrated that expression and function of art-miR150 was more than art-miR30 and artmiR122 in both HEK-293T and Jurkat cell lines. Since the main difference in these artificial miRNAs was flanking sequences and terminal loop structure, the change between the expression and function of artificial miRNAs can be attributed to these structures. This study showed that expression of cell-specific artificial miRNA in target and nontarget cells is not different, but variation in flanking sequences and terminal loop can be involved in expression and function of artificial miRNAs. These results can be important for improving artificial miRNA design in RNAi-based gene therapy.

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

    NASA Astrophysics Data System (ADS)

    Hamuro, Yoshitomo

    2017-03-01

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

  10. Construction aggregates

    USGS Publications Warehouse

    Tepordei, V.V.

    1995-01-01

    Part of the 1994 Industrial Minerals Review. The production, consumption, and applications of construction aggregates are reviewed. In 1994, the production of construction aggregates, which includes crushed stone and construction sand and gravel combined, increased 7.7 percent to 2.14 Gt compared with the previous year. These record production levels are mostly a result of funding for highway construction work provided by the Intermodal Surface Transportation Efficiency Act of 1991. Demand is expected to increase for construction aggregates in 1995.

  11. Epitaxy-assisted creation of PCBM nanocrystals and its application in constructing optimized morphology for bulk-heterojunction polymer solar cells.

    PubMed

    Li, Ligui; Lu, Guanghao; Li, Sijun; Tang, Haowei; Yang, Xiaoniu

    2008-12-11

    PCBM (a C60 derivative) is so far the most successful electron acceptor for bulk-heterojunction polymer photovoltaic (PV) cells. Here we present a novel method epitaxy-assisted creation of PCBM nanocrystals and their homogeneous distribution in the matrix using freshly cleaved mica sheet as the substrate. The highly matched epitaxy relationship between the unit cell of PCBM crystal and crystallographic (001) surface of mica induces abundant PCBM nuclei, which subsequently develop into nanoscale crystals with homogeneous dispersion in the composite film. Both the shape and size of these nanocrystals could be tuned via choosing the type of matrix polymer, film thickness, ratio of PCBM in the composite film, and annealing temperature. Thus, the obtained thin composite film is removed from the original mica substrate via the flotation technique and transferred to a real substrate for device completion. The success of this method has been verified by the substantially improved device performance, in particular the increased short-circuit current, which is heavily dependent on the morphology of the photoactive layer. Therefore, we have actually demonstrated a novel approach to construct preferred morphology for high-performance optoelectronic devices via resorting to other specific substrates which could induce the formation of this type morphology.

  12. BLV-CoCoMo-qPCR-2: improvements to the BLV-CoCoMo-qPCR assay for bovine leukemia virus by reducing primer degeneracy and constructing an optimal standard curve.

    PubMed

    Takeshima, Shin-nosuke; Kitamura-Muramatsu, Yuri; Yuan, Yuan; Polat, Meripet; Saito, Susumu; Aida, Yoko

    2015-05-01

    Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle. Because BLV infection can remain clinically silent, the proviral load is an important index for estimating disease progression. CoCoMo-qPCR, an assay developed to estimate BLV proviral load, allows the highly sensitive detection of BLV originating in different countries. Here, we developed a modified version of the CoCoMo-qPCR assay, the "BLV-CoCoMo-qPCR-2" assay, which uses optimized degenerate primers. We also constructed a new plasmid standard. Finally, we used both assays to examine DNA samples from BLV-infected cattle and compared the results.

  13. Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

    SciTech Connect

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-07

    We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of C{sub α} atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

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

    PubMed

    Kumar, Pawan; Sharma, Pawan K; Madsen, Charlotte S; Petersen, Michael; Nielsen, Poul

    2013-06-17

    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.

  15. Designed protein G core variants fold to native-like structures: Sequence selection by ORBIT tolerates variation in backbone specification

    PubMed Central

    Ross, Scott A.; Sarisky, Catherine A.; Su, Alyce; Mayo, Stephen L.

    2001-01-01

    The solution structures of two computationally designed core variants of the β1 domain of streptococcal protein G (Gβ1) were solved by 1H NMR methods to assess the robustness of amino acid sequence selection by the ORBIT protein design package under changes in protein backbone specification. One variant has mutations at three of 10 core positions and corresponds to minimal perturbations of the native Gβ1 backbone. The other, with mutations at six of 10 positions, was calculated for a backbone in which the separation between Gβ1's α-helix and β-sheet was increased by 15% relative to native Gβ1. Exchange broadening of some resonances and the complete absence of others in spectra of the sixfold mutant bespeak conformational heterogeneity in this protein. The NMR data were sufficiently abundant, however, to generate structures of similar, moderately high quality for both variants. Both proteins adopt backbone structures similar to their target folds. Moreover, the sequence selection algorithm successfully predicted all core χ1 angles in both variants, five of six χ2 angles in the threefold mutant and four of seven χ2 angles in the sixfold mutant. We conclude that ORBIT calculates sequences that fold specifically to a geometry close to the template, even when the template is moderately perturbed relative to a naturally occurring structure. There are apparently limits to the size of acceptable perturbations: In this study, the larger perturbation led to undesired dynamic behavior. PMID:11266631

  16. Noncanonical α/γ Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field.

    PubMed

    Zgarbová, Marie; Jurečka, Petr; Banáš, Pavel; Havrila, Marek; Šponer, Jiří; Otyepka, Michal

    2017-03-23

    The sugar-phosphate backbone of RNA can exist in diverse rotameric substates, giving RNA molecules enormous conformational variability. The most frequent noncanonical backbone conformation in RNA is α/γ = t/t, which is derived from the canonical backbone by a crankshaft motion and largely preserves the standard geometry of the RNA duplex. A similar conformation also exists in DNA, where it has been extensively studied and shown to be involved in DNA-protein interactions. However, the function of the α/γ = t/t conformation in RNA is poorly understood. Here, we present molecular dynamics simulations of several prototypical RNA structures obtained from X-ray and NMR experiments, including canonical and mismatched RNA duplexes, UUCG and GAGA tetraloops, Loop E, the sarcin-ricin loop, a parallel guanine quadruplex, and a viral pseudoknot. The stability of various noncanonical α/γ backbone conformations was analyzed with two AMBER force fields, ff99bsc0χOL3 and ff99bsc0χOL3 with the recent εζOL1 and βOL1 corrections for DNA. Although some α/γ substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer α/γ = t/t was unstable in both tested force fields. Possible reasons for this instability are discussed. Our work reveals a potentially important artifact in RNA force fields and highlights a need for further force field refinement.

  17. Slow dynamics of a protein backbone in molecular dynamics simulation revealed by time-structure based independent component analysis

    NASA Astrophysics Data System (ADS)

    Naritomi, Yusuke; Fuchigami, Sotaro

    2013-12-01

    We recently proposed the method of time-structure based independent component analysis (tICA) to examine the slow dynamics involved in conformational fluctuations of a protein as estimated by molecular dynamics (MD) simulation [Y. Naritomi and S. Fuchigami, J. Chem. Phys. 134, 065101 (2011)]. Our previous study focused on domain motions of the protein and examined its dynamics by using rigid-body domain analysis and tICA. However, the protein changes its conformation not only through domain motions but also by various types of motions involving its backbone and side chains. Some of these motions might occur on a slow time scale: we hypothesize that if so, we could effectively detect and characterize them using tICA. In the present study, we investigated slow dynamics of the protein backbone using MD simulation and tICA. The selected target protein was lysine-, arginine-, ornithine-binding protein (LAO), which comprises two domains and undergoes large domain motions. MD simulation of LAO in explicit water was performed for 1 μs, and the obtained trajectory of Cα atoms in the backbone was analyzed by tICA. This analysis successfully provided us with slow modes for LAO that represented either domain motions or local movements of the backbone. Further analysis elucidated the atomic details of the suggested local motions and confirmed that these motions truly occurred on the expected slow time scale.

  18. Oxidation Responsive Polymers with a Triggered Degradation via Arylboronate Self-Immolative Motifs on a Polyphosphazene Backbone

    PubMed Central

    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. PMID:28251035

  19. Two-dimensional NMR spectroscopy reveals cation-triggered backbone degradation in polysulfone-based anion exchange membranes

    PubMed Central

    Arges, Christopher G.; Ramani, Vijay

    2013-01-01

    Anion exchange membranes (AEMs) find widespread applications as an electrolyte and/or electrode binder in fuel cells, electrodialysis stacks, flow and metal-air batteries, and electrolyzers. AEMs exhibit poor stability in alkaline media; their degradation is induced by the hydroxide ion, a potent nucleophile. We have used 2D NMR techniques to investigate polymer backbone stability (as opposed to cation stability) of the AEM in alkaline media. We report the mechanism behind a peculiar, often-observed phenomenon, wherein a demonstrably stable polysulfone backbone degrades rapidly in alkaline solutions upon derivatization with alkaline stable fixed cation groups. Using COSY and heteronuclear multiple quantum correlation spectroscopy (2D NMR), we unequivocally demonstrate that the added cation group triggers degradation of the polymer backbone in alkaline via quaternary carbon hydrolysis and ether hydrolysis, leading to rapid failure. This finding challenges the existing perception that having a stable cation moiety is sufficient to yield a stable AEM and emphasizes the importance of the often ignored issue of backbone stability. PMID:23335629

  20. Design and Construction of a High Energy X-Ray R and D Facility, and the Development and Optimization of Real Time Radioisotopic Characterization of Remote Handled Waste at MeV Energies

    SciTech Connect

    Halliwell, S.; Georgiev, G.

    2007-07-01

    Real time radioscopy (RTR) is used extensively for the non-destructive examination (NDE) modality in the characterization of waste using x-ray energies of up to 450 keV. The majority of contact handled waste in drums and boxes such as the standard waste box (SWB) and the B25 box, can be penetrated by x-rays at these energies. However, the shielding within remote handled (RH) waste packages, the high density of many waste matrices, and the large size of other waste packages containing both remote handled and contact handled waste, require x-rays at MeV energies, in order to penetrate the waste matrices to enable x-ray images to be made. To develop, optimize and validate the performance of high energy x-ray imaging systems, requires a shielded vault complete with remote handling equipment for the manipulation of the x-ray generating equipment, the imaging chain, and the surrogate waste being inspected. This paper describes the design and construction of a High Energy X-Ray, R and D facility, and the results of the initial program of work to optimize systems for the real time inspection of RH waste. (authors)

  1. Electrochemical construction

    DOEpatents

    Einstein, Harry; Grimes, Patrick G.

    1983-08-23

    An electrochemical cell construction features a novel co-extruded plastic electrode in an interleaved construction with a novel integral separator-spacer. Also featured is a leak and impact resistant construction for preventing the spill of corrosive materials in the event of rupture.

  2. Dual-functional ROMP-based betaines: effect of hydrophilicity and backbone structure on nonfouling properties.

    PubMed

    Colak, Semra; Tew, Gregory N

    2012-01-10

    Foundational materials for nonfouling coatings were designed and synthesized from a series of novel dual-functional zwitterionic polymers, Poly[NRZI], which were easily obtained via ring-opening metathesis polymerization (ROMP) followed by a single step transformation of the cationic precursor, Poly[NR(+)], to the zwitterion, Poly[NRZI]. The resulting unique dual-functional structure contained the anion and the cation within the same repeat unit but on separate side chains, enabling the hydrophilicity of the system to be tuned at the repeat unit level. These dual-functional zwitterionic polymers were specifically designed to investigate the impact of structural changes, including the backbone, hydrophilicity, and charge, on the overall nonfouling properties. To evaluate the importance of backbone structure, and as a direct comparison to previously studied methacrylate-based betaines, norbornene-based carbo- and sulfobetaines (Poly[NCarboZI] and Poly[NSulfoZI]) as well as a methacrylate-based sulfobetaine (Poly[MASulfoZI]) were synthesized. These structures contain the anion-cation pairs on the same side chain. Nonfouling coatings were prepared from copolymers, composed of the zwitterionic/cationic precursor monomer and an ethoxysilane-containing monomer. The coatings were evaluated by using protein adsorption studies, which clearly indicated that the overall hydrophilicity has a major influence on the nonfouling character of the materials. The most hydrophilic coating, from the oligoethylene glycol (OEG)-containing dual-functional betaine, Poly[NOEGZI-co-NSi], showed the best resistance to nonspecific protein adsorption (Γ(FIB) = 0.039 ng/mm(2)). Both norbornene-based polymers systems, Poly[NSulfoZI] and Poly[NCarboZI], were more hydrophilic and thus more resistant to protein adsorption than the methacrylate-based Poly[MASulfoZI]. Comparing the protein resistance of the dual-functional zwitterionic coatings, Poly[NRZI-co-NSi], to that of their cationic

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

    PubMed

    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

  4. Effect of Bulky Substituents in the Polymer Backbone on the Properties of Polyimide Aerogels.

    PubMed

    Viggiano, Rocco P; Williams, Jarrod C; Schiraldi, David A; Meador, Mary Ann B

    2017-03-08

    With unique advantages over inorganic aerogels including higher strengths and compressive moduli, greater toughness, and the ability to be fabricated as a flexible thin film, polymer aerogels have the potential to supplant inorganic aerogels in numerous applications. Among polymer aerogels, polyimide aerogels possess a high degree of high thermal stability as well as outstanding mechanical properties. However, while the onset of thermal decomposition for these materials is typically very high (greater than 500 °C), the polyimide aerogels undergo dramatic thermally induced shrinkage at temperatures well below their glass transition (Tg) or decomposition temperature, which limits their use. In this study, we show that shrinkage is reduced when a bulky moiety is incorporated in the polymer backbone. Twenty different formulations of polyimide aerogels were synthesized from 3,3,'4,4'-biphenyltetracarboxylic dianhydride (BPDA) and 4,4'-oxidianiline (ODA) or a combination of ODA and 9,9'-bis(4-aminophenyl)fluorene (BAPF) and cross-linked with 1,3,5-benzenetricarbonyl trichloride (BTC) in a statistically designed study. The polymer concentration, n-value, and molar concentration of ODA and BAPF were varied to demonstrate the effect of these variables on certain properties. Samples containing BAPF showed a reduction in shrinkage by as much as 50% after aging at elevated temperatures for 500 h compared to those made with ODA alone.

  5. Robust Chemical Synthesis of Membrane Proteins through a General Method of Removable Backbone Modification.

    PubMed

    Zheng, Ji-Shen; He, Yao; Zuo, Chao; Cai, Xiao-Ying; Tang, Shan; Wang, Zhipeng A; Zhang, Long-Hua; Tian, Chang-Lin; Liu, Lei

    2016-03-16

    Chemical protein synthesis can provide access to proteins with post-translational modifications or site-specific labelings. Although this technology is finding increasing applications in the studies of water-soluble globular proteins, chemical synthesis of membrane proteins remains elusive. In this report, a general and robust removable backbone modification (RBM) method is developed for the chemical synthesis of membrane proteins. This method uses an activated O-to-N acyl transfer auxiliary to install in the Fmoc solid-phase peptide synthesis process a RBM group with switchable reactivity toward trifluoroacetic acid. The method can be applied to versatile membrane proteins because the RBM group can be placed at any primary amino acid. With RBM, the membrane proteins and their segments behave almost as if they were water-soluble peptides and can be easily handled in the process of ligation, purification, and mass characterizations. After the full-length protein is assembled, the RBM group can be readily removed by trifluoroacetic acid. The efficiency and usefulness of the new method has been demonstrated by the successful synthesis of a two-transmembrane-domain protein (HCV p7 ion channel) with site-specific isotopic labeling and a four-transmembrane-domain protein (multidrug resistance transporter EmrE). This method enables practical synthesis of small- to medium-sized membrane proteins or membrane protein domains for biochemical and biophysical studies.

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

    PubMed Central

    Tufail, Ali; Khayam, Syed Ali; Raza, Muhammad Taqi; Ali, Amna; Kim, Ki-Hyung

    2010-01-01

    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. PMID:22294890

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

    PubMed Central

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

    2016-01-01

    START domain proteins are conserved α/β helix-grip fold that play a role in