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Sample records for antibody-antigen docking compensates

  1. Noncovalent mass spectrometry for the characterization of antibody/antigen complexes.

    Science.gov (United States)

    Atmanene, Cédric; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Sanglier-Cianférani, Sarah

    2013-01-01

    Monoclonal antibodies (mAbs) have taken on an increasing importance for the treatment of various diseases including cancers, immunological disorders, and other pathologies. These large biomolecules display specific structural features, which affect their efficiency and need therefore to be extensively characterized using sensitive and orthogonal analytical techniques. Among them, mass spectrometry (MS) has become the method of choice to study mAb amino acid sequences as well as their posttranslational modifications with the aim of reducing their chemistry, manufacturing, and control liabilities. This chapter will provide the reader with a description of the general approach allowing antibody/antigen systems to be characterized by noncovalent MS. In the present chapter, we describe how recent noncovalent MS technologies are used to characterize immune complexes involving both murine and humanized mAb 6F4 directed against human JAM-A, a newly identified antigenic protein (Ag) over-expressed in tumor cells. We will detail experimental conditions (sample preparation, optimization of instrumental parameters, etc.) required for the detection of noncovalent antibody/antigen complexes by MS. We will then focus on the type and the reliability of the information that we get from noncovalent MS data, with emphasis on the determination of the stoichiometry of antibody/antigen systems. Noncovalent MS appears as an additional supporting technique for therapeutic mAbs lead characterization and development.

  2. Rationalization and design of the complementarity determining region sequences in an antibody-antigen recognition interface.

    Directory of Open Access Journals (Sweden)

    Chung-Ming Yu

    Full Text Available Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes.

  3. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.

  4. Effect of the Protein Corona on Antibody-Antigen Binding in Nanoparticle Sandwich Immunoassays.

    Science.gov (United States)

    de Puig, Helena; Bosch, Irene; Carré-Camps, Marc; Hamad-Schifferli, Kimberly

    2017-01-18

    We investigated the effect of the protein corona on the function of nanoparticle (NP) antibody (Ab) conjugates in dipstick sandwich immunoassays. Ab specific for Zika virus nonstructural protein 1 (NS1) were conjugated to gold NPs, and another anti-NS1 Ab was immobilized onto the nitrocellulose membrane. Sandwich immunoassay formation was influenced by whether the strip was run in corona forming conditions, i.e., in human serum. Strips run in buffer or pure solutions of bovine serum albumin exhibited false positives, but those run in human serum did not. Serum pretreatment of the nitrocellulose also eliminated false positives. Corona formation around the NP-Ab in serum was faster than the immunoassay time scale. Langmuir binding analysis determined how the immobilized Ab affinity for the NP-Ab/NS1 was impacted by corona formation conditions, quantified as an effective dissociation constant, KD(eff). Results show that corona formation mediates the specificity and sensitivity of the antibody-antigen interaction of Zika biomarkers in immunoassays, and plays a critical but beneficial role.

  5. Study of antibody/antigen binding kinetics by total internal reflection ellipsometry.

    Science.gov (United States)

    Baleviciute, Ieva; Balevicius, Zigmas; Makaraviciute, Asta; Ramanaviciene, Almira; Ramanavicius, Arunas

    2013-01-15

    Total internal reflection ellipsometry (TIRE) has been applied for the investigation of (i) kinetics of biosensing layer formation, which was based on the immobilization of fragmented and intact antibodies, and (ii) kinetics of antigen interaction with the immobilized antibodies. It has been demonstrated that ellipsometric parameter Δ(t) showed much higher sensitivity at the initial phase of Au-protein and protein-protein interaction, while the parameter Ψ(t) was more sensitive when the steady-state conditions were established. A new method, which taking into consideration this feature and nonlinear change of Δ(t) and Ψ(t) parameters during various stages of biological layer formation process, was used for the calculation of antibody and antigen adsorption/interaction kinetics. The obtained results were analyzed using a model, which took into account partial reversibility during the formation of both antibody and antigen based monolayers. It was shown that the immobilization rate of antibody during the preparation of the sensing layer was similar for the formation of both intact and fragmented antibody based layers; however, the residence time was 25 times longer for intact antibody based layer formation in comparison to that of fragmented antibody based layer formation. On the contrary, residence time of antigen interaction with immobilized antibodies was about 8 times longer for the sensor based on fragmented antibodies. Moreover, it has been determined that the structural differences of immobilized antibodies (fragmented or intact) significantly influence antibody-antigen interaction rate, the major difference being in the residence time of antigen interaction with both types of immobilized antibodies.

  6. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity

    NARCIS (Netherlands)

    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F.O.; Diebold, S.S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is par

  7. Effect of polyethylene glycol conjugation on conformational and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab').

    Science.gov (United States)

    Roque, Cristopher; Sheung, Anthony; Rahman, Nausheen; Ausar, S Fernando

    2015-02-01

    We have investigated the effects of site specific "hinge" polyethylene glycol conjugation (PEGylation) on thermal, pH, and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab') using a variety of biophysical techniques. The results obtained by circular dichroism (CD), ultraviolet (UV) absorbance, and fluorescence spectroscopy suggested that the physical stability of the Fab' is maximized at pH 6-7 with no apparent differences due to PEGylation. Temperature-induced aggregation experiments revealed that PEGylation was able to increase the transition temperature, as well as prevent the formation of visible and subvisible aggregates. Statistical comparison of the three-index empirical phase diagram (EPD) revealed significant differences in thermal and pH stability signatures between Fab' and PEG-Fab'. Upon mechanical stress, micro-flow imaging (MFI) and measurement of the optical density at 360 nm showed that the PEG-Fab' had significantly higher resistance to surface-induced aggregation compared to the Fab'. Analysis of the interaction parameter, kD, indicated repulsive intermolecular forces for PEG-Fab' and attractive forces for Fab'. In conclusion, PEGylation appears to protect Fab' against thermal and mechanical stress-induced aggregation, likely due to a steric hindrance mechanism.

  8. A Co-expression System Based on Phage and Phagemid to Select Cognate Antibody-antigen Pairs in vivo

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A modified selectively-infective phage (SIP) is developed to facilitate the selection of interacting antibody-antigen pairs from a large single-chain antibody (scFv) library in vivo. The system is constructed with a modified helper phage M13KO7 and phagemid pCANTAB 5 E. The antigen fused to the C-terminal of N1-N2 domain and the scFv to the N-terminal of CT domain of the gIIIp of filamentous phage are encoded on the phage and phagemid vectors respectively. The phages produced by co-transformants restore infectivity via interaction between antigen and antibody fusions in the cell periplasm. In a model system, the scFv fragment of the anti-hemagglutinin 17/9 antibody and its corresponding antigen are detected in the presence of a 105 fold excess of a non-interacting control pairs, which demonstrates this system to be very sensitive and facile to screen a large single-chain antibody library.

  9. Restricted diversity of antigen binding residues of antibodies revealed by computational alanine scanning of 227 antibody-antigen complexes.

    Science.gov (United States)

    Robin, Gautier; Sato, Yoshiteru; Desplancq, Dominique; Rochel, Natacha; Weiss, Etienne; Martineau, Pierre

    2014-11-11

    Antibody molecules are able to recognize any antigen with high affinity and specificity. To get insight into the molecular diversity at the source of this functional diversity, we compiled and analyzed a non-redundant aligned collection of 227 structures of antibody-antigen complexes. Free energy of binding of all the residue side chains was quantified by computational alanine scanning, allowing the first large-scale quantitative description of antibody paratopes. This demonstrated that as few as 8 residues among 30 key positions are sufficient to explain 80% of the binding free energy in most complexes. At these positions, the residue distribution is not only different from that of other surface residues but also dependent on the role played by the side chain in the interaction, residues participating in the binding energy being mainly aromatic residues, and Gly or Ser otherwise. To question the generality of these binding characteristics, we isolated an antibody fragment by phage display using a biased synthetic repertoire with only two diversified complementarity-determining regions and solved its structure in complex with its antigen. Despite this restricted diversity, the structure demonstrated that all complementarity-determining regions were involved in the interaction with the antigen and that the rules derived from the natural antibody repertoire apply to this synthetic binder, thus demonstrating the robustness and universality of our results.

  10. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Directory of Open Access Journals (Sweden)

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  11. International Docking Standardization NASA

    Science.gov (United States)

    Donahoe, Stanley; Lewis, J.; Carroll, M.; Le, T.

    2009-01-01

    This slide presentation reviews the different types of docking types. The objective is the pressurized vehicle connection and crew transfer. Androgynous Docking is defined as the joining or coming together of two free flying space vehicles with alike interfaces. Androgynous mating allows for collaboration between any two vehicles. The subsytems of an androgynous mating system are reviewed, including: Hard docking subsystems: latch system, tunnel housing, alignment system and seal.

  12. Development of an Antigen-DNAzyme Based Probe for a Direct Antibody-Antigen Assay Using the Intrinsic DNAzyme Activity of a Daunomycin Aptamer

    Directory of Open Access Journals (Sweden)

    Noorsharmimi Omar

    2013-12-01

    Full Text Available G-Quadruplex (G-4 structures are formed when G-rich DNA sequences fold into intra- or intermolecular four-stranded structures in the presence of metal ions. G-4-hemin complexes are often effective peroxidase-mimicking DNAzymes that are applied in many detection systems. This work reports the application of a G-rich daunomycin-specific aptamer for the development of an antibody-antigen detection assay. We investigated the ability of the daunomycin aptamer to efficiently catalyze the hemin-dependent peroxidase activity independent of daunomycin. A reporter probe consisting of biotinylated antigen and daunomycin aptamer coupled to streptavidin gold nanoparticles was successfully used to generate a colorimetric readout. In conclusion, the daunomycin aptamer can function as a robust alternative DNAzyme for the development of colorimetric assays.

  13. Prediction of site-specific interactions in antibody-antigen complexes: the proABC method and server.

    KAUST Repository

    Olimpieri, Pier Paolo

    2013-06-26

    MOTIVATION: Antibodies or immunoglobulins are proteins of paramount importance in the immune system. They are extremely relevant as diagnostic, biotechnological and therapeutic tools. Their modular structure makes it easy to re-engineer them for specific purposes. Short of undergoing a trial and error process, these experiments, as well as others, need to rely on an understanding of the specific determinants of the antibody binding mode. RESULTS: In this article, we present a method to identify, on the basis of the antibody sequence alone, which residues of an antibody directly interact with its cognate antigen. The method, based on the random forest automatic learning techniques, reaches a recall and specificity as high as 80% and is implemented as a free and easy-to-use server, named prediction of Antibody Contacts. We believe that it can be of great help in re-design experiments as well as a guide for molecular docking experiments. The results that we obtained also allowed us to dissect which features of the antibody sequence contribute most to the involvement of specific residues in binding to the antigen. AVAILABILITY: http://www.biocomputing.it/proABC. CONTACT: anna.tramontano@uniroma1.it or paolo.marcatili@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  14. Studies on the intermolecular forces involved in the antibody-antigen interactions, using V3 synthetic peptides and sera from HIV1 seropositive patients.

    Science.gov (United States)

    Măgureanu, C G; Diaconu, C; Alexandrescu, R; Tirdei, G; Cernescu, C

    1994-01-01

    The nature of physical forces responsible for the antibody-antigen (Ab-Ag) reaction was analyzed in an original system, represented by synthetic peptides derived from the V3 consensus sequences of some HIV1 subtypes gp 120 and HIV1 positive human serum. For locating antigenic determines, flexibility, hydrophilicity and hydrophobicity profiles of the V3 peptides were analysed. The hydrophilicity indicates that V3 apex borders are involved in the first stage of the reaction. The flexibility and hydrophobicity suggest that the apex of the V3 loop (GPGR/Q) is involved in the stabilization of the complex by hydrophobic interactions. Further, we followed up the influence of the dielectric constant and of the pH upon the forces established between Ab and Ag. Modifications in the dielectric constant and pH reveal a significant contribution of electrostatic and van der Waals forces in securing the intermolecular complementarity. D2O produces the highest augmentation of the antibody affinity for the most hydrophilic peptides, while a very slight one was recorded for the most hydrophobic sequence. A high affinity of antibodies for the peptides MN, R and Z was registered at an acid pH, when their His residue was protonated. On the contrary, no influence was recorded in the case of the peptide A, which does not contain any His residue.

  15. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  16. Deserved Compensation

    Institute of Scientific and Technical Information of China (English)

    LI LI

    2010-01-01

    @@ China's National People's Congress (NPC), the top legislature, recently adopted amendments to the Law on State Compensation, granting citizens greater power to obtain compensation when their rights are violated by the state.

  17. Spacecraft rendezvous and docking

    DEFF Research Database (Denmark)

    Jørgensen, John Leif

    1999-01-01

    procedures. The method described generates, based on a single camera and a priory information about the target vehicle and orbit data, all necessary guidance information for closed-loop autonomous navigation, from first detection at far distance, to a close up a hold point. Furthermore, the system provide...... been based entirely on direct human supervision and control. This paper describes a vision-based system and methodology, that autonomously generates accurate guidance information that may assist a human operator in performing the tasks associated with both the rendezvous and docking navigation...

  18. DockingShop: A Tool for Interactive Molecular Docking

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ting-Cheng; Max, Nelson L.; Ding, Jinhui; Bethel, E. Wes; Crivelli, Silvia N.

    2005-04-24

    Given two independently determined molecular structures, the molecular docking problem predicts the bound association, or best fit between them, while allowing for conformational changes of the individual molecules during construction of a molecular complex. Docking Shop is an integrated environment that permits interactive molecular docking by navigating a ligand or protein to an estimated binding site of a receptor with real-time graphical feedback of scoring factors as visual guides. Our program can be used to create initial configurations for a protein docking prediction process. Its output--the structure of aprotein-ligand or protein-protein complex--may serve as an input for aprotein docking algorithm, or an optimization process. This tool provides molecular graphics interfaces for structure modeling, interactive manipulation, navigation, optimization, and dynamic visualization to aid users steer the prediction process using their biological knowledge.

  19. DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

    Science.gov (United States)

    Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

    2017-02-01

    Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

  20. DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

    Science.gov (United States)

    Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

    2017-01-01

    Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

  1. Creative compensation

    Energy Technology Data Exchange (ETDEWEB)

    Coll, D

    1994-09-19

    A discussion is presented of executive compensation in Canada's petroleum industry. Mandatory disclosure of executive compensation and benefits is regulated by the Ontario Securities Commission. Examination of the compensation packages of 80 oilpatch CEOs shows a clear difference in philosophy between large and small companies. Larger companies pay larger salaries, offer pension plans, and reward long-term loyalty. Within smaller companies, compensation tends to be linked with stock performance. Trends in compensation are to lower base salaries with more variables such as bonuses, cash incentives and gain-sharing programs. Increasing shareholder scrutiny is prompting more stringent guidelines on stock option plans. Some companies place performance conditions on stock vesting. Another option is to grant premium priced options to executives, to increase the gains required for the executive to post a profit. Other comapanies are granting stock options to their field personnel, or are granting stock to all employees. Directors are playing an increasing role in executive compensation. 4 tabs.

  2. Autonomous spacecraft rendezvous and docking

    Science.gov (United States)

    Tietz, J. C.; Almand, B. J.

    A storyboard display is presented which summarizes work done recently in design and simulation of autonomous video rendezvous and docking systems for spacecraft. This display includes: photographs of the simulation hardware, plots of chase vehicle trajectories from simulations, pictures of the docking aid including image processing interpretations, and drawings of the control system strategy. Viewgraph-style sheets on the display bulletin board summarize the simulation objectives, benefits, special considerations, approach, and results.

  3. Questioning Compensation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Transparent management and open information needed for the fund set up to compensate victims of the 2008 Sanlu milk scandal Almost three years after the Sanlu milk scandal that caused thousands of infants in China to develop urinary disease after drinking melamine

  4. A python-based docking program utilizing a receptor bound ligand shape: PythDock.

    Science.gov (United States)

    Chung, Jae Yoon; Cho, Seung Joo; Hah, Jung-Mi

    2011-09-01

    PythDock is a heuristic docking program that uses Python programming language with a simple scoring function and a population based search engine. The scoring function considers electrostatic and dispersion/repulsion terms. The search engine utilizes a particle swarm optimization algorithm. A grid potential map is generated using the shape information of a bound ligand within the active site. Therefore, the searching area is more relevant to the ligand binding. To evaluate the docking performance of PythDock, two well-known docking programs (AutoDock and DOCK) were also used with the same data. The accuracy of docked results were measured by the difference of the ligand structure between x-ray structure, and docked pose, i.e., average root mean squared deviation values of the bound ligand were compared for fourteen protein-ligand complexes. Since the number of ligands' rotational flexibility is an important factor affecting the accuracy of a docking, the data set was chosen to have various degrees of flexibility. Although PythDock has a scoring function simpler than those of other programs (AutoDock and DOCK), our results showed that PythDock predicted more accurate poses than both AutoDock4.2 and DOCK6.2. This indicates that PythDock could be a useful tool to study ligand-receptor interactions and could also be beneficial in structure based drug design.

  5. Text Mining for Protein Docking.

    Directory of Open Access Journals (Sweden)

    Varsha D Badal

    2015-12-01

    Full Text Available The rapidly growing amount of publicly available information from biomedical research is readily accessible on the Internet, providing a powerful resource for predictive biomolecular modeling. The accumulated data on experimentally determined structures transformed structure prediction of proteins and protein complexes. Instead of exploring the enormous search space, predictive tools can simply proceed to the solution based on similarity to the existing, previously determined structures. A similar major paradigm shift is emerging due to the rapidly expanding amount of information, other than experimentally determined structures, which still can be used as constraints in biomolecular structure prediction. Automated text mining has been widely used in recreating protein interaction networks, as well as in detecting small ligand binding sites on protein structures. Combining and expanding these two well-developed areas of research, we applied the text mining to structural modeling of protein-protein complexes (protein docking. Protein docking can be significantly improved when constraints on the docking mode are available. We developed a procedure that retrieves published abstracts on a specific protein-protein interaction and extracts information relevant to docking. The procedure was assessed on protein complexes from Dockground (http://dockground.compbio.ku.edu. The results show that correct information on binding residues can be extracted for about half of the complexes. The amount of irrelevant information was reduced by conceptual analysis of a subset of the retrieved abstracts, based on the bag-of-words (features approach. Support Vector Machine models were trained and validated on the subset. The remaining abstracts were filtered by the best-performing models, which decreased the irrelevant information for ~ 25% complexes in the dataset. The extracted constraints were incorporated in the docking protocol and tested on the Dockground unbound

  6. Docking of Secretory Vesicles Is Syntaxin Dependent

    Science.gov (United States)

    de Wit, Heidi; Cornelisse, L. Niels; Toonen, Ruud F.G.; Verhage, Matthijs

    2006-01-01

    Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones. PMID:17205130

  7. Docking of secretory vesicles is syntaxin dependent.

    Directory of Open Access Journals (Sweden)

    Heidi de Wit

    Full Text Available Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones.

  8. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    Directory of Open Access Journals (Sweden)

    Masao Terasawa

    Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

  9. Flexible Ligand Docking Using Differential Evolution

    DEFF Research Database (Denmark)

    Thomsen, René

    2003-01-01

    Molecular docking of biomolecules is becoming an increasingly important part in the process of developing new drugs, as well as searching compound databases for promising drug candidates. The docking of ligands to proteins can be formulated as an optimization problem where the task is to find...

  10. Why are most EU pigs tail docked?

    DEFF Research Database (Denmark)

    D'eath, R.B.; Niemi, J.K.; Vosough Ahmadi, B.

    2016-01-01

    To limit tail biting incidence, most pig producers in Europe tail dock their piglets. This is despite EU Council Directive 2008/120/EC banning routine tail docking and allowing it only as a last resort. The paper aims to understand what it takes to fulfil the intentions of the Directive by examin...

  11. Faculty Compensation Policies.

    Science.gov (United States)

    Silander, Fred

    1983-01-01

    Faculty compensation policy is seen as one means by which an institution influences the faculty to work toward institutional goals. Among the broad criteria for compensation are worth, equity, need, and market measures. Benefits and issues in compensation including differentials in compensation, merit, part-time instruction, etc. are discussed.…

  12. A Review on Quantitative Approaches for Dock Door Assignment in Cross-Docking

    Directory of Open Access Journals (Sweden)

    Adibah Shuib

    2012-01-01

    Full Text Available Cross docking is a relatively new technique in supply chain operations. It offers limited storage time to maximize the efficiency of goods transshipment. Efficient operation of a cross docking system requires an appropriate coordination of inbound and outbound flows, accurate planning and dynamic scheduling.  The planning strategies at cross docking terminals, which are receiving growing attention today, are the truck-to-door assignment and destination to door assignment problems. This paper provides a comprehensive literature review of quantitative approaches in dock door assignment problems of cross docking planning. The contributions of this paper are to identify the gap of knowledge in operational levels mainly in dock door assignment and to point out the future research direction in cross docking.

  13. Dock180 expression in epithelial ovarian tumors

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Huhua Ling; Zhenwei Yao

    2012-01-01

    Objective: The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer.Methods: Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases.Results: Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor (P < 0.01).In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade.Conclusion: Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.

  14. Computational methods for molecular docking

    Energy Technology Data Exchange (ETDEWEB)

    Klebe, G. [BASF AG, Ludwigshafen (Germany); Lengauer, T.

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Recently, it has been demonstrated that the knowledge of the three-dimensional structure of the protein can be used to derive new protein ligands with improved binding properties. This tutorial focuses on the following questions: What is its binding affinity toward a particular receptor? What are putative conformations of a ligand at the binding site? What are the similarities of different ligands in terms of their recognition capabilities? Where and in which orientation will a ligand bind to the active site? How is a new putative protein ligand selected? An overview is presented of the algorithms which are presently used to handle and predict protein-ligand interactions and to dock small molecule ligands into proteins.

  15. Laser docking sensor engineering model

    Science.gov (United States)

    Dekome, Kent; Barr, Joseph M.

    NASA JSC has been involved in the development of Laser sensors for the past ten years in order to support future rendezvous and docking missions, both manned and unmanned. Although many candidate technologies have been breadboarded and evaluated, no sensor hardware designed specifically for rendezvous and docking applications has been demonstrated on-orbit. It has become apparent that representative sensors need to be flown and demonstrated as soon as possible, with minimal cost, to provide the capability of the technology in meeting NASA's future AR&C applications. Technology and commercial component reliability have progressed to where it is now feasible to fly hardware as a detailed test objective minimizing the overall cost and development time. This presentation will discuss the ongoing effort to convert an existing in-house developed breadboard to an engineering model configuration suitable for flight. The modifications include improving the ranger resolution and stability with an in-house design, replacing the rack mounted galvanometric scanner drivers with STD-bus cards, replacing the system controlling personal computer with a microcontroller, and repackaging the subsystems as appropriate. The sensor will use the performance parameters defined in previous JSC requirements working groups as design goals and be built to withstand the space environment where fiscally feasible. Testing of the in-house ranger design is expected to be completed in October. The results will be included in the presentation. Preliminary testing of the ranging circuitry indicates a range resolution of 4mm is possible. The sensor will be mounted in the payload bay on a shelf bracket and have command, control, and display capabilities using the payload general support computer via an RS422 data line.

  16. Advanced Docking System With Magnetic Initial Capture

    Science.gov (United States)

    Lewis, James L.; Carroll, Monty B.; Morales, Ray; Le, Thang

    2004-01-01

    An advanced docking system is undergoing development to enable softer, safer docking than was possible when using prior docking systems. This system is intended for original use in docking of visiting spacecraft and berthing the Crew Return Vehicle at the International Space Station (ISS). The system could also be adapted to a variety of other uses in outer space and on Earth, including mating submersible vehicles, assembling structures, and robotic berthing/handling of payloads and cargo. Heretofore, two large spacecraft have been docked by causing the spacecraft to approach each other at a speed sufficient to activate capture latches - a procedure that results in large docking loads and is made more difficult because of the speed. The basic design and mode of operation of the present advanced docking system would eliminate the need to rely on speed of approach to activate capture latches, thereby making it possible to reduce approach speed and thus docking loads substantially. The system would comprise an active subsystem on one spacecraft and a passive subsystem on another spacecraft with which the active subsystem will be docked. The passive subsystem would include an extensible ring containing magnetic striker plates and guide petals. The active subsystem would include mating guide petals and electromagnets containing limit switches and would be arranged to mate with the magnetic striker plates and guide petals of the passive assembly. The electromagnets would be carried on (but not rigidly attached to) a structural ring that would be instrumented with load sensors. The outputs of the sensors would be sent, along with position information, as feedback to an electronic control subsystem. The system would also include electromechanical actuators that would extend or retract the ring upon command by the control subsystem.

  17. Development of a Robotics-based Satellites Docking Simulator

    NARCIS (Netherlands)

    Zebenay, M.

    2014-01-01

    The European Proximity Operation Simulator (EPOS) is a hardware-in-the-loop (HIL) system aiming, among other objectives, at emulating on-orbit docking of spacecraft for verification and validation of the docking phase. This HIL docking simulator set-up essentially consists of docking interfaces, sim

  18. Fully automated flexible docking of ligands into flexible synthetic receptors using forward and inverse docking strategies.

    Science.gov (United States)

    Kämper, Andreas; Apostolakis, Joannis; Rarey, Matthias; Marian, Christel M; Lengauer, Thomas

    2006-01-01

    The prediction of the structure of host-guest complexes is one of the most challenging problems in supramolecular chemistry. Usual procedures for docking of ligands into receptors do not take full conformational freedom of the host molecule into account. We describe and apply a new docking approach which performs a conformational sampling of the host and then sequentially docks the ligand into all receptor conformers using the incremental construction technique of the FlexX software platform. The applicability of this approach is validated on a set of host-guest complexes with known crystal structure. Moreover, we demonstrate that due to the interchangeability of the roles of host and guest, the docking process can be inverted. In this inverse docking mode, the receptor molecule is docked around its ligand. For all investigated test cases, the predicted structures are in good agreement with the experiment for both normal (forward) and inverse docking. Since the ligand is often smaller than the receptor and, thus, its conformational space is more restricted, the inverse docking approach leads in most cases to considerable speed-up. By having the choice between two alternative docking directions, the application range of the method is significantly extended. Finally, an important result of this study is the suitability of the simple energy function used here for structure prediction of complexes in organic media.

  19. Effects of tail docking and docking length on neuroanatomical changes in healed tail tips of pigs

    DEFF Research Database (Denmark)

    Herskin, M S; Thodberg, K; Jensen, Henrik Elvang

    2015-01-01

    In pig production, piglets are tail docked at birth in order to prevent tail biting later in life. In order to examine the effects of tail docking and docking length on the formation of neuromas, we used 65 pigs and the following four treatments: intact tails (n=18); leaving 75% (n=17); leaving 50......% (n=19); or leaving 25% (n=11) of the tail length on the pigs. The piglets were docked between day 2 and 4 after birth using a gas-heated apparatus, and were kept under conventional conditions until slaughter at 22 weeks of age, where tails were removed and examined macroscopically and histologically...

  20. Dockomatic - automated ligand creation and docking

    OpenAIRE

    Hampikian Greg; McDougal Owen M; Jacob Reed B; Bullock Casey W; Andersen Tim

    2010-01-01

    Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user frie...

  1. Essays in Executive Compensation

    NARCIS (Netherlands)

    D. Zhang (Dan)

    2012-01-01

    textabstractThis dissertation focuses on how executive compensation is designed and its implications for corporate finance and government regulations. Chapter 2 analyzes several proposals to restrict CEO compensation and calibrates two models of executive compensation that describe how firms would r

  2. Dockomatic - automated ligand creation and docking

    Directory of Open Access Journals (Sweden)

    Hampikian Greg

    2010-11-01

    Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  3. Triangulation methods for automated docking

    Science.gov (United States)

    Bales, John W.

    1996-01-01

    An automated docking system must have a reliable method for determining range and orientation of the passive (target) vehicle with respect to the active vehicle. This method must also provide accurate information on the rates of change of range to and orientation of the passive vehicle. The method must be accurate within required tolerances and capable of operating in real time. The method being developed at Marshall Space Flight Center employs a single TV camera, a laser illumination system and a target consisting, in its minimal configuration, of three retro-reflectors. Two of the retro-reflectors are mounted flush to the same surface, with the third retro-reflector mounted to a post fixed midway between the other two and jutting at a right angle from the surface. For redundancy, two additional retroreflectors are mounted on the surface on a line at right angles to the line containing the first two retro-reflectors, and equally spaced on either side of the post. The target vehicle will contain a large target for initial acquisition and several smaller targets for close range.

  4. SwissDock, a protein-small molecule docking web service based on EADock DSS.

    Science.gov (United States)

    Grosdidier, Aurélien; Zoete, Vincent; Michielin, Olivier

    2011-07-01

    Most life science processes involve, at the atomic scale, recognition between two molecules. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Docking programs have a wide range of applications ranging from protein engineering to drug design. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. A wiki and a forum are available to the community to promote interactions between users. The SwissDock web site is available online at http://www.swissdock.ch. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling community.

  5. Protein-protein docking with F(2Dock 2.0 and GB-rerank.

    Directory of Open Access Journals (Sweden)

    Rezaul Chowdhury

    Full Text Available MOTIVATION: Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F(2 Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error. RESULTS: The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F(2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F(2 Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F(2 Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F(2 Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other. AVAILABILITY: The docking protocol has been implemented as a server with a graphical client (TexMol which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server

  6. PTools: an opensource molecular docking library

    Directory of Open Access Journals (Sweden)

    Poulain Pierre

    2009-05-01

    Full Text Available Abstract Background Macromolecular docking is a challenging field of bioinformatics. Developing new algorithms is a slow process generally involving routine tasks that should be found in a robust library and not programmed from scratch for every new software application. Results We present an object-oriented Python/C++ library to help the development of new docking methods. This library contains low-level routines like PDB-format manipulation functions as well as high-level tools for docking and analyzing results. We also illustrate the ease of use of this library with the detailed implementation of a 3-body docking procedure. Conclusion The PTools library can handle molecules at coarse-grained or atomic resolution and allows users to rapidly develop new software. The library is already in use for protein-protein and protein-DNA docking with the ATTRACT program and for simulation analysis. This library is freely available under the GNU GPL license, together with detailed documentation.

  7. Udock, the interactive docking entertainment system.

    Science.gov (United States)

    Levieux, Guillaume; Tiger, Guillaume; Mader, Stéphanie; Zagury, Jean-François; Natkin, Stéphane; Montes, Matthieu

    2014-01-01

    Protein-protein interactions play a crucial role in biological processes. Protein docking calculations' goal is to predict, given two proteins of known structures, the associate conformation of the corresponding complex. Here, we present a new interactive protein docking system, Udock, that makes use of users' cognitive capabilities added up. In Udock, the users tackle simplified representations of protein structures and explore protein-protein interfaces' conformational space using a gamified interactive docking system with on the fly scoring. We assumed that if given appropriate tools, a naïve user's cognitive capabilities could provide relevant data for (1) the prediction of correct interfaces in binary protein complexes and (2) the identification of the experimental partner in interaction among a set of decoys. To explore this approach experimentally, we conducted a preliminary two week long playtest where the registered users could perform a cross-docking on a dataset comprising 4 binary protein complexes. The users explored almost all the surface of the proteins that were available in the dataset but favored certain regions that seemed more attractive as potential docking spots. These favored regions were located inside or nearby the experimental binding interface for 5 out of the 8 proteins in the dataset. For most of them, the best scores were obtained with the experimental partner. The alpha version of Udock is freely accessible at http://udock.fr.

  8. Protein docking prediction using predicted protein-protein interface

    Directory of Open Access Journals (Sweden)

    Li Bin

    2012-01-01

    Full Text Available Abstract Background Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. Results We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm, is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. Conclusion We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  9. Rationalizing vaccine injury compensation.

    Science.gov (United States)

    Mello, Michelle M

    2008-01-01

    Legislation recently adopted by the United States Congress provides producers of pandemic vaccines with near-total immunity from civil lawsuits without making individuals injured by those vaccines eligible for compensation through the Vaccine Injury Compensation Program. The unusual decision not to provide an alternative mechanism for compensation is indicative of a broader problem of inconsistency in the American approach to vaccine-injury compensation policy. Compensation policies have tended to reflect political pressures and economic considerations more than any cognizable set of principles. This article identifies a set of ethical principles bearing on the circumstances in which vaccine injuries should be compensated, both inside and outside public health emergencies. A series of possible bases for compensation rules, some grounded in utilitarianism and some nonconsequentialist, are discussed and evaluated. Principles of fairness and reasonableness are found to constitute the strongest bases. An ethically defensible compensation policy grounded in these principles would make a compensation fund available to all individuals with severe injuries and to individuals with less-severe injuries whenever the vaccination was required by law or professional duty.

  10. Dynamic/control interactions between flexible orbiting space-robot during grasping, docking and post-docking manoeuvres

    Science.gov (United States)

    Gasbarri, Paolo; Pisculli, Andrea

    2015-05-01

    Robotic systems are expected to play an increasingly important role in future space activities, such as repairing, upgrading, refuelling, and re-orbiting spacecraft. These technologies could potentially extend the life of satellites, enhance the capability of space systems, reduce the operation costs, and clean up the increasing space debris. Recent proposals for missions involving the use of space manipulators and/or automated transfer vehicles are presented as a solution for a lot of problems, which now affect the procedures and the performance of the in-orbit space systems. Other projects involving space manipulators have been developed by DARPA aiming to demonstrate several satellite servicing operations and technologies including rendez-vous, proximity operations and station-keeping, capture, docking, fluid transfer (specifically, "hydrazine"), and Orbit Replaceable Unit (ORU) transfer. Of course the dynamic coupling between the manipulator and its base mounting flexible solar arrays is very difficult to model. Furthermore, the motion planning of space robots is usually much more complicated than the motion planning of fixed-base manipulators. In this paper first of all the authors present a mixed NE/EL formulation suitable for synthesizing optimal control strategies during the deploying manoeuvres of robotic arms mounted on flexible orbiting platform (i.e. the chaser). Then two new control strategies able to compensate the flexibility excitations of the chaser satellite solar panels during the capturing of a flexible target spacecraft with the use of two robotic arms are presented and applied to a grasping manoeuvre. The mission is here divided into three main phases: the approaching, the docking and the post-grasping phase. Several numerical examples will complete the work.

  11. SwarmDock and the Use of Normal Modes in Protein-Protein Docking

    Directory of Open Access Journals (Sweden)

    Paul A. Bates

    2010-09-01

    Full Text Available Here is presented an investigation of the use of normal modes in protein-protein docking, both in theory and in practice. Upper limits of the ability of normal modes to capture the unbound to bound conformational change are calculated on a large test set, with particular focus on the binding interface, the subset of residues from which the binding energy is calculated. Further, the SwarmDock algorithm is presented, to demonstrate that the modelling of conformational change as a linear combination of normal modes is an effective method of modelling flexibility in protein-protein docking.

  12. A New Scoring Function for Molecular Docking Based on AutoDock and AutoDock Vina.

    Science.gov (United States)

    Tanchuk, Vsevolod Yu; Tanin, Volodymyr O; Vovk, Andriy I; Poda, Gennady

    2015-01-01

    Molecular docking of small molecules in the protein binding sites is the most widely used computational technique in modern structure-based drug discovery. Although accurate prediction of binding modes of small molecules can be achieved in most cases, estimation of their binding affinities remains mediocre at best. As an attempt to improve the correlation between the inhibitory constants, pKi, and scoring, we created a new, hybrid scoring function. The new function is a linear combination of the terms of the scoring functions of AutoDock and AutoDock Vina. It was trained on 2,412 protein-ligand complexes from the PDBbind database (www.pdbbind.org.cn, version 2012) and validated on a set of 313 complexes released in the 2013 version as a test set. The new function was included in a modified version of AutoDock. The hybrid scoring function showed a statistically significant improvement in both training and test sets in terms of correlation with and root mean square and mean absolute errors in prediction of pKi values. It was also tested on the CSAR 2014 Benchmark Exercise dataset (team T) and produced reasonably good results.

  13. AutoDock4(Zn): an improved AutoDock force field for small-molecule docking to zinc metalloproteins.

    Science.gov (United States)

    Santos-Martins, Diogo; Forli, Stefano; Ramos, Maria João; Olson, Arthur J

    2014-08-25

    Zinc is present in a wide variety of proteins and is important in the metabolism of most organisms. Zinc metalloenzymes are therapeutically relevant targets in diseases such as cancer, heart disease, bacterial infection, and Alzheimer's disease. In most cases a drug molecule targeting such enzymes establishes an interaction that coordinates with the zinc ion. Thus, accurate prediction of the interaction of ligands with zinc is an important aspect of computational docking and virtual screening against zinc containing proteins. We have extended the AutoDock force field to include a specialized potential describing the interactions of zinc-coordinating ligands. This potential describes both the energetic and geometric components of the interaction. The new force field, named AutoDock4Zn, was calibrated on a data set of 292 crystal complexes containing zinc. Redocking experiments show that the force field provides significant improvement in performance in both free energy of binding estimation as well as in root-mean-square deviation from the crystal structure pose. The new force field has been implemented in AutoDock without modification to the source code.

  14. Cooperation, compensation and transition

    NARCIS (Netherlands)

    Ju, Y.

    2004-01-01

    Cooperation and compensation are two important and well-linked issues in economics. The central question in cooperation is how to share the joint gains among participating players. Compensation is a specific aspect of surplus sharing problems providing incentives for agents to sacrifice their own di

  15. Options in Compensation

    DEFF Research Database (Denmark)

    Flor, Christian Riis; Frimor, Hans; Munk, Claus

    2014-01-01

    We derive the optimal compensation contract in a principal–agent setting in which outcome is used to provide incentives for both effort and risky investments. To motivate investment, optimal compensation entails rewards for high as well as low outcomes, and it is increasing at the mean outcome to...

  16. The HADDOCK web server for data-driven biomolecular docking

    NARCIS (Netherlands)

    de Vries, S.J.; van Dijk, M.; Bonvin, A.M.J.J.

    2010-01-01

    Computational docking is the prediction or modeling of the three-dimensional structure of a biomolecular complex, starting from the structures of the individual molecules in their free, unbound form. HADDOC K is a popular docking program that takes a datadriven approach to docking, with support for

  17. Climate change and compensation

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint; Flanagan, Tine Bech

    2013-01-01

    This paper presents a case for compensation of actual harm from climate change in the poorest countries. First, it is shown that climate change threatens to reverse the fight to eradicate poverty. Secondly, it is shown how the problems raised in the literature for compensation to some extent...... are based on misconceptions and do not apply to compensation of present actual harm. Finally, two arguments are presented to the effect that, in so far as developed countries accept a major commitment to mitigate climate change, they should also accept a commitment to address or compensate actual harm from...... in the future, then there is also moral reason to address these harms if they materialize now. We argue that these principles are applicable to climate change, and that given the commitment of wealthy countries to a "common but differentiated responsibility," they lead to a commitment to address or compensate...

  18. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Sander, Tommy; Bruun, Anne T; Balle, Thomas

    2010-01-01

    Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural...

  19. Flexible Ligand Docking Using Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Thomsen, Rene

    2003-01-01

    The docking of ligands to proteins can be formulated as a computational problem where the task is to find the most favorable energetic conformation among the large space of possible protein–ligand complexes. Stochastic search methods such as evolutionary algorithms (EAs) can be used to sample large...

  20. Vision-guided heterogeneous mobile robot docking

    Science.gov (United States)

    Spofford, John R.; Blitch, John; Klarquist, William N.; Murphy, Robin R.

    1999-08-01

    Teams of heterogeneous mobile robots are a key aspect of future unmanned system for operations in complex and dynamic urban environments, such as that envisioned by DARPA's Tactical Mobile Robotics program. One examples of an interaction among such team members is the docking of small robot of limited sensory and processing capability with a larger, more capable robot. Applications for such docking include the transfer of power, data, and materia, as well as physically combined maneuver or manipulation. A two-robot system is considered in this paper. The smaller 'throwable' robot contains a video camera capable of imaging the larger 'packable' robot and transmitting the imagery. The packable robot can both sense the throwable robot through an onboard camera, as well as sense itself through the throwable robot's transmitted video, and is capable of processing imagery from either source. This paper describes recent results in the development of control and sensing strategies for automatic mid-range docking of these two robots. Decisions addressed include the selection of which robot's image sensor to use and which robot to maneuver. Initial experimental results are presented for docking using sensor data from each robot.

  1. VORFFIP-Driven Dock: V-D2OCK, a Fast and Accurate Protein Docking Strategy

    Science.gov (United States)

    Segura, Joan; Marín-López, Manuel Alejandro; Jones, Pamela F.; Oliva, Baldo; Fernandez-Fuentes, Narcis

    2015-01-01

    The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers. PMID:25763838

  2. VORFFIP-driven dock: V-D2OCK, a fast and accurate protein docking strategy.

    Directory of Open Access Journals (Sweden)

    Joan Segura

    Full Text Available The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK. This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.

  3. Side docking of the da Vinci robotic system for radical prostatectomy: advantages over traditional docking.

    Science.gov (United States)

    Cestari, Andrea; Ferrari, Matteo; Zanoni, Matteo; Sangalli, Mattia; Ghezzi, Massimo; Fabbri, Fabio; Sozzi, Francesco; Rigatti, Patrizio

    2015-09-01

    The standard low lithotomic position, used during robot-assisted radical prostatectomy (RARP), with prolonged positioning in stirrups together with steep Trendelenburg may expose the patient to neurapraxia phenomena of the lower limbs and can rarely be used in patients with problems of hip abduction. To overcome these hurdles, we evaluated the clinical benefits of "side docking" (SD) of the da Vinci(®) robotic system in comparison to "traditional docking" (TD). A cohort of 120 patients submitted to RARP were prospectively randomized into two groups by docking approach: SD with the patient supine with lower limbs slightly abducted on the operating table, and TD docking time, intraoperative number of collisions between the robotic arms and postoperative neurological problems in the lower limbs were noted. Descriptive statistics was used to analyze outcomes. Docking time was shorter for the SD group [SD: median 13 min (range 10-18); TD: median 21 min (range 15-34)]. None in the SD group and six of 60 patients (10%) in the TD group suffered from temporary (<30 days) unilateral neurological deficits of the lower limbs. In both groups no collisions between the robotic arms occurred. The SD approach is technically feasible. It does not cause collisions between the robotic arms, and is a reliable method for reducing the setup time of RARP. The supine position of the patient may prevent neurological complications of the lower limbs. Based on these results, SD has become the standard docking technique used by our department.

  4. Workers Compensation Claim Data -

    Data.gov (United States)

    Department of Transportation — This data set contains DOT employee workers compensation claim data for current and past DOT employees. Types of data include claim data consisting of PII data (SSN,...

  5. Climate change and compensation

    DEFF Research Database (Denmark)

    Jensen, Karsten Klint; Flanagan, Tine Bech

    2013-01-01

    This paper presents a case for compensation of actual harm from climate change in the poorest countries. First, it is shown that climate change threatens to reverse the fight to eradicate poverty. Secondly, it is shown how the problems raised in the literature for compensation to some extent...... are based on misconceptions and do not apply to compensation of present actual harm. Finally, two arguments are presented to the effect that, in so far as developed countries accept a major commitment to mitigate climate change, they should also accept a commitment to address or compensate actual harm from...... climate change. The first argument appeals to the principle that if it is an injustice to cause risk of incurring harm in the future, then it is also an injustice to cause a similar harm now. The second argument appeals to the principle that if there is moral reason to reduce the risk of specific harms...

  6. ACTS Rain Fade Compensation

    Science.gov (United States)

    Coney, Thom A.

    1996-01-01

    Performance status of the Adaptive Rain Fade Compensation includes: (1) The rain fade protocol is functional detecting fades, providing an additional 10 dB of margin and seamless transitions to and from coded operation; (2) The stabilization of the link margins and the optimization of rain fade decision thresholds has resulted in improved BER performance; (3) Characterization of the fade compensation algorithm is ongoing.

  7. Dosage compensation in birds

    OpenAIRE

    McQueen, H A; McBride, D; Miele, G; Bird, A.P.; Clinton, M

    2001-01-01

    The Z and W sex chromosomes of birds have evolved independently from the mammalian X and Y chromosomes [1]. Unlike mammals, female birds are heterogametic (ZW), while males are homogametic (ZZ). Therefore male birds, like female mammals, carry a double dose of sex-linked genes relative to the other sex. Other animals with nonhomologous sex chromosomes possess "dosage compensation" systems to equalize the expression of sex-linked genes. Dosage compensation occurs in animals as diverse as mamma...

  8. Autonomous Rendezvous and Docking Conference, volume 1

    Science.gov (United States)

    1990-01-01

    This document consists of the presentation submitted at the Autonomous Rendezvous and Docking (ARD) Conference. It contains three volumes: ARD hardware technology; ARD software technology; and ARD operations. The purpose of this conference is to identify the technologies required for an on orbit demonstration of the ARD, assess the maturity of these technologies, and provide the necessary insight for a quality assessment of the programmatic management, technical, schedule, and cost risks.

  9. Autonomous Rendezvous and Docking Conference, volume 3

    Science.gov (United States)

    1990-01-01

    This document consists of the presentation submitted at the Autonomous Rendezvous and Docking (ARD) Conference. The document contains three volumes: ARD hardware technology; ARD software technology; and ARD operations. The purpose of this conference is to identify the technologies required for an on orbit demonstration of ARD, assess the maturity of these technologies, and provide the necessary insight for a quality assessment of programmatic management, technical, schedule, and cost risks.

  10. Combined Immunodeficiency Associated with DOCK8 Mutations

    Science.gov (United States)

    Zhang, Qian; Davis, Jeremiah C.; Lamborn, Ian T.; Freeman, Alexandra F.; Jing, Huie; Favreau, Amanda J.; Matthews, Helen F.; Davis, Joie; Turner, Maria L.; Uzel, Gulbu; Holland, Steven M.; Su, Helen C.

    2010-01-01

    BACKGROUND Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features of some variants of combined immunodeficiency. The genetic causes of these variants are unknown. METHODS We collected longitudinal clinical data on 11 patients from eight families who had recurrent sinopulmonary and cutaneous viral infections. We performed comparative genomic hybridization arrays and targeted gene sequencing. Variants with predicted loss-of-expression mutations were confirmed by means of a quantitative reverse-transcriptase –polymerase-chain-reaction assay and immunoblotting. We evaluated the number and function of lymphocytes with the use of in vitro assays and flow cytometry. RESULTS Patients had recurrent otitis media, sinusitis, and pneumonias; recurrent Staphylococcus aureus skin infections with otitis externa; recurrent, severe herpes simplex virus or herpes zoster infections; extensive and persistent infections with molluscum contagiosum; and human papillomavirus infections. Most patients had severe atopy with anaphylaxis; several had squamous-cell carcinomas, and one had T-cell lymphoma –leukemia. Elevated serum IgE levels, hypereosinophilia, low numbers of T cells and B cells, low serum IgM levels, and variable IgG antibody responses were common. Expansion in vitro of activated CD8 T cells was impaired. Novel homozygous or compound heterozygous deletions and point mutations in the gene encoding the dedicator of cytokinesis 8 protein (DOCK8) led to the absence of DOCK8 protein in lymphocytes. CONCLUSIONS Autosomal recessive DOCK8 deficiency is associated with a novel variant of combined immunodeficiency. PMID:19776401

  11. Executive Compensation: A Brief Review

    OpenAIRE

    Bognanno, Michael L.

    2010-01-01

    Chief executive officer (CEO) compensation is defined as the sum of base pay, bonuses, stock grants, stock options, other forms of compensation and benefits. Inflation?adjusted, median total CEO compensation in the United States almost tripled between 1992 and 2000, with grants of stock options evolving to be the largest component of compensation. This article presents the arguments for and against this level and composition of CEO compensation.

  12. InterEvDock: a docking server to predict the structure of protein-protein interactions using evolutionary information.

    Science.gov (United States)

    Yu, Jinchao; Vavrusa, Marek; Andreani, Jessica; Rey, Julien; Tufféry, Pierre; Guerois, Raphaël

    2016-07-01

    The structural modeling of protein-protein interactions is key in understanding how cell machineries cross-talk with each other. Molecular docking simulations provide efficient means to explore how two unbound protein structures interact. InterEvDock is a server for protein docking based on a free rigid-body docking strategy. A systematic rigid-body docking search is performed using the FRODOCK program and the resulting models are re-scored with InterEvScore and SOAP-PP statistical potentials. The InterEvScore potential was specifically designed to integrate co-evolutionary information in the docking process. InterEvDock server is thus particularly well suited in case homologous sequences are available for both binding partners. The server returns 10 structures of the most likely consensus models together with 10 predicted residues most likely involved in the interface. In 91% of all complexes tested in the benchmark, at least one residue out of the 10 predicted is involved in the interface, providing useful guidelines for mutagenesis. InterEvDock is able to identify a correct model among the top10 models for 49% of the rigid-body cases with evolutionary information, making it a unique and efficient tool to explore structural interactomes under an evolutionary perspective. The InterEvDock web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock/.

  13. Protein Alpha Shape (PAS) Dock: A new gaussian-based score function suitable for docking in homology modelled protein structures

    Science.gov (United States)

    Tøndel, Kristin; Anderssen, Endre; Drabløs, Finn

    2006-03-01

    Protein Alpha Shape (PAS) Dock is a new empirical score function suitable for virtual library screening using homology modelled protein structures. Here, the score function is used in combination with the geometry search method Tabu search. A description of the protein binding site is generated using gaussian property fields like in Protein Alpha Shape Similarity Analysis (PASSA). Gaussian property fields are also used to describe the ligand properties. The overlap between the receptor and ligand hydrophilicity and lipophilicity fields is maximised, while minimising steric clashes. Gaussian functions introduce a smoothing of the property fields. This makes the score function robust against small structural variations, and therefore suitable for use with homology models. This also makes it less critical to include protein flexibility in the docking calculations. We use a fast and simplified version of the score function in the geometry search, while a more detailed version is used for the final prediction of the binding free energies. This use of a two-level scoring makes PAS-Dock computationally efficient, and well suited for virtual screening. The PAS-Dock score function is trained on 218 X-ray structures of protein- ligand complexes with experimental binding affinities. The performance of PAS-Dock is compared to two other docking methods, AutoDock and MOE-Dock, with respect to both accuracy and computational efficiency. According to this study, PAS-Dock is more computationally efficient than both AutoDock and MOE-Dock, and gives a better prediction of the free energies of binding. PAS-Dock is also more robust against structural variations than AutoDock.

  14. Scheduling Trucks in a Cross-Dock with Mixed Service Mode Dock Doors

    DEFF Research Database (Denmark)

    Bodnar, Peter; Azadeh, Kaveh; Koster, René de

    2015-01-01

    The problem considered in this paper is how to schedule inbound and outbound trucks subject to time windows at a multidoor cross-dock. Dock doors can either be dedicated to inbound or outbound trucks or be capable of handling both truck types. In addition, loads are allowed to be temporarily...... buffered to bridge the time between load arrival and departure. We minimize operational costs consisting of the cost of handling loads in temporary storage, as well as the cost of tardiness caused by processing outbound trucks after their respective due times. A mathematical model is derived...

  15. Power factor compensation

    Energy Technology Data Exchange (ETDEWEB)

    Barra R, Felipe [Schneider Electric Chile (Chile)

    2010-07-01

    Every company is looking for ways to increase productivity as a way to gain a competitive advantage. Energy is a significant element in making any product and so it is important to assess production processes from an energy perspective. This paper discusses the impact of power factor compensation on energy efficiency. The life cycle solution for energy efficiency involves optimization of active energy using automation and regulation. A brief explanation is given of how each component of a company plays a part in this cycle. Examples include simulations and analysis, modeling, performance monitoring facilities, and environmental sustainability. Reactive energy suppliers and the installation of capacitors are also explained. Types of compensation include fixed and automation compensations. Economic advantages include a reduction in the electricity bill and active energy consumption. Technical advantages include reduction in voltage drop and an increase in available power. The power correction factor also improves reliability and contributes to conservation of the environment.

  16. Compensation neurosis rides again.

    Science.gov (United States)

    Levy, A

    1992-01-01

    Compensation neurosis (CN), also known as accident neurosis, has generally not been considered to be a 'real' disorder. In 1961 it was seemingly laid to rest by Henry Miller, a distinguished neurologist, in a sharp article which appeared in the British Medical Journal. Miller's view of patients who presented psychological symptoms following accidents or traumas was suspicious. Compensated or not, his view seemed to be that they should have their legal process finished as quickly as possible and then they will miraculously convalescence. Miller's work, it appeared, was the coup de grâce for this ill-defined diagnosis. Today, however, compensation neurosis seems to ride again. After a prolonged silence in the psychiatric literature, new papers are emerging, strongly suggesting that this vanishing diagnosis be reconsidered. This new trend will be presented.

  17. A Review: Mathematical Modles for Cross Docking Planning

    Directory of Open Access Journals (Sweden)

    Dwi Agustina

    2010-09-01

    Full Text Available This paper provides a comprehensive literature review of mathematical models in cross docking planning. From the reviews, the models are classified in three different levels regarding its decisions level which are operational, tactical, and strategic level. The researches in operational level are mainly related to develop model in scheduling, dock door assignment, transhipment problem, vehicle routing, and product allocation. For tactical and strategic level, the researches are mainly proposing model to design the layout and the network of cross docking respectively. The contribution of this paper is to realize the gaps of knowledge in strategic, tactical and operational levels and point out the future research directions in cross docking.

  18. Autonomous Rendezvous and Docking Conference, volume 2

    Science.gov (United States)

    1990-01-01

    Autonomous Rendezvous and Docking (ARD) will be a requirement for future space programs. Clear examples include satellite servicing, repair, recovery, and reboost in the near term, and the longer range lunar and planetary exploration programs. ARD will permit more aggressive unmanned space activities, while providing a valuable operational capability for manned missions. The purpose of the conference is to identify the technologies required for an on-orbit demonstration of ARD, assess the maturity of those technologies, and provide the necessary insight for a quality assessment of programmatic management, technical, schedule, and cost risks.

  19. RELIABILITY OF LENTICULAR EXPANSION COMPENSATORS

    Directory of Open Access Journals (Sweden)

    Gabriel BURLACU,

    2011-11-01

    Full Text Available Axial lenticular compensators are made to take over the longitudinal heat expansion, shock , vibration and noise, made elastic connections for piping systems. In order to have a long life for installations it is necessary that all elements, including lenticular compensators, have a good reliability. This desire can be did by technology of manufactoring and assembly of compensators, the material for lenses and by maintenance.of compensator

  20. A hierarchical method for molecular docking using cloud computing.

    Science.gov (United States)

    Kang, Ling; Guo, Quan; Wang, Xicheng

    2012-11-01

    Discovering small molecules that interact with protein targets will be a key part of future drug discovery efforts. Molecular docking of drug-like molecules is likely to be valuable in this field; however, the great number of such molecules makes the potential size of this task enormous. In this paper, a method to screen small molecular databases using cloud computing is proposed. This method is called the hierarchical method for molecular docking and can be completed in a relatively short period of time. In this method, the optimization of molecular docking is divided into two subproblems based on the different effects on the protein-ligand interaction energy. An adaptive genetic algorithm is developed to solve the optimization problem and a new docking program (FlexGAsDock) based on the hierarchical docking method has been developed. The implementation of docking on a cloud computing platform is then discussed. The docking results show that this method can be conveniently used for the efficient molecular design of drugs.

  1. Layout and control policies for cross docking operations

    NARCIS (Netherlands)

    Vis, Iris F. A.; Roodbergen, Kees Jan

    2011-01-01

    Many supply chains strive to shorten the time between a customer's order and the actual delivery of the ordered goods. Cross docking is one of the options to reduce these response times. Cross docking facilities are dynamic environments where products arrive and leave the same day. To deal with thes

  2. Protein-Ligand Docking Based on Beta-Shape

    Science.gov (United States)

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

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

  3. Evaluation of molecular docking using polynomial empirical scoring functions.

    Science.gov (United States)

    Dias, Raquel; Timmers, Luis Fernando Saraiva Macedo; Caceres, Rafael Andrade; de Azevedo, Walter Filgueira

    2008-12-01

    Molecular docking simulations are of pivotal importance for analysis of protein-ligand interactions and also an essential resource for virtual-screening initiatives. In molecular docking simulations several possible docked structures are generated, which create an ensemble of structures representing binary complexes. Therefore, it is crucial to find the best solution for the simulation. One approach to this problem is to employ empirical scoring function to identify the best docked structure. It is expected that scoring functions show a descriptive funnel-shaped energy surface without many false minima to impair the efficiency of conformational sampling. We employed this methodology against a test set with 300 docked structures. Docking simulations of these ligands against enzyme binding pocket indicated a funnel-shaped behavior of the complexation for this system. This review compares a set of recently proposed polynomial empirical scoring functions, implemented in a program called POLSCORE, with two popular scoring function programs (XSCORE and DrugScore). Overall comparison indicated that POLSCORE works better to predict the correct docked position, for the ensemble of docked structures analyzed in the present work.

  4. Compensability index for compensation radiotherapy after treatment interruptions

    Directory of Open Access Journals (Sweden)

    Putora Paul

    2012-12-01

    Full Text Available Abstract Background The goal of our work was to develop a simple method to evaluate a compensation treatment after unplanned treatment interruptions with respect to their tumour- and normal tissue effect. Methods We developed a software tool in java programming language based on existing recommendations to compensate for treatment interruptions. In order to express and visualize the deviations from the originally planned tumour and normal tissue effects we defined the compensability index. Results The compensability index represents an evaluation of the suitability of compensatory radiotherapy in a single number based on the number of days used for compensation and the preference of preserving the originally planned tumour effect or not exceeding the originally planned normal tissue effect. An automated tool provides a method for quick evaluation of compensation treatments. Conclusions The compensability index calculation may serve as a decision support system based on existing and established recommendations.

  5. Compensation for Occupational Cancer

    OpenAIRE

    Kim, Inah; Kim, Eun-A; Kim, Jae Young

    2014-01-01

    The legal scope and criteria for occupational cancer in Korea was out of date. The aim of this study was to review the current criteria for occupational cancer and amend the existent criteria on the basis of recent scientific evidence. The scientific evidence and the legal list of occupational cancer were analyzed to identify the causes of occupational cancer on a global scale. The relationship between compensated occupational cancer cases and carcinogen exposure in Korea was examined. The fa...

  6. PERANCANGAN FLOATING DOCK UNTUK DAERAH PERAIRAN PELABUHAN KOTA TEGAL

    Directory of Open Access Journals (Sweden)

    Kiryanto Kiryanto

    2013-06-01

    Full Text Available Floating dock merupakan bangunan air sebagai tempat reparasi kapal yang dinilai cukup efisien dalam pembangunannya karena tidak membutuhkan dana yang terlalu mahal. Di sektor indusrti perkapalan kota tegal sudah memiliki galangan dan dock reparasi kapal yang cukup berkembang.  Ide perancangan floating dock ini dirancang sebagai alternatif baru pelayanan reparasi kapal. Perancangan floating dock ini juga memperhatikan dengan detail kapasitas kapal – kapal yang pernah melakukan repararasi di sekitar galangan di Kota Tegal agar ditemukan ukuran utama floating dock yang tepat. Dari Kapasitas kapal yang ada dan berdasarkan metode perbandingan ukuran beberapa floating dock, maka ditemukan ukuran utama yang tepat untuk menampung kebutuhan pelayanan reparasi kapal yaitu LOA = 136,37 m, Lpt = 114.80 m, Bmax = 36,40 m, Bmd: 30,80 m, Tmin = 0,86 m, Tmax = 1,58 m, Hpt = 2,10 m, HOA = 9,60 m. Berdasarkan perhitungan ditemukan juga Ton Lifting Capacity (TLC sebesar 3000 ton. Perancangan menggunakan software perkapalan yaitu dengan menggunakan AutoCad, Delftship, Maxsurf dan Hidromax. Dengan analisa stabilitas menggunakan software Hidromax diketahui bahwa floating dock ini mampu memiliki stabilitas yang baik dengan 4 kondisi yang semua memenuhi criteria  International Maritime Organisation (IMO. Perancangan floating dock ini juga menghitung analisa ekonomis dan investasi. Dari rekapitulasi dana investasi pembangunan floating dock yaitu sebesar Rp.136.622.888.000,00 dengan nilai kembali atau break even point selama 10 tahun dengan modal sendiri, 14 tahun dengan 50% modal sendiri dan 50 % pinjaman bank, dan break event point 18 tahun untuk dana pembangunan floating dock yang berasal dari 100 % pinjaman bank

  7. A New, Improved Hybrid Scoring Function for Molecular Docking and Scoring Based on AutoDock and AutoDock Vina.

    Science.gov (United States)

    Tanchuk, Vsevolod Yu; Tanin, Volodymyr O; Vovk, Andriy I; Poda, Gennady

    2016-04-01

    Automated docking is one of the most important tools for structure-based drug design that allows prediction of ligand binding poses and also provides an estimate of how well small molecules fit in the binding site of a protein. A new scoring function based on AutoDock and AutoDock Vina has been introduced. The new hybrid scoring function is a linear combination of the two scoring function components derived from a multiple linear regression fitting procedure. The scoring function was built on a training set of 2412 protein-ligand complexes from pdbbind database (www.pdbbind.org.cn, version 2012). A test set of 313 complexes that appeared in the 2013 version was used for validation purposes. The new hybrid scoring function performed better than the original functions, both on training and test sets of protein-ligand complexes, as measured by the non-parametric Pearson correlation coefficient, R, mean absolute error (MAE), and root-mean-square error (RMSE) between the experimental binding affinities and the docking scores. The function also gave one of the best results among more than 20 scoring functions tested on the core set of the pdbbind database. The new AutoDock hybrid scoring function will be implemented in modified version of AutoDock.

  8. Robust adaptive backstepping neural networks control for spacecraft rendezvous and docking with input saturation.

    Science.gov (United States)

    Xia, Kewei; Huo, Wei

    2016-05-01

    This paper presents a robust adaptive neural networks control strategy for spacecraft rendezvous and docking with the coupled position and attitude dynamics under input saturation. Backstepping technique is applied to design a relative attitude controller and a relative position controller, respectively. The dynamics uncertainties are approximated by radial basis function neural networks (RBFNNs). A novel switching controller consists of an adaptive neural networks controller dominating in its active region combined with an extra robust controller to avoid invalidation of the RBFNNs destroying stability of the system outside the neural active region. An auxiliary signal is introduced to compensate the input saturation with anti-windup technique, and a command filter is employed to approximate derivative of the virtual control in the backstepping procedure. Globally uniformly ultimately bounded of the relative states is proved via Lyapunov theory. Simulation example demonstrates effectiveness of the proposed control scheme.

  9. Initial Investigation of Reaction Control System Design on Spacecraft Handling Qualities for Earth Orbit Docking

    Science.gov (United States)

    Bailey, Randall E.; Jackson, E. Bruce; Goodrich, Kenneth H.; Ragsdale, W. Al; Neuhaus, Jason; Barnes, Jim

    2008-01-01

    A program of research, development, test, and evaluation is planned for the development of Spacecraft Handling Qualities guidelines. In this first experiment, the effects of Reaction Control System design characteristics and rotational control laws were evaluated during simulated proximity operations and docking. Also, the influence of piloting demands resulting from varying closure rates was assessed. The pilot-in-the-loop simulation results showed that significantly different spacecraft handling qualities result from the design of the Reaction Control System. In particular, cross-coupling between translational and rotational motions significantly affected handling qualities as reflected by Cooper-Harper pilot ratings and pilot workload, as reflected by Task-Load Index ratings. This influence is masked but only slightly by the rotational control system mode. While rotational control augmentation using Rate Command Attitude Hold can reduce the workload (principally, physical workload) created by cross-coupling, the handling qualities are not significantly improved. The attitude and rate deadbands of the RCAH introduced significant mental workload and control compensation to evaluate when deadband firings would occur, assess their impact on docking performance, and apply control inputs to mitigate that impact.

  10. Activation of initiation factor 2 by ligands and mutations for rapid docking of ribosomal subunits

    Science.gov (United States)

    Pavlov, Michael Y; Zorzet, Anna; Andersson, Dan I; Ehrenberg, Måns

    2011-01-01

    We previously identified mutations in the GTPase initiation factor 2 (IF2), located outside its tRNA-binding domain, compensating strongly (A-type) or weakly (B-type) for initiator tRNA formylation deficiency. We show here that rapid docking of 30S with 50S subunits in initiation of translation depends on switching 30S subunit-bound IF2 from its inactive to active form. Activation of wild-type IF2 requires GTP and formylated initiator tRNA (fMet-tRNAi). In contrast, extensive activation of A-type IF2 occurs with only GTP or with GDP and fMet-tRNAi, implying a passive role for initiator tRNA as activator of IF2 in subunit docking. The theory of conditional switching of GTPases quantitatively accounts for all our experimental data. We find that GTP, GDP, fMet-tRNAi and A-type mutations multiplicatively increase the equilibrium ratio, K, between active and inactive forms of IF2 from a value of 4 × 10−4 for wild-type apo-IF2 by factors of 300, 8, 80 and 20, respectively. Functional characterization of the A-type mutations provides keys to structural interpretation of conditional switching of IF2 and other multidomain GTPases. PMID:21151095

  11. 38 CFR 3.4 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Compensation. 3.4 Section..., Compensation, and Dependency and Indemnity Compensation General § 3.4 Compensation. (a) Compensation. This term...) Disability compensation. (1) Basic entitlement for a veteran exists if the veteran is disabled as the...

  12. Combining docking with pharmacophore filtering for improved virtual screening

    Directory of Open Access Journals (Sweden)

    Peach Megan L

    2009-05-01

    Full Text Available Abstract Background Virtual screening is used to distinguish potential leads from inactive compounds in a database of chemical samples. One method for accomplishing this is by docking compounds into the structure of a receptor binding site in order to rank-order compounds by the quality of the interactions they form with the receptor. It is generally established that docking can be reasonably successful at generating good poses of a ligand in an active site. However, the scoring functions that are used with docking are typically not successful at correctly ranking ligands according to binding affinity or even distinguishing correct poses of a given ligand from incorrect ones. Results We have developed a simple method for reducing the number of false positives in a virtual screen, meaning ligands which are scored highly by the docking program but do not bind well in reality. This method uses a docking program for pose generation without regard to scoring, followed by filtering with receptor-based pharmacophore searches. We applied it to three test-case targets: neuraminidase A, cyclin-dependent kinase 2, and the C1 domain of protein kinase C. Conclusion The pharmacophore filtering method can perform better than more traditional docking + scoring methods, and allows the advantages of both docking-based and pharmacophore-based approaches to virtual screening to be fully realized.

  13. Sequence alignment reveals possible MAPK docking motifs on HIV proteins.

    Directory of Open Access Journals (Sweden)

    Perry Evans

    Full Text Available Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs. MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.

  14. Investigation of MM-PBSA rescoring of docking poses.

    Science.gov (United States)

    Thompson, David C; Humblet, Christine; Joseph-McCarthy, Diane

    2008-05-01

    Target-based virtual screening is increasingly used to generate leads for targets for which high quality three-dimensional (3D) structures are available. To allow large molecular databases to be screened rapidly, a tiered scoring scheme is often employed whereby a simple scoring function is used as a fast filter of the entire database and a more rigorous and time-consuming scoring function is used to rescore the top hits to produce the final list of ranked compounds. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches are currently thought to be quite effective at incorporating implicit solvation into the estimation of ligand binding free energies. In this paper, the ability of a high-throughput MM-PBSA rescoring function to discriminate between correct and incorrect docking poses is investigated in detail. Various initial scoring functions are used to generate docked poses for a subset of the CCDC/Astex test set and to dock one set of actives/inactives from the DUD data set. The effectiveness of each of these initial scoring functions is discussed. Overall, the ability of the MM-PBSA rescoring function to (i) regenerate the set of X-ray complexes when docking the bound conformation of the ligand, (ii) regenerate the X-ray complexes when docking conformationally expanded databases for each ligand which include "conformation decoys" of the ligand, and (iii) enrich known actives in a virtual screen for the mineralocorticoid receptor in the presence of "ligand decoys" is assessed. While a pharmacophore-based molecular docking approach, PhDock, is used to carry out the docking, the results are expected to be general to use with any docking method.

  15. Game Theoretic Approach to Post-Docked Satellite Control

    Science.gov (United States)

    Hiramatsu, Takashi; Fitz-Coy, Norman G.

    2007-01-01

    This paper studies the interaction between two satellites after docking. In order to maintain the docked state with uncertainty in the motion of the target vehicle, a game theoretic controller with Stackelberg strategy to minimize the interaction between the satellites is considered. The small perturbation approximation leads to LQ differential game scheme, which is validated to address the docking interactions between a service vehicle and a target vehicle. The open-loop solution are compared with Nash strategy, and it is shown that less control efforts are obtained with Stackelberg strategy.

  16. Linear Actuator System for the NASA Docking System

    Science.gov (United States)

    Dick, Brandon; Oesch, Chris

    2017-01-01

    The Linear Actuator System (LAS) is a major sub-system within the NASA Docking System (NDS). The NDS Block 1 will be used on the Boeing Crew Space Transportation (CST-100) system to achieve docking with the International Space Station. Critical functions in the Soft Capture aspect of docking are performed by the LAS, which implements the Soft Impact Mating and Attenuation Concept (SIMAC). This paper describes the general function of the LAS, the system's key requirements and technical challenges, and the development and qualification approach for the system.

  17. DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015

    Science.gov (United States)

    Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

    2016-09-01

    Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

  18. Economic Impacts From Spending by Private Dock Owners at Hartwell Lake

    Science.gov (United States)

    2008-03-01

    cost is variable. The lakes and market segments studied were: • Table Rock Lake, community dock • Rough River Lake, community dock • Pomme de... Terre Lake, community dock • Harry S. Truman Dam and Reservoir, marina • Raystown Lake, marina • Hartwell Lake, private dock • Lake Barkley, private

  19. Urban agglomeration and CEO compensation

    OpenAIRE

    Francis, Bill; Hasan, Iftekhar; John, Kose; Waisman , Maya

    2012-01-01

    An underlying assumption in the executive compensation literature is that there is a national labor market for CEOs. The urban economics literature, however, documents higher ability among workers in large metropolitans, which results in a real and stable urban wage premium. In this paper, we investigate the link between the spatial clustering of firms in big, central cities (i.e., urban agglomeration) and the level and structure of CEO compensation. Using CEO compensation data for the period...

  20. Docking and scoring of metallo-beta-lactamases inhibitors

    DEFF Research Database (Denmark)

    Olsen, Lars; Pettersson, Ingrid; Hemmingsen, Lars

    2004-01-01

    The performance of the AutoDock, GOLD and FlexX docking programs was evaluated for docking of dicarboxylic acid inhibitors into metallo-beta-lactamases (MBLs). GOLD provided the best overall performance, with RMSDs between experimental and docked structures of 1.8-2.6 A and a good correlation...... between the experimentally determined MBL-inhibitor affinities and the GOLD scores. GOLD was selected for a test including a broad spectrum of inhibitors for which experimental MBL-inhibitor binding affinities are available. This study revealed that (1) for most compound classes (dicarboxylic acids...... and descriptors associated with binding of the IMP-1 inhibitors to the enzyme. The external Q2 for the test set is 0.73. This final model for prediction of IMP-1 MBL-inhibitor affinity handled all known classes of MBL-inhibitors, except small sulphur compounds....

  1. Virtual Screening with AutoDock: Theory and Practice

    Science.gov (United States)

    Cosconati, Sandro; Forli, Stefano; Perryman, Alex L.; Harris, Rodney; Goodsell, David S.; Olson, Arthur J.

    2011-01-01

    Importance to the field Virtual screening is a computer-based technique for identifying promising compounds to bind to a target molecule of known structure. Given the rapidly increasing number of protein and nucleic acid structures, virtual screening continues to grow as an effective method for the discovery of new inhibitors and drug molecules. Areas covered in this review We describe virtual screening methods that are available in the AutoDock suite of programs, and several of our successes in using AutoDock virtual screening in pharmaceutical lead discovery. What the reader will gain A general overview of the challenges of virtual screening is presented, along with the tools available in the AutoDock suite of programs for addressing these challenges. Take home message Virtual screening is an effective tool for the discovery of compounds for use as leads in drug discovery, and the free, open source program AutoDock is an effective tool for virtual screening. PMID:21532931

  2. Yada: a novel tool for molecular docking calculations

    Science.gov (United States)

    Piotto, S.; Di Biasi, L.; Fino, R.; Parisi, R.; Sessa, L.; Concilio, S.

    2016-09-01

    Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at >www.yada.unisa.it.

  3. Optimal Rendezvous and Docking Simulator for Elliptical Orbits Project

    Data.gov (United States)

    National Aeronautics and Space Administration — It is proposed to develop and implement a simulation of spacecraft rendezvous and docking guidance, navigation, and control in elliptical orbit. The foundation of...

  4. Discovery of potential cyclooxygenase inhibitors using in silico docking studies

    Directory of Open Access Journals (Sweden)

    Arumugam Madeswaran

    2012-03-01

    Full Text Available This study deals with the evaluation of the cyclooxygenase inhibitory activity of flavonoids (tangeritin, morin, rhamnetin, theaflavin, pachypodol, eriodictyol, homoeriodictyol, aromadedrin, okanin using in silico docking studies. In silico docking studies were carried out using AutoDock 4.2. Three important parameters like binding energy, inhibition constant and intermolecular energy were determined. The results showed that all the selected flavonoids showed binding energy ranging between -8.77 kcalmol-1 to -6.10 kcalmol-1 when compared with that of the standard (-8.30 kcalmol-1. Intermolecular energy (-10.56 kcalmol-1 to -7.89 kcalmol-1 and inhibition constant (373.91 nM to 34.03 µM of the ligands also coincide with the binding energy. All the selected flavonoids contributed cyclooxygenase inhibitory activity because of its structural parameters. These molecular docking analyses could lead to the further development of potent cyclooxygenase inhibitors.

  5. AggieSat: Autonomous Rendezvous and Docking Technology Demonstrator Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Current autonomous rendezvous and docking (AR&D) capability in low Earth orbit (LEO) is constrained by sensor and effector mass, power, and accuracy limits. To...

  6. 300,000-tonnage Crude Oil Dock Put into Operation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Aproject of Jointly establishing 300,000-tonnage crude oil dock of Tianjin Port has been put into operations, thanks to its outut grid successfully connected with oil pipeline of Sinopec Tanggu reservior.

  7. Companies hone in on radar-docking technology

    Science.gov (United States)

    Howell, Elizabeth

    2009-11-01

    As NASA prepares to retire the Space Shuttle next year, two private space firms have tested docking technology that could be used on the next generation of US spacecraft. In September, Canadian firm Neptec tested a new radar system on the Space Shuttle Discovery that allows spacecraft to dock more easily. Meanwhile, Space Exploration Technologies (SpaceX) based in California has revealed that it tested out a new proximity sensor, dubbed "Dragoneye", on an earlier shuttle mission in July.

  8. Scheduling inbound and outbound trucks at cross docking terminals

    OpenAIRE

    Nils Boysen; Malte Fliedner; Armin Scholl

    2007-01-01

    At cross docking terminals, shipments from inbound trucks are unloaded, sorted and moved to dispatch points where they are directly loaded onto outbound trucks for an immediate delivery elsewhere in the distribution system. This warehouse management concept aims at realizing economies in transportation cost by consolidating divergent shipments to full truckloads without requiring excessive inventory at the cross dock. The efficient operation of such a system requires an appropriate coordinati...

  9. Effects of administration of a local anaesthetic and/or an NSAID and of docking length on the behaviour of piglets during 5 h after tail docking

    DEFF Research Database (Denmark)

    Herskin, Mette S.; Di Giminiani, Pierpaolo; Thodberg, Karen

    2016-01-01

    In many countries, piglets are tail docked to prevent tail biting. The aim of this study was 1) to evaluate the efficacy of a local anaesthetic and/or NSAID to reduce pain caused by tail docking; and 2) to examine interactions with docking length. This was examined in 295 piglets docked by hot iron...... cautery 2–4 days after birth and based on behaviour during docking as well as the following 5 h. The study involved three main factors: local anaesthetic (Lidocain), NSAID (Meloxicam) and docking length. Either 100%, 75%, 50% or 25% of the tails were left on the body of the piglets. Irrespective...... of the tail length, tail docking led to signs of procedural pain, which could be reduced by administration of Lidocain. Preemptive use of Meloxicam did not affect the signs of procedural pain. The results show that tail docking led to behavioural changes throughout the 5 h observation period indicating...

  10. Compensation: The Impact of Policy.

    Science.gov (United States)

    Morrell, Louis R.

    1994-01-01

    Complexity of employee compensation policy is examined as it applies to colleges and universities. It is argued that sound compensation policy helps the institution attract and retain qualified, skilled employees. New approaches that shift the focus from job to employee are outlined, and their implications for institutions of higher education are…

  11. Alternative Teacher Compensation: A Primer

    Science.gov (United States)

    Koppich, Julia E.; Rigby, Jessica

    2009-01-01

    This policy primer is designed to provide base-line information about new forms of teacher pay that are emerging around the country, to support the local conversations and negotiations that will lead to the development of innovative compensation systems. It identifies reasons why teacher compensation is high on local, state, and federal policy…

  12. 38 CFR 3.459 - Death compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Death compensation. 3.459..., Compensation, and Dependency and Indemnity Compensation Apportionments § 3.459 Death compensation. (a) Death compensation will be apportioned if the child or children of the deceased veteran are not in the custody of...

  13. Workers' compensation law: an overview.

    Science.gov (United States)

    Yorker, B

    1994-09-01

    1. The workers' compensation system provides benefits to workers who are injured or made ill in the course of employment or their dependents regardless of fault. 2. The current workers' compensation laws benefit both the employer and the employee; however, workers' compensation is an exclusive remedy which bars recovery through a negligence lawsuit. 3. Workers' compensation regulations interact with other federal statutes such as the Americans With Disabilities Act and the Family Medical Leave Act. 4. Workers' compensation covers occupational injuries and occupational diseases, which may include cumulative trauma and mental stress claims. Nurses may be instrumental in evaluating and planning for an injured employee's return to work and occasionally in detecting fraudulent claims.

  14. ARCADE small-scale docking mechanism for micro-satellites

    Science.gov (United States)

    Boesso, A.; Francesconi, A.

    2013-05-01

    The development of on-orbit autonomous rendezvous and docking (ARD) capabilities represents a key point for a number of appealing mission scenarios that include activities of on-orbit servicing, automated assembly of modular structures and active debris removal. As of today, especially in the field of micro-satellites ARD, many fundamental technologies are still missing or require further developments and micro-gravity testing. In this framework, the University of Padova, Centre of Studies and Activities for Space (CISAS), developed the Autonomous Rendezvous Control and Docking Experiment (ARCADE), a technology demonstrator intended to fly aboard a BEXUS stratospheric balloon. The goal was to design, build and test, in critical environment conditions, a proximity relative navigation system, a custom-made reaction wheel and a small-size docking mechanism. The ARCADE docking mechanism was designed against a comprehensive set of requirements and it can be classified as small-scale, central, gender mating and unpressurized. The large use of commercial components makes it low-cost and simple to be manufactured. Last, it features a good tolerance to off-nominal docking conditions and a by-design soft docking capability. The final design was extensively verified to be compliant with its requirements by means of numerical simulations and physical testing. In detail, the dynamic behaviour of the mechanism in both nominal and off-nominal conditions was assessed with the multibody dynamics analysis software MD ADAMS 2010 and functional tests were carried out within the fully integrated ARCADE experiment to ensure the docking system efficacy and to highlight possible issues. The most relevant results of the study will be presented and discussed in conclusion to this paper.

  15. Combining docking and molecular dynamic simulations in drug design.

    Science.gov (United States)

    Alonso, Hernán; Bliznyuk, Andrey A; Gready, Jill E

    2006-09-01

    A rational approach is needed to maximize the chances of finding new drugs, and to exploit the opportunities of potential new drug targets emerging from genomic and proteomic initiatives, and from the large libraries of small compounds now readily available through combinatorial chemistry. Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery. This happy outcome results from development of more accurate and reliable algorithms, use of more thoughtfully planned strategies to apply them, and greatly increased computer power to allow studies with the necessary reliability to be performed. Our review focuses on applications and protocols, with the main emphasis on critical analysis of recent studies where docking calculations and molecular dynamics (MD) simulations were combined to dock small molecules into protein receptors. We highlight successes to demonstrate what is possible now, but also point out drawbacks and future directions. The review is structured to lead the reader from the simpler to more compute-intensive methods. Thus, while inexpensive and fast docking algorithms can be used to scan large compound libraries and reduce their size, more accurate but expensive MD simulations can be applied when a few selected ligand candidates remain. MD simulations can be used: during the preparation of the protein receptor before docking, to optimize its structure and account for protein flexibility; for the refinement of docked complexes, to include solvent effects and account for induced fit; to calculate binding free energies, to provide an accurate ranking of the potential ligands; and in the latest developments, during the docking process itself to find the binding site and correctly dock the ligand a priori.

  16. Machine Vision for Relative Spacecraft Navigation During Approach to Docking

    Science.gov (United States)

    Chien, Chiun-Hong; Baker, Kenneth

    2011-01-01

    This paper describes a machine vision system for relative spacecraft navigation during the terminal phase of approach to docking that: 1) matches high contrast image features of the target vehicle, as seen by a camera that is bore-sighted to the docking adapter on the chase vehicle, to the corresponding features in a 3d model of the docking adapter on the target vehicle and 2) is robust to on-orbit lighting. An implementation is provided for the case of the Space Shuttle Orbiter docking to the International Space Station (ISS) with quantitative test results using a full scale, medium fidelity mock-up of the ISS docking adapter mounted on a 6-DOF motion platform at the NASA Marshall Spaceflight Center Flight Robotics Laboratory and qualitative test results using recorded video from the Orbiter Docking System Camera (ODSC) during multiple orbiter to ISS docking missions. The Natural Feature Image Registration (NFIR) system consists of two modules: 1) Tracking which tracks the target object from image to image and estimates the position and orientation (pose) of the docking camera relative to the target object and 2) Acquisition which recognizes the target object if it is in the docking camera Field-of-View and provides an approximate pose that is used to initialize tracking. Detected image edges are matched to the 3d model edges whose predicted location, based on the pose estimate and its first time derivative from the previous frame, is closest to the detected edge1 . Mismatches are eliminated using a rigid motion constraint. The remaining 2d image to 3d model matches are used to make a least squares estimate of the change in relative pose from the previous image to the current image. The changes in position and in attitude are used as data for two Kalman filters whose outputs are smoothed estimate of position and velocity plus attitude and attitude rate that are then used to predict the location of the 3d model features in the next image.

  17. Seismic vulnerability assessment of an Italian historical masonry dry dock

    Directory of Open Access Journals (Sweden)

    Marco Zucca

    2017-01-01

    Full Text Available The paper presents the seismic vulnerability analysis of the military dry dock built in 1861 inside the Messina’s harbor. The study appears very important not only for the relevance of the dry dock itself, but also for its social, military and symbolic role. As a first step, the historical documentation about the dry dock delivered by the Military Technical Office, in charge of its maintenance, was thoroughly examined. This activity was fundamental to understand the construction methods, the rehabilitation works executed after the severe earthquake of 1908 and, finally, the works carried out to increase the size of the dry dock in 1950. After this first step, numerical seismic analyses were done with some implemented finite element models (FEM of the structure. In each FEM, the vertical loads were applied according to the “construction stages” analysis technique, in order to achieve an appropriate representation of the soil stresses around the structure. The analysis results were evaluated according to the Italian design code (NTC 2008 in order to determine the seismic vulnerability of the dry dock.

  18. GOMoDo: A GPCRs online modeling and docking webserver.

    Directory of Open Access Journals (Sweden)

    Massimo Sandal

    Full Text Available G-protein coupled receptors (GPCRs are a superfamily of cell signaling membrane proteins that include >750 members in the human genome alone. They are the largest family of drug targets. The vast diversity and relevance of GPCRs contrasts with the paucity of structures available: only 21 unique GPCR structures have been experimentally determined as of the beginning of 2013. User-friendly modeling and small molecule docking tools are thus in great demand. While both GPCR structural predictions and docking servers exist separately, with GOMoDo (GPCR Online Modeling and Docking, we provide a web server to seamlessly model GPCR structures and dock ligands to the models in a single consistent pipeline. GOMoDo can automatically perform template choice, homology modeling and either blind or information-driven docking by combining together proven, state of the art bioinformatic tools. The web server gives the user the possibility of guiding the whole procedure. The GOMoDo server is freely accessible at http://molsim.sci.univr.it/gomodo.

  19. Molecular docking assessment of pyridone derivatives as glucokinase activators

    Directory of Open Access Journals (Sweden)

    Y. Nanda Kumar

    2012-10-01

    Full Text Available Background: Mutations in glucokinase (GK gene results in maturity onset diabetes of the young 2 (MODY2. It has been observed that GK activators (GKAs can activate GK structure and promote glucose phosphorylation and bring blood glucose levels to normal condition. The present study is aimed to identify the binding mode of pyridone derivatives (PDs as GKAs through molecular docking study. Methods: GK structure was retrieved from the Protein Data Bank (PDB, protonated and energy minimized. A database was constructed with 29 PDs and docked into the allosteric site specified with Y61, R63, S69 and Y215 residues using Molecular Operating Environment (MOE software. Docking conformations were generated using triangle match algorithm and ranked by London dG scoring function. The binding orientations and strength of interactions were evaluated by ligand interaction module of MOE. Results: Molecular docking of 29 PDs in allosteric site of GK gave reliable docking scores, interestingly arene cationic interactions were observed with the compounds PD1, PD12, PD20 and PD21. R63 residue of allosteric site played a predominant role in binding with PDs. Conclusions: PDs can be potentially useful agents in future management strategies of type 2 diabetes mellitus.

  20. How well do the substrates KISS the enzyme? Molecular docking program selection for feruloyl esterases

    DEFF Research Database (Denmark)

    Udatha, D. B. R. K. Gupta; Sugaya, Nobuyoshi; Olsson, Lisbeth;

    2012-01-01

    Molecular docking is the most commonly used technique in the modern drug discovery process where computational approaches involving docking algorithms are used to dock small molecules into macromolecular target structures. Over the recent years several evaluation studies have been reported...... by independent scientists comparing the performance of the docking programs by using default 'black box' protocols supplied by the software companies. Such studies have to be considered carefully as the docking programs can be tweaked towards optimum performance by selecting the parameters suitable...... Score System' (KISS), a more biochemically meaningful measure for evaluation of docking programs based on pose prediction accuracy....

  1. Molecular docking and structure-based drug design strategies.

    Science.gov (United States)

    Ferreira, Leonardo G; Dos Santos, Ricardo N; Oliva, Glaucius; Andricopulo, Adriano D

    2015-07-22

    Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  2. Stock Repurchases and Incentive Compensation

    OpenAIRE

    Christine Jolls

    1998-01-01

    A longstanding puzzle in corporate finance is the rise of stock repurchases as a means of distributing earnings to shareholders. While most attempts to explain repurchase behavior focus on the incentives of firms, this paper focuses on the incentives of the agents who run firms, as determined by those agents' compensation packages. The increased use of repurchases coincided with an increasing reliance on stock options to compensate top managers, and stock options encourage managers to choose ...

  3. Solvent structure improves docking prediction in lectin-carbohydrate complexes.

    Science.gov (United States)

    Gauto, Diego F; Petruk, Ariel A; Modenutti, Carlos P; Blanco, Juan I; Di Lella, Santiago; Martí, Marcelo A

    2013-02-01

    Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico docking methods have a long-standing tradition in predicting protein-ligand complexes, and allow a potentially fast exploration of a number of possible protein-carbohydrate complex structures. However, determining which of these predicted complexes represents the correct structure is not always straightforward. In this work, we present a modification of the scoring function provided by AutoDock4, a widely used docking software, on the basis of analysis of the solvent structure adjacent to the protein surface, as derived from molecular dynamics simulations, that allows the definition and characterization of regions with higher water occupancy than the bulk solvent, called water sites. They mimic the interaction held between the carbohydrate -OH groups and the protein. We used this information for an improved docking method in relation to its capacity to correctly predict the protein-carbohydrate complexes for a number of tested proteins, whose ligands range in size from mono- to tetrasaccharide. Our results show that the presented method significantly improves the docking predictions. The resulting solvent-structure-biased docking protocol, therefore, appears as a powerful tool for the design and optimization of development of glycomimetic drugs, while providing new insights into protein-carbohydrate interactions. Moreover, the achieved improvement also underscores the relevance of the solvent structure to the protein carbohydrate recognition process.

  4. Improved Evolutionary Hybrids for Flexible Ligand Docking in Autodock

    Energy Technology Data Exchange (ETDEWEB)

    Belew, R.K.; Hart, W.E.; Morris, G.M.; Rosin, C.

    1999-01-27

    In this paper we evaluate the design of the hybrid evolutionary algorithms (EAs) that are currently used to perform flexible ligand binding in the Autodock docking software. Hybrid EAs incorporate specialized operators that exploit domain-specific features to accelerate an EA's search. We consider hybrid EAs that use an integrated local search operator to reline individuals within each iteration of the search. We evaluate several factors that impact the efficacy of a hybrid EA, and we propose new hybrid EAs that provide more robust convergence to low-energy docking configurations than the methods currently available in Autodock.

  5. The pickup and delivery problem with cross-docking opportunity

    DEFF Research Database (Denmark)

    Petersen, Hanne Løhmann; Røpke, Stefan

    2011-01-01

    In this paper, we consider the pickup and delivery problem with cross-docking opportunity (PDPCD). The problem arises from an industry application, and includes pickup requests, delivery requests, and pickup-and-delivery requests. Each pickup-and-delivery request can be served either as direct...... delivery by one truck, or by being picked up and transported to the cross-dock by one vehicle, and subsequently delivered at its final destination by another vehicle. Handling times at customers sites and terminal are given. A typical daily instance includes 500-1,000 requests. We solve the problem using...

  6. SYNTHESIS, DOCKING AND BIOLOGICAL STUDIES OF THE LINEAR TETRAPEPTIDE PWPV

    Directory of Open Access Journals (Sweden)

    M. Himaja

    2012-06-01

    Full Text Available Linear Tetrapeptides L-PWPV (Pro-Trp-Pro-Val was designed and synthesized by solution phase peptide synthesis based on dock score. The molecular docking studies of the designed tetrapeptide L-PWPV was carried out using Molegro Virtual Docker software for tumor cancer protein(1OLG. The linear tetrapeptide was synthesized by coupling protected amino acids (dipeptides using EDC (ethyl-3-(N,N-dimethylaminopropyl carbodiimide as coupling reagent. The compounds were analyzed by FTIR, 1H NMR and MASS data and subjected to antioxidant activity using 1,1-dipheny-2-picryl-hydrazil (DPPH method and insecticidal activity using Morita et al method.

  7. Scheduling trucks in cross docking systems with temporary storage and dock repeat truck holding pattern using genetic algorithm

    Directory of Open Access Journals (Sweden)

    Ehsan Ghobadian

    2013-02-01

    Full Text Available Cross docking is one of the most important issues in management of supply chains. In cross docking, different items delivered to a warehouse by inbound trucks are directly arranged and reorganized based on customer demands, routed and loaded into outbound trucks for delivery purposes to customers without virtually keeping them at the warehouse. If any item is kept in storage, it is normally for a short amount of time, say less than 24 hours. In this paper, we consider a special case of cross docking where there is temporary storage and implements genetic algorithm to solve the resulted problem for some realistic test problems. In our method, we first use some heuristics as initial solutions and then improve the final solution using genetic algorithm. The performance of the proposed model is compared with alternative solution strategy, the GRASP method.

  8. Technology Development of Automated Rendezvous and Docking/Capture Sensors and Docking Mechanism for the Asteroid Redirect Crewed Mission

    Science.gov (United States)

    Hinkel, Heather; Strube, Matthew; Zipay, John J.; Cryan, Scott

    2016-01-01

    This paper will describe the technology development efforts NASA has underway for Automated Rendezvous and Docking/Capture (AR&D/C) sensors and a docking mechanism and the challenges involved. The paper will additionally address how these technologies will be extended to other missions requiring AR&D/C whether robotic or manned. NASA needs AR&D/C sensors for both the robotic and crewed segments of the Asteroid Redirect Mission (ARM). NASA recently conducted a commonality assessment of the concept of operations for the robotic Asteroid Redirect Vehicle (ARV) and the crewed mission segment using the Orion spacecraft. The commonality assessment also considered several future exploration and science missions requiring an AR&D/C capability. Missions considered were asteroid sample return, satellite servicing, and planetary entry, descent, and landing. This assessment determined that a common sensor suite consisting of one or more visible wavelength cameras, a three-dimensional LIDAR along with long-wavelength infrared cameras for robustness and situational awareness could be used on each mission to eliminate the cost of multiple sensor developments and qualifications. By choosing sensor parameters at build-time instead of at design-time and, without having to requalify flight hardware, a specific mission can design overlapping bearing, range, relative attitude, and position measurement availability to suit their mission requirements with minimal non-recurring engineering costs. The resulting common sensor specification provides the union of all performance requirements for each mission and represents an improvement over the current systems used for AR&D/C today. These sensor specifications are tightly coupled to the docking system capabilities and requirements for final docking conditions. The paper will describe NASA's efforts to develop a standard docking system for use across NASA human spaceflight missions to multiple destinations. It will describe the current

  9. 14 CFR 158.53 - Collection compensation.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Collection compensation. 158.53 Section 158... Collection compensation. (a) As compensation for collecting, handling, and remitting the PFC revenue, the... a new compensation level based on an analysis of the data provided under paragraph (c)(1) of...

  10. 48 CFR 752.7007 - Personnel compensation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Personnel compensation... Personnel compensation. The following clause shall be used in all USAID cost-reimbursement contracts. Personnel Compensation (JUL 2007) (a) Direct compensation of the Contractor's personnel will be...

  11. 22 CFR 96.34 - Compensation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Compensation. 96.34 Section 96.34 Foreign... Financial and Risk Management § 96.34 Compensation. (a) The agency or person does not compensate any... for compensation within the intercountry adoption community in that country, to the extent that...

  12. 30 CFR 90.103 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Compensation. 90.103 Section 90.103 Mineral..., Rights of Part 90 Miners § 90.103 Compensation. (a) The operator shall compensate each Part 90 miner at... part. (d) In addition to the compensation required to be paid under paragraphs (a), (b) and (c) of...

  13. 48 CFR 970.2270 - Unemployment compensation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Unemployment compensation... Unemployment compensation. (a) Each state has its own unemployment compensation system to provide payments to... unemployment compensation benefits through a payroll tax on employers. Most DOE contractors are subject to...

  14. 43 CFR 4.355 - Omitted compensation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Omitted compensation. 4.355 Section 4.355... Compensation § 4.355 Omitted compensation. When, subsequent to the issuance of a final order determining heirs under § 4.352, it is found that certain additional compensation had been due the decedent and had...

  15. 7 CFR 930.133 - Compensation rate.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Compensation rate. 930.133 Section 930.133 Agriculture... Regulations § 930.133 Compensation rate. A compensation rate of $250 per meeting shall be paid to the public member and to the alternate public member when attending Board meetings. Such compensation is a...

  16. 12 CFR 9.15 - Fiduciary compensation.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Fiduciary compensation. 9.15 Section 9.15 Banks... BANKS Regulations § 9.15 Fiduciary compensation. (a) Compensation of bank. If the amount of a national bank's compensation for acting in a fiduciary capacity is not set or governed by applicable law,...

  17. 23 CFR 751.15 - Just compensation.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Just compensation. 751.15 Section 751.15 Highways... AND ACQUISITION § 751.15 Just compensation. (a) Just compensation shall be paid the owner for the... removed, relocated, or disposed of pursuant to 23 U.S.C. 136. (b) No rights to compensation accrue until...

  18. 12 CFR 7.2011 - Compensation plans.

    Science.gov (United States)

    2010-01-01

    ... Corporate Practices § 7.2011 Compensation plans. Consistent with safe and sound banking practices and the compensation provisions of 12 CFR part 30, a national bank may adopt compensation plans, including, among... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Compensation plans. 7.2011 Section 7.2011...

  19. 29 CFR 525.6 - Compensable time.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Compensable time. 525.6 Section 525.6 Labor Regulations... WITH DISABILITIES UNDER SPECIAL CERTIFICATES § 525.6 Compensable time. Individuals employed subject to this part must be compensated for all hours worked. Compensable time includes not only those...

  20. Combining pharmacophore search, automated docking, and molecular dynamics simulations as a novel strategy for flexible docking. Proof of concept: docking of arginine-glycine-aspartic acid-like compounds into the alphavbeta3 binding site.

    Science.gov (United States)

    Moitessier, Nicolas; Henry, Christophe; Maigret, Bernard; Chapleur, Yves

    2004-08-12

    A novel and highly efficient flexible docking approach is presented where the conformations (internal degrees of freedom) and orientations (external degrees of freedom) of the ligands are successively considered. This hybrid method takes advantage of the synergistic effects of structure-based and ligand-based drug design techniques. Preliminary antagonist-derived pharmacophore determination provides the postulated bioactive conformation. Subsequent docking of this pharmacophore to the receptor crystal structure results in a postulated pharmacophore/receptor binding mode. Pharmacophore-oriented docking of antagonists is subsequently achieved by matching ligand interacting groups with pharmacophore points. Molecular dynamics in water refines the proposed complexes. To validate the method, arginine-glycine-aspartic acid (RGD) containing peptides, pseudopeptides, and RGD-like antagonists were docked to the crystal structure of alphavbeta3 holoprotein and apoprotein. The proposed directed docking was found to be more accurate, faster, and less biased with respect to the protein structure (holo and apoprotein) than DOCK, Autodock, and FlexX docking methods. The successful docking of an antagonist recently cocrystallized with the receptor to both apo and holoprotein is particularly appealing. The results summarized in this report illustrated the efficiency of our light CoMFA/rigid body docking hybrid method.

  1. Economic Impacts from Spending by Community Dock Owners at Table Rock Lake

    Science.gov (United States)

    2008-01-01

    Rock Lake, community dock • Rough River Lake, community dock • Pomme de Terre Lake, community dock • Harry S. Truman Dam and Reservoir, marina...owners at Table Rock Lake (Missouri/Arkansas), Rough River Lake (Kentucky), and Pomme de Terre Lake (Missouri). The ERB staff designed the survey

  2. Application of the docking program SOL for CSAR benchmark.

    Science.gov (United States)

    Sulimov, Alexey V; Kutov, Danil C; Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Vladimir B

    2013-08-26

    This paper is devoted to results obtained by the docking program SOL and the post-processing program DISCORE at the CSAR benchmark. SOL and DISCORE programs are described. SOL is the original docking program developed on the basis of the genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in the frame of simplified GB model, vdW, and electrostatic interactions and taking into account the ligand internal strain energy. An important SOL feature is the single- or multi-processor performance for up to hundreds of CPUs. DISCORE improves the binding energy scoring by the local energy optimization of the ligand docked pose and a simple linear regression on the base of available experimental data. The docking program SOL has demonstrated a good ability for correct ligand positioning in the active sites of the tested proteins in most cases of CSAR exercises. SOL and DISCORE have not demonstrated very exciting results on the protein-ligand binding free energy estimation. Nevertheless, for some target proteins, SOL and DISCORE were among the first in prediction of inhibition activity. Ways to improve SOL and DISCORE are discussed.

  3. System for deflection measurements of floating dry docks

    Science.gov (United States)

    Gorbachev, Alexey A.; Pantyushin, Anton V.; Serikova, Mariya G.; Korotaev, Valery V.; Timofeev, Aleksandr N.

    2015-05-01

    In this paper we introduce a system for deflection measurement of floating dry docks. The system contains two measurement channels observing opposite directions of the dock. It also includes set of reference marks, an industrial computer and a display. Each channel contains CMOS camera with long focal-length lens. Reference marks are implemented as IR LED arrays with 940 nm working wavelength for better performance within bad weather conditions (e.g. fog, rain, high humidity etc.). In the paper we demonstrate results of an analysis of different optical schemes for coupling the oppositely directed channels of the measurement unit and show that the scheme with two image sensors with separated lenses is an optimal option, because it allows usage of nonequidistant location of reference marks and demonstrates the least value of parasitic shift caused by rotations of the measuring unit. The developed system was tested both on specially-designed setup and in real infrastructure of a floating dry dock. The conducted tests proved that a measuring error of the system is smaller than +/- 1.5 mm within the measurement range of +/- 150 mm when deflection of 100 m dock is measured. Obtained results showed that the system demonstrates an ability to work in a harsh environment including poor weather conditions.

  4. Spacecraft Rendevouz and Docking. An Autonomy assisted Human Operator Approach

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Thuesen, Gøsta

    1999-01-01

    The phenomena and problems encountered when a rendezvous maneuver, and possible docking, of two spacecrafts has to be performed, have been the topic for numerous studies and details of a variety of scenarios has been analyzed. So far, all solutions that have been brought into realization have bee...

  5. A fast flexible docking method using an incremental construction algorithm.

    Science.gov (United States)

    Rarey, M; Kramer, B; Lengauer, T; Klebe, G

    1996-08-23

    We present an automatic method for docking organic ligands into protein binding sites. The method can be used in the design process of specific protein ligands. It combines an appropriate model of the physico-chemical properties of the docked molecules with efficient methods for sampling the conformational space of the ligand. If the ligand is flexible, it can adopt a large variety of different conformations. Each such minimum in conformational space presents a potential candidate for the conformation of the ligand in the complexed state. Our docking method samples the conformation space of the ligand on the basis of a discrete model and uses a tree-search technique for placing the ligand incrementally into the active site. For placing the first fragment of the ligand into the protein, we use hashing techniques adapted from computer vision. The incremental construction algorithm is based on a greedy strategy combined with efficient methods for overlap detection and for the search of new interactions. We present results on 19 complexes of which the binding geometry has been crystallographically determined. All considered ligands are docked in at most three minutes on a current workstation. The experimentally observed binding mode of the ligand is reproduced with 0.5 to 1.2 A rms deviation. It is almost always found among the highest-ranking conformations computed.

  6. Simulation of carbohydrates, from molecular docking to dynamics in water.

    Science.gov (United States)

    Sapay, Nicolas; Nurisso, Alessandra; Imberty, Anne

    2013-01-01

    Modeling of carbohydrates is particularly challenging because of the variety of structures resulting for the high number of monosaccharides and possible linkages and also because of their intrinsic flexibility. The development of carbohydrate parameters for molecular modeling is still an active field. Nowadays, main carbohydrates force fields are GLYCAM06, CHARMM36, and GROMOS 45A4. GLYCAM06 includes the largest choice of compounds and is compatible with the AMBER force fields and associated. Furthermore, AMBER includes tools for the implementation of new parameters. When looking at protein-carbohydrate interaction, the choice of the starting structure is of importance. Such complex can be sometimes obtained from the Protein Data Bank-although the stereochemistry of sugars may require some corrections. When no experimental data is available, molecular docking simulation is generally used to the obtain protein-carbohydrate complex coordinates. As molecular docking parameters are not specifically dedicated to carbohydrates, inaccuracies should be expected, especially for the docking of polysaccharides. This issue can be addressed at least partially by combining molecular docking with molecular dynamics simulation in water.

  7. Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

    Directory of Open Access Journals (Sweden)

    2005-04-01

    Full Text Available The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.

  8. Normal mode-based approaches in receptor ensemble docking.

    Science.gov (United States)

    Cavasotto, Claudio N

    2012-01-01

    Explicitly accounting for target flexibility in docking still constitutes a difficult challenge due to the high dimensionality of the conformational space to be sampled. This especially applies to the high-throughput scenario, where the screening of hundreds of thousands compounds takes place. The use of multiple receptor conformations (MRCs) to perform ensemble docking in a sequential fashion is a simple but powerful approach that allows to incorporate binding site structural diversity in the docking process. Whenever enough experimental structures to build a diverse ensemble are not available, normal mode analysis provides an appealing and efficient approach to in silico generate MRCs by distortion along few low-frequency modes that represent collective mid- and large-scale displacements. In this way, the dimension of the conformational space to be sampled is heavily reduced. This methodology is especially suited to incorporate target flexibility at the backbone level. In this chapter, the main components of normal mode-based approaches in the context of ensemble docking are presented and explained, including the theoretical and practical considerations needed for the successful development and implementation of this methodology.

  9. I-AUV Docking and Panel Intervention at Sea

    Directory of Open Access Journals (Sweden)

    Narcís Palomeras

    2016-10-01

    Full Text Available The use of commercially available autonomous underwater vehicles (AUVs has increased during the last fifteen years. While they are mainly used for routine survey missions, there is a set of applications that nowadays can be only addressed by manned submersibles or work-class remotely operated vehicles (ROVs equipped with teleoperated arms: the intervention applications. To allow these heavy vehicles controlled by human operators to perform intervention tasks, underwater structures like observatory facilities, subsea panels or oil-well Christmas trees have been adapted, making them more robust and easier to operate. The TRITON Spanish founded project proposes the use of a light-weight intervention AUV (I-AUV to carry out intervention applications simplifying the adaptation of these underwater structures and drastically reducing the operational cost. To prove this concept, the Girona 500 I-AUV is used to autonomously dock into an adapted subsea panel and once docked perform an intervention composed of turning a valve and plugging in/unplugging a connector. The techniques used for the autonomous docking and manipulation as well as the design of an adapted subsea panel with a funnel-based docking system are presented in this article together with the results achieved in a water tank and at sea.

  10. 75 FR 49595 - Performance of Functions; Claims for Compensation Under the Federal Employees' Compensation Act...

    Science.gov (United States)

    2010-08-13

    ... Labor Office of Workers' Compensation Programs 20 CFR Parts 1, 10, and 25 Performance of Functions; Claims for Compensation Under the Federal Employees' Compensation Act; Compensation for Disability and... Workers' Compensation Programs 20 CFR Parts 1, 10, and 25 RIN 1240-AA03 Performance of Functions;...

  11. Tail Docking and Ear Cropping Dogs: Public Awareness and Perceptions.

    Directory of Open Access Journals (Sweden)

    Katelyn E Mills

    Full Text Available Tail docking and ear cropping are two surgical procedures commonly performed on many dog breeds. These procedures are classified as medically unnecessary surgeries whose purpose is primarily cosmetic. Available attitude research surrounding these controversial practices has been limited to surveys of veterinarians and dog breeders familiar with both practices. The aim of this project was to: 1 assess public awareness of tail docking and ear cropping, 2 determine whether physical alteration of a dog affects how the dog, and 3 owner are perceived. In Experiment 1 awareness was measured using a combination of both explicit and implicit measures. We found that 42% of participants (n = 810 were unable to correctly explain the reason why tail docked and ear cropped dogs had short ears and tails. Similarly, an implicit measure of awareness ('nature vs nurture task', found that the majority of participants believed short tails and erect ears were a consequence of genetics rather than something the owner or breeder had done. The results obtained in Experiment 2 (n = 392 provide evidence that ear cropped and tail docked dogs are perceived differently than an identical dog in its 'natural' state. Modified dogs were perceived as being more aggressive, more dominant, less playful and less attractive than natural dogs. Experiment 3 (n = 410 is the first evidence that owners of modified dogs are perceived as being more aggressive, more narcissistic, less playful, less talkative and less warm compared to owners of natural dogs. Taken together, these results suggest that although a significant proportion of subjects appear unaware of the practices of tail docking and ear cropping in dogs, these procedures have significant impacts on how modified dogs and their owners are perceived by others.

  12. Tail Docking and Ear Cropping Dogs: Public Awareness and Perceptions

    Science.gov (United States)

    Mills, Katelyn E.; Robbins, Jesse; von Keyserlingk, Marina A. G.

    2016-01-01

    Tail docking and ear cropping are two surgical procedures commonly performed on many dog breeds. These procedures are classified as medically unnecessary surgeries whose purpose is primarily cosmetic. Available attitude research surrounding these controversial practices has been limited to surveys of veterinarians and dog breeders familiar with both practices. The aim of this project was to: 1) assess public awareness of tail docking and ear cropping, 2) determine whether physical alteration of a dog affects how the dog, and 3) owner are perceived. In Experiment 1 awareness was measured using a combination of both explicit and implicit measures. We found that 42% of participants (n = 810) were unable to correctly explain the reason why tail docked and ear cropped dogs had short ears and tails. Similarly, an implicit measure of awareness (‘nature vs nurture task’), found that the majority of participants believed short tails and erect ears were a consequence of genetics rather than something the owner or breeder had done. The results obtained in Experiment 2 (n = 392) provide evidence that ear cropped and tail docked dogs are perceived differently than an identical dog in its ‘natural’ state. Modified dogs were perceived as being more aggressive, more dominant, less playful and less attractive than natural dogs. Experiment 3 (n = 410) is the first evidence that owners of modified dogs are perceived as being more aggressive, more narcissistic, less playful, less talkative and less warm compared to owners of natural dogs. Taken together, these results suggest that although a significant proportion of subjects appear unaware of the practices of tail docking and ear cropping in dogs, these procedures have significant impacts on how modified dogs and their owners are perceived by others. PMID:27348817

  13. Tail Docking and Ear Cropping Dogs: Public Awareness and Perceptions.

    Science.gov (United States)

    Mills, Katelyn E; Robbins, Jesse; von Keyserlingk, Marina A G

    2016-01-01

    Tail docking and ear cropping are two surgical procedures commonly performed on many dog breeds. These procedures are classified as medically unnecessary surgeries whose purpose is primarily cosmetic. Available attitude research surrounding these controversial practices has been limited to surveys of veterinarians and dog breeders familiar with both practices. The aim of this project was to: 1) assess public awareness of tail docking and ear cropping, 2) determine whether physical alteration of a dog affects how the dog, and 3) owner are perceived. In Experiment 1 awareness was measured using a combination of both explicit and implicit measures. We found that 42% of participants (n = 810) were unable to correctly explain the reason why tail docked and ear cropped dogs had short ears and tails. Similarly, an implicit measure of awareness ('nature vs nurture task'), found that the majority of participants believed short tails and erect ears were a consequence of genetics rather than something the owner or breeder had done. The results obtained in Experiment 2 (n = 392) provide evidence that ear cropped and tail docked dogs are perceived differently than an identical dog in its 'natural' state. Modified dogs were perceived as being more aggressive, more dominant, less playful and less attractive than natural dogs. Experiment 3 (n = 410) is the first evidence that owners of modified dogs are perceived as being more aggressive, more narcissistic, less playful, less talkative and less warm compared to owners of natural dogs. Taken together, these results suggest that although a significant proportion of subjects appear unaware of the practices of tail docking and ear cropping in dogs, these procedures have significant impacts on how modified dogs and their owners are perceived by others.

  14. Prediction of substrates for glutathione transferases by covalent docking.

    Science.gov (United States)

    Dong, Guang Qiang; Calhoun, Sara; Fan, Hao; Kalyanaraman, Chakrapani; Branch, Megan C; Mashiyama, Susan T; London, Nir; Jacobson, Matthew P; Babbitt, Patricia C; Shoichet, Brian K; Armstrong, Richard N; Sali, Andrej

    2014-06-23

    Enzymes in the glutathione transferase (GST) superfamily catalyze the conjugation of glutathione (GSH) to electrophilic substrates. As a consequence they are involved in a number of key biological processes, including protection of cells against chemical damage, steroid and prostaglandin biosynthesis, tyrosine catabolism, and cell apoptosis. Although virtual screening has been used widely to discover substrates by docking potential noncovalent ligands into active site clefts of enzymes, docking has been rarely constrained by a covalent bond between the enzyme and ligand. In this study, we investigate the accuracy of docking poses and substrate discovery in the GST superfamily, by docking 6738 potential ligands from the KEGG and MetaCyc compound libraries into 14 representative GST enzymes with known structures and substrates using the PLOP program [ Jacobson Proteins 2004 , 55 , 351 ]. For X-ray structures as receptors, one of the top 3 ranked models is within 3 Å all-atom root mean square deviation (RMSD) of the native complex in 11 of the 14 cases; the enrichment LogAUC value is better than random in all cases, and better than 25 in 7 of 11 cases. For comparative models as receptors, near-native ligand-enzyme configurations are often sampled but difficult to rank highly. For models based on templates with the highest sequence identity, the enrichment LogAUC is better than 25 in 5 of 11 cases, not significantly different from the crystal structures. In conclusion, we show that covalent docking can be a useful tool for substrate discovery and point out specific challenges for future method improvement.

  15. Autonomous Vision-Based Tethered-Assisted Rover Docking

    Science.gov (United States)

    Tsai, Dorian; Nesnas, Issa A.D.; Zarzhitsky, Dimitri

    2013-01-01

    Many intriguing science discoveries on planetary surfaces, such as the seasonal flows on crater walls and skylight entrances to lava tubes, are at sites that are currently inaccessible to state-of-the-art rovers. The in situ exploration of such sites is likely to require a tethered platform both for mechanical support and for providing power and communication. Mother/daughter architectures have been investigated where a mother deploys a tethered daughter into extreme terrains. Deploying and retracting a tethered daughter requires undocking and re-docking of the daughter to the mother, with the latter being the challenging part. In this paper, we describe a vision-based tether-assisted algorithm for the autonomous re-docking of a daughter to its mother following an extreme terrain excursion. The algorithm uses fiducials mounted on the mother to improve the reliability and accuracy of estimating the pose of the mother relative to the daughter. The tether that is anchored by the mother helps the docking process and increases the system's tolerance to pose uncertainties by mechanically aligning the mating parts in the final docking phase. A preliminary version of the algorithm was developed and field-tested on the Axel rover in the JPL Mars Yard. The algorithm achieved an 80% success rate in 40 experiments in both firm and loose soils and starting from up to 6 m away at up to 40 deg radial angle and 20 deg relative heading. The algorithm does not rely on an initial estimate of the relative pose. The preliminary results are promising and help retire the risk associated with the autonomous docking process enabling consideration in future martian and lunar missions.

  16. A combinatorial scoring function for protein-RNA docking.

    Science.gov (United States)

    Zhang, Zhao; Lu, Lin; Zhang, Yue; Hua Li, Chun; Wang, Cun Xin; Zhang, Xiao Yi; Tan, Jian Jun

    2017-04-01

    Protein-RNA docking is still an open question. One of the main challenges is to develop an effective scoring function that can discriminate near-native structures from the incorrect ones. To solve the problem, we have constructed a knowledge-based residue-nucleotide pairwise potential with secondary structure information considered for nonribosomal protein-RNA docking. Here we developed a weighted combined scoring function RpveScore that consists of the pairwise potential and six physics-based energy terms. The weights were optimized using the multiple linear regression method by fitting the scoring function to L_rmsd for the bound docking decoys from Benchmark II. The scoring functions were tested on 35 unbound docking cases. The results show that the scoring function RpveScore including all terms performs best. Also RpveScore was compared with the statistical mechanics-based method derived potential ITScore-PR, and the united atom-based statistical potentials QUASI-RNP and DARS-RNP. The success rate of RpveScore is 71.6% for the top 1000 structures and the number of cases where a near-native structure is ranked in top 30 is 25 out of 35 cases. For 32 systems (91.4%), RpveScore can find the binding mode in top 5 that has no lower than 50% native interface residues on protein and nucleotides on RNA. Additionally, it was found that the long-range electrostatic attractive energy plays an important role in distinguishing near-native structures from the incorrect ones. This work can be helpful for the development of protein-RNA docking methods and for the understanding of protein-RNA interactions. RpveScore program is available to the public at http://life.bjut.edu.cn/kxyj/kycg/2017116/14845362285362368_1.html Proteins 2017; 85:741-752. © 2016 Wiley Periodicals, Inc.

  17. Compensation for electrical converter nonlinearities

    Science.gov (United States)

    Perisic, Milun; Ransom, Ray M; Kajouke, Lateef A

    2013-11-19

    Systems and methods are provided for delivering energy from an input interface to an output interface. An electrical system includes an input interface, an output interface, an energy conversion module between the input interface and the output interface, an inductive element between the input interface and the energy conversion module, and a control module. The control module determines a compensated duty cycle control value for operating the energy conversion module to produce a desired voltage at the output interface and operates the energy conversion module to deliver energy to the output interface with a duty cycle that is influenced by the compensated duty cycle control value. The compensated duty cycle control value is influenced by the current through the inductive element and accounts for voltage across the switching elements of the energy conversion module.

  18. Adaptive Motion Compensation in Radiotherapy

    CERN Document Server

    Murphy, Martin J

    2011-01-01

    External-beam radiotherapy has long been challenged by the simple fact that patients can (and do) move during the delivery of radiation. Recent advances in imaging and beam delivery technologies have made the solution--adapting delivery to natural movement--a practical reality. Adaptive Motion Compensation in Radiotherapy provides the first detailed treatment of online interventional techniques for motion compensation radiotherapy. This authoritative book discusses: Each of the contributing elements of a motion-adaptive system, including target detection and tracking, beam adaptation, and pati

  19. Electronic amplifiers for automatic compensators

    CERN Document Server

    Polonnikov, D Ye

    1965-01-01

    Electronic Amplifiers for Automatic Compensators presents the design and operation of electronic amplifiers for use in automatic control and measuring systems. This book is composed of eight chapters that consider the problems of constructing input and output circuits of amplifiers, suppression of interference and ensuring high sensitivity.This work begins with a survey of the operating principles of electronic amplifiers in automatic compensator systems. The succeeding chapters deal with circuit selection and the calculation and determination of the principal characteristics of amplifiers, as

  20. Depth Compensated Spectral Domain Optical Coherence Tomography via Digital Compensation

    CERN Document Server

    Boroomand, Ameneh; Shafiee, Mohammad Javad; Bizheva, Kostadinka; Wong, Alexander

    2015-01-01

    Spectral Domain Optical Coherence Tomography (SD-OCT) is a well-known imaging modality which allows for \\textit{in-vivo} visualization of the morphology of different biological tissues at cellular level resolutions. The overall SD-OCT imaging quality in terms of axial resolution and Signal-to-Noise Ratio (SNR) degrades with imaging depth, while the lateral resolution degrades with distance from the focal plane. This image quality degradation is due both to the design of the SD-OCT imaging system and the optical properties of the imaged object. Here, we present a novel Depth Compensated SD-OCT (DC-OCT) system that integrates a Depth Compensating Digital Signal Processing (DC-DSP) module to improve the overall imaging quality via digital compensation. The designed DC-DSP module can be integrated to any SD-OCT system and is able to simultaneously compensate for the depth-dependent loss of axial and lateral resolutions, depth-varying SNR, as well as sidelobe artifact for improved imaging quality. The integrated D...

  1. No dry dock: safely strategy for avoiding unplanned dry dock and reducing safety, health and environment risks

    Energy Technology Data Exchange (ETDEWEB)

    Constantinis, Danny A.; Brett, David E. [EM and I Alliance, Cheshire (United Kingdom)

    2012-07-01

    There are currently over 150 operational FPUs with an expected increase of a further 100 units in the next 5 years. This results from several factors: increasing demand for hydrocarbons; new reserves in deep water; pipeline infrastructure is not required and FPU design fits many field requirements. FPUs are increasingly chosen for large, deep water, longer life developments. Units are bigger and more complex. Regulators and oil majors are imposing more stringent integrity requirements to protect against safety, environmental and operational risks related to loss of containment and loss of hull structure integrity which could lead to HSE risks, increased costs and production losses which would become particularly onerous should the unit have to dry dock. There are a number of other important components the context of asset integrity, e.g. mooring and sub sea systems, but these are outside the scope of this paper. The 'No Dry dock....Safely' approach is based on the principle of Criticality Based Integrity which identifies components whose integrity is critical to avoiding incidents and the risk of dry docking. Once critical components are identified the challenge is to establish integrity status and maintain fitness-for-service. Various JIPs e.g. the Hull Inspection Techniques and Strategies are looking at best practice inspection methodologies. The industry is progressing ways of maintaining and repairing critical items without going to dry dock. The challenges include coating maintenance, structural and pressure system repairs. Advances in cathodic protection and coating maintenance strategies are proving successful as are techniques for carrying out major structural repairs. The 'No Dry dock...Safely' methodology is a proven solution and case histories have been included. Technological advances will further improve integrity in the industry. There is no reason why FPUs cannot be kept on station and in production for 25 years or more whilst

  2. ATTRACT and PTools: open source programs for protein-protein docking.

    Science.gov (United States)

    Schneider, Sebastian; Saladin, Adrien; Fiorucci, Sébastien; Prévost, Chantal; Zacharias, Martin

    2012-01-01

    The prediction of the structure of protein-protein complexes based on structures or structural models of isolated partners is of increasing importance for structural biology and bioinformatics. The ATTRACT program can be used to perform systematic docking searches based on docking energy minimization. It is part of the object-oriented PTools library written in Python and C++. The library contains various routines to manipulate protein structures, to prepare and perform docking searches as well as analyzing docking results. It also intended to facilitate further methodological developments in the area of macromolecular docking that can be easily integrated. Here, we describe the application of PTools to perform systematic docking searches and to analyze the results. In addition, the possibility to perform multi-component docking will also be presented.

  3. Virtual fragment screening: an exploration of various docking and scoring protocols for fragments using Glide

    Science.gov (United States)

    Kawatkar, Sameer; Wang, Hongming; Czerminski, Ryszard; Joseph-McCarthy, Diane

    2009-08-01

    Fragment-based drug discovery approaches allow for a greater coverage of chemical space and generally produce high efficiency ligands. As such, virtual and experimental fragment screening are increasingly being coupled in an effort to identify new leads for specific therapeutic targets. Fragment docking is employed to create target-focussed subset of compounds for testing along side generic fragment libraries. The utility of the program Glide with various scoring schemes for fragment docking is discussed. Fragment docking results for two test cases, prostaglandin D2 synthase and DNA ligase, are presented and compared to experimental screening data. Self-docking, cross-docking, and enrichment studies are performed. For the enrichment runs, experimental data exists indicating that the docking decoys in fact do not inhibit the corresponding enzyme being examined. Results indicate that even for difficult test cases fragment docking can yield enrichments significantly better than random.

  4. Ongoing transients in carbonate compensation

    NARCIS (Netherlands)

    Boudreau, B.P.; Middelburg, J.J.; Hofmann, A.F.; Meysman, F.J.R.

    2010-01-01

    Uptake of anthropogenic CO2 is acidifying the oceans. Over the next 2000 years, this will modify the dissolution and preservation of sedimentary carbonate. By coupling new formulas for the positions of the calcite saturation horizon, zsat, the compensation depth, zcc, and the snowline, zsnow, to a b

  5. Compensation for oil pollution damage

    Science.gov (United States)

    Matugina, E. G.; Glyzina, T. S.; Kolbysheva, Yu V.; Klyuchnikov, A. S.; Vusovich, O. V.

    2015-11-01

    The commitment of national industries to traditional energy sources, as well as constantly growing energy demand combined with adverse environmental impact of petroleum production and transportation urge to establish and maintain an appropriate legal and administrative framework for oil pollution damage compensation. The article considers management strategies for petroleum companies that embrace not only production benefits but also environmental issues.

  6. Can Education Compensate for Society?

    Science.gov (United States)

    Pring, Richard

    2011-01-01

    The extent to which education can compensate for social disadvantage is a matter of political controversy, especially in the context of policies for social mobility. On the one hand, to blame poor achievement on social class or poverty was seen to dodge the professional responsibility of teachers. On the other, the strong correlation between…

  7. Working conditions, compensation and absenteeism.

    Science.gov (United States)

    Ose, Solveig Osborg

    2005-01-01

    This paper examines absence behaviour in relation to the working environment. A theoretical model is built in order to separate the effects of voluntary absences and absences related to ill health, where health effects are assumed to be tied to working conditions. This model is based on the Shapiro and Stiglitz efficiency wage model. In addition, work environment is introduced as a part of the compensation package. The model gives a testable hypothesis of compensating wage differentials. A panel of quarterly firm level data from 1990 to 1998 are used and the theoretical model is supported by the empirical findings. The result indicates that the workers may not be fully compensated when experiencing high levels of noise in the work area, or when the job involves a high degree of monotonous work, heavy or frequent lifting or poor work postures. Ill health, and thus increased long-term absence, is not highly related to economic variables. However, long-term absence is relatively higher if the firm is troubled with many accidents or near misses. In addition, disamenities for which workers are not fully compensated cause ill health and increased long-term absence.

  8. Design of an Automatic Autonomous Mini Prone-cone Microsatellite Docking Mechanism

    Institute of Scientific and Technical Information of China (English)

    LAI Yinan; DAI Ye; TIAN Hao; ZHANG Dawei

    2010-01-01

    The capability of docking, refueling, repairing, and updating microsatellites using automatic autonomous vehicles will be of significance critical value for design and operation of several space systems in the near feature. Automatic docking capability was successfully tested by many institutions such as National Space Development Agency in Japan, European Space Agency, National Aeronautics and Space Administration in USA, etc. However, there is still much more space for improvement of degree of automation during the process of docking with large deviations of the initial attitude. A novel automatic autonomous probe-cone docking mechanism used for microsatellite docking is proposed. This docking mechanism is designed according to the design indices such as miniaturization, degree of automation and automatic capture capability within large deviation of the initial attitude. On the basis of the virtual work principle, the dynamics modeling of the docking process is presented. The position of the contact point is then analyzed. Comprehensive system level simulation is conducted in the 13 kinds of typical operating conditions with the initial deviations. Capture performance is analyzed. The simulation results show that the docking mechanism can be smoothly captured within 2 s in all cases of large attitude deviation between the active and passive spacecrafts. A virtual prototype model of the docking mechanism is established through ADAMS for further verifying the correctness of the buffer parameter model and the autonomous docking capability. A laboratory platform is designed for on-the-ground experimental validation of the property of mini probe-cone docking mechanism. Repeated docking tests prove the proposed design of the mini probe-cone docking mechanism system for its high reliability, and automatic capture capability within large attitude range. The kinetic model of the docking capture process and the mechanism structure could provide some References for similar

  9. Communications, tracking, and docking on the Space Station

    Science.gov (United States)

    Erwin, H. O.; Coden, M. H.; Scholl, F. W.

    1982-01-01

    Many of the communications, tracking, and docking functions on a large manned orbiting Space Station - one that is modular and made of metal - will have to be performed by optical systems out of necessity. This paper discusses four practical approaches to accomplishing Space Station functions using optical communications technology. It also provides the results of preliminary experiments involved in the design of particular systems. Major operational factors considered in each system design include: (a) electromagnetic interference problems, (b) data bandwidth requirements, (c) zero-gravity operations, (d) free-space operations, (e) data security, and (f) modular expansion of the Space Station structure. The technologies discussed are the following: (a) local infrared communications, (b) optical tracking and docking techniques, (c) long distance free space optical communications, and (d) local area optical networks.

  10. Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker

    Directory of Open Access Journals (Sweden)

    Maryam Iman

    2013-09-01

    Full Text Available   Objective(s: Recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. Therefore, in the present study, a series of 19 compounds of phthalimide pharmacophore possessing a variety of substituents (NO2, NH2 , Me, Cl, COOH, MeO at 2-, 3-, and 4- position of the N-phenyl ring and N-(3-amino-2-methylphenyl succinimide, were subjected to docking studies in order to inhibit voltage-gated sodium channels.   Materials and Methods : Chemical structures of all compounds were designed using HYPERCHEM program and Conformational studies were performed through semi-empirical molecular orbital calculations method followed by PM3 force field. Total energy gradient calculated as a root mean square (RMS value, until the RMS gradient was 0.01 kcal mol-1. Among all energy minima conformers, the global minimum of compounds was used in docking calculations. Using a model of the open pore of Na channels, docking study was performed by AUTODOCK4.2 program. Results : Docking studies have revealed that these types of ligands interacted mainly with II-S6 residues of NaV1.2 through making hydrogen bonds and have additional hydrophobic interactions with domain I, II, III and IV in the channel's inner pore. Conclusion   : These computational studies have displayed that these compounds are capable of inhibiting Na channel, efficiently.

  11. Genetic, Clinical, and Laboratory Markers for DOCK8 Immunodeficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Jeremiah C. Davis

    2010-01-01

    Full Text Available DOCK8 immunodeficiency syndrome (DIDS is a combined immunodeficiency characterized by recurrent viral infections, severe atopy, and early onset malignancy. Genetic studies revealed large, unique deletions in patients from different families and ethnic backgrounds. Clinical markers of DIDS include atopic dermatitis, allergies, cutaneous viral infections, recurrent respiratory tract infections, and malignancy. Immune assessments showed T cell lymphopenia, hyper-IgE, hypo-IgM, and eosinophilia. The impaired lymphocyte functions in DIDS patients appear central for disease pathogenesis.

  12. Ultrafast de novo docking combining pharmacophores and combinatorics.

    Science.gov (United States)

    Gastreich, Marcus; Lilienthal, Markus; Briem, Hans; Claussen, Holger

    2006-12-01

    We report on a successful de novo design approach which relies on the combination of multi-million compound combinatorial docking under receptor-based pharmacophore constraints. Inspired by a rationale by A.R. Leach et al., we document on the unification of two steps into one for ligand assembly. In the original work, fragments known to bind in protein active sites were connected forming novel ligand compounds by means of generic skeleton linkers and following a combinatorial approach. In our approach, the knowledge of fragments binding to the protein has been expressed in terms of a receptor-based pharmacophore definition. The combinatorial linking step is performed in situ during docking, starting from combinatorial libraries. Three sample scenarios growing in size and complexity (combinatorial libraries of 1 million, 1.3 million, and 22.4 million compounds) have been created to illustrate the method. Docking could be accomplished between minutes and several hours depending on the outset; the results were throughout promising. Technically, a module compatibility between FlexX(C) and FlexX-Pharm has been established. The background is explained, and the crucial points from an information scientist's perspective are highlighted.

  13. Molecular Docking and Structure-Based Drug Design Strategies

    Directory of Open Access Journals (Sweden)

    Leonardo G. Ferreira

    2015-07-01

    Full Text Available Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  14. In silico docking analysis of piperine with cyclooxygenases

    Directory of Open Access Journals (Sweden)

    Prashantha Karunakar

    2012-08-01

    Full Text Available The structure of 1-[5-(1,3-benzodioxol- 5-yl-1-oxo-2,4-pentadienyl]piperidine (Piperine, C17H19O3N, a versatile bioactive molecule has been redetermined at 100(2 K by X-raycrystallography to explore their potential utilization in inhibition of prostaglandin release. The crystal structure is stabilized by weaknonclassical intermolecular C-H…O hydrogen bonds and also intermolecular C-H…π interactions. The crystallographiccoordinates of the compound were extrapolated to docking studies to elucidate the action of piperine against the enzymes,cyclooxygenases (COX-1 and COX-2 involved in biosynthesis of prostaglandin release. Using AutoDock suite, piperine was docked at the binding site of COX-1 and COX-2 enzyme and a strong affinity (-9.06kcal/mol, Ki =227.73nM and -8.77kcal/mol, Ki = 375.62nM, respectively was formed by Hydrogen bonds and hydrophobic interactions. These results suggest that piperine can be a promising lead for the development of COX family inhibitors.

  15. Comparison of neural histomorphology in tail tips from pigs docked using clippers or cautery iron.

    Science.gov (United States)

    Kells, N J; Beausoleil, N J; Johnson, C B; Sutherland, M A; Morrison, R S; Roe, W

    2016-12-01

    Tail docking of pigs is commonly performed to reduce the incidence of unwanted tail-biting behaviour. Two docking methods are commonly used: blunt trauma cutting (i.e. using side clippers), or cutting and concurrent cauterisation using a hot cautery iron. A potential consequence of tail amputation is the development of neuromas at the docking site. Neuromas have been linked to neuropathic pain, which can influence the longer-term welfare of affected individuals. To determine whether method of tail docking influences the extent of neuroma formation, 75 pigs were allocated to one of three treatments at birth: tail docked using clippers; tail docked using cautery iron; tail left intact. Tail docking was performed at 2 days of age and pigs were kept under conventional conditions until slaughter at 21 weeks of age. Tails were removed following slaughter and subjected to histological examination. Nerve histomorphology was scored according to the following scale: 1=discrete well-organised nerve bundles; 2=moderate neural proliferation and disorganisation affecting more than half of the circumference of the tail; 3=marked neural proliferation to form almost continuous disorganised bundles or non-continuous enlarged bundles compressing the surrounding connective tissue. Scores of 2 or 3 indicated neuroma formation. Scores were higher in docked pigs than undocked pigs (Pclippers and those docked using cautery (P=0.23). The results indicate that tail docking using either clippers or cautery results in neuroma formation, thus having the potential to affect long-term pig welfare.

  16. A New Approach for Flexible Molecular Docking Based on Swarm Intelligence

    Directory of Open Access Journals (Sweden)

    Yi Fu

    2015-01-01

    Full Text Available Molecular docking methods play an important role in the field of computer-aided drug design. In the work, on the basis of the molecular docking program AutoDock, we present QLDock as a tool for flexible molecular docking. For the energy evaluation, the algorithm uses the binding free energy function that is provided by the AutoDock 4.2 tool. The new search algorithm combines the features of a quantum-behaved particle swarm optimization (QPSO algorithm and local search method of Solis and Wets for solving the highly flexible protein-ligand docking problem. We compute the interaction of 23 protein-ligand complexes and compare the results with those of the QDock and AutoDock programs. The experimental results show that our approach leads to substantially lower docking energy and higher docking precision in comparison to Lamarckian genetic algorithm and QPSO algorithm alone. QPSO-ls algorithm was able to identify the correct binding mode of 74% of the complexes. In comparison, the accuracy of QPSO and LGA is 52% and 61%, respectively. This difference in performance rises with increasing complexity of the ligand. Thus, the novel algorithm QPSO-ls may be used to dock ligand with many rotatable bonds with high accuracy.

  17. 16 CFR 16.16 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Compensation. 16.16 Section 16.16 Commercial... MANAGEMENT § 16.16 Compensation. (a) Committee members. Unless otherwise provided by law, the Commission... cost to the Commission. The compensation to be paid to such consultant may not exceed the maximum...

  18. 75 FR 76079 - Sound Incentive Compensation Guidance

    Science.gov (United States)

    2010-12-07

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0129. Form Number: N/A... compensation arrangements at a financial institution do not encourage employees to take excessive risks....

  19. 45 CFR 1604.5 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Compensation. 1604.5 Section 1604.5 Public Welfare... Compensation. (a) Except as provided in paragraph (b) of this section and § 1604.7(a), a recipient's written policies shall not permit a full-time attorney to receive any compensation for the outside practice of...

  20. 34 CFR 106.54 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Compensation. 106.54 Section 106.54 Education... Compensation. A recipient shall not make or enforce any policy or practice which, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages...

  1. 6 CFR 17.515 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Compensation. 17.515 Section 17.515 Domestic... in Employment in Education Programs or Activities Prohibited § 17.515 Compensation. A recipient shall... of pay or other compensation; (b) Results in the payment of wages to employees of one sex at a...

  2. 22 CFR 146.515 - Compensation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Compensation. 146.515 Section 146.515 Foreign... Education Programs or Activities Prohibited § 146.515 Compensation. A recipient shall not make or enforce... compensation; (b) Results in the payment of wages to employees of one sex at a rate less than that paid...

  3. 32 CFR 196.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Compensation. 196.515 Section 196.515 National... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  4. 41 CFR 101-4.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Compensation. 101-4.515... Employment in Education Programs or Activities Prohibited § 101-4.515 Compensation. A recipient shall not... pay or other compensation; (b) Results in the payment of wages to employees of one sex at a rate...

  5. 45 CFR 618.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Compensation. 618.515 Section 618.515 Public... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  6. 24 CFR 3.515 - Compensation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Compensation. 3.515 Section 3.515... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  7. 10 CFR 5.515 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Compensation. 5.515 Section 5.515 Energy NUCLEAR... Activities Prohibited § 5.515 Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in...

  8. 45 CFR 86.54 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Compensation. 86.54 Section 86.54 Public Welfare... in Employment in Education Programs or Activities Prohibited § 86.54 Compensation. A recipient shall... of pay or other compensation; (b) Results in the payment of wages to employees of one sex at a...

  9. 7 CFR 15a.54 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Compensation. 15a.54 Section 15a.54 Agriculture Office... Activities Prohibited § 15a.54 Compensation. A recipient shall not make or enforce any policy or practice which, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results...

  10. 13 CFR 113.515 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Compensation. 113.515 Section 113... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  11. 22 CFR 229.515 - Compensation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Compensation. 229.515 Section 229.515 Foreign... in Education Programs or Activities Prohibited § 229.515 Compensation. A recipient shall not make or... compensation; (b) Results in the payment of wages to employees of one sex at a rate less than that paid...

  12. 18 CFR 1317.515 - Compensation.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Compensation. 1317.515... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  13. 47 CFR 51.221 - Reciprocal compensation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Reciprocal compensation. 51.221 Section 51.221... Obligations of All Local Exchange Carriers § 51.221 Reciprocal compensation. The rules governing reciprocal compensation are set forth in subpart H of this part....

  14. 45 CFR 2555.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Compensation. 2555.515 Section 2555.515 Public... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  15. 43 CFR 41.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Compensation. 41.515 Section 41.515 Public... in Employment in Education Programs or Activities Prohibited § 41.515 Compensation. A recipient shall... of pay or other compensation; (b) Results in the payment of wages to employees of one sex at a...

  16. 48 CFR 836.577 - Workers' compensation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Workers' compensation. 836.577 Section 836.577 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SPECIAL...' compensation. The contracting officer shall insert the clause at 852.236-86, Workers' compensation,...

  17. 49 CFR 25.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Compensation. 25.515 Section 25.515 Transportation... Education Programs or Activities Prohibited § 25.515 Compensation. A recipient shall not make or enforce any... compensation; (b) Results in the payment of wages to employees of one sex at a rate less than that paid...

  18. 38 CFR 23.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Compensation. 23.515... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  19. 29 CFR 36.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Compensation. 36.515 Section 36.515 Labor Office of the... Activities Prohibited § 36.515 Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results...

  20. 15 CFR 8a.515 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Compensation. 8a.515 Section 8a.515... in Employment in Education Programs or Activities Prohibited § 8a.515 Compensation. A recipient shall... of pay or other compensation; (b) Results in the payment of wages to employees of one sex at a...

  1. 75 FR 22679 - Sound Incentive Compensation Guidance

    Science.gov (United States)

    2010-04-29

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0NEW. Form Number: N/A... compensation arrangements at a financial institution do not encourage employees to take excessive risks....

  2. 36 CFR 1211.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Compensation. 1211.515... Prohibited § 1211.515 Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the...

  3. 33 CFR 5.55 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Compensation. 5.55 Section 5.55 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL COAST GUARD AUXILIARY § 5.55 Compensation. No member of the Auxiliary shall receive any compensation for his services as...

  4. 45 CFR 1607.5 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Compensation. 1607.5 Section 1607.5 Public Welfare... Compensation. (a) While serving on the governing body of a recipient, no attorney member shall receive compensation from that recipient, but any member may receive a reasonable per diem expense payment...

  5. 10 CFR 1042.515 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Compensation. 1042.515 Section 1042.515 Energy DEPARTMENT... Education Programs or Activities Prohibited § 1042.515 Compensation. A recipient shall not make or enforce... compensation; (b) Results in the payment of wages to employees of one sex at a rate less than that paid...

  6. Dynamic Phase Compensation of wind turbines

    DEFF Research Database (Denmark)

    Soerensen, P.; Skaarup, J.; Iov, Florin

    2004-01-01

    This paper describes a dynamic phase compensation unit for a wind turbine with directly connected induction generators. The compensation unit is based on thyristor switched capacitors, where conventional wind turbine compensations use mechanical contactors to switch the capacitors. The unit modul...

  7. 12 CFR 620.31 - Compensation committees.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Compensation committees. 620.31 Section 620.31 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DISCLOSURE TO SHAREHOLDERS Bank and Association Audit and Compensation Committees § 620.31 Compensation committees. Each Farm Credit bank...

  8. 77 FR 4885 - Patent Compensation Board Regulations

    Science.gov (United States)

    2012-02-01

    ... Part 780 RIN 1990-AA33 Patent Compensation Board Regulations AGENCY: Office of the General Counsel... Patent ] Compensation Board regulations to provide that the Secretary of Energy, or a person acting in that position, shall appoint, as needed, a three member panel to serve as the Patent Compensation...

  9. Scheduling trucks in cross docking systems with temporary storage and dock repeat truck holding pattern using GRASP method

    Directory of Open Access Journals (Sweden)

    Hassan Javanshir

    2012-10-01

    Full Text Available Cross docking play an important role in management of supply chains where items delivered to a warehouse by inbound trucks are directly sorted out, reorganized based on customer demands, routed and loaded into outbound trucks for delivery to customers without virtually keeping them at the warehouse. If any item is held in storage, it is usually for a short time, which is normally less than 24 hours. The proposed model of this paper considers a special case of cross docking where there is temporary storage and uses GRASP technique to solve the resulted problem for some realistic test problems. In our method, we first use some heuristics as initial solutions and then improve the final solution using GRASP method. The preliminary test results indicate that the GRASP method performs better than alternative solution strategies.

  10. 76 FR 37897 - Performance of Functions; Claims for Compensation Under the Federal Employees' Compensation Act...

    Science.gov (United States)

    2011-06-28

    ..., Office of Workers' Compensation Programs, Federal Employees' Compensation Act File, 67 FR 16826 (April 8... Office of Workers' Compensation Programs (OWCP) by Employment Standards Order No. 2-74 (39 FR 34722). The... Programs (37 FR 20533) and an Office of Federal Employees' Compensation (37 FR 22979). In 1974, these...

  11. 75 FR 66589 - Shareholder Approval of Executive Compensation and Golden Parachute Compensation

    Science.gov (United States)

    2010-10-28

    ... cash compensation, golden parachute policy, severance or other aspects of compensation.'' See Report of... compensation policies and practices as they relate to risk management and risk-taking incentives, these... extent that risk considerations are a material aspect of the issuer's compensation policies or...

  12. Docking validation resources: protein family and ligand flexibility experiments.

    Science.gov (United States)

    Mukherjee, Sudipto; Balius, Trent E; Rizzo, Robert C

    2010-11-22

    A database consisting of 780 ligand-receptor complexes, termed SB2010, has been derived from the Protein Databank to evaluate the accuracy of docking protocols for regenerating bound ligand conformations. The goal is to provide easily accessible community resources for development of improved procedures to aid virtual screening for ligands with a wide range of flexibilities. Three core experiments using the program DOCK, which employ rigid (RGD), fixed anchor (FAD), and flexible (FLX) protocols, were used to gauge performance by several different metrics: (1) global results, (2) ligand flexibility, (3) protein family, and (4) cross-docking. Global spectrum plots of successes and failures vs rmsd reveal well-defined inflection regions, which suggest the commonly used 2 Å criteria is a reasonable choice for defining success. Across all 780 systems, success tracks with the relative difficulty of the calculations: RGD (82.3%) > FAD (78.1%) > FLX (63.8%). In general, failures due to scoring strongly outweigh those due to sampling. Subsets of SB2010 grouped by ligand flexibility (7-or-less, 8-to-15, and 15-plus rotatable bonds) reveal that success degrades linearly for FAD and FLX protocols, in contrast to RGD, which remains constant. Despite the challenges associated with FLX anchor orientation and on-the-fly flexible growth, success rates for the 7-or-less (74.5%) and, in particular, the 8-to-15 (55.2%) subset are encouraging. Poorer results for the very flexible 15-plus set (39.3%) indicate substantial room for improvement. Family-based success appears largely independent of ligand flexibility, suggesting a strong dependence on the binding site environment. For example, zinc-containing proteins are generally problematic, despite moderately flexible ligands. Finally, representative cross-docking examples, for carbonic anhydrase, thermolysin, and neuraminidase families, show the utility of family-based analysis for rapid identification of particularly good or bad

  13. Ground Demonstration on the Autonomous Docking of Two 3U CubeSats Using a Novel Permanent-Magnet Docking Mechanism

    Science.gov (United States)

    Pei, Jing; Murchison, Luke; BenShabat, Adam; Stewart, Victor; Rosenthal, James; Follman, Jacob; Branchy, Mark; Sellers, Drew; Elandt, Ryan; Elliott, Sawyer; Choueiri, Marc; Finch, Peter

    2017-01-01

    Small spacecraft autonomous rendezvous and docking is an essential technology for future space structure assembly missions. A novel magnetic capture and latching mechanism is analyzed that allows for docking of two CubeSats without precise sensors and actuators. The proposed magnetic docking hardware not only provides the means to latch the CubeSats but it also significantly increases the likelihood of successful docking in the presence of relative attitude and position errors. The simplicity of the design allows it to be implemented on many CubeSat rendezvous missions. A CubeSat 3-DOF ground demonstration effort is on-going at NASA Langley Research Center that enables hardware-in-the loop testing of the autonomous approach and docking of a follower CubeSat to an identical leader CubeSat. The test setup consists of a 3 meter by 4 meter granite table and two nearly frictionless air bearing systems that support the two CubeSats. Four cold-gas on-off thrusters are used to translate the follower towards the leader, while a single reaction wheel is used to control the attitude of each CubeSat. An innovative modified pseudo inverse control allocation scheme was developed to address interactions between control effectors. The docking procedure requires relatively high actuator precision, a novel minimal impulse bit mitigation algorithm was developed to minimize the undesirable deadzone effects of the thrusters. Simulation of the ground demonstration shows that the Guidance, Navigation, and Control system along with the docking subsystem leads to successful docking under 3-sigma dispersions for all key system parameters. Extensive simulation and ground testing will provide sufficient confidence that the proposed docking mechanism along with the choosen suite of sensors and actuators will perform successful docking in the space environment.

  14. Dynamical compensation in physiological circuits.

    Science.gov (United States)

    Karin, Omer; Swisa, Avital; Glaser, Benjamin; Dor, Yuval; Alon, Uri

    2016-11-08

    Biological systems can maintain constant steady-state output despite variation in biochemical parameters, a property known as exact adaptation. Exact adaptation is achieved using integral feedback, an engineering strategy that ensures that the output of a system robustly tracks its desired value. However, it is unclear how physiological circuits also keep their output dynamics precise-including the amplitude and response time to a changing input. Such robustness is crucial for endocrine and neuronal homeostatic circuits because they need to provide a precise dynamic response in the face of wide variation in the physiological parameters of their target tissues; how such circuits compensate their dynamics for unavoidable natural fluctuations in parameters is unknown. Here, we present a design principle that provides the desired robustness, which we call dynamical compensation (DC). We present a class of circuits that show DC by means of a nonlinear feedback loop in which the regulated variable controls the functional mass of the controlling endocrine or neuronal tissue. This mechanism applies to the control of blood glucose by insulin and explains several experimental observations on insulin resistance. We provide evidence that this mechanism may also explain compensation and organ size control in other physiological circuits.

  15. Compensation Techniques in Accelerator Physics

    Energy Technology Data Exchange (ETDEWEB)

    Sayed, Hisham Kamal [Old Dominion Univ., Norfolk, VA (United States)

    2011-05-01

    Accelerator physics is one of the most diverse multidisciplinary fields of physics, wherein the dynamics of particle beams is studied. It takes more than the understanding of basic electromagnetic interactions to be able to predict the beam dynamics, and to be able to develop new techniques to produce, maintain, and deliver high quality beams for different applications. In this work, some basic theory regarding particle beam dynamics in accelerators will be presented. This basic theory, along with applying state of the art techniques in beam dynamics will be used in this dissertation to study and solve accelerator physics problems. Two problems involving compensation are studied in the context of the MEIC (Medium Energy Electron Ion Collider) project at Jefferson Laboratory. Several chromaticity (the energy dependence of the particle tune) compensation methods are evaluated numerically and deployed in a figure eight ring designed for the electrons in the collider. Furthermore, transverse coupling optics have been developed to compensate the coupling introduced by the spin rotators in the MEIC electron ring design.

  16. PMD compensation based on a new type dynamic first-order PMD compensator

    Institute of Scientific and Technical Information of China (English)

    Jiajun Wang; Shilong Pan; Jia Jia; Yanfu Yang; Caiyun Lou

    2006-01-01

    @@ A dynamic first-order polarization mode dispersion (PMD) compensator based on garnet and yttrium vanadate crystal has been proposed and implemented. Consisting of a differential group delay (DGD) generator and a Faraday rotator (FR), this PMD compensator has only two degrees of freedom. Feedback control and compensation algorithm are both very simple. Experimental results reveal the compensator behaviors to be excellent for PMD compensation in 40-Gb/s optical time domain multiplexing (OTDM)system.

  17. In Pursuit of Fully Flexible Protein-Ligand Docking: Modeling the Bilateral Mechanism of Binding.

    Science.gov (United States)

    Henzler, Angela M; Rarey, Matthias

    2010-03-15

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

  18. Androgynous, Reconfigurable Closed Loop Feedback Controlled Low Impact Docking System With Load Sensing Electromagnetic Capture Ring

    Science.gov (United States)

    Lewis, James L. (Inventor); Carroll, Monty B. (Inventor); Morales, Ray H. (Inventor); Le, Thang D. (Inventor)

    2002-01-01

    The present invention relates to a fully androgynous, reconfigurable closed loop feedback controlled low impact docking system with load sensing electromagnetic capture ring. The docking system of the present invention preferably comprises two Docking- assemblies, each docking assembly comprising a load sensing ring having an outer face, one of more electromagnets, one or more load cells coupled to said load sensing ring. The docking assembly further comprises a plurality of actuator arms coupled to said load sensing ring and capable of dynamically adjusting the orientation of said load sensing ring and a reconfigurable closed loop control system capable of analyzing signals originating from said plurality of load cells and of outputting real time control for each of the actuators. The docking assembly of the present invention incorporates an active load sensing system to automatically dynamically adjust the load sensing ring during capture instead of requiring significant force to push and realign the ring.

  19. Molecular docking for thrombolytic activity of some isolated compounds from Clausena lansium.

    Directory of Open Access Journals (Sweden)

    Arkajyoti Paul

    2017-03-01

    Full Text Available Clausena lansium (Family- Rutaceae is commonly known as wampee, is found in fallow lands throughout Bangladesh. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Clausena lansium, namely Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol for searching of lead molecule for thrombolytic activity. A wide range of docking score found during molecular docking by Schrodinger. Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol showed the docking score -6.926, -4.041, -4.889 , -4.356, -3.007 and -5.816 respectively. Among all the compounds Clausemarin B showed the best docking score. So, Clausemarin B is the best compounds for thrombolytic activity, as it possessed the best value in Molecular docking. Further in vivo investigation need to identify the thrombolytic activity of isolated compounds from Clausena lansium.

  20. 78 FR 68867 - Division of Longshore and Harbor Workers' Compensation

    Science.gov (United States)

    2013-11-15

    ... of Workers' Compensation Programs Division of Longshore and Harbor Workers' Compensation Proposed... Office of Workers' Compensation (OWCP) is soliciting comments concerning the proposed collection...). SUPPLEMENTARY INFORMATION: I. Background: The Office of Workers' Compensation Programs, (OWCP) administers...

  1. ASTP crewmen in Docking Module trainer during training session at JSC

    Science.gov (United States)

    1975-01-01

    An interior view of the Docking Module trainer in bldg 35 during Apollo Soyuz Test Project (ASTP) joint crew training at JSC. Astronaut Donald K. Slayton (right) is the docking module pilot of the American ASTP prime crew. The other man is Cosmonaut Valeriy N. Kubasov, engineer on the Soviet ASTP first (prime) crew. The training session simulated activities on the second day in space. The Docking module is designed to link the Apollo and Soyuz spacecraft.

  2. Effects of protein conformation in docking: improved pose prediction through protein pocket adaptation.

    Science.gov (United States)

    Jain, Ajay N

    2009-06-01

    Computational methods for docking ligands have been shown to be remarkably dependent on precise protein conformation, where acceptable results in pose prediction have been generally possible only in the artificial case of re-docking a ligand into a protein binding site whose conformation was determined in the presence of the same ligand (the "cognate" docking problem). In such cases, on well curated protein/ligand complexes, accurate dockings can be returned as top-scoring over 75% of the time using tools such as Surflex-Dock. A critical application of docking in modeling for lead optimization requires accurate pose prediction for novel ligands, ranging from simple synthetic analogs to very different molecular scaffolds. Typical results for widely used programs in the "cross-docking case" (making use of a single fixed protein conformation) have rates closer to 20% success. By making use of protein conformations from multiple complexes, Surflex-Dock yields an average success rate of 61% across eight pharmaceutically relevant targets. Following docking, protein pocket adaptation and rescoring identifies single pose families that are correct an average of 67% of the time. Consideration of the best of two pose families (from alternate scoring regimes) yields a 75% mean success rate.

  3. Hypomorphic function and somatic reversion of DOCK8 cause combined immunodeficiency without hyper-IgE.

    Science.gov (United States)

    Kienzler, Anne-Kathrin; van Schouwenburg, Pauline A; Taylor, John; Marwah, Ishita; Sharma, Richa U; Noakes, Charlotte; Thomson, Kate; Sadler, Ross; Segal, Shelley; Ferry, Berne; Taylor, Jenny C; Blair, Edward; Chapel, Helen; Patel, Smita Y

    2016-02-01

    Loss-of-function mutations in DOCK8 are linked to hyper-IgE syndrome. Patients typically present with recurrent sinopulmonary infections, severe cutaneous viral infections, food allergies and elevated serum IgE. Although patients may present with a spectrum of disease-related symptoms, molecular mechanisms explaining phenotypic variability in patients are poorly defined. Here we characterized a novel compound heterozygous mutation in DOCK8 in a patient diagnosed with primary combined immunodeficiency which was not typical of classical DOCK8 deficiency. In contrast to previously identified mutations in DOCK8 which result in complete loss of function, the newly identified single nucleotide insertion results in expression of a truncated DOCK8 protein. Functional evaluation of the truncated DOCK8 protein revealed its hypomorphic function. In addition we found somatic reversion of DOCK8 predominantly in T cells. The combination of somatic reversion and hypomorphic DOCK8 function explains the milder and atypical phenotype of the patient and further broadens the spectrum of DOCK8-associated disease.

  4. Molecular Recognition Analyzed by Docking Simulations: The Aspartate Receptor and Isocitrate Dehydrogenase from Escherichia coli

    Science.gov (United States)

    Stoddard, Barry L.; Koshland, Daniel E., Jr.

    1993-02-01

    Protein docking protocols are used for the prediction of both small molecule binding to DNA and protein macromolecules and of complexes between macromolecules. These protocols are becoming increasingly automated and powerful tools for computer-aided drug design. We review the basic methodologies and strategies used for analyzing molecular recognition by computer docking algorithms and discuss recent experiments in which (i) substrate and substrate analogues are docked to the active site of isocitrate dehydrogenase and (ii) maltose binding protein is docked to the extracellular domain of the receptor, which signals maltose chemotaxis.

  5. SPACECRAFT DOCKING SIMULATION USING HARDWARE-IN-THE-LOOP SIMULATOR WITH STEWART PLATFORM

    Institute of Scientific and Technical Information of China (English)

    Huang Qitao; Jiang Hongzhou; Zhang Shangying; Han Junwei

    2005-01-01

    A ground-based hardware-in-the-loop (HIL) simulation system with hydraulically driven Stewart platform for spacecraft docking simulation is presented. The system is used for simulating docking process of the on-orbit spacecraft. Principle and structure of the six-degree-of-freedom simulation system are introduced. The docking process dynamic of the vehicles is modeled. Experiment results and mathematical simulation data are compared to validating the simulation system. The comparisons of the results prove that the simulation system proposed can effectively simulate the on-orbit docking process of the spacecraft.

  6. Ligand pose and orientational sampling in molecular docking.

    Directory of Open Access Journals (Sweden)

    Ryan G Coleman

    Full Text Available Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys-Enhanced (DUD-E benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20,000 molecular orientations in the binding site (and so from about 1×10(10 to 4×10(10 to 1×10(11 to 2×10(11 to 5×10(11 mean atoms scored per target, since multiple conformations are sampled per orientation, the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.

  7. Solving Molecular Docking Problems with Multi-Objective Metaheuristics

    Directory of Open Access Journals (Sweden)

    María Jesús García-Godoy

    2015-06-01

    Full Text Available Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II, speed modulation multi-objective particle swarm optimization (SMPSO, third evolution step of generalized differential evolution (GDE3, multi-objective evolutionary algorithm based on decomposition (MOEA/D and S-metric evolutionary multi-objective optimization (SMS-EMOA. We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA provided by the AutoDock tool. Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery.

  8. Solving molecular docking problems with multi-objective metaheuristics.

    Science.gov (United States)

    García-Godoy, María Jesús; López-Camacho, Esteban; García-Nieto, José; Aldana-Montes, Antonio J Nebroand José F

    2015-06-02

    Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II), speed modulation multi-objective particle swarm optimization (SMPSO), third evolution step of generalized differential evolution (GDE3), multi-objective evolutionary algorithm based on decomposition (MOEA/D) and S-metric evolutionary multi-objective optimization (SMS-EMOA). We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA) provided by the AutoDock tool). Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery.

  9. DC-Compensated Current Transformer.

    Science.gov (United States)

    Ripka, Pavel; Draxler, Karel; Styblíková, Renata

    2016-01-20

    Instrument current transformers (CTs) measure AC currents. The DC component in the measured current can saturate the transformer and cause gross error. We use fluxgate detection and digital feedback compensation of the DC flux to suppress the overall error to 0.15%. This concept can be used not only for high-end CTs with a nanocrystalline core, but it also works for low-cost CTs with FeSi cores. The method described here allows simultaneous measurements of the DC current component.

  10. Docking study of HIV-1 reverse transcriptase with phytochemicals.

    Science.gov (United States)

    Seal, Abhik; Aykkal, Riju; Babu, Rosana O; Ghosh, Mriganka

    2011-02-15

    Natural products are important sources of drug discovery. In this context groups of different set of phytochemicals were taken and docked into the different cavities of the Reverse transcriptase (PDB ID: 1REV) of Human immunodeficiency virus (HIV) and results were discussed. Natural compounds such as Curcumin, Geranin, Gallotannin, Tiliroside, Kaempferol-3-o-glucoside and Trachelogenin were found to very effective according to its binding energy and ligand efficiency score. Those compounds also were found to have no adverse effect as carcinogenicity and mutagenicity and favorable drug likeness score. Hence, considering the facts those compounds could use effectively for HIV-1 drug discovery.

  11. APOLLO 14: Docking trouble (pt 1/2)

    Science.gov (United States)

    1974-01-01

    APOLLO 14: The crew are having problems docking the command module to the lunar module: the locking mechanism will not engage. From the film documentary 'APOLLO 14: 'Mission to Fra Mauro'', part of a documentary series on the APOLLO missions made in the early '70's and narrated by Burgess Meredith. APOLO 14: Third manned lunar landing with Alan B. Shepard, Jr.,Stuart A. Roosa, and Edgar D. Mitchell. Landed in the Fra Mauro area on Ferurary 5, 1971; performed EVA, deployed lunar experiments, returned lunar samples. Mission Duration 216 hrs 1 min 58 sec

  12. StarDock: shipping customized computing environments to the data

    Science.gov (United States)

    Young, Michael D.; Hayashi, Soichi; Gopu, Arvind

    2016-08-01

    Surging data volumes make it increasingly unfeasible to transfer astronomical datasets to the local systems of individual scientists. Centralized pipelines offer some relief, but lack flexibility to fulfill the needs of all users. We have developed a system that leverages the Docker container application virtualization software. Along with a suite of commonly used astronomy applications, users can configure a container with their own custom software and analysis tools. Our StarDock system will move the users container to the data, and expose the requested dataset, allowing our users to safely and securely process their data without needlessly transferring hundreds of gigabytes.

  13. Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives.

    Science.gov (United States)

    Huczyński, Adam; Majcher, Urszula; Maj, Ewa; Wietrzyk, Joanna; Janczak, Jan; Moshari, Mahshad; Tuszynski, Jack A; Bartl, Franz

    2016-02-01

    In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.

  14. SYNTHESIS, DOCKING STUDIES AND ANTIOXIDANT ACTIVITY OF LINEAR TETRAPEPTIDE FAYV

    Directory of Open Access Journals (Sweden)

    Sreekanth K.

    2011-07-01

    Full Text Available The linear tetrapeptide Phe-Ala-Tyr-Val (FAYV was designed based on docking results using Schrodinger Software tool. The tetrapeptide was conveniently synthesized by solution phase peptide synthesis using Dicyclohexylcarbidomide (DCC as coupling agent and triethyl amine as the base. Qikprop (a tool to predict drug like properties results showed that the ligands mostly show antihypertensive and antidiabetic properties. The compounds were evaluated for antioxidant property by using 1,1-diphenyl-2-picryl-hydrazil (DPPH. method and were found to possess significant antioxidant activity.

  15. Bio-inspired algorithms applied to molecular docking simulations.

    Science.gov (United States)

    Heberlé, G; de Azevedo, W F

    2011-01-01

    Nature as a source of inspiration has been shown to have a great beneficial impact on the development of new computational methodologies. In this scenario, analyses of the interactions between a protein target and a ligand can be simulated by biologically inspired algorithms (BIAs). These algorithms mimic biological systems to create new paradigms for computation, such as neural networks, evolutionary computing, and swarm intelligence. This review provides a description of the main concepts behind BIAs applied to molecular docking simulations. Special attention is devoted to evolutionary algorithms, guided-directed evolutionary algorithms, and Lamarckian genetic algorithms. Recent applications of these methodologies to protein targets identified in the Mycobacterium tuberculosis genome are described.

  16. Error Modeling and Compensation of Circular Motion on a New Circumferential Drilling System

    Directory of Open Access Journals (Sweden)

    Qiang Fang

    2015-01-01

    Full Text Available A new flexible circumferential drilling system is proposed to drill on the fuselage docking area. To analyze the influence of the circular motion error to the drilling accuracy, the nominal forward kinematic model is derived using Denavit-Hartenberg (D-H method and this model is further developed to model the kinematic errors caused by circular positioning error and synchronization error using homogeneous transformation matrices (HTM. A laser tracker is utilized to measure the circular motion error of the two measurement points at both sides. A circular motion compensation experiment is implemented according to the calculated positioning error and synchronization error. Experimental results show that the positioning error and synchronization error were reduced by 65.0% and 58.8%, respectively, due to the adopted compensation, and therefore the circular motion accuracy is substantially improved. Finally, position errors of the two measurement points are analyzed to have little influence on the measurement result and the validity of the proposed compensation method is proved.

  17. Accurate refinement of docked protein complexes using evolutionary information and deep learning.

    Science.gov (United States)

    Akbal-Delibas, Bahar; Farhoodi, Roshanak; Pomplun, Marc; Haspel, Nurit

    2016-06-01

    One of the major challenges for protein docking methods is to accurately discriminate native-like structures from false positives. Docking methods are often inaccurate and the results have to be refined and re-ranked to obtain native-like complexes and remove outliers. In a previous work, we introduced AccuRefiner, a machine learning based tool for refining protein-protein complexes. Given a docked complex, the refinement tool produces a small set of refined versions of the input complex, with lower root-mean-square-deviation (RMSD) of atomic positions with respect to the native structure. The method employs a unique ranking tool that accurately predicts the RMSD of docked complexes with respect to the native structure. In this work, we use a deep learning network with a similar set of features and five layers. We show that a properly trained deep learning network can accurately predict the RMSD of a docked complex with 1.40 Å error margin on average, by approximating the complex relationship between a wide set of scoring function terms and the RMSD of a docked structure. The network was trained on 35000 unbound docking complexes generated by RosettaDock. We tested our method on 25 different putative docked complexes produced also by RosettaDock for five proteins that were not included in the training data. The results demonstrate that the high accuracy of the ranking tool enables AccuRefiner to consistently choose the refinement candidates with lower RMSD values compared to the coarsely docked input structures.

  18. International Oil Pollution Compensation Fund

    Energy Technology Data Exchange (ETDEWEB)

    1979-11-01

    The International Oil Pollution Compensation Fund was established under a 1971 Intergovernmental Maritime Consultative Organization Convention to supplement the 1969 Civil Liability Convention (CLC) under which shipowners were held liable for damage caused by oil spills up to $18 million per incident; the new fund increases the amount payable per incident to $57 million as of April 1979. A further increase up to about $76 million is now under consideration. During 1979, the Fund has been concerned in particular with claims arising out of oil spills in Japan and the Baltic Sea. In the former case, some 540 tons of oil was lost by Miya Maru No. 8 after a collision in March 1979 in the Japanese Inland Sea; cleanup costs and compensation to fishermen were about (pound sterling)400,000. In the latter phase, crude oil apparently coming from the Russian tanker Antonio Gramsci, which grounded off Ventspils in February 1979, drifted across the Baltic and was trapped in or under the ice. After the ice melted, it spread to more than 2000 islands in the Swedish Archipelaso; cleanup measures may result in claims as high as (pound sterling) 8 million.

  19. An Automated Strategy for Binding-Pose Selection and Docking Assessment in Structure-Based Drug Design.

    Science.gov (United States)

    Ballante, Flavio; Marshall, Garland R

    2016-01-25

    Molecular docking is a widely used technique in drug design to predict the binding pose of a candidate compound in a defined therapeutic target. Numerous docking protocols are available, each characterized by different search methods and scoring functions, thus providing variable predictive capability on a same ligand-protein system. To validate a docking protocol, it is necessary to determine a priori the ability to reproduce the experimental binding pose (i.e., by determining the docking accuracy (DA)) in order to select the most appropriate docking procedure and thus estimate the rate of success in docking novel compounds. As common docking programs use generally different root-mean-square deviation (RMSD) formulas, scoring functions, and format results, it is both difficult and time-consuming to consistently determine and compare their predictive capabilities in order to identify the best protocol to use for the target of interest and to extrapolate the binding poses (i.e., best-docked (BD), best-cluster (BC), and best-fit (BF) poses) when applying a given docking program over thousands/millions of molecules during virtual screening. To reduce this difficulty, two new procedures called Clusterizer and DockAccessor have been developed and implemented for use with some common and "free-for-academics" programs such as AutoDock4, AutoDock4(Zn), AutoDock Vina, DOCK, MpSDockZn, PLANTS, and Surflex-Dock to automatically extrapolate BD, BC, and BF poses as well as to perform consistent cluster and DA analyses. Clusterizer and DockAccessor (code available over the Internet) represent two novel tools to collect computationally determined poses and detect the most predictive docking approach. Herein an application to human lysine deacetylase (hKDAC) inhibitors is illustrated.

  20. Engineering Compensations in Web Service Environment

    DEFF Research Database (Denmark)

    Schäfer, Micahel; Dolog, Peter; Nejdl, Wolfgang

    2007-01-01

    Business to business integration has recently been performed by employing Web service environments. Moreover, such environments are being provided by major players on the technology markets. Those environments are based on open specifications for transaction coordination. When a failure...... compensations based on forward recovery principles. We extend the existing Web service transaction coordination architecture and infrastructure in order to support flexible compensation operations. A contract-based approach is being used, which allows the specification of permitted compensations at runtime. We...... introduce the abstract service and adapter components which allow us to separate the compensation logic from the coordination logic. In this way, we can easily plug in or plug out different compensation strategies based on a specification language defined on top of basic compensation activities and complex...

  1. How to avoid deferred-compensation troubles.

    Science.gov (United States)

    Freeman, Todd I

    2005-06-01

    Executive compensation packages have long included stock options and deferred compensation plans in order to compete for talent. Last year, Congress passed a law in response to the Enron debacle, in which executives were perceived to be protecting their deferred compensation at the expense of employees, creditors, and investors. The new law is designed to protect companies and their shareholders from being raided by the very executives that guided the company to financial ruin. Physicians who are part owners of medical practices need to know about the changes in the law regarding deferred compensation and how to avoid costly tax penalties. This article discusses how the changes affect medical practices as well as steps physician-owned clinics can take to avoid the risk of penalty, such as freezing deferred compensation and creating a new deferred compensation plan.

  2. Seigniorage Compensation for Swaziland and Policy Implication.

    OpenAIRE

    Mkhonta, Simiso F.

    1992-01-01

    Seigniorage compensation for Swaziland is found to depend on Emalangeni in circulation in Swaziland besides the obvious effect of an increase in ZAR/Rands in circulation in South Africa. Where a percent increase in Emalangeni in circulation in Swaziland at time t decreases seigniorage compensation by 0.186 percent and a percent increase in Emalangeni in circulation at time t-1 decreases seigniorage compensation by 0.134 percent through both substitution and base effects respectively. Thus a...

  3. Docks and Piers, Port of Green Bay docks along the Fox River are complete, Published in 2008, 1:1200 (1in=100ft) scale, Brown County, WI.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Docks and Piers dataset, published at 1:1200 (1in=100ft) scale, was produced all or in part from Orthoimagery information as of 2008. It is described as 'Port...

  4. Undulator with dynamic compensation of magnetic forces

    Energy Technology Data Exchange (ETDEWEB)

    Gluskin, Efim; Trakhtenberg, Emil; Xu, Joseph Z.

    2016-05-31

    A method and apparatus for implementing dynamic compensation of magnetic forces for undulators are provided. An undulator includes a respective set of magnet arrays, each attached to a strongback, and placed on horizontal slides and positioned parallel relative to each other with a predetermined gap. Magnetic forces are compensated by a set of compensation springs placed along the strongback. The compensation springs are conical springs having exponential-force characteristics that substantially match undulator magnetic forces independently of the predetermined gap. The conical springs are positioned along the length of the magnets.

  5. 14 CFR 1253.515 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 1253.515 Compensation. A...

  6. Enthalpy-entropy compensation in protein unfolding

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Enthalpy-entropy compensation was found to be a universal law in protein unfolding based on over 3 000 experimental data. Water molecular reorganization accompanying the protein unfolding was suggested as the origin of the enthalpy-entropy compensation in protein unfolding. It is indicated that the enthalpy-entropy compensation constitutes the physical foundation that satisfies the biological need of the small free energy changes in protein unfolding, without the sacrifice of the bio-diversity of proteins. The enthalpy-entropy compensation theory proposed herein also provides valuable insights into the Privalov's puzzle of enthalpy and entropy convergence in protein unfolding.

  7. Log amplifier with pole-zero compensation

    Science.gov (United States)

    Brookshier, William

    1987-01-01

    A logarithmic amplifier circuit provides pole-zero compensation for improved stability and response time over 6-8 decades of input signal frequency. The amplifier circuit includes a first operational amplifier with a first feedback loop which includes a second, inverting operational amplifier in a second feedback loop. The compensated output signal is provided by the second operational amplifier with the log elements, i.e., resistors, and the compensating capacitors in each of the feedback loops having equal values so that each break point or pole is offset by a compensating break point or zero.

  8. Lithium compensation for full cell operation

    Science.gov (United States)

    Xiao, Jie; Zheng, Jianming; Chen, Xilin; Lu, Dongping; Liu, Jun; Jiguang, Jiguang

    2016-05-17

    Disclosed herein are embodiments of a lithium-ion battery system comprising an anode, an anode current collector, and a layer of lithium metal in contact with the current collector, but not in contact with the anode. The lithium compensation layer dissolves into the electrolyte to compensate for the loss of lithium ions during usage of the full cell. The specific placement of the lithium compensation layer, such that there is no direct physical contact between the lithium compensation layer and the anode, provides certain advantages.

  9. Broadband dispersion compensation using microstructure fibers

    Institute of Scientific and Technical Information of China (English)

    Xia Zhang; Xiaomin Ren; Yongzhao Xu; Zinan Wang; Yongqing Huang; Xue Chen

    2007-01-01

    Beijing University of Posts and Telecommunications, Beijing 100876Dispersion and dispersion slope compensation of 10-Gb/s pulses using microstructure fibers (MFs) is demonstrated experimentally. A 26-m MF is used to compensate the dispersion of 2-km standard singe mode fiber in a 20-nm range in C band. The experimental results show that a significant improvement can be achieved in the quality of the observed pulses with the dispersion compensation. Moreover, the further research shows that the MF can compensate the anomalous dispersion of a single mode fiber within ±0.27 ps/(nm·km) over a 50-nm wavelength range from 1520 to 1570 nm.

  10. Connecting in Space: Docking with the International Space Station. Educational Brief.

    Science.gov (United States)

    National Aeronautics and Space Administration, Washington, DC.

    This brief discusses the space shuttle and the docking procedures used with the International Space Station (ISS). Using this activity designed for grades 5-12, students demonstrate and identify procedures for determining the best method for completing the docking activity. Students will also study and identify Newton's Laws of Motion. A mockup…

  11. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol.

    Science.gov (United States)

    Gabrielsen, Mari; Kurczab, Rafał; Ravna, Aina W; Kufareva, Irina; Abagyan, Ruben; Chilmonczyk, Zdzisław; Bojarski, Andrzej J; Sylte, Ingebrigt

    2012-01-01

    The two main groups of antidepressant drugs, the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs), as well as several other compounds, act by inhibiting the serotonin transporter (SERT). However, the binding mode and molecular mechanism of inhibition in SERT are not fully understood. In this study, five classes of SERT inhibitors were docked into an outward-facing SERT homology model using a new 4D ensemble docking protocol. Unlike other docking protocols, where protein flexibility is not considered or is highly dependent on the ligand structure, flexibility was here obtained by side chain sampling of the amino acids of the binding pocket using biased probability Monte Carlo (BPMC) prior to docking. This resulted in the generation of multiple binding pocket conformations that the ligands were docked into. The docking results showed that the inhibitors were stacked between the aromatic amino acids of the extracellular gate (Y176, F335) presumably preventing its closure. The inhibitors interacted with amino acids in both the putative substrate binding site and more extracellular regions of the protein. A general structure-docking-based pharmacophore model was generated to explain binding of all studied classes of SERT inhibitors. Docking of a test set of actives and decoys furthermore showed that the outward-facing ensemble SERT homology model consistently and selectively scored the majority of active compounds above decoys, which indicates its usefulness in virtual screening.

  12. 48 CFR 52.247-40 - Ex Dock, Pier, or Warehouse, Port of Importation.

    Science.gov (United States)

    2010-10-01

    ... Warehouse, Port of Importation. 52.247-40 Section 52.247-40 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.247-40 Ex Dock, Pier, or Warehouse, Port of Importation. As prescribed in 47.303-12..., pier, or warehouse, port of importation: Ex Dock, Pier, or Warehouse, Port of Importation (APR 1984)...

  13. 75 FR 38831 - Repair Kalaupapa Dock Structure: Kalaupapa National Historical Park, Hawaii; Notice of...

    Science.gov (United States)

    2010-07-06

    ... National Park Service Repair Kalaupapa Dock Structure: Kalaupapa National Historical Park, Hawaii; Notice... Impact Statement (EIS) as previously noticed in the Federal Register on April 17, 2009, for repair of... environmental consequences of the proposed dock repairs, including minor to moderate effects on water...

  14. Economic Impacts from Spending by Community Dock Owners at Rough River Lake

    Science.gov (United States)

    2008-01-01

    community dock • Pomme de Terre Lake, community dock • Harry S. Truman Dam and Reservoir, marina • Raystown Lake, marina • Hartwell Lake, private...Rock Lake (Missouri/Arkansas), Rough River Lake (Kentucky), and Pomme de Terre Lake (Missouri). The ERB staff designed the survey, constructed the

  15. Attitudes of Dutch Pig Farmers Towards Tail Biting and Tail Docking

    NARCIS (Netherlands)

    Bracke, M.B.M.; Lauwere, de C.C.; Wind, S.M.M.; Zonderland, J.J.

    2013-01-01

    The Dutch policy objective of a fully sustainable livestock sector without mutilations by 2023 is not compatible with the routine practice of tail docking to minimize the risk of tail biting. To examine farmer attitudes towards docking, a telephone survey was conducted among 487 conventional and 33

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

    Science.gov (United States)

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

    2015-06-01

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

  17. DOCK8 Deficiency : Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients

    NARCIS (Netherlands)

    Aydin, Susanne E.; Kilic, Sara Sebnem; Aytekin, Caner; Kumar, Ashish; Porras, Oscar; Kainulainen, Leena; Kostyuchenko, Larysa; Genel, Ferah; Kutukculer, Necil; Karaca, Neslihan; Gonzalez-Granado, Luis; Abbott, Jordan; Al-Zahrani, Daifulah; Rezaei, Nima; Baz, Zeina; Thiel, Jens; Ehl, Stephan; Marodi, Laszlo; Orange, Jordan S.; Sawalle-Belohradsky, Julie; Keles, Sevgi; Holland, Steven M.; Sanal, Ozden; Ayvaz, Deniz C.; Tezcan, Ilhan; Al-Mousa, Hamoud; Alsum, Zobaida; Hawwari, Abbas; Metin, Ayse; Matthes-Martin, Susanne; Hoenig, Manfred; Schulz, Ansgar; Picard, Capucine; Barlogis, Vincent; Gennery, Andrew; Ifversen, Marianne; van Montfrans, JM; Kuijpers, Taco; Bredius, Robbert; Duckers, Gregor; Al-Herz, Waleed; Pai, Sung-Yun; Geha, Raif; Notheis, Gundula; Schwarze, Carl-Philipp; Tavil, Betul; Azik, Fatih; Bienemann, Kirsten; Grimbacher, Bodo; Heinz, Valerie; Gaspar, H. Bobby; Aydin, Roland; Hagl, Beate; Gathmann, Benjamin; Belohradsky, Bernd H.; Ochs, Hans D.; Chatila, Talal; Renner, Ellen D.; Su, Helen; Freeman, Alexandra F.; Engelhardt, Karin; Albert, Michael H.

    2015-01-01

    Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8

  18. DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations

    Directory of Open Access Journals (Sweden)

    Alberto Cuzzolin

    2015-05-01

    Full Text Available Virtual screening (VS is a computational methodology that streamlines the drug discovery process by reducing costs and required resources through the in silico identification of potential drug candidates. Structure-based VS (SBVS exploits knowledge about the three-dimensional (3D structure of protein targets and uses the docking methodology as search engine for novel hits. The success of a SBVS campaign strongly depends upon the accuracy of the docking protocol used to select the candidates from large chemical libraries. The identification of suitable protocols is therefore a crucial step in the setup of SBVS experiments. Carrying out extensive benchmark studies, however, is usually a tangled task that requires users’ proficiency in handling different file formats and philosophies at the basis of the plethora of existing software packages. We present here DockBench 1.0, a platform available free of charge that eases the pipeline by automating the entire procedure, from docking benchmark to VS setups. In its current implementation, DockBench 1.0 handles seven docking software packages and offers the possibility to test up to seventeen different protocols. The main features of our platform are presented here and the results of the benchmark study of human Checkpoint kinase 1 (hChk1 are discussed as validation test.

  19. PaFlexPepDock: parallel ab-initio docking of peptides onto their receptors with full flexibility based on Rosetta.

    Directory of Open Access Journals (Sweden)

    Haiou Li

    Full Text Available Structural information related to protein-peptide complexes can be very useful for novel drug discovery and design. The computational docking of protein and peptide can supplement the structural information available on protein-peptide interactions explored by experimental ways. Protein-peptide docking of this paper can be described as three processes that occur in parallel: ab-initio peptide folding, peptide docking with its receptor, and refinement of some flexible areas of the receptor as the peptide is approaching. Several existing methods have been used to sample the degrees of freedom in the three processes, which are usually triggered in an organized sequential scheme. In this paper, we proposed a parallel approach that combines all the three processes during the docking of a folding peptide with a flexible receptor. This approach mimics the actual protein-peptide docking process in parallel way, and is expected to deliver better performance than sequential approaches. We used 22 unbound protein-peptide docking examples to evaluate our method. Our analysis of the results showed that the explicit refinement of the flexible areas of the receptor facilitated more accurate modeling of the interfaces of the complexes, while combining all of the moves in parallel helped the constructing of energy funnels for predictions.

  20. Docking of B-cell epitope antigen to specific hepatitis B antibody

    Indian Academy of Sciences (India)

    R Rajkannan; E J Padma Malar

    2007-09-01

    The interaction of pres1 region of hepatitis B virus B-cell epitope antigen with specific hepatitis B neutralizing monoclonal antibody was examined by docking study. We modelled the 3D complex structure of B-cell epitope antigen residues CTTPAQGNSMFPSCCCTKPTDGNCY by homology modelling and docked it with the crystal structure of monoclonal antibody specific for the pres1 region of the hepatitis B virus. At the optimized docked conformation, the interactions between the amino acids of antigen and antibody were examined. It is found that the docked complex is stabilized by 59.3 kcal/mol. The stability of the docked antigen-antibody complex is due to hydrogen bonding and van der Waals interactions. The amino acids of the antigen and antibody responsible for the interaction were identified.

  1. Theoretical Studies on Docking Dynamics and Electronic Structure in Metalloprotein Complexes

    Science.gov (United States)

    Sugiyama, Ayumu; Nishikawa, Keigo; Yamamoto, Tetsunori; Purqon, Acep; Nishikawa, Kiyoshi; Nagao, Hidemi

    2007-12-01

    An investigating of docking structure and dynamics between metalloprotein is interested from the viewpoint of searching the function of protein. We investigate the cytochrome c551 and azurin complexes by three computational methods, quantum mechanical calculation, docking searching algorism and molecular dynamics simulation. At first we present the docking structure of the cytochrome c551-azurin complexes expected by ZDOCK searching algorism. Quantum chemical calculation is tools to estimate the charge distrubution around the active site for each protein and force field parameters. From these parameters, we reproduce the protein docking dynamics by molecular dynamics simulation. We analyze some physical properties of complex system such as binding free energy, dynamical cross correlation map, and so on. We discuss the docking stability and dynamical effect of the cytochrome c551-azurin complexes.

  2. Developing a cross-docking network design model under uncertain environment

    Science.gov (United States)

    Seyedhoseini, S. M.; Rashid, Reza; Teimoury, E.

    2014-09-01

    Cross-docking is a logistic concept, which plays an important role in supply chain management by decreasing inventory holding, order packing, transportation costs and delivery time. Paying attention to these concerns, and importance of the congestion in cross docks, we present a mixed-integer model to optimize the location and design of cross docks at the same time to minimize the total transportation and operating costs. The model combines queuing theory for design aspects, for that matter, we consider a network of cross docks and customers where two M/M/c queues have been represented to describe operations of indoor trucks and outdoor trucks in each cross dock. To prepare a perfect illustration for performance of the model, a real case also has been examined that indicated effectiveness of the proposed model.

  3. Two-dimensional PSD based automatic docking of self-reconfiguration modular exploration robot system

    Institute of Scientific and Technical Information of China (English)

    Zhang Liping; Ma Shugen; Li Bin; Zhang Zheng; Cao Binggang

    2007-01-01

    Based on the design of a docking mechanism, this paper thoroughly investigates the space automatic docking of self-reconfiguration modular exploration robot system (RMERS). The method that leads robot to achieve space docking by using two-dimensional PSD is put forward innovatively for the median size robot system. At the same time, in order to enlarge the detecting extension and the precision of PSD and reduce its dependence on lighting signal, the PSD was remade by increasing the optical device over its light-sensitive surface. The emission board and LED light scheduling were designed according to docking arithmetic, and the operating principle of docking process was analyzed based on these. The simulation experiments were carried out and their results are presented.

  4. Accessible high-throughput virtual screening molecular docking software for students and educators.

    Directory of Open Access Journals (Sweden)

    Reed B Jacob

    2012-05-01

    Full Text Available We survey low cost high-throughput virtual screening (HTVS computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms.

  5. A new compensator at CERN

    CERN Document Server

    Kahle, K

    2005-01-01

    In 2001 a first Static Var Compensator (SVC) based on a set of thyristor-controlled reactors was commissioned for the SPS. This was the first step in the process of replacing the obsolete saturated reactors installed in the early seventies. The second step is now in preparation: dismantling of the so-called “North compensator” and replacing it with a second SVC, essentially identical to the one commissioned in 2001. This paper describes the project and its consequences for the operation of the 400/18 kV main substation. The paper describes briefly the recuperation of certain existing components, civil engineering and other hardware. Finally a budget estimation and the planning are presented.

  6. MOLS 2.0: software package for peptide modeling and protein-ligand docking.

    Science.gov (United States)

    Paul, D Sam; Gautham, N

    2016-10-01

    We previously developed an algorithm to perform conformational searches of proteins and peptides, and to perform the docking of ligands to protein receptors. In order to identify optimal conformations and docked poses, this algorithm uses mutually orthogonal Latin squares (MOLS) to rationally sample the vast conformational (or docking) space, and then analyzes this relatively small sample using a variant of mean field theory. The conformational search part of the algorithm was denoted MOLS 1.0. The docking portion of the algorithm, which allows only "flexible ligand/rigid receptor" docking, was denoted MOLSDOCK. Both are FORTRAN-based command-line-only molecular docking computer programs, though a GUI was developed later for MOLS 1.0. Both the conformational search and the rigid receptor docking parts of the algorithm have been extensively validated. We have now further enhanced the capabilities of the program by incorporating "induced fit" side-chain receptor flexibility for docking peptide ligands. Benchmarking and extensive testing is now being carried out for the flexible receptor portion of the docking. Additionally, to make both the peptide conformational search and docking algorithms (the latter including both flexible ligand/rigid receptor and flexible ligand/flexible receptor techniques) more accessible to the research community, we have developed MOLS 2.0, which incorporates a new Java-based graphical user interface (GUI). Here, we give a detailed description of MOLS 2.0. The source code and binary for MOLS 2.0 are distributed free (under a GNU Lesser General Public License) to the scientific community. They are freely available for download at https://sourceforge.net/projects/mols2-0/files/ .

  7. 76 FR 6009 - Shareholder Approval of Executive Compensation and Golden Parachute Compensation

    Science.gov (United States)

    2011-02-02

    ... more specific shareholder opinion through separate votes on cash compensation, golden parachute policy... 402(s) \\65\\ of Regulation S-K about the issuer's compensation policies and practices as they relate to... the issuer's compensation policies or decisions for named executive officers, the issuer is...

  8. Synthesis and docking studies of novel antitumor benzimidazoles.

    Science.gov (United States)

    Omar, Mohamed A; Shaker, Yasser M; Galal, Shadia A; Ali, Mamdouh M; Kerwin, Sean M; Li, Jing; Tokuda, Harukuni; Ramadan, Raghda A; El Diwani, Hoda I

    2012-12-15

    In this work, the benzimidazole-pyrrole conjugates 6a-h and benzimidazole-tetracycles conjugates 12-14 were prepared. The cytotoxicity of the compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 was tested against lung cancer cell line A549. Compound 6b exhibited higher activity than the bis-benzoxazole natural product (UK-1), the standard. The tested 4g,h, 6a-h, 10 and 12-14 exhibited remarkable cytotoxicity activity against breast cancer cell line MCF-7 with higher activity than tamoxifen. Furthermore, compound 4h was found to be also more potent than doxurubicin. The antitumor promotion activity of synthesized compounds 4g,h, 6a-h, 10 and 12-14 has been estimated by studying their possible inhibitory effects on EBV-EA activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds, the inhibitory activities of compounds 8, 13 and 14 demonstrated strong inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation without showing any cytotoxicity on the Raji cells and their effects being stronger than that of a representative control, oleanolic acid. Moreover, the molecular docking of the new compounds into plasminogen activator (uPA) receptor has been in correlation with the antitumor activity. All synthesized compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 were docked into same groove of the binding site of the native co-crystalized (4-iodobenzo[b]thiophene-2-carboxamidine) ligand (PDB code:1c5x) for activity explaination. Compounds 4h, 6b and 13, giving the best docking results, were further studied to estimate their effect on the level of uPA using AssayMax human urokinase (uPA) ELISA kit. In case of A549 cell line, compound 6 exhibited similar activity to MMC, and for MCF-7 cell line, compound 4h exhibited similar activity to doxorubicin, in inhibiting the expression of uPA.

  9. Time-varying phase diversity turbulence compensation

    NARCIS (Netherlands)

    Eekeren, A.W.M. van; Schutte, K.; Dijk, J.; Schwering, P.B.W.

    2011-01-01

    Long range object identification needs visual identification over large distances. However, atmospheric turbulence does hinder long range imaging. Therefore it is crucial to compensate the visual artifacts due to atmospheric turbulence. In this paper we propose a new method to compensate these turbu

  10. 45 CFR 63.35 - Dual compensation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Dual compensation. 63.35 Section 63.35 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GRANT PROGRAMS ADMINISTERED BY THE... compensation. If a project staff member or consultant of one grantee is involved simultaneously in two or...

  11. 28 CFR 345.54 - Overtime compensation.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Overtime compensation. 345.54 Section 345.54 Judicial Administration FEDERAL PRISON INDUSTRIES, INC., DEPARTMENT OF JUSTICE FEDERAL PRISON INDUSTRIES (FPI) INMATE WORK PROGRAMS Inmate Pay and Benefits § 345.54 Overtime compensation. An...

  12. 28 CFR 34.111 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Compensation. 34.111 Section 34.111 Judicial Administration DEPARTMENT OF JUSTICE OJJDP COMPETITION AND PEER REVIEW PROCEDURES Peer Review § 34.111 Compensation. All peer reviewers will be eligible to be paid according to applicable...

  13. 24 CFR 964.340 - Resident compensation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Resident compensation. 964.340 Section 964.340 Housing and Urban Development Regulations Relating to Housing and Urban Development...) Program § 964.340 Resident compensation. Residents employed to provide services or renovation...

  14. 33 CFR 136.113 - Other compensation.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Other compensation. 136.113 Section 136.113 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT General Procedure § 136.113 Other compensation....

  15. Individual Hearing Loss: Characterization, Modelling, Compensation Strategies

    DEFF Research Database (Denmark)

    Santurette, Sébastien; Dau, Torsten; Christensen-Dalsgaard, Jakob;

    2016-01-01

    account for such individual differences, which make it challenging to find adequate compensation strategies in hearing devices. How to characterize, model, and compensate for individual hearing loss were the main topics of the fifth International Symposium on Auditory and Audiological Research (ISAAR...

  16. Springback Compensation: Fundamental Topics and Practical Application

    NARCIS (Netherlands)

    Lingbeek, R.; Meinders, T.; Ohnimus, S.; Petzoldt, M.; Weiher, J.

    2006-01-01

    Now that the simulation of deep drawing processes has become more reliable the virtual compensation of the forming tools has become reality. In literature, the Displacement Adjustment (DA) algorithm has proved to be most effective. In this article it is shown how the compensation factor, required fo

  17. Motion compensator for holographic motion picture camera

    Science.gov (United States)

    Kurtz, R. L.

    1973-01-01

    When reference beam strikes target it undergoes Doppler shift dependent upon target velocity. To compensate, object beam is first reflected from rotating cylinder that revolves in direction opposite to target but at same speed. When beam strikes target it is returned to original frequency and is in phase with reference beam. Alternatively this motion compensator may act on reference beam.

  18. A brief history of dosage compensation

    Indian Academy of Sciences (India)

    Stanley M. Gartler

    2014-08-01

    In 1914, H. J. Muller postulated the origin of the Y chromosome as having resulted from restricted recombination between homologous sex chromosomes in the male and the accumulation of deleterious mutations. This evolutionary process leads to dosage compensation. This article lays out a brief history of dosage compensation in genetics.

  19. 20 CFR 211.15 - Verification of compensation claimed.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Verification of compensation claimed. 211.15... CREDITABLE RAILROAD COMPENSATION § 211.15 Verification of compensation claimed. Compensation claimed by an... Board before it may be credited. An employee's claim to compensation not credited shall be processed...

  20. 20 CFR 211.2 - Definition of compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Definition of compensation. 211.2 Section 211... CREDITABLE RAILROAD COMPENSATION § 211.2 Definition of compensation. (a) The term compensation means any form... termination allowance paid under section 702 of that Act. Compensation may be paid as money, a commodity,...

  1. 20 CFR 211.14 - Maximum creditable compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Maximum creditable compensation. 211.14... CREDITABLE RAILROAD COMPENSATION § 211.14 Maximum creditable compensation. Maximum creditable compensation... Employment Accounts shall notify each employer of the amount of maximum creditable compensation applicable...

  2. 20 CFR 226.62 - Computing average monthly compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Computing average monthly compensation. 226... Compensation § 226.62 Computing average monthly compensation. The employee's average monthly compensation is computed by first determining the employee's highest 60 months of railroad compensation...

  3. 5 CFR 9701.313 - Homeland Security Compensation Committee.

    Science.gov (United States)

    2010-01-01

    ... compensation matters such as Departmental compensation policies and principles, the annual allocation of funds... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Homeland Security Compensation Committee... Homeland Security Compensation Committee. (a) DHS will establish a Homeland Security Compensation...

  4. Comprehensive Monitor-Oriented Compensation Programming

    Directory of Open Access Journals (Sweden)

    Christian Colombo

    2014-04-01

    Full Text Available Compensation programming is typically used in the programming of web service compositions whose correct implementation is crucial due to their handling of security-critical activities such as financial transactions. While traditional exception handling depends on the state of the system at the moment of failure, compensation programming is significantly more challenging and dynamic because it is dependent on the runtime execution flow — with the history of behaviour of the system at the moment of failure affecting how to apply compensation. To address this dynamic element, we propose the use of runtime monitors to facilitate compensation programming, with monitors enabling the modeller to be able to implicitly reason in terms of the runtime control flow, thus separating the concerns of system building and compensation modelling. Our approach is instantiated into an architecture and shown to be applicable to a case study.

  5. Compensating large PMD by a fiber grating

    Institute of Scientific and Technical Information of China (English)

    Tangjun Li(李唐军); Muguang Wang(王目光); Cao Diao(刁操); Shuisheng Jian(简水生)

    2004-01-01

    In this paper, the first- and second-order polarization mode dispersion (PMD) with the amount of 132.994-ps differential group-delay (DGD) and maximum 476.129-ps/nm second-order PMD can be compensated by a two-stages PMD compensator at a 40-Gb/s optical fiber communication system. The first stage has one free degree that is used for first order and high orders PMD compensations by rotating the state of polarization. The second-stage is used for remainder PMD compensations. After compensation, the average DGD and the maximum second-order PMD are reduced to 345.310 fs and 3.102 ps/nm, respectively.

  6. Rectangular Laser Resonators with Astigmatic Compensation

    DEFF Research Database (Denmark)

    Skettrup, Torben

    2005-01-01

    An investigation of rectangular resonators with a view to the compensation of astigmatism has been performed. In order to have beam waists placed at the same positions in the tangential and sagittal planes, pairs of equal mirrors were considered. It was found that at least two concave mirrors...... are necessary to obtain compensation. Four-concave-mirror systems are most stable close to the quadratic geometry, although the symmetric quadratic resonator itself cannot be compensated for astigmatism. Using four equal concave mirrors, compensation of astigmatism can be obtained in two arms at the same time....... Usually several stability ranges are found for four-mirror resonators with pair-wise equal mirrors, and it is possible with these systems to obtain small compensated beam waist radii suitable for frequency conversion. Relevant formulae are given and several relevant examples are shown using simulation...

  7. Synthesis, Evaluation and Docking studies of Cholecalciferol Derivative

    Directory of Open Access Journals (Sweden)

    Sultanat

    2014-09-01

    Full Text Available Improved synthesis of 3b-acetoxy-9, 10-seco-19, 8(8-spiro-5(10, 6-cholestadiene has been reported after reacting cholecalciferol acetate with dimethylbutadiene by incorporating BF3·OEt2, SnCl4, ZnBr2, p-TsOH in toluene under Diels-Alder condition to get better yields. Agarose gel electrophoresis showed the potential in vitro DNA damaging nature while as the comet assay depicted the genotoxic nature by mobilizing the tail of the comet in lymphocytes. The molecular docking depicted the intercalation of steroid derivative with minor groove of the DNA molecule and in this configuration the phosphodiester bond of DNA stabilizes the acetoxy group. The bioactivity score and PASS software analysis confirmed the potential physicochemical features of the compound to act as active drug.

  8. Vision Based Navigation Sensors for Spacecraft Rendezvous and Docking

    DEFF Research Database (Denmark)

    Benn, Mathias

    . Denmark has, with DTUs design of the Swarm mission, ESAs next Earth Observation Programme magnetic mapping mission, and DTUs participation in GRACE, ELISA and Alsat2, a leading role in designing and verifying sensor systems for this new class of spacecraft. The Swedish led PRISMA mission...... is a technological demonstration mission, where all aspects of space rendezvous and docking to both a cooperative and a non-cooperative target is researched, with the use of novel methods, instruments and technologies. Amongst other equipment, DTU has delivered a vision based sensor package to the Main spacecraft...... of this constellation, providing both position and pose information for the Target vehicle. This dissertation will describe the study, implementation and verification methods that has led to the realization of this optical Vision Based Sensor (VBS), which is used on the PRISMA mission. On June 15th 2010 the PRISMA...

  9. FACILE SYNTHESIS, DOCKING STUDIES AND ANTIOXIDANT ACTIVITY OF FGVR

    Directory of Open Access Journals (Sweden)

    Himaja M

    2011-08-01

    Full Text Available A rational designing of linear Tetrapeptide FGVR was done and was synthesized by solution phase peptide synthesis. The docking studies of designed linear tetrapeptide FGVR was carried out by using Schrodinger Software Solutions, USA. Qikprop results show the ligand FGVR mostly act as antihypertensive and anti coagulant properties. The solution phase synthesis of FGVR is carried out by using 1-Ethyl-3-(3-dimethylaminopropyl carbodiimide (EDC as coupling agents and N-Methyl morpholine (NMM as base. Structure of synthesized FGVR was confirmed by FTIR, 1H NMR and Mass spectral data, and evaluated for antioxidant property by using 1,1-diphenyl-2-picryl-hydrazil (DPPH. method and the synthesized peptides FGVR possess moderate antioxidant activity.

  10. SYNTHESIS, DOCKING STUDIES AND ANTIOXIDANT ACTIVITY OF TETRAPEPTIDE FGVY

    Directory of Open Access Journals (Sweden)

    Md. Abdulla

    2011-03-01

    Full Text Available A rational designing of linear Tetrapeptide FGVY was done and was synthesized by solution phase peptide synthesis. The docking studies of designed linear tetrapeptide FGVY was carried out by using Schrodinger Software Solutions, USA. Qikprop results show the ligand FGVY mostly act as antihypertensive and anti coagulant properties. The solution phase synthesis of FGVY is carried out by using Dicyclohexyl carbodiimide (DCC as coupling agents and triethyl amine as base. Structure of synthesized FGVY was confirmed by FTIR, 1H NMR and Mass spectral data, and evaluated for antioxidant property by using 1,1-diphenyl-2-picryl-hydrazil (DPPH. method and the synthesized peptides FGVY possess moderate antioxidant activity.

  11. Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Pawan Kaushik

    2014-01-01

    Full Text Available The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β, dipeptidyl peptidase-IV (DPP-IV, aldose reductase (AR, and insulin receptor (IR with help of docking software Molegro virtual docker (MVD. From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

  12. Proposed docking interface between peptidoglycan and the target recognition domain of zoocin A

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yinghua [Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487 (United States); Simmonds, Robin S. [Department of Microbiology and Immunology, University of Otago, Dunedin (New Zealand); Timkovich, Russell, E-mail: rtimkovi@bama.ua.edu [Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487 (United States)

    2013-11-15

    Highlights: •Peptidoglycan added to zoocin rTRD perturbs NMR resonances around W115. •Simulations predict docking to a shallow surface groove near W115. •The docking interface is similar to mammalian antibody–antigen sites. •EDTA binds to a distinct surface site. -- Abstract: A docking model is proposed for the target recognition domain of the lytic exoenzyme zoocin A with the peptidoglycan on the outer cell surface of sensitive bacterial strains. Solubilized fragments from such peptidoglycans perturb specific backbone and side chain amide resonances in the recombinant form of the domain designated rTRD as detected in two-dimensional {sup 1}H–{sup 15}N correlation NMR spectra. The affected residues comprise a shallow surface cleft on the protein surface near W115, N53, N117, and Q105 among others, which interacts with the peptide portion of the peptidoglycan. Calculations with AutoDock Vina provide models of the docking interface. There is approximate homology between the rTDR-peptidoglycan docking site and the antigen binding site of Fab antibodies with the immunoglobin fold. EDTA was also found to bind to rTRD, but at a site distinct from the proposed peptidoglycan docking site.

  13. Dissecting docking and tethering of secretory vesicles at the target membrane

    Science.gov (United States)

    Toonen, Ruud F; Kochubey, Olexiy; de Wit, Heidi; Gulyas-Kovacs, Attila; Konijnenburg, Bas; Sørensen, Jakob B; Klingauf, Jurgen; Verhage, Matthijs

    2006-01-01

    Secretory vesicles dock at their target in preparation for fusion. Using single-vesicle total internal reflection fluorescence microscopy in chromaffin cells, we show that most approaching vesicles dock only transiently, but that some are captured by at least two different tethering modes, weak and strong. Both vesicle delivery and tethering depend on Munc18-1, a known docking factor. By decreasing the amount of cortical actin by Latrunculin A application, morphological docking can be restored artificially in docking-deficient munc18-1 null cells, but neither strong tethering nor fusion, demonstrating that morphological docking is not sufficient for secretion. Deletion of the t-SNARE and Munc18-1 binding partner syntaxin, but not the v-SNARE synaptobrevin/VAMP, also reduces strong tethering and fusion. We conclude that docking vesicles either undock immediately or are captured by minimal tethering machinery and converted in a munc18-1/syntaxin-dependent, strongly tethered, fusion-competent state. PMID:16902411

  14. Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro.

    Science.gov (United States)

    Oda, Toshiyuki; Abe, Tatsuki; Yanagisawa, Haruaki; Kikkawa, Masahide

    2016-04-15

    The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods. We found that the ODAs can bind to DMTs and porcine microtubules with 24-nm periodicities even in the absence of the docking complexin vitro Using cryo-electron tomography and structural labeling, we observed that the docking complex took an unexpectedly flexible conformation and did not lie along the length of DMTs. In the absence of docking complex, ODAs were released from the DMT at relatively low ionic strength conditions, suggesting that the docking complex strengthens the electrostatic interactions between the ODA and DMT. Based on these results, we conclude that the docking complex serves as a flexible stabilizer of the ODA rather than as a molecular ruler.

  15. The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion

    DEFF Research Database (Denmark)

    Frank, S R; Köllmann, C P; van Lidth de Jeude, J F;

    2017-01-01

    DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest...... with these cells. Collectively, our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases.Oncogene advance online publication, 26 September 2016; doi...

  16. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

    Science.gov (United States)

    Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

    2016-01-01

    Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

  17. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

    Directory of Open Access Journals (Sweden)

    Ye Fang

    Full Text Available Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU. First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

  18. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

    Science.gov (United States)

    Fang, Ye; Ding, Yun; Feinstein, Wei P; Koppelman, David M; Moreno, Juana; Jarrell, Mark; Ramanujam, J; Brylinski, Michal

    2016-01-01

    Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

  19. Self Organization in Compensated Semiconductors

    Science.gov (United States)

    Berezin, Alexander A.

    2004-03-01

    In partially compensated semiconductor (PCS) Fermi level is pinned to donor sub-band. Due to positional randomness and almost isoenergetic hoppings, donor-spanned electronic subsystem in PCS forms fluid-like highly mobile collective state. This makes PCS playground for pattern formation, self-organization, complexity emergence, electronic neural networks, and perhaps even for origins of life, bioevolution and consciousness. Through effects of impact and/or Auger ionization of donor sites, whole PCS may collapse (spinodal decomposition) into microblocks potentially capable of replication and protobiological activity (DNA analogue). Electronic screening effects may act in RNA fashion by introducing additional length scale(s) to system. Spontaneous quantum computing on charged/neutral sites becomes potential generator of informationally loaded microstructures akin to "Carl Sagan Effect" (hidden messages in Pi in his "Contact") or informational self-organization of "Library of Babel" of J.L. Borges. Even general relativity effects at Planck scale (R.Penrose) may affect the dynamics through (e.g.) isotopic variations of atomic mass and local density (A.A.Berezin, 1992). Thus, PCS can serve as toy model (experimental and computational) at interface of physics and life sciences.

  20. Compensation following bilateral vestibular damage

    Directory of Open Access Journals (Sweden)

    Bill J Yates

    2011-12-01

    Full Text Available Bilateral loss of vestibular inputs affects far fewer patients than unilateral inner ear damage, and thus has been understudied. In both animal subjects and human patients, bilateral vestibular hypofunction (BVH produces a variety of clinical problems, including impaired balance control, inability to maintain stable blood pressure during postural changes, difficulty in visual targeting of images, and disturbances in spatial memory and navigational performance. Experiments in animals have shown that nonlabyrinthine inputs to the vestibular nuclei are rapidly amplified following the onset of BVH, which may explain the recovery of postural stability and orthostatic tolerance that occurs within 10 days. However, the loss of the vestibulo-ocular reflex and degraded spatial cognition appear to be permanent in animals with BVH. Current concepts of the compensatory mechanisms in humans with BVH are largely inferential, as there is a lack of data from patients early in the disease process. Translation of animal studies of compensation for BVH into therapeutic strategies and subsequent application in the clinic is the most likely route to improve treatment. In addition to physical therapy, two types of prosthetic devices have been proposed to treat individuals with bilateral loss of vestibular inputs: those that provide tactile stimulation to indicate body position in space, and those that deliver electrical stimuli to branches of the vestibular nerve in accordance with head movements. The relative efficacy of these two treatment paradigms, and whether they can be combined to facilitate recovery, is yet to be ascertained.

  1. GVD compensation schemes with considering PMD

    Institute of Scientific and Technical Information of China (English)

    Aiying Yang(杨爱英); Anshi Xu(徐安士); Deming Wu(吴德明)

    2003-01-01

    Three group velocity dispersion (GVD) compensation schemes, i.e., the post-compensation, pre-compensation and hybrid-compensation schemes, are discussed with considering polarization mode disper-sion (PMD). In the 10- and 40-Gbit/s non-return-zero (NRZ) on-off-key (OOK) systems, three physicalfactors, Kerr effect, GVD and PMD are considered. The numerical results show that, when the impactof PMD is taken into account, the GVD pre-compensation scheme performs best with more than 1 dBbetter of average eye-opening penalty (EOP) when input power is up to 10 dBm in the 10-Gbit/s system.However the GVD post-compensation scheme perforns best for the case of 40 Gbit/s with input power lessthan 13 dBm, and GVD pre-compensation will be better if the input power increased beyond this range.The results are different from those already reported under the assumption that the impact of PMD isneglected. Therefore, the research in this paper provide a different insight into the system optimizationwhen PMD, Kerr effect and GVD are considered.

  2. Docking System Design and Self-Assembly Control of Distributed Swarm Flying Robots

    Directory of Open Access Journals (Sweden)

    Hongxing Wei

    2012-11-01

    Full Text Available This paper presents a novel docking system design and the distributed self‐assembly control strategy for a Distributed Swarm Flying Robot (DSFR. The DSFR is a swarm robot comprising many identical robot modules that are able to move on the ground, dock with each other and fly coordinately once self‐assembled into a robotic structure. A generalized adjacency matrix method is proposed to describe the configurations of robotic structures. Based on the docking system and the adjacency matrix, experiments are performed to demonstrate and verify the self‐assembly control strategy.

  3. Small-molecule library screening by docking with PyRx.

    Science.gov (United States)

    Dallakyan, Sargis; Olson, Arthur J

    2015-01-01

    Virtual molecular screening is used to dock small-molecule libraries to a macromolecule in order to find lead compounds with desired biological function. This in silico method is well known for its application in computer-aided drug design. This chapter describes how to perform small-molecule virtual screening by docking with PyRx, which is open-source software with an intuitive user interface that runs on all major operating systems (Linux, Windows, and Mac OS). Specific steps for using PyRx, as well as considerations for data preparation, docking, and data analysis, are also described.

  4. A holistic molecular docking approach for predicting protein-protein complex structure

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A holistic protein-protein molecular docking approach,HoDock,was established,composed of such steps as binding site prediction,initial complex structure sampling,refined complex structure sampling,structure clustering,scoring and final structure selection.This article explains the detailed steps and applications for CAPRI Target 39.The CAPRI result showed that three predicted binding site residues,A191HIS,B512ARG and B531ARG,were correct,and there were five submitted structures with a high fraction of correct receptor-ligand interface residues,indicating that this docking approach may improve prediction accuracy for protein-protein complex structures.

  5. Protein-protein docking using region-based 3D Zernike descriptors

    Directory of Open Access Journals (Sweden)

    Sael Lee

    2009-12-01

    Full Text Available Abstract Background Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-αRMSD ≤ 2.5 Å within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for

  6. Ligand-protein docking using a quantum stochastic tunneling optimization method.

    Science.gov (United States)

    Mancera, Ricardo L; Källblad, Per; Todorov, Nikolay P

    2004-04-30

    A novel hybrid optimization method called quantum stochastic tunneling has been recently introduced. Here, we report its implementation within a new docking program called EasyDock and a validation with the CCDC/Astex data set of ligand-protein complexes using the PLP score to represent the ligand-protein potential energy surface and ScreenScore to score the ligand-protein binding energies. When taking the top energy-ranked ligand binding mode pose, we were able to predict the correct crystallographic ligand binding mode in up to 75% of the cases. By using this novel optimization method run times for typical docking simulations are significantly shortened.

  7. Result of Rendezvous Docking Experiment of ETS.35zw .5zw .25mmVII

    Science.gov (United States)

    Kawano, Isao; Mokuno, Masaaki; Suzuki, Takashi; Koyama, Hiroshi; Kunugi, Makoto

    ETS VII is a test satellite to perform in-orbit demonstration of autonomous rendezvous docking (RVD) technology, which will be necessary for advanced space activities in the early 21st century. ETS VII performed three RVD experiment flights, and verified all technical items. ETS VII demonstrated first autonomous RVD between unmanned vehicles, and remote piloted rendezvous flight position accuracy at docking was about 1cm, and acceleration was less than 1.5mG (low impact docking). In the second RVD experiment flight, ETS VII detected attitude anomaly and executed disable abort for safety insurance. We present the results and evaluation of three RVD experiment flights in this paper.

  8. Compensator configurations for load currents' symmetrization

    Science.gov (United States)

    Rusinaru, D.; Manescu, L. G.; Dinu, R. C.

    2016-02-01

    This paper approaches aspects regarding the mitigation effects of asymmetries in 3-phase 3-wire networks. The measure consisting in connecting of load current symmetrization devices at the load coupling point is presented. A time-variation of compensators parameters is determined as a function of the time-recorded electrical values. The general sizing principle of the load current symmetrization reactive components is based on a simple equivalent model of the unbalanced 3-phase loads. By using these compensators a certain control of the power components transits is ensured in the network. The control is based on the variations laws of the compensators parameters as functions of the recorded electrical values: [B] = [T]·[M]. The link between compensator parameters and measured values is ensured by a transformation matrix [T] for each operation conditions of the supply network. Additional conditions for improving of energy and efficiency performance of the compensator are considered: i.e. reactive power compensation. The compensator sizing algorithm was implemented into a MATLAB environment software, which generate the time-evolution of the parameters of load current symmetrization device. The input data of application takes into account time-recording of the electrical values. By using the compensator sizing software, some results were achieved for the case of a consumer connected at 20 kV busbar of a distribution substation, during 24 hours measurement session. Even the sizing of the compensators aimed some additional network operation aspects (power factor correction) correlated with the total or major load symmetrizations, the harmonics aspects of the network values were neglected.

  9. Lossless Compression of Video using Motion Compensation

    DEFF Research Database (Denmark)

    Martins, Bo; Forchhammer, Søren

    1998-01-01

    We investigate lossless coding of video using predictive coding andmotion compensation. The methods incorporate state-of-the-art lossless techniques such ascontext based prediction and bias cancellation, Golomb coding, high resolution motion field estimation,3d-dimensional predictors, prediction...... using one or multiple previous images, predictor dependent error modelling, and selection of motion field by code length. For slow pan or slow zoom sequences, coding methods that use multiple previous images are up to 20% better than motion compensation using a single previous image and up to 40% better...... than coding that does not utilize motion compensation....

  10. Ion dynamics in plasma compensation scheme

    Energy Technology Data Exchange (ETDEWEB)

    Timofeev, I.V.; Lotov, K.V. E-mail: lotov@inp.nsk.su

    2002-06-11

    In this paper the ability of a plasma to compensate beam-induced fields at the interaction point of muon colliders is discussed. Among numerous factors that limit beam and plasma parameters for which a given compensation degree can be achieved, one of the most important limitations (the motion of plasma ions) is analyzed in details. It is found that this limitation is determined by an instability of the relative motion of plasma electrons and ions. It is shown that discussed parameters of ultimate muon colliders fall outside the applicability area of plasma compensation.

  11. Compensation for occupational diseases in the RSA.

    Science.gov (United States)

    Myers, J E; Garisch, D; Cornell, J E

    1987-03-01

    Compensation legislation for occupational disease in the RSA is at present complex and non-uniform, and the administrative bodies that process compensation claims are understaffed. In this setting occupational disease, particularly in migrant workers who are often ignorant of their rights under the law, frequently goes uncompensated. General practitioners and medical officers need to be aware of the basic provisions in the law, and how to submit claims in the best interests of their patients. Some case studies are included to illustrate problematic areas. The responsibilities of doctors in the diagnosis and compensation of occupational diseases are addressed.

  12. A salaried compensation model for postanesthesia nurses.

    Science.gov (United States)

    Mushala, M E; Henderson, M A

    1995-08-01

    Health care organizations involved in innovative and creative work redesign projects may find traditional pay structures inadequate to meet the needs of the changing environment. The idea of salaried compensation for registered nurses is not unprecedented. However, few salaried compensation models for nurses are described in the literature. This article presents a model that we believe will be of particular interest to nurses in PACUs, because its design allows for adequate call coverage plus flexibility in scheduling. In addition, this compensation model eliminates incidental overtime, thus allowing for a more predictable salary budget.

  13. Advanced median method for timing jitter compensation

    Institute of Scientific and Technical Information of China (English)

    Wang Chen; Zhu Jiangmiao; Jan Verspecht; Liu Mingliang; Li Yang

    2008-01-01

    Timing jitter is one of the main factors that influence on the accuracy of time domain precision measurement. Timing jitter compensation is one of the problems people concern. Because of the flaws of median method, PDF deconvolution method and synthetic method, we put forward a new method for timing jitter compensation, which is called advanced median method. The theory of the advanced median method based on probability and statistics is analyzed, and the process of the advanced median method is summarized in this paper. Simulation and experiment show that compared with other methods, the new method could compensate timing jitter effectively.

  14. A Study on Compensation for Advertisement Translation

    Institute of Scientific and Technical Information of China (English)

    杨兰兰

    2012-01-01

    Considering the linguistic and cultural difference between English and Chinese, it is inevitable to lose the original musical beauty, visual beauty and original rhetorical devices in advertisements translation. So compensation measures are always taken to compensate the lost information. This paper focuses on the discussion of the features of advertisement, cultural and linguistic differences between English and Chinese advertisements, which result in the loss of information. And compensation strategies on words, musical beauty and rhetorical devices in advertisement translation are introduced in this paper.

  15. Ablation of the microglial protein DOCK2 reduces amyloid burden in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Cimino, Patrick J; Yang, Yue; Li, Xianwu; Hemingway, Jake F; Cherne, Makenzie K; Khademi, Shawn B; Fukui, Yoshinori; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-04-01

    Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity. EP2 ablation in experimental AD results in reduced oxidative damage and amyloid beta (Aβ) burden. This discovery led us to hypothesize that genetic ablation of DOCK2 would replicate the anti-Aβ effects of loss of EP2 in experimental AD. To test this hypothesis, we crossed mice that lacked DOCK2 (DOCK2-/-), were hemizygous for DOCK2 (DOCK2+/-), or that expressed two DOCK2 genes (DOCK2+/+) with APPswe-PS1Δe9 mice (a model of AD). While we found no DOCK2-dependent differences in cortex or in hippocampal microglia density or morphology in APPswe-PS1Δe9 mice, cerebral cortical and hippocampal Aβ plaque area and size were significantly reduced in 10-month-old APPswe-PS1Δe9/DOCK2-/- mice compared with APPswe-PS1Δe9/DOCK2+/+ controls. DOCK2 hemizygous APPswe-PS1Δe9 mice had intermediate Aβ plaque levels. Interestingly, soluble Aβ42 was not significantly different among the three genotypes, suggesting the effects were mediated specifically in fibrillar Aβ. In combination with earlier cell culture results, our in vivo results presented here suggest DOCK2 contributes to Aβ plaque burden via regulation of microglial innate immune function and may represent a novel therapeutic target for AD.

  16. 7 CFR 930.61 - Handler compensation.

    Science.gov (United States)

    2010-01-01

    ... Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES... Handling Regulations § 930.61 Handler compensation. Each handler handling cherries from a...

  17. 40 CFR 5.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 5.515 Compensation. A recipient...

  18. 28 CFR 54.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 54.515 Compensation. A recipient...

  19. Comprehensive Environmental Response, Compensation and Liability Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), commonly known as Superfund, provides a federal "superfund" to clean up...

  20. Compensating for estimation smoothing in kriging

    Science.gov (United States)

    Olea, R.A.; Pawlowsky, Vera

    1996-01-01

    Smoothing is a characteristic inherent to all minimum mean-square-error spatial estimators such as kriging. Cross-validation can be used to detect and model such smoothing. Inversion of the model produces a new estimator-compensated kriging. A numerical comparison based on an exhaustive permeability sampling of a 4-fr2 slab of Berea Sandstone shows that the estimation surface generated by compensated kriging has properties intermediate between those generated by ordinary kriging and stochastic realizations resulting from simulated annealing and sequential Gaussian simulation. The frequency distribution is well reproduced by the compensated kriging surface, which also approximates the experimental semivariogram well - better than ordinary kriging, but not as well as stochastic realizations. Compensated kriging produces surfaces that are more accurate than stochastic realizations, but not as accurate as ordinary kriging. ?? 1996 International Association for Mathematical Geology.

  1. Boring crustaceans damage polystyrene floats under docks polluting marine waters with microplastic.

    Science.gov (United States)

    Davidson, Timothy M

    2012-09-01

    Boring isopods damage expanded polystyrene floats under docks and, in the process, expel copious numbers of microplastic particles. This paper describes the impacts of boring isopods in aquaculture facilities and docks, quantifies and discusses the implications of these microplastics, and tests if an alternate foam type prevents boring. Floats from aquaculture facilities and docks were heavily damaged by thousands of isopods and their burrows. Multiple sites in Asia, Australia, Panama, and the USA exhibited evidence of isopod damage. One isopod creates thousands of microplastic particles when excavating a burrow; colonies can expel millions of particles. Microplastics similar in size to these particles may facilitate the spread of non-native species or be ingested by organisms causing physical or toxicological harm. Extruded polystyrene inhibited boring, suggesting this foam may prevent damage in the field. These results reveal boring isopods cause widespread damage to docks and are a novel source of microplastic pollution.

  2. Flexibility and explicit solvent in molecular-dynamics-based docking of protein-glycosaminoglycan systems.

    Science.gov (United States)

    Samsonov, Sergey A; Gehrcke, Jan-Philip; Pisabarro, M Teresa

    2014-02-24

    We present Dynamic Molecular Docking (DMD), a novel targeted molecular dynamics-based protocol developed to address ligand and receptor flexibility as well as the inclusion of explicit solvent in local molecular docking. A class of ligands for which docking performance especially benefits from overcoming these challenges is the glycosaminoglycans (GAGs). GAGs are periodic, highly flexible, and negatively charged polysaccharides playing an important role in the extracellular matrix via interaction with proteins such as growth factors and chemokines. The goal of our work has been to develop a proof of concept for an MD-based docking approach and to analyze its applicability for protein-GAG systems. DMD exploits the electrostatics-driven attraction of a ligand to its receptor, treats both as entirely flexible, and considers solvent explicitly. We show that DMD has high predictive significance for systems dominated by electrostatic attraction and demonstrate its capability to reliably identify the receptor residues contributing most to binding.

  3. Why old tires are still being preferred as dock bumpers in harbours

    CERN Document Server

    Lagos, Miguel

    2012-01-01

    The usage of old tires as dock and tugboat bumpers has been a common practice from long ago, proving to be safe for docking even the largest freighters. The reaction force and stored energy of an axially compressed tire is studied in order to determine the specific features of these variables that make tires so adequate as docking protections. The reaction force is attributed to the elastic deformation of the tread, which is modeled as a not too thin cylindrical shell. Most energy absorption takes place after tread buckling, which bends tread and increases its circumference, inducing strong tensile forces that contribute to stabilize the buckled structure. Results shed light on the mechanical properties that a designed dock bumper should exhibit.

  4. Docks and Piers, Fishing Piers in, Published in unknown, Manatee County Information Services Dept..

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Docks and Piers dataset as of unknown. It is described as 'Fishing Piers in'. Data by this publisher are often provided in State Plane coordinate system; in a...

  5. A Ground Testbed to Advance US Capability in Autonomous Rendezvous and Docking Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The entire Agency supports development of a Commodity for Autonomous Rendezvous and Docking (CARD) as outlined in the Agency-wide Community of Practice whitepaper...

  6. In Silico Molecular Docking Analysis of Natural Pyridoacridines as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Vikas Sharma

    2016-01-01

    Full Text Available Docking studies are proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In this study, pyridoacridines containing natural anticancer pigments were subjected to docking studies using Glide (Schrodinger. Investigations were carried out to find out the potential molecular targets for these selected pigments. The docking was carried out on different cancer macromolecules involved in different cell cycle pathways, that is, CDK-2, CDK-6, Bcl-2, VEGFR-2, IGF-1R kinase, and G-Quadruplexes. CDK-6 was found to be the most suitable anticancer target for the pyridoacridines. In addition, effectiveness of the study was further evaluated by performing docking of known inhibitors against their respective selected macromolecules. However, the results are preliminary and experimental evaluation will be carried out in near future.

  7. JL-2: A Mobile Multi-robot System with Docking and Manipulating Capabilities

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2010-02-01

    Full Text Available This paper presents a new version of the JL series reconfigurable multi-robot system called JL-2. By virtue of the docking manipulator composed of a parallel mechanism and a cam gripper, every mobile robot in the JL-2 system is able to not only perform tasks in parallel, e.g. moving and grasping, but also dock with each other even if there are large misalignments between two robots. A motorized spherical joint is formed between two docked robots to enhance the locomotion capability of JL-2. To fulfill the demands of reconfiguration, a distributed control system and sonar based docking guidance system are designed for the JL-2 prototype. Based on the above design, the JL-2 prototype has been built and successfully demonstrated to confirm the validity and functionality of the proposed capabilities.

  8. Multichannel Adaptive Polarization Mode Dispersion Compensation with One Compensator in Dense Wavelength Division Multiplexing Transmission Systems

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qi; CHEN Ming-hua; ZHANG Ji-yu; XIE Shi-zhong

    2007-01-01

    A simple two-section polarization mode dispersion(PMD) compensator is proposed for multichannel PMD compensation, which can compensate two or even more channels simultaneously. Because of the statistical characteristics and the frequency-dependence of PMD, for current single mode fiber with moderate PMD, the probability that all channels are severely degraded at the same time is extremely small, which makes it possible to compensate a dense wavelength division multiplexing(DWDM) transmission system with moderate PMD using this compensator. It is shown that the outage probability of a 40×43Gb/s DWDM transmission system using this compensator is decreased significantly from 3.6×10-3 to 3.6×10-5.

  9. Reversible thyristor converters of brushless synchronous compensators

    Directory of Open Access Journals (Sweden)

    А.М.Galynovskiy

    2013-12-01

    Full Text Available Behavior of models of three-phase-to-single-phase rotary reversible thyristor converters of brushless synchronous compensators in a circuit simulation system is analyzed. It is shown that combined control mode of opposite-connected thyristors may result in the exciter armature winding short circuits both at the thyristor feed-forward and lagging current delay angles. It must be taken into consideration when developing brushless compensator excitation systems.

  10. Reactive power compensation a practical guide

    CERN Document Server

    Hofmann, Wolfgang; Just, Wolfgang

    2012-01-01

    The comprehensive resource on reactive power compensation, presenting the design, application and operation of reactive power equipment and installations The area of reactive power compensation is gaining increasing importance worldwide. If suitably designed, it is capable of improving voltage quality significantly, meaning that losses in equipment and power systems are reduced, the permissible loading of equipment can be increased, and the over-all stability of system operation improved. Ultimately, energy use and CO2 emisson are reduced. This unique guide discusses the

  11. Nonlinear Thermal Compensators for WGM Resonators

    Science.gov (United States)

    Savchenkov, Anatoliy; Matsko, Andrey; Strekalov, Dmitry; Maleki, Lute; Yu, Nan; Iltchenko, Vladimir

    2009-01-01

    In an alternative version of a proposed bimaterial thermal compensator for a whispering-gallery-mode (WGM) optical resonator, a mechanical element having nonlinear stiffness would be added to enable stabilization of a desired resonance frequency at a suitable fixed working temperature. The previous version was described in "Bimaterial Thermal Compensators for WGM Resonators." Both versions are intended to serve as inexpensive means of preventing (to first order) or reducing temperature-related changes in resonance frequencies.

  12. Stock Option Compensation and Managerial Turnover

    OpenAIRE

    Raluca Georgiana NASTASESCU

    2009-01-01

    This study examines the association between managerial turnover and equity-based compensation. I investigate whether stock options act to bond executives to their firms and whether retention of managers is a motivation of companies in designing CEO incentive contracts. The results show that stock options do negatively influence the probability of a CEO leaving the company. The monetary cost of losing the value of equity-based compensation package keeps the manager with his company. I also fin...

  13. Transitioning to value-based physician compensation.

    Science.gov (United States)

    Epstein, Johanna

    2014-12-01

    An effective strategy for creating a viable physician compensation plan should include nine key steps or tactics: Get physicians on board early. Engage a physician champion. Create a compensation committee. Address department-level issues and differences. Verify the plan's affordability. Adopt a routine review schedule. Understand the payer environment and keep in contact with payers. Stay abreast of industry trends. Maintain an ongoing dialogue with physicians.

  14. Improved charge amplifier using hybrid hysteresis compensation

    Science.gov (United States)

    Amin-Shahidi, Darya; Trumper, David L.

    2013-08-01

    We present a novel charge amplifier, with a robust feedback circuit and a method for compensating piezoelectric actuator's hysteresis at low frequencies. The amplifier uses a modified feedback circuit which improves robustness to the addition of series load impedance such as in cabling. We also describe a hybrid hysteresis compensation method for enabling the charge amplifier to reduce hysteresis at low frequencies. Experimental results demonstrate the utility of the new amplifier design.

  15. Compensated Fiber-Optic Frequency Distribution Equipment

    Science.gov (United States)

    2010-11-01

    Meeting 447 UNCOMPENSATED RESULTS The results of the thermal tests are shown in Figures 8 and 9. For the uncompensated link test, we used a...used in IFLs that rely on long-term stability. Figure 8. Thermal test results of the uncompensated link...Figure 9. Thermal test results of the compensated link. The phase variation is almost completely eliminated, confirming the thermal compensation

  16. Dynamic Strain Conductivity of Compensated Silicon

    Science.gov (United States)

    Zainabidinov, S. Z.; Mamatkarimov, O. O.; Tursunov, I. G.; Tuychiev, U. A.

    In this paper the strain thermal Hall effect has been investigated in initial n-Si(P) and strongly compensated n-Si(Ni) samples of different compensation degree, which have been subject to uniform hydrostatic compression (UHC) under a pulse pressure regime ranging from 0 to 7×108 Pa. An experimental investigation of the strain thermal effect in the n-Si(Ni) sample leads to an essential strain conductivity increase, which is largely controlled by density variations of majority carriers.

  17. FlexAID: Revisiting Docking on Non-Native-Complex Structures.

    Science.gov (United States)

    Gaudreault, Francis; Najmanovich, Rafael J

    2015-07-27

    Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. In the present work we introduce FlexAID, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity. The pairwise energy parameters were derived from a large dataset of true positive poses and negative decoys from the PDBbind database through an iterative process using Monte Carlo simulations. The prediction of binding poses is tested using the widely used Astex dataset as well as the HAP2 dataset, while performance in virtual screening is evaluated using a subset of the DUD dataset. We compare FlexAID to AutoDock Vina, FlexX, and rDock in an extensive number of scenarios to understand the strengths and limitations of the different programs as well as to reported results for Glide, GOLD, and DOCK6 where applicable. The most relevant among these scenarios is that of docking on flexible non-native-complex structures where as is the case in reality, the target conformation in the bound form is not known a priori. We demonstrate that FlexAID, unlike other programs, is robust against increasing structural variability. FlexAID obtains equivalent sampling success as GOLD and performs better than AutoDock Vina or FlexX in all scenarios against non-native-complex structures. FlexAID is better than rDock when there is at least one critical side-chain movement required upon ligand binding. In virtual screening, FlexAID results are lower on average than those of AutoDock Vina and rDock. The higher accuracy in flexible targets where critical movements are required, intuitive PyMOL-integrated graphical user interface and free source code as well as precompiled executables for Windows, Linux, and Mac OS make FlexAID a welcome addition to the arsenal of existing small-molecule protein docking methods.

  18. A Minimal Rac Activation Domain in the Unconventional Guanine Nucleotide Exchange Factor Dock180†

    OpenAIRE

    Xin WU; Ramachandran, Sekar; Cerione, Richard A.; Erickson, Jon W.

    2011-01-01

    Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by catalyzing the exchange of bound GDP for GTP, thereby resulting in downstream effector recognition. Two metazoan families of GEFs have been described: Dbl-GEF family members that share conserved Dbl homology (DH) and Pleckstrin homology (PH) domains and the more recently described Dock180 family members that share little sequence homology with the Dbl family and are characterized by conserved Dock homology regions 1 and 2 (DHR...

  19. Evaluation of the coarse-grained OPEP force field for protein-protein docking

    OpenAIRE

    Kynast, Philipp; Derreumaux, Philippe; Strodel, Birgit

    2016-01-01

    International audience; Background: Knowing the binding site of protein–protein complexes helps understand their function and shows possible regulation sites. The ultimate goal of protein–protein docking is the prediction of the three-dimensional structure of a protein–protein complex. Docking itself only produces plausible candidate structures, which must be ranked using scoring functions to identify the structures that are most likely to occur in nature. Methods: In this work, we rescore ri...

  20. Souring control in fluid samples of oil industry using a multiple ligand simultaneous docking (MLSD) strategy.

    Science.gov (United States)

    dos Santos, Elias Silva; de Souza, Leila Cristiane Virgens; de Assis, Patrícia Nascimento; de Almeida, Paulo Fernando; Ramos-de-Souza, Elias

    2015-01-01

    We have used docking techniques in order to propose potential inhibitors to the enzymes adenosine phosphosulfate reductase and adenosine triphosphate sulfurylase that are responsible, among other deleterious effects, for causing souring of oil and gas reservoirs. Three candidates selected through molecular docking revealed new and improved polar and hydrophobic interactions with the above-mentioned enzymes. Microbiological laboratory assays performed subsequently corroborated the results of computer modelling that the three compounds can efficiently control the biogenic sulfide production.

  1. Ranking multiple docking solutions based on the conservation of inter-residue contacts

    KAUST Repository

    Oliva, Romina M.

    2013-06-17

    Molecular docking is the method of choice for investigating the molecular basis of recognition in a large number of functional protein complexes. However, correctly scoring the obtained docking solutions (decoys) to rank native-like (NL) conformations in the top positions is still an open problem. Herein we present CONSRANK, a simple and effective tool to rank multiple docking solutions, which relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. First it calculates a conservation rate for each inter-residue contact, then it ranks decoys according to their ability to match the more frequently observed contacts. We applied CONSRANK to 102 targets from three different benchmarks, RosettaDock, DOCKGROUND, and Critical Assessment of PRedicted Interactions (CAPRI). The method performs consistently well, both in terms of NL solutions ranked in the top positions and of values of the area under the receiver operating characteristic curve. Its ideal application is to solutions coming from different docking programs and procedures, as in the case of CAPRI targets. For all the analyzed CAPRI targets where a comparison is feasible, CONSRANK outperforms the CAPRI scorers. The fraction of NL solutions in the top ten positions in the RosettaDock, DOCKGROUND, and CAPRI benchmarks is enriched on average by a factor of 3.0, 1.9, and 9.9, respectively. Interestingly, CONSRANK is also able to specifically single out the high/medium quality (HMQ) solutions from the docking decoys ensemble: it ranks 46.2 and 70.8% of the total HMQ solutions available for the RosettaDock and CAPRI targets, respectively, within the top 20 positions. © 2013 Wiley Periodicals, Inc.

  2. ClusPro: a fully automated algorithm for protein–protein docking

    OpenAIRE

    Comeau, Stephen R.; Gatchell, David W.; Vajda, Sandor; Camacho, Carlos J.

    2004-01-01

    ClusPro (http://nrc.bu.edu/cluster) represents the first fully automated, web-based program for the computational docking of protein structures. Users may upload the coordinate files of two protein structures through ClusPro's web interface, or enter the PDB codes of the respective structures, which ClusPro will then download from the PDB server (http://www.rcsb.org/pdb/). The docking algorithms evaluate billions of putative complexes, retaining a preset number with favorable surface compleme...

  3. A compensation index for multiattribute decision strategies.

    Science.gov (United States)

    Koele, P; Westenberg, M R

    1995-09-01

    In multiattribute decision problems, the subject has to evaluate a number of alternatives with given values on a number of attributes, in order to arrive at some conclusion about the attractiveness or utility of these alternatives. The information processing procedure leading to a conclusion is called adecision strategy, and one of the main research topics in multiattribute decision research has been the extent to which these strategies follow compensatory principles. Judges are said to follow compensatory strategies when low values on some attributes are compensated for by high values on other attributes. In process tracing studies using the information board technique, descriptions of decision strategies are usually based on three indices of the information search process:variability of search,search pattern (Payne, 1976), anddepth of search. Variability of search, defined as the standard deviation of the proportion of information searched per alternative, is considered to give an indication of the degree of compensation of a decision strategy, compensation being smaller as variability increases. In this article, we propose an alternative way for establishing the degree of compensation of decision strategies in information board studies. We argue that the degree of compensation depends on both variability of searchand depth of search (the proportion of information searched), and that a valid compensation index has to be a multiplicative function of these two indices.

  4. Statutory Compensation for the Wrongly Imprisoned.

    Science.gov (United States)

    Simms, Tina

    2016-04-01

    This article provides an overview of the unique challenges faced by men and women who have been wrongly convicted, imprisoned, and subsequently exonerated, and discusses the relevance of social work to exoneration. The ways in which exonerees can seek compensation are described, and state compensation statutes are examined, delineating monetary and reentry support provisions. Currently, 30 states and the District of Columbia have compensation statutes. Monetary and reentry support provisions vary greatly by state, with few providing both. The wrongly imprisoned experience the same effects of incarceration as other prisoners; their psychological trauma, however, is exacerbated by the fact that they are innocent. Furthermore, upon release, exonerees have fewer reentry supports available to them compared with prisoners released on parole. This article supports the position that the state has a responsibility to provide adequate compensation, monetarily and servicewise, to the wrongly imprisoned, and that compensation by statutory means should be standard in every state. This article also highlights how social workers are uniquely qualified to provide immediate and long-term social and mental health services to exonerees, as well as to advocate for comprehensive exoneree compensation through state statutes.

  5. Overcoming maladaptive plasticity through plastic compensation

    Institute of Scientific and Technical Information of China (English)

    Matthew R.J.MORRIS; Sean M.ROGERS

    2013-01-01

    Most species evolve within fluctuating environments,and have developed adaptations to meet the challenges posed by environmental heterogeneity.One such adaptation is phenotypic plasticity,or the ability of a single genotype to produce multiple environmentally-induced phenotypes.Yet,not all plasticity is adaptive.Despite the renewed interest in adaptive phenotypic plasticity and its consequences for evolution,much less is known about maladaptive plasticity.However,maladaptive plasticity is likely an important driver of phenotypic similarity among populations living in different environments.This paper traces four strategies for overcoming maladaptive plasticity that result in phenotypic similarity,two of which involve genetic changes (standing genetic variation,genetic compensation) and two of which do not (standing epigenetic variation,plastic compensation).Plastic compensation is defined as adaptive plasticity overcoming maladaptive plasticity.In particular,plastic compensation may increase the likelihood of genetic compensation by facilitating population persistence.We provide key terms to disentangle these aspects of phenotypic plasticity and introduce examples to reinforce the potential importance of plastic compensation for understanding evolutionary change.

  6. A comparison of various optimization algorithms of protein-ligand docking programs by fitness accuracy.

    Science.gov (United States)

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

    2014-07-01

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

  7. Connection stiffness and dynamical docking process of flux pinned spacecraft modules

    Science.gov (United States)

    Lu, Yong; Zhang, Mingliang; Gao, Dong

    2014-02-01

    This paper describes a novel kind of potential flux pinned docking system that consists of guidance navigation and control system, the traditional extrusion type propulsion system, and a flux pinned docking interface. Because of characteristics of passive stability of flux pinning, the docking control strategy of flux pinned docking system only needs a series of sequential control rather than necessary active feedback control, as well as avoidance of hazardous collision accident. The flux pinned force between YBaCuO (YBCO) high temperature superconductor bulk and permanent magnet is able to be given vent based on the identical current loop model and improved image dipole model, which can be validated experimentally. Thus, the connection stiffness between two flux pinned spacecraft modules can be calculated based on Hooke's law. This connection stiffness matrix at the equilibrium position has the positive definite performance, which can validate the passively stable connection of two flux pinned spacecraft modules theoretically. Furthermore, the relative orbital dynamical equation of two flux pinned spacecraft modules can be established based on Clohessy-Wiltshire's equations and improved image dipole model. The dynamical docking process between two flux pinned spacecraft modules can be obtained by way of numerical simulation, which suggests the feasibility of flux pinned docking system.

  8. Connection stiffness and dynamical docking process of flux pinned spacecraft modules

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yong; Zhang, Mingliang, E-mail: niudun12@126.com; Gao, Dong [School of Mechatronics Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150001 (China)

    2014-02-14

    This paper describes a novel kind of potential flux pinned docking system that consists of guidance navigation and control system, the traditional extrusion type propulsion system, and a flux pinned docking interface. Because of characteristics of passive stability of flux pinning, the docking control strategy of flux pinned docking system only needs a series of sequential control rather than necessary active feedback control, as well as avoidance of hazardous collision accident. The flux pinned force between YBaCuO (YBCO) high temperature superconductor bulk and permanent magnet is able to be given vent based on the identical current loop model and improved image dipole model, which can be validated experimentally. Thus, the connection stiffness between two flux pinned spacecraft modules can be calculated based on Hooke's law. This connection stiffness matrix at the equilibrium position has the positive definite performance, which can validate the passively stable connection of two flux pinned spacecraft modules theoretically. Furthermore, the relative orbital dynamical equation of two flux pinned spacecraft modules can be established based on Clohessy-Wiltshire's equations and improved image dipole model. The dynamical docking process between two flux pinned spacecraft modules can be obtained by way of numerical simulation, which suggests the feasibility of flux pinned docking system.

  9. Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking

    Directory of Open Access Journals (Sweden)

    Tyagi Sadhna

    2009-06-01

    Full Text Available Abstract Background Previously, ways to adapt docking programs that were developed for modelling inhibitor-receptor interaction have been explored. Two main issues were discussed. First, when trying to model catalysis a reaction intermediate of the substrate is expected to provide more valid information than the ground state of the substrate. Second, the incorporation of protein flexibility is essential for reliable predictions. Results Here we present a predictive and robust method to model substrate specificity and enantioselectivity of lipases and esterases that uses reaction intermediates and incorporates protein flexibility. Substrate-imprinted docking starts with covalent docking of reaction intermediates, followed by geometry optimisation of the resulting enzyme-substrate complex. After a second round of docking the same substrate into the geometry-optimised structures, productive poses are identified by geometric filter criteria and ranked by their docking scores. Substrate-imprinted docking was applied in order to model (i enantioselectivity of Candida antarctica lipase B and a W104A mutant, (ii enantioselectivity and substrate specificity of Candida rugosa lipase and Burkholderia cepacia lipase, and (iii substrate specificity of an acetyl- and a butyrylcholine esterase toward the substrates acetyl- and butyrylcholine. Conclusion The experimentally observed differences in selectivity and specificity of the enzymes were reproduced with an accuracy of 81%. The method was robust toward small differences in initial structures (different crystallisation conditions or a co-crystallised ligand, although large displacements of catalytic residues often resulted in substrate poses that did not pass the geometric filter criteria.

  10. Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

    Science.gov (United States)

    Li, Huameng; Li, Chenglong

    2010-07-30

    Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively.

  11. Vehicle Routing Problem for Fashion Supply Chains with Cross-Docking

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Hu

    2013-01-01

    Full Text Available Cross-docking, as a strategy to reduce lead time and enhance the efficiency of the fashion supply chain, has attracted substantial attention from both the academy and the industry. Cross-docking is a critical part of many fashion and textiles supply chains in practice because it can help to achieve many supply chain strategies such as postponement. We consider a model where there are multiple suppliers and customers in a single cross-docking center. With such a model setting, the issue concerning the coordinated routing between the inbound and outbound routes is much more complex than many traditional vehicle routing problems (VRPs. We formulate the optimal route selection problems from the suppliers to the cross-docking center and from the cross-docking center to the customers as the respective VRPs. Based on the relationships between the suppliers and the customers, we integrate the two VRP models to optimize the overall traveling time, distance, and waiting time at the cross-docking center. In addition, we propose a novel mixed 0/1 integer linear programming model by which the complexity of the problem can be reduced significantly. As demonstrated by the simulation analysis, our proposed model can be solved very efficiently by a commonly used optimization software package.

  12. A possibilistic programming approach for the location problem of multiple cross-docks and vehicle routing scheduling under uncertainty

    Science.gov (United States)

    Meysam Mousavi, S.; Tavakkoli-Moghaddam, Reza; Jolai, Fariborz

    2013-10-01

    This article considers the design of cross-docking systems under uncertainty in a model that consists of two phases: (1) a strategic-based decision-making process for selecting the location of cross-docks to operate, and (2) an operational-based decision-making process for vehicle routing scheduling with multiple cross-docks. This logistic system contains three echelons, namely suppliers, cross-docks and retailers, in an uncertain environment. In the first phase, a new multi-period cross-dock location model is introduced to determine the minimum number of cross-docks among a set of location sites so that each retailer demand should be met. Then, in the second phase, a new vehicle routing scheduling model with multiple cross-docks is formulated in which each vehicle is able to pickup from or deliver to more than one supplier or retailer, and the pickup and delivery routes start and end at the corresponding cross-dock. This article is the first attempt to introduce an integrated model for cross-docking systems design under a fuzzy environment. To solve the presented two-phase mixed-integer programming (MIP) model, a new fuzzy mathematical programming-based possibilistic approach is used. Furthermore, experimental tests are carried out to demonstrate the effectiveness of the presented model. The computational results reveal the applicability and suitability of the developed fuzzy possibilistic two-phase model in a variety of problems in the domain of cross-docking systems.

  13. Clustering molecular dynamics trajectories for optimizing docking experiments.

    Science.gov (United States)

    De Paris, Renata; Quevedo, Christian V; Ruiz, Duncan D; Norberto de Souza, Osmar; Barros, Rodrigo C

    2015-01-01

    Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

  14. Low-Impact Mating System for Docking Spacecraft

    Science.gov (United States)

    Lewis, James L.; Robertson, Brandan; Carroll, Monty B.; Le, Thang; Morales, Ray

    2008-01-01

    A document describes a low-impact mating system suitable for both docking (mating of two free-flying spacecraft) and berthing (in which a robot arm in one spacecraft positions an object for mating with either spacecraft). The low-impact mating system is fully androgynous: it mates with a copy of itself, i.e., all spacecraft and other objects to be mated are to be equipped with identical copies of the system. This aspect of the design helps to minimize the number of unique parts and to standardize and facilitate mating operations. The system includes a closed-loop feedback control subsystem that actively accommodates misalignments between mating spacecraft, thereby attenuating spacecraft dynamics and mitigating the need for precise advance positioning of the spacecraft. The operational characteristics of the mating system can be easily configured in software, during operation, to enable mating of spacecraft having various masses, center-of-gravity offsets, and closing velocities. The system design provides multi-fault tolerance for critical operations: for example, to ensure unmating at a critical time, a redundant unlatching mechanism and two independent pyrotechnic release subsystems are included.

  15. Reducing Seal Adhesion in Low Impact Docking Systems

    Science.gov (United States)

    Banks, Bruce A.; Miller, Sharon K.

    2010-01-01

    Silicone elastomers, used in seals for airlocks or other sealing surfaces in space, are sticky in their as-received condition. Because of the sticking, a greater force may be needed to separate the mating surfaces. If the adhesion is sufficiently high, a sudden unpredicted movement of the spacecraft during undocking, vibration, or uneven release could pull off the seal, resulting in a damage that would have to be repaired before another docking. The damaged seal can result in significant gas leakage and possibly in a catastrophic mishap impacting the safety of the crew. It is also possible that a compromised seal could result in a delayed but sudden gas leak that could put the crew at unexpected risk. This is especially of concern for androgynous seals, which have identical mating surfaces on both sides for interchangeability and redundancy. Such seals typically have elastomer-on-elastomer sealing surfaces. To reduce sticking, one could use release agents such as powders and lubricants, but these can be easily removed and transferred to other surfaces, causing uneven sealing and contamination. Modification of the elastomer surface to make a more slippery and less sticky surface that is integral with the bulk elastomer would be more desirable.

  16. Spectroscopic, quantum chemical calculation and molecular docking of dipfluzine

    Science.gov (United States)

    Srivastava, Karnica; Srivastava, Anubha; Tandon, Poonam; Sinha, Kirti; Wang, Jing

    2016-12-01

    Molecular structure and vibrational analysis of dipfluzine (C27H29FN2O) were presented using FT-IR and FT-Raman spectroscopy and quantum chemical calculations. The theoretical ground state geometry and electronic structure of dipfluzine are optimized by the DFT/B3LYP/6-311++G (d,p) method and compared with those of the crystal data. The 1D potential energy scan was performed by varying the dihedral angle using B3LYP functional at 6-31G(d,p) level of theory and thus the most stable conformer of the compound were determined. Molecular electrostatic potential surface (MEPS), frontier orbital analysis and electronic reactivity descriptor were used to predict the chemical reactivity of molecule. Energies of intra- and inter-molecular hydrogen bonds in molecule and their electronic aspects were investigated by natural bond orbital (NBO). To find out the anti-apoptotic activity of the title compound molecular docking studies have been performed against protein Fas.

  17. Multi-sensor Testing for Automated Rendezvous and Docking

    Science.gov (United States)

    Howard, Richard T.; Carrington, Connie K.

    2008-01-01

    During the past two years, many sensors have been tested in an open-loop fashion in the Marshall Space Flight Center (MSFC) Flight Robotics Laboratory (FRL) to both determine their suitability for use in Automated Rendezvous and Docking (AR&D) systems and to ensure the test facility is prepared for future multi-sensor testing. The primary focus of this work was in support of the CEV AR&D system, because the AR&D sensor technology area was identified as one of the top risks in the program. In 2006, four different sensors were tested individually or in a pair in the MSFC FRL. In 2007, four sensors, two each of two different types, were tested simultaneously. In each set of tests, the target was moved through a series of pre-planned trajectories while the sensor tracked it. In addition, a laser tracker "truth" sensor also measured the target motion. The tests demonstrated the functionality of testing four sensors simultaneously as well as the capabilities (both good and bad) of all of the different sensors tested. This paper outlines the test setup and conditions, briefly describes the facility, summarizes the earlier results of the individual sensor tests, and describes in some detail the results of the four-sensor testing. Post-test analysis includes data fusion by minimum variance estimation and sequential Kalman filtering. This Sensor Technology Project work was funded by NASA's Exploration Technology Development Program.

  18. Inhibitors of polyhydroxyalkanoate (PHA) synthases: synthesis, molecular docking, and implications.

    Science.gov (United States)

    Zhang, Wei; Chen, Chao; Cao, Ruikai; Maurmann, Leila; Li, Ping

    2015-01-01

    Polyhydroxyalkanoate (PHA) synthases (PhaCs) catalyze the formation of biodegradable PHAs that are considered to be ideal alternatives to non-biodegradable synthetic plastics. However, study of PhaCs has been challenging because the rate of PHA chain elongation is much faster than that of initiation. This difficulty, along with lack of a crystal structure, has become the main hurdle to understanding and engineering PhaCs for economical PHA production. Here we report the synthesis of two carbadethia CoA analogues--sT-CH2-CoA (26 a) and sTet-CH2-CoA (26 b)--as well as sT-aldehyde (saturated trimer aldehyde, 29), as new PhaC inhibitors. Study of these analogues with PhaECAv revealed that 26 a/b and 29 are competitive and mixed inhibitors, respectively. Both the CoA moiety and extension of PHA chain will increase binding affinity; this is consistent with our docking study. Estimation of the Kic values of 26 a and 26 b predicts that a CoA analogue incorporating an octameric hydroxybutanoate (HB) chain might facilitate the formation of a kinetically well-behaved synthase.

  19. Molecular docking, spectroscopic studies and quantum calculations on nootropic drug.

    Science.gov (United States)

    Uma Maheswari, J; Muthu, S; Sundius, Tom

    2014-04-05

    A systematic vibrational spectroscopic assignment and analysis of piracetam [(2-oxo-1-pyrrolidineacetamide)] have been carried out using FT-IR and FT-Raman spectral data. The vibrational analysis was aided by an electronic structure calculation based on the hybrid density functional method B3LYP using a 6-311G++(d,p) basis set. Molecular equilibrium geometries, electronic energies, IR and Raman intensities, and harmonic vibrational frequencies have been computed. The assignments are based on the experimental IR and Raman spectra, and a complete assignment of the observed spectra has been proposed. The UV-visible spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies and the maximum absorption wavelengths λmax were determined by the time-dependent DFT (TD-DFT) method. The geometrical parameters, vibrational frequencies and absorption wavelengths were compared with the experimental data. The complete vibrational assignments are performed on the basis of the potential energy distributions (PED) of the vibrational modes in terms of natural internal coordinates. The simulated FT-IR, FT-Raman, and UV spectra of the title compound have been constructed. Molecular docking studies have been carried out in the active site of piracetam by using Argus Lab. In addition, the potential energy surface, HOMO and LUMO energies, first-order hyperpolarizability and the molecular electrostatic potential have been computed.

  20. Noncatalytic Docking Domains of Cellulosomes of Anaerobic Fungi

    Science.gov (United States)

    Steenbakkers, Peter J. M.; Li, Xin-Liang; Ximenes, Eduardo A.; Arts, Jorik G.; Chen, Huizhong; Ljungdahl, Lars G.; Op den Camp, Huub J. M.

    2001-01-01

    A method is presented for the specific isolation of genes encoding cellulosome components from anaerobic fungi. The catalytic components of the cellulosome of anaerobic fungi typically contain, besides the catalytic domain, mostly two copies of a 40-amino-acid cysteine-rich, noncatalytic docking domain (NCDD) interspaced by short linkers. Degenerate primers were designed to anneal to the highly conserved region within the NCDDs of the monocentric fungus Piromyces sp. strain E2 and the polycentric fungus Orpinomyces sp. strain PC-2. Through PCR using cDNA from Orpinomyces sp. and genomic DNA from Piromyces sp. as templates, respectively, 9 and 19 PCR products were isolated encoding novel NCDD linker sequences. Screening of an Orpinomyces sp. cDNA library with four of these PCR products resulted in the isolation of new genes encoding cellulosome components. An alignment of the partial NCDD sequence information obtained and an alignment of database-accessible NCDD sequences, focusing on the number and position of cysteine residues, indicated the presence of three structural subfamilies within fungal NCDDs. Furthermore, evidence is presented that the NCDDs in CelC from the polycentric fungus Orpinomyces sp. strain PC-2 specifically recognize four proteins in a cellulosome preparation, indicating the presence of multiple scaffoldins. PMID:11514516

  1. Identification of Novel Smoothened Ligands Using Structure-Based Docking

    Science.gov (United States)

    Torosyan, Hayarpi; Parathaman, Pranavan; Irwin, John J.; Shoichet, Brian K.

    2016-01-01

    The seven transmembrane protein Smoothened is required for Hedgehog signaling during embryonic development and adult tissue homeostasis. Inappropriate activation of the Hedgehog signalling pathway leads to cancers such as basal cell carcinoma and medulloblastoma, and Smoothened inhibitors are now available clinically to treat these diseases. However, resistance to these inhibitors rapidly develops thereby limiting their efficacy. The determination of Smoothened crystal structures enables structure-based discovery of new ligands with new chemotypes that will be critical to combat resistance. In this study, we docked 3.2 million available, lead-like molecules against Smoothened, looking for those with high physical complementarity to its structure; this represents the first such campaign against the class Frizzled G-protein coupled receptor family. Twenty-one high-ranking compounds were selected for experimental testing, and four, representing three different chemotypes, were identified to antagonize Smoothened with IC50 values better than 50 μM. A screen for analogs revealed another six molecules, with IC50 values in the low micromolar range. Importantly, one of the most active of the new antagonists continued to be efficacious at the D473H mutant of Smoothened, which confers clinical resistance to the antagonist vismodegib in cancer treatment. PMID:27490099

  2. Peptides Trapping Dioxins: A Docking-Based Inverse Screening Approach

    Directory of Open Access Journals (Sweden)

    German Perez

    2013-01-01

    Full Text Available A rapid and cost-effective computational methodology for designing and rationalizing the selection of small peptides as receptors for dioxin-like compounds was proposed. The backbone of the dioxin Ah receptor binding site was used to design a series of penta- and hexapeptide libraries, with 1400 elements in total. Peptide flexibility was considered and 10 conformers were found to be a good option to represent peptide conformational space with fair speed-accuracy ratio. Each peptide conformer was treated as a possible receptor, generating a dedicated box and then running a docking process using as ligands a family of 76 dibenzo-p-dioxins and 113 dibenzofurans mono- and polychlorinated. Significant predictions were confirmed by comparing primary structure of top and bottom ranked peptides binding dioxins confirming that scrambled positions of the same amino acids gave completely different predicted binding. The hexapeptide EWFQPW, with the best binding score, was chosen as selective sorbent material in solid-phase extraction. The retention performances were tested using the 2,3,7,8-tetrachlorodibenzo-p-dioxin and two polychlorinated biphenyls in order to verify the hexapeptide specificity. The solid-phase extraction experimental procedure was optimized, and analytical parameters of hexapeptide sorbent material were compared with the resin without hexapeptide and a commercial reversed phase cartridge.

  3. 20 CFR 226.63 - Determining monthly compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Determining monthly compensation. 226.63... COMPUTING EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Years of Service and Average Monthly Compensation § 226.63 Determining monthly compensation. (a) Based on yearly compensation. If Board records do...

  4. 20 CFR 336.4 - Base year compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Base year compensation. 336.4 Section 336.4... DURATION OF NORMAL AND EXTENDED BENEFITS Normal Benefits § 336.4 Base year compensation. (a) Formula. For the purposes of this part, an employee's base year compensation includes any compensation in excess...

  5. 46 CFR 535.803 - Ocean freight forwarder compensation.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Ocean freight forwarder compensation. 535.803 Section... Mandatory and Prohibited Provisions § 535.803 Ocean freight forwarder compensation. No conference or group... compensation paid to an ocean freight forwarder; or (b) Agree to limit the payment of compensation to an...

  6. 50 CFR 296.4 - Claims eligible for compensation.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Claims eligible for compensation. 296.4... compensation. (a) Claimants. Damage or loss eligible for Fund compensation must be suffered by a commercial fisherman. (b) Damage or loss of fishing gear. Damage or loss is eligible for Fund compensation if it...

  7. 47 CFR 64.1310 - Payphone compensation procedures.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Payphone compensation procedures. 64.1310... compensation procedures. (a) Unless the payphone service provider consents to an alternative compensation... not unreasonably withhold its consent to an alternative compensation arrangement. (1) Each...

  8. 46 CFR 2.01-60 - Overtime compensation.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Overtime compensation. 2.01-60 Section 2.01-60 Shipping... Inspecting and Certificating of Vessels § 2.01-60 Overtime compensation. (a) General. Extra compensations for... method of computing such extra compensation. (b) Application and certification of time. Application...

  9. 48 CFR 852.236-86 - Workers' compensation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Workers' compensation. 852... Workers' compensation. As prescribed in 836.577, insert the following clause: Workers' Compensation (JAN... workers compensation laws to all lands and premises owned or held by the United States. (End of clause)...

  10. 39 CFR 3.2 - Compensation of Board.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Compensation of Board. 3.2 Section 3.2 Postal... (ARTICLE III) § 3.2 Compensation of Board. Section 202(a)(1) of title 39 provides for the compensation of... meetings. Compensation is provided for not more than 42 days of meetings per year....

  11. 20 CFR 211.5 - Employee representative compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Employee representative compensation. 211.5... CREDITABLE RAILROAD COMPENSATION § 211.5 Employee representative compensation. All payments made by a railway... office he occupies with such organization are creditable as compensation, including payments made...

  12. 31 CFR 30.0 - Executive compensation and corporate governance.

    Science.gov (United States)

    2010-07-01

    ... STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.0 Executive compensation and corporate governance. The following questions and answers reflect the executive compensation and corporate governance... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Executive compensation and...

  13. 12 CFR 918.2 - Annual directors' compensation policy.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Annual directors' compensation policy. 918.2... HOME LOAN BANKS BANK DIRECTOR COMPENSATION AND EXPENSES § 918.2 Annual directors' compensation policy... written policy to provide for the payment to Bank directors of reasonable compensation for the...

  14. 76 FR 18966 - Listing Standards for Compensation Committees

    Science.gov (United States)

    2011-04-06

    ... the compensation consultant, legal counsel, or other adviser; The policies and procedures of the... COMMISSION 17 CFR Parts 229 and 240 RIN 3235-AK95 Listing Standards for Compensation Committees AGENCY... issuer that is not in compliance with Section 10C's compensation committee and compensation...

  15. 12 CFR 918.3 - Compensation policy requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Compensation policy requirements. 918.3 Section... LOAN BANKS BANK DIRECTOR COMPENSATION AND EXPENSES § 918.3 Compensation policy requirements. Payment to directors under each Bank's policy on director compensation may be based upon factors that the...

  16. Neurovestibular Compensation following Ototoxic Lesion and Labyrinthectomy

    Directory of Open Access Journals (Sweden)

    Yazdanshenas, Hamed

    2016-03-01

    Full Text Available Introduction Unilateral labyrinthectomy and intra-tympanic gentamycin have been employed in the treatment of Ménière's disease, but the efficacy of these techniques has not been well established. Objective The objective of this study is to measure the time course of recovery from a unilateral labyrinthectomy either after ipsilateral topical treatment with gentamicin to the inner ear or without the previous insult. Methods Twenty-nine adult Mongolian gerbils were randomized into two experimental groups. Group 1 (n = 17 received a right ear gentamicin drug-induced lesion by unilateral labyrinthectomy (UL. Group 2 (n = 12 only received a right unilateral labyrinthectomy lesion. We measured the horizontal vestibulo-ocular responses in gerbils before and after the lesion. The gerbils received an angular acceleration stimulus and their eye movements were recorded. Results The gentamicin lesion resulted in a quicker recovery. Experimental groups underwent a similar time course of recovery. Statistical analysis showed no significant difference between the two groups. Both groups displayed adaptation to the lesion by day 21, but long-term compensation did not completely revert to the original pre-lesion state. Conclusions In a lesion requiring both static and dynamic compensation as in UL, the need for a static compensation may alter pre-existing compensation from a previous dynamic insult and require a new compensation. A previous lesion and adaptation is not preserved for a second lesion and the subject has to re-compensate. Therefore, surgical treatment in Meniere's disease such as UL can be considered without prior gentamicin treatment. Static and dynamic compensations do not appear to be as independent as previous studies have suggested.

  17. Nonlinear scoring functions for similarity-based ligand docking and binding affinity prediction.

    Science.gov (United States)

    Brylinski, Michal

    2013-11-25

    A common strategy for virtual screening considers a systematic docking of a large library of organic compounds into the target sites in protein receptors with promising leads selected based on favorable intermolecular interactions. Despite a continuous progress in the modeling of protein-ligand interactions for pharmaceutical design, important challenges still remain, thus the development of novel techniques is required. In this communication, we describe eSimDock, a new approach to ligand docking and binding affinity prediction. eSimDock employs nonlinear machine learning-based scoring functions to improve the accuracy of ligand ranking and similarity-based binding pose prediction, and to increase the tolerance to structural imperfections in the target structures. In large-scale benchmarking using the Astex/CCDC data set, we show that 53.9% (67.9%) of the predicted ligand poses have RMSD of <2 Å (<3 Å). Moreover, using binding sites predicted by recently developed eFindSite, eSimDock models ligand binding poses with an RMSD of 4 Å for 50.0-39.7% of the complexes at the protein homology level limited to 80-40%. Simulations against non-native receptor structures, whose mean backbone rearrangements vary from 0.5 to 5.0 Å Cα-RMSD, show that the ratio of docking accuracy and the estimated upper bound is at a constant level of ∼0.65. Pearson correlation coefficient between experimental and predicted by eSimDock Ki values for a large data set of the crystal structures of protein-ligand complexes from BindingDB is 0.58, which decreases only to 0.46 when target structures distorted to 3.0 Å Cα-RMSD are used. Finally, two case studies demonstrate that eSimDock can be customized to specific applications as well. These encouraging results show that the performance of eSimDock is largely unaffected by the deformations of ligand binding regions, thus it represents a practical strategy for across-proteome virtual screening using protein models. eSimDock is freely

  18. 38 CFR 21.3023 - Nonduplication; pension, compensation, and dependency and indemnity compensation.

    Science.gov (United States)

    2010-07-01

    ... parents. Where, however, entitlement is based on the death of more than one parent in the same parental... before attaining age 18 or while helpless based on the service of another parent in the same parental... concurrently with pension, compensation or dependency and indemnity compensation. (Authority: 38 U.S.C....

  19. An Economic Analysis of Compensation for Rural Land Expropriation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    To study which method is more effective in complete compensation and zero compensation for rural land expropriation,we use economic models to analyze whether the government is benevolent and which compensation method can achieve the social optimal level.The results show that both complete compensation and zero compensation will lead to over-investment of land owners,and consequently result in loss of social welfare.

  20. Producer Compensation under Government Programs: What Should the Magnitude Be?

    OpenAIRE

    Haynes, Dwayne J.; Schmitz, Andrew; Troy G. SCHMITZ

    2015-01-01

    When policies are changed it is not uncommon for losers to be compensated. Economic theory and quantitative analysis are useful in determining the efficiency gains/losses associated with a policy change, but are little help in deciding what the approach to compensation should be. The amount of compensation varies, depending on, in part, the political clout of the parties being negatively affected by a policy change—compensation is what politicians and the sector demanding compensation can agr...

  1. [Dosage compensation mechanism of X chromosome].

    Science.gov (United States)

    Wang, Yan-Yun; Chen, Mei; Li, Bin

    2012-08-01

    Dosage compensation mechanism is crucial for the balance expression of X chromosome genes, which ensures the protein or enzyme encoded by the X chromosome to be equal or almost equal expression amounts between males and females. However, different organisms have evolved distinct dosage compensation strategies, and so far three kinds of dosage compensation strategies among organisms have been reported. The first strategy is that the single male X chromosome expression is doubly activated; the second one is to inactivate one female X chromosome by leaving both sexes with one active allele; and the third one is to reduce the expression to half activity in both X chromosomes of the female. The study of dosage compensation will be useful to reveal the mechanism of regulation of X-linked genes as well as the evolution and the differentiation progress of the sex chromosome, and it can also contribute to illustrate mutation and distortion of sex chromosome. Therefore, this paper briefly reviewed and discussed the progresses and prospects of the important mechanism of dosage compensation.

  2. Managerial Stock Compensation and Risky Investment

    Directory of Open Access Journals (Sweden)

    Raluca Georgiana Nastasescu

    2009-06-01

    Full Text Available This study analyzes the relationship between the mix of CEO equity-based compensation, namely stock options and restricted stock, and firms' risky investment. In general, the theory suggests that long-term compensation aligns CEOs' and shareholders' interests by inducing the managers to undertake risky investment, which has a positive impact on longterm well-being of the firm. However, as my results show, it is important to distinguish between types of awards since they can have different effects on the riskiness of the firm. In this respect, I answer the question how are different types of stock based compensation related to the executives' determination to increase or not the intensity of the firm's risky investment? I find that awarding the CEOs preponderantly with stock options positively affects the firm's level of R&D investment. Conversely, a higher proportion of restricted stock in the CEO's compensation is related to lower investment in (risky R&D. The inverse relation of causality also holds. Firms that make intensive R&D investments are more likely to award their CEOs with more stock options relative to restricted stock. Overall, the results are consistent with the theoretical prediction, in that the managerial compensation scheme plays an important role in determining the level of R&D investment.

  3. Temperature compensation and entrainment in circadian rhythms

    Science.gov (United States)

    Bodenstein, C.; Heiland, I.; Schuster, S.

    2012-06-01

    To anticipate daily variations in the environment and coordinate biological activities into a daily cycle many organisms possess a circadian clock. In the absence of external time cues the circadian rhythm persists with a period of approximately 24 h. The clock phase can be shifted by single pulses of light, darkness, chemicals, or temperature and this allows entrainment of the clock to exactly 24 h by cycles of these zeitgebers. On the other hand, the period of the circadian rhythm is kept relatively constant within a physiological range of constant temperatures, which means that the oscillator is temperature compensated. The mechanisms behind temperature compensation and temperature entrainment are not fully understood, neither biochemically nor mathematically. Here, we theoretically investigate the interplay of temperature compensation and entrainment in general oscillatory systems. We first give an analytical treatment for small temperature shifts and derive that every temperature-compensated oscillator is entrainable to external small-amplitude temperature cycles. Temperature compensation ensures that this entrainment region is always centered at the endogenous period regardless of possible seasonal temperature differences. Moreover, for small temperature cycles the entrainment region of the oscillator is potentially larger for rectangular pulses. For large temperature shifts we numerically analyze different circadian clock models proposed in the literature with respect to these properties. We observe that for such large temperature shifts sinusoidal or gradual temperature cycles allow a larger entrainment region than rectangular cycles.

  4. Using robotics to fold proteins and dock ligands.

    Science.gov (United States)

    Brutlag, Douglas; Apaydin, Serkan; Guestrin, Carlos; Hsu, David; Varma, Chris; Singh, Amit; Latombe, Jean-Claude

    2002-01-01

    The problems of protein folding and ligand docking have been explored largely using molecular dynamics or Monte Carlo methods. These methods are very compute intensive because they often explore a much wider range of energies, conformations and time than necessary. In addition, Monte Carlo methods often get trapped in local minima. We initially showed that robotic motion planning permitted one to determine the energy of binding and dissociation of ligands from protein binding sites (Singh et al., 1999). The robotic motion planning method maps complicated three-dimensional conformational states into a much simpler, but higher dimensional space in which conformational rearrangements can be represented as linear paths. The dimensionality of the conformation space is of the same order as the number of degrees of conformational freedom in three-dimensional space. We were able to determine the relative energy of association and dissociation of a ligand to a protein by calculating the energetics of interaction for a few thousand conformational states in the vicinity of the protein and choosing the best path from the roadmap. More recently, we have applied roadmap planning to the problem of protein folding (Apaydin et al., 2002a). We represented multiple conformations of a protein as nodes in a compact graph with the edges representing the probability of moving between neighboring states. Instead of using Monte Carlo simulation to simulate thousands of possible paths through various conformational states, we were able to use Markov methods to calculate the steady state occupancy of each conformation, needing to calculate the energy of each conformation only once. We referred to this Markov method of representing multiple conformations and transitions as stochastic roadmap simulation or SRS. We demonstrated that the distribution of conformational states calculated with exhaustive Monte Carlo simulations asymptotically approached the Markov steady state if the same Boltzman

  5. Crusader Automated Docking System: Technology support for the Crusader Resupply Team. Interim report, Ammunition Logistics Program

    Energy Technology Data Exchange (ETDEWEB)

    Kring, C.T.; Varma, V.K.; Jatko, W.B.

    1995-11-01

    The US Army and Team Crusader (United Defense, Lockheed Martin Armament Systems, etc.) are developing the next generation howitzer, the Crusader. The development program includes an advanced, self-propelled liquid propellant howitzer and a companion resupply vehicle. The resupply vehicle is intended to rendezvous with the howitzer near the battlefront and replenish ammunition, fuel, and other material. The Army has recommended that Crusader incorporate new and innovative technologies to improve performance and safety. One conceptual design proposes a robotic resupply boom on the resupply vehicle to upload supplies to the howitzer. The resupply boom would normally be retracted inside the resupply vehicle during transit. When the two vehicles are within range of the resupply boom, the boom would be extended to a receiving port on the howitzer. In order to reduce exposure to small arms fire or nuclear, biological, and chemical hazards, the crew would remain inside the resupply vehicle during the resupply operation. The process of extending the boom and linking with the receiving port is called docking. A boom operator would be designated to maneuver the boom into contact with the receiving port using a mechanical joystick. The docking operation depends greatly upon the skill of the boom operator to manipulate the boom into docking position. Computer simulations at the National Aeronautics and Space Administration have shown that computer-assisted or autonomous docking can improve the ability of the operator to dock safely and quickly. This document describes the present status of the Crusader Autonomous Docking System (CADS) implemented at Oak Ridge National laboratory (ORNL). The purpose of the CADS project is to determine the feasibility and performance limitations of vision systems to satisfy the autonomous docking requirements for Crusader and conduct a demonstration under controlled conditions.

  6. Position Control of Motion Compensation Cardiac Catheters

    Science.gov (United States)

    Kesner, Samuel B.; Howe, Robert D.

    2011-01-01

    Robotic catheters have the potential to revolutionize cardiac surgery by enabling minimally invasive structural repairs within the beating heart. This paper presents an actuated catheter system that compensates for the fast motion of cardiac tissue using 3D ultrasound image guidance. We describe the design and operation of the mechanical drive system and catheter module and analyze the catheter performance limitations of friction and backlash in detail. To mitigate these limitations, we propose and evaluate mechanical and control system compensation methods, including inverse and model-based backlash compensation, to improve the system performance. Finally, in vivo results are presented that demonstrate that the catheter can track the cardiac tissue motion with less than 1 mm RMS error. The ultimate goal of this research is to create a fast and dexterous robotic catheter system that can perform surgery on the delicate structures inside of the beating heart. PMID:21874124

  7. Automatic Transaction Compensation for Reliable Grid Applications

    Institute of Scientific and Technical Information of China (English)

    Fei-Long Tang; Ming-Lu Li; Joshua Zhexue Huang

    2006-01-01

    As grid technology is expanding from scientific computing to business applications, service oriented grid computing is aimed at providing reliable services for users and hiding complexity of service processes from them. The grid services for coordinating long-lived transactions that occur in business applications play an important role in reliable grid applications. In this paper, the grid transaction service (GridTS) is proposed for dealing with long-lived business transactions. We present a compensation-based long-lived transaction coordination algorithm that enables users to select results from committed sub-transactions. Unlike other long-lived transaction models that require application programmers to develop corresponding compensating transactions, GridTS can automatically generate compensating transactions on execution of a long-lived grid transaction. The simulation result has demonstrated the feasibility of GridTS and effectiveness of the corresponding algorithm.

  8. Power analysis of static VAr compensators

    Energy Technology Data Exchange (ETDEWEB)

    Quintela, F.R.; Arevalo, J.M.G.; Redondo, R.C. [Escuela Tecnica Superior de Ingenieria Industrial, Universidad de Salamanca, 37700 Bejar (Spain)

    2008-07-15

    Analysis of three-phase loads usually assume them to be three impedances in a star or triangle connection. This is the reason why obtained results can only be considered valid for passive loads, strictly speaking. Analysis leading to the proposal of some static compensators is usually performed in this way, which induces to believe that this compensators are only valid for passive loads. An analysis procedure, which uses only powers to describe loads, is expounded in this paper. If applied to the analysis of static compensators, it reveals unequivocally their usefulness with active and passive three-phase loads. Therefore, this method is more general and, as it will be seen, easier. (author)

  9. Supersymmetric composite gauge fields with compensators

    Science.gov (United States)

    Nishino, Hitoshi; Rajpoot, Subhash

    2016-06-01

    We study supersymmetric composite gauge theory, supplemented with compensator mechanism. As our first example, we give the formulation of N = 1 supersymmetric non-Abelian composite gauge theory without the kinetic term of a non-Abelian gauge field. The important ingredient is the Proca-Stueckelberg-type compensator scalar field that makes the gauge-boson field equation non-singular, i.e., the field equation can be solved for the gauge field algebraically as a perturbative expansion. As our second example, we perform the gauging of chiral-symmetry for N = 1 supersymmetry in four dimensions by a composite gauge field. These results provide supporting evidence for the consistency of the mechanism that combines the composite gauge field formulations and compensator formulations, all unified under supersymmetry.

  10. Bimaterial Thermal Compensators for WGM Resonators

    Science.gov (United States)

    Savchenkov, Anatoliy; Yu, Nan; Maleki, Lute; Iltchenko, Vladimir; Strekalov, Dmitry

    2008-01-01

    Bimaterial thermal compensators have been proposed as inexpensive means of preventing (to first order) or reducing temperature-related changes in the resonance frequencies of whispering-gallery-mode (WGM) optical resonators. A bimaterial compensator would apply, to a WGM resonator, a pressure that would slightly change the shape of the resonator and thereby change its resonance frequencies. Through suitable choice of the compensator dimensions and materials, it should be possible to make the temperature dependence of the pressure-induced frequency shift equal in magnitude and opposite in sign to the temperature dependence of the frequency shift of the uncompensated resonator so that, to first order, a change in temperature would cause zero net change in frequency.

  11. Cross Cutting Relative Navigation Technologies for Improved Landing Accuracy and Vehicle-to-Vehicle Rendezvous and Docking

    Science.gov (United States)

    Miller, K. L.; Masciarelli, J.; Rohrschneider, R. R.

    2012-06-01

    This presentation addresses recent development and test progress, as well as future technology advancement plans for precision landing and Autonomous Rendezvous, Proximity Operations and Docking (ARPOD).

  12. Hybrid compensation arrangement in dispersed generation systems

    DEFF Research Database (Denmark)

    Chen, Zhe; Blaabjerg, Frede; Pedersen, John Kim

    2005-01-01

    This paper presents a hybrid compensation system consisting of an active filter and distributed passive filters. In the system, each individual passive filter is connected to a distortion source and designed to eliminate main harmonics and supply reactive power for the distortion source, while...... are performed for a power system including the dispersed generation units connected into the system through power electronic converters and diode rectifier loads, which produce the distorted waveforms. The simulation results have demonstrated that good compensation effects can be achieved by using the combined...

  13. Filament stretching rheometer: inertia compensation revisited

    DEFF Research Database (Denmark)

    Szabo, Peter; McKinley, Gareth H.

    2003-01-01

    The necessary inertia compensation used in the force balance for the filament stretching rheometer is derived for an arbitrary frame of reference. This enables the force balance to be used to extract correctly the extensional viscosity from measurements of the tensile force at either end of the e......The necessary inertia compensation used in the force balance for the filament stretching rheometer is derived for an arbitrary frame of reference. This enables the force balance to be used to extract correctly the extensional viscosity from measurements of the tensile force at either end...

  14. Security careers skills, compensation, and career paths

    CERN Document Server

    Walker, Stephen W

    2014-01-01

    The third edition of Security Careers is the authoritative reference for current job descriptions and pay practices of security, compliance, ethics, environmental, health and safety occupations. The job descriptions and compensation ranges in this report are drawn from research from the Foushée Group, which has been conducting this research since 1980. Security Careers includes more than 75 job descriptions for security-related positions, which range from the entry-level security guard to the top global corporate executive. It also provides four years of compensation trend data to give a th

  15. Static compensators (STATCOMs) in power systems

    CERN Document Server

    Shahnia, Farhad; Ghosh, Arindam

    2014-01-01

    A static compensator (STATCOM), also known as static synchronous compensator, is a member of the flexible alternating current transmission system (FACTS) devices. It is a power-electronics based regulating device which is composed of a voltage source converter (VSC) and is shunt-connected to alternating current electricity transmission and distribution networks. The voltage source is created from a DC capacitor and the STATCOM can exchange reactive power with the network. It can also supply some active power to the network, if a DC source of power is connected across the capacitor. A STATCOM

  16. Use of industrial robots for hardware-in-the-loop simulation of satellite rendezvous and docking

    Science.gov (United States)

    Ma, Ou; Flores-Abad, Angel; Boge, Toralf

    2012-12-01

    One of the most challenging and risky operations for spacecraft is to perform rendezvous and docking autonomously in space. To ensure a safe and reliable operation, such a mission must be carefully designed and thoroughly verified before a real space mission can be launched. This paper describes the control strategy for achieving high fidelity contact dynamics simulation of a new, robotics-based, hardware-in-the-loop (HIL) rendezvous and docking simulation facility that uses two industrial robots to physically simulate the 6-DOF dynamic maneuvering of two docking satellites. The facility is capable of physically simulating the final approaching within a 25-meter range and the entire docking/capturing process for a satellite on-orbit servicing mission. The key difficulties of using industrial robots for high-fidelity HIL contact dynamics simulation were found and different solution techniques were investigated in the presented project. An admittance control method was proposed to achieve the goal of making the robots in the HIL simulation process match the impedance of the two docking satellites. Simulation study showed the effectiveness and performance of the proposed solution method.

  17. Fully Blind Docking at the Atomic Level for Protein-Peptide Complex Structure Prediction.

    Science.gov (United States)

    Yan, Chengfei; Xu, Xianjin; Zou, Xiaoqin

    2016-10-04

    Protein-peptide interactions play an important role in many cellular processes. In silico prediction of protein-peptide complex structure is highly desirable for mechanistic investigation of these processes and for therapeutic design. However, predicting all-atom structures of protein-peptide complexes without any knowledge about the peptide binding site and the bound peptide conformation remains a big challenge. Here, we present a docking-based method for predicting protein-peptide complex structures, referred to as MDockPeP, which starts with the peptide sequence and globally docks the all-atom, flexible peptide onto the protein structure. MDockPeP was tested on the peptiDB benchmarking database using both bound and unbound protein structures. The results show that MDockPeP successfully generated near-native peptide binding modes in 95.0% of the bound docking cases and in 92.2% of the unbound docking cases. The performance is significantly better than other existing docking methods. MDockPeP is computationally efficient and suitable for large-scale applications.

  18. DockScreen: A Database of In Silico Biomolecular Interactions to Support Computational Toxicology

    Directory of Open Access Journals (Sweden)

    Michael-Rock Goldsmith

    2014-01-01

    Full Text Available We have developed DockScreen, a database of in silico biomolecular interactions designed to enable rational molecular toxicological insight within a computational toxicology framework. This database is composed of chemical/target (receptor and enzyme binding scores calculated by molecular docking of more than 1000 chemicals into 150 protein targets and contains nearly 135 thousand unique ligand/target binding scores. Obtaining this dataset was achieved using eHiTS (Simbiosys Inc., a fragment-based molecular docking approach with an exhaustive search algorithm, on a heterogeneous distributed high-performance computing framework. The chemical landscape covered in DockScreen comprises selected environmental and therapeutic chemicals. The target landscape covered in DockScreen was selected based on the availability of high-quality crystal structures that covered the assay space of phase I ToxCast in vitro assays. This in silico data provides continuous information that establishes a means for quantitatively comparing, on a structural biophysical basis, a chemical’s profile of biomolecular interactions. The combined minimum-score chemical/target matrix is provided.

  19. Full structure building and docking of NifS from extremophile Acidithiobacillus ferrooxidans

    Institute of Scientific and Technical Information of China (English)

    LIU Yuan-dong; QIU Guan-zhou; WANG Hai-dong; JIANG Ying; ZHANG Cheng-gui; XIA Le-xia

    2008-01-01

    The gene iscS-2 from extremophile Acidithiobacillus ferrooxidans may play a crucial role in nitrogenase maturation. To investigate the protein encoded by this gene, a reliable integral three-dimensional molecular structure was built. The obtained structure was further used to search binding sites, carry out the flexible docking with cofactor pyridoxal 5′-phosphate(PLP) and substrate cysteine, and identify its key residues. The docking results of PLP reveal that the residues of Lys203, His100, Thr73, Ser200, His202, Asp177 and Gln180 have large interaction energies and/or hydrogen bonds fixation with PLP. The docking results of cysteine show that the amino group in cysteine is very near His100, Lys203 and PLP, and the interaction energies for cysteine with them are very big. These identified residues are in line with the experimental facts of NifS from other sources. Moreover, the four residues of Asn152, Val179, Ala102 and Met148 in the PLP docking and the two residues of Lys208 and Ala102 in the cysteine docking also have large interaction energies, which are fitly conserved in NifS from all kinds of sources but have not been identified before. According to these results, this gene encodes NifS protein, and the substrate cysteine can be effectively recruited into the active site. Furthermore, all of the above detected key residues are directly responsible for the binding and/or catalysis of PLP and cysteine.

  20. Extension of QM/MM docking and its applications to metalloproteins.

    Science.gov (United States)

    Cho, Art E; Rinaldo, David

    2009-12-01

    To overcome the limitation of conventional docking methods which assume fixed charge model from force field parameters, combined quantum mechanics/molecular mechanics (QM/MM) method has been applied to docking as a variable charge model and shown to exhibit improvement on the docking accuracy over fixed charge based methods. However, it has also been shown that there are a number of examples for which adoption of variable-charge model fails to reproduce the native binding modes. In particular, for metalloproteins, previously implemented method of QM/MM docking failed most often. This class of proteins has highly polarized binding sites at which high-coordinate-numbered metal ions reside. We extend the QM/MM docking method so that protein atoms surrounding the binding site along with metal ions are included as quantum region, as opposed to only ligand atoms. This extension facilitates the required scaling of partial charges on metal ions leading to prediction of correct binding modes in metalloproteins.

  1. Effects of Low Earth Orbit on Docking Seal Materials

    Science.gov (United States)

    Imka, Emily C.; Asmar, Olivia C.; deGroh, Henry C., III; Banks, Bruce A.

    2014-01-01

    Spacecraft docking seals are typically made of silicone elastomers. When such seals are exposed to low Earth orbit (LEO) conditions, they can suffer damage from ultraviolet (UV) radiation and atomic oxygen (AO, or monoatomic oxygen, the predominant oxygen species in LEO). An experiment flew on the International Space Station (ISS) to measure the effects of LEO on seal materials S0383-70 and ELA-SA-401 and various mating counterface materials which included anodized aluminum. Samples flown in different orientations received different amounts of UV and AO. The hypotheses were that most of the damage would be from UV, and 10 days or more of exposure in LEO would badly damage the seals. Eighteen seals were exposed for 543 days in ram (windward), zenith (away from Earth), or wake (leeward) orientations, and 15 control samples (not flown) provided undamaged baseline leakage. To determine post-flight leak rates, each of the 33 seals were placed in an O-ring groove of a leak test fixture and pressure tested over time. Resistance temperature detectors (RTDs), pressure transducers, and LabVIEW (National Instruments) programs were used to measure and analyze the temperature and pressure and calculate leakage. Average leakage of control samples was 2.6 x 10(exp -7) lbs/day. LEO exposure did not considerably damage ELA-SA-401. The S0383-70 flight samples leaked at least 10 times more than ELA-SA-401 in all cases except one, demonstrating that ELA-SA-401 may be a more suitable sealing material in LEO. AO caused greater damage than UV; samples in ram orientation (receiving an AO fluence of 4.3 x 10(exp 21) atoms/(sq cm) and in wake (2.9x 10(exp 20) atoms/(sq cm)) leaked more than those in zenith orientation (1.58 x 10(exp 20) atoms/(sq cm)), whereas variations in UV exposure did not seem to affect the samples. Exposure to LEO did less damage to the seals than hypothesized, and the data did not support the conjecture that UV causes more damage than AO.

  2. Large PMD Compensated by Four Free Degrees in OTDM System

    Institute of Scientific and Technical Information of China (English)

    LUO Rui; LI Tang-jun; WANG Mu-guang; JIAN Shui-sheng; XU Jing-jing

    2004-01-01

    By introducing a two-stage polarization mode dispersion (PMD) compensator after a optical fiber link with a large PMD,over 270 ps first-order and 2 000 ps2 high-order PMD was compensated. The results show that the two-stage compensator can be used to PMD compensation in the 20 Gb/s optical time division multiplexing system with 60 km high PMD fiber. After compensating,the 270 ps DGD is changed into max. 7 ps. Moreover,the tunable FBG has a function of dispersion compensation.

  3. The Compensation Committee. Effective Committees. Board Basics.

    Science.gov (United States)

    Tranquada, Robert E.

    2001-01-01

    This booklet describes some of the practices of committees charged with setting the compensation of the college or university president or chancellor. Whether the institution is private or public, the president's income will become public information, and apart from any public relations implications, it simply makes good sense for the compensation…

  4. A slow gravity compensated atom laser

    DEFF Research Database (Denmark)

    Kleine Büning, G.; Will, J.; Ertmer, W.

    2010-01-01

    We report on a slow guided atom laser beam outcoupled from a Bose–Einstein condensate of 87Rb atoms in a hybrid trap. The acceleration of the atom laser beam can be controlled by compensating the gravitational acceleration and we reach residual accelerations as low as 0.0027 g. The outcoupling me...

  5. An Analysis of Military Disability Compensation

    Science.gov (United States)

    2005-01-01

    2005. Durbin, David and Jennifer Kish. “Factors Affecting Permanent Partial Disability Ratings in Workers’ Compensation,” The Journal of Risk and Insurance , 65...USA Today, May 5, 2004, 1. Park, Yong-Seung and Richard Butler. “Permanent Partial Disability Awards and Wage Loss.” Journal of Risk and Insurance 67

  6. 7 CFR 301.74-5 - Compensation.

    Science.gov (United States)

    2010-01-01

    ... marketers. Orchard owners eligible for compensation under this paragraph who market all fruit they produce...) Direct marketers. Owners of commercial stone fruit orchards who APHIS has determined meet the eligibility... marketers. The completed application must be accompanied by: (i) A copy of the emergency action...

  7. Compensation for forest ecological services in China

    Institute of Scientific and Technical Information of China (English)

    Liu Can; Wang Sen; Zhang Wei; Liang Dan

    2007-01-01

    The paper discusses methods to compensate for the costs incurred in the supply of forest ecological services (FES), i.e.government dominated and market-based instruments as well as progress made so far in China. Factors which constrain the supply of these services and potential policy improvements are presented.

  8. On the compensation effect in heterogeneous catalysis

    DEFF Research Database (Denmark)

    Pedersen, Thomas Bligaard; Honkala, Johanna Karoliina; Logadottir, Ashildur

    2003-01-01

    For a class of heterogeneously catalyzed reactions, we explain the compensation effect in terms of a switching of kinetic regimes leading to a concomitant change in the apparent activation energy and in the prefactor for the overall rate of the reaction. We first use the ammonia synthesis...

  9. Granulate of stainless steel as compensator material

    NARCIS (Netherlands)

    J.P.C. van Santvoort (J. P C)

    1995-01-01

    textabstractCompensators produced with computer controlled milling devices usually consist of a styrofoam mould, filled with an appropriate material. We investigated granulate of stainless steel as filling material. This cheap, easy to use, clean and re-usable material can be obtained with an averag

  10. 31 CFR 28.515 - Compensation.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Compensation. 28.515 Section 28.515 Money and Finance: Treasury Office of the Secretary of the Treasury NONDISCRIMINATION ON THE BASIS OF... of which requires equal skill, effort, and responsibility, and that are performed under...

  11. 77 FR 5381 - Plum Pox Compensation

    Science.gov (United States)

    2012-02-03

    ... owners of non-fruit-bearing ornamental tree nurseries and to increase the amount of compensation that may be paid to eligible owners of commercial stone fruit orchards and fruit tree nurseries whose trees... of commercial stone fruit orchards, including direct marketers, and fruit tree...

  12. T1 VSAT Fade Compensation Statistical Results

    Science.gov (United States)

    Johnson, Sandra K.; Acosta, Roberto; Ugweje, Oke

    2000-01-01

    New satellite communication systems are steadily seeking to use higher frequency bands to accommodate the requirements for additional capacity. At these higher frequencies, propagation impairments that did not significantly affect the signal at lower frequencies begin to have considerable impact. In Ka-band. the next logical commercial frequency band to be used for satellite communication, attenuation of the signal due to rain is a primary concern. An experimental satellite built by NASA, the Advanced Communication Technology Satellite (ACTS). launched in September 1993, is the first U.S. communication satellite operating in the Ka-band. In addition to higher carrier frequencies, a number of other new technologies, including on-board baseband processing. multiple beam antennas, and rain fade detection and compensation techniques, were designed into the ACTS. Verification experiments have been conducted since the launch to characterize the new technologies. The focus of this paper is to characterize the method used by the ACTS TI Very Small Aperture Terminal (TI VSAT) ground stations in detecting the presence of fade in the communication signal and to adaptively compensate for it by the addition of burst rate reduction and forward error correction. Measured data obtained from the ACTS program was used to validate the compensation technique. A software process was developed and demonstrated to statistically characterize the increased availability achieved by the compensation techniques in terms of the bit error rate time enhancement factor. Several improvements to the ACTS technique are discussed and possible implementations for future Ka band system are offered.

  13. 33 CFR 136.211 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.211 Section 136.211 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.211...

  14. 33 CFR 136.205 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.205 Section 136.205 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.205...

  15. 33 CFR 136.241 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.241 Section 136.241 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.241...

  16. 33 CFR 136.223 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.223 Section 136.223 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.223...

  17. 33 CFR 136.217 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.217 Section 136.217 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.217...

  18. 33 CFR 136.235 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.235 Section 136.235 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.235...

  19. 33 CFR 136.229 - Compensation allowable.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Compensation allowable. 136.229 Section 136.229 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.229...

  20. Externalities and Compensation : Primeval Games and Solutions

    NARCIS (Netherlands)

    Ju, Y.; Borm, P.E.M.

    2005-01-01

    The classical literature (Pigou (1920), Coase (1960), Arrow (1970)) and the relatively recent studies (cf.Varian (1994)) associate the externality problem with efficiency.This paper focuses explicitly on the compensation problem in the context of externalities.To capture the features of inter-indivi

  1. 47 CFR 32.24 - Compensated absences.

    Science.gov (United States)

    2010-10-01

    ..., sick leave, etc.) in the year in which these benefits are earned by employees. (b) With respect to the... 47 Telecommunication 2 2010-10-01 2010-10-01 false Compensated absences. 32.24 Section 32.24 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF...

  2. One-Way Temperature Compensated Fiber Link

    Science.gov (United States)

    2011-05-01

    individual compensated links. [1] R. Wynands and S. Weyers, “Atomic Fountain Clocks,” Metrologia , vol. 42, pp. S64-S79, 2005. [2] A. D. Ludlow...3] A. Bauch, et al. ,”Comparison Between Frequency Standards oin Europe and the USA at the 10-15 Uncertainty Level,” Metrologia , vol. 43, pp.109

  3. 44 CFR 19.515 - Compensation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Compensation. 19.515 Section 19.515 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... employees of the opposite sex for equal work on jobs the performance of which requires equal skill,...

  4. Leverage, Bank Employee Compensation and Institutions

    NARCIS (Netherlands)

    Bertay, Ata; Uras, Burak

    2016-01-01

    This paper investigates the empirical relationship between financial structure and employee compensation in the banking industry. Using an international panel of banks, we show that well-capitalized banks pay higher wages to their employees. Our results are robust to changes in measurement, model sp

  5. Paternity fraud and compensation for misattributed paternity.

    Science.gov (United States)

    Draper, Heather

    2007-08-01

    Claims for reimbursement of child support, the reversal of property settlements and compensation can arise when misattributed paternity is discovered. The ethical justifications for such claims seem to be related to the financial cost of bringing up children, the absence of choice about taking on these expenses, the hard work involved in child rearing, the emotional attachments that are formed with children, the obligation of women to make truthful claims about paternity, and the deception involved in infidelity. In this paper it is argued that there should not be compensation for infidelity and that reimbursement is appropriate where the claimant has made child support payments but has not taken on the social role of father. Where the claimant's behaviour suggests a social view of fatherhood, on the other hand, claims for compensation are less coherent. Where the genetic model of fatherhood dominates, the "other" man (the woman's lover and progenitor of the children) might also have a claim for the loss of the benefits of fatherhood. It is concluded that claims for reimbursement and compensation in cases of misattributed paternity produce the same distorted and thin view of what it means to be a father that paternity testing assumes, and underscores a trend that is not in the interests of children.

  6. 12 CFR 2.5 - Bank compensation.

    Science.gov (United States)

    2010-01-01

    ... the bank's loan customers. (b) Income derived from credit life insurance sales to loan customers may... seq., or to a trust for the benefit of all shareholders, provided that the bank receives reasonable... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Bank compensation. 2.5 Section 2.5 Banks...

  7. PRECISELY COMPENSATED EFFICIENT COMPONENT MODE SYNTHESIS METHOD

    Institute of Scientific and Technical Information of China (English)

    Zhu Yutian; Ichiro Hagiwara

    2004-01-01

    Based on the improved mode superposition method proposed by Z.D.Ma and I.Hagiwara, a precisely compensated efficient mode synthesis method is developed.The calculation procedure is discussed in detail and the truncation error is also analyzed.By comparison, it is shown that this method has a higher accuracy and a less calculation time than the general used ones.

  8. Assessing the applicability of template-based protein docking in the twilight zone.

    Science.gov (United States)

    Negroni, Jacopo; Mosca, Roberto; Aloy, Patrick

    2014-09-02

    The structural modeling of protein interactions in the absence of close homologous templates is a challenging task. Recently, template-based docking methods have emerged to exploit local structural similarities to help ab-initio protocols provide reliable 3D models for protein interactions. In this work, we critically assess the performance of template-based docking in the twilight zone. Our results show that, while it is possible to find templates for nearly all known interactions, the quality of the obtained models is rather limited. We can increase the precision of the models at expenses of coverage, but it drastically reduces the potential applicability of the method, as illustrated by the whole-interactome modeling of nine organisms. Template-based docking is likely to play an important role in the structural characterization of the interaction space, but we still need to improve the repertoire of structural templates onto which we can reliably model protein complexes.

  9. What in silico molecular docking can do for the `bench-working biologists'

    Indian Academy of Sciences (India)

    Marius Mihăşan

    2012-12-01

    Required by an increasing amount of scientists, the in silico docking field is in full expansion, new algorithms and methods appearing at an exponential rate. The sheer range of available programs is overwhelming for the bench-working biologist, which is often discouraging by the lack of a graphical user interface, good user manual or literature to validate a given program. This mini-review attempts to present the docking problem and available solutions from a non-bioinformatician point of view and makes a selection of the available servers and programs. These tools are evaluated from several points of view, as numbers of citations, ease of usage and computer requirements. Finally, the capabilities and limitations as well as specific applications of in silico docking techniques are presented.

  10. A role of proton transfer in peroxidase-catalyzed process elucidated by substrates docking calculations

    Directory of Open Access Journals (Sweden)

    Ziemys Arturas

    2001-08-01

    Full Text Available Abstract Background Previous kinetic investigations of fungal-peroxidase catalyzed oxidation of N-aryl hydroxamic acids (AHAs and N-aryl-N-hydroxy urethanes (AHUs revealed that the rate of reaction was independent of the formal redox potential of substrates. Moreover, the oxidation rate was 3–5 orders of magnitude less than for oxidation of physiological phenol substrates, though the redox potential was similar. Results To explain the unexpectedly low reactivity of AHAs and AHUs we made ab initio calculations of the molecular structure of the substrates following in silico docking in the active center of the enzyme. Conclusions AHAs and AHUs were docked at the distal side of heme in the sites formed by hydrophobic amino acid residues that retarded a proton transfer and finally the oxidation rate. The analogous phenol substrates were docked at different sites permitting fast proton transfer in the relay of distal His and water that helped fast substrate oxidation.

  11. Methods of determining the optimal project of reconstruction of The Petrovsky Dock in Kronstadt

    Directory of Open Access Journals (Sweden)

    Romanovich Marina

    2016-01-01

    Full Text Available Today in Russia there are many historical monuments, which are in a derelict and not the operational state. So, this is actual question about their reconstruction with preservation of historical significance, with current technology, and innovation. One of these abandoned objects is The Petrovsky Dock in Kronstadt. Priority idea of its reconstruction it is museum. The Russian and foreign experience in development of the modern sea museums is analysed. In article the existing options of reconstruction of Dock are considered. The method of calculation of total optimality project coefficient of reconstruction is offered. Survey of experts showing what functions are most interesting to the museum is conducted. As a result, we determine the optimal reconstruction project of Dock with unique functionality.

  12. CoMFA 3D-QSAR Analysis of Epothilones Based on Docking Conformation and Alignment

    Institute of Scientific and Technical Information of China (English)

    YUAN,Wei; LUAN,Lin-Bo; LI,Yan-Ni

    2007-01-01

    Epothilones belong to a class of novel microtubule stabilizing and anti-mitotic agents.which have a paclitaxel-like mechanism of action.A three-dimensional quantitative structure-activity relationship(3D-QSAR)model was built for epothilones by the method of comparative molecular field analysis (CoMFA)combined with the flexible docking technology.The docking CoMFA model gave a good cross-validated value of q2=0.784 with an optimized component of 6 and the conventional correlation coefficient of r2=0.985.The statistical results show that the model has good ability to predict the activity of the studied compounds.At last.the docking CoMFA model was analyzed through contour maps complemented with MOLCAD-generated active site potential surface in the α,β-tubulin receptor,which can provide important information for the structure-based drug design.

  13. Using RosettaLigand for small molecule docking into comparative models.

    Directory of Open Access Journals (Sweden)

    Kristian W Kaufmann

    Full Text Available Computational small molecule docking into comparative models of proteins is widely used to query protein function and in the development of small molecule therapeutics. We benchmark RosettaLigand docking into comparative models for nine proteins built during CASP8 that contain ligands. We supplement the study with 21 additional protein/ligand complexes to cover a wider space of chemotypes. During a full docking run in 21 of the 30 cases, RosettaLigand successfully found a native-like binding mode among the top ten scoring binding modes. From the benchmark cases we find that careful template selection based on ligand occupancy provides the best chance of success while overall sequence identity between template and target do not appear to improve results. We also find that binding energy normalized by atom number is often less than -0.4 in native-like binding modes.

  14. Modulation of current through a nanopore induced by a charged globule: implications for DNA-docking

    CERN Document Server

    Chinappi, Mauro; Cecconi, Fabio; Marconi, Umberto Marini Bettolo; Melchionna, Simone

    2015-01-01

    The passage of DNA through a nanopore can be effectively decomposed into two distinct phases, docking and actual translocation. In experiments each phase is characterized by a distinct current signature which allows the discrimination of the two events. However, at low voltages a clear distinction of the two phases is lost. By using numerical simulations we clarify how the current signature associated to the docking events depends on the applied voltage. The simulations show that at small voltage the DNA globule enhances the pore conductance due to an enrichment of charge carriers. At high voltage, the globule drains substantial charge carriers from the pore region, thereby reducing the overall conductance. The results provide a new interpretation to the experimental data on conductance and show how docking interferes with the translocation signal, of potential interest for sequencing applications.

  15. DOCK2介导神经炎症与阿尔茨海默病

    Institute of Scientific and Technical Information of China (English)

    宋军营; 赵昊譞; 袁永; 张振强; 宫洪涛

    2016-01-01

    神经炎症在阿尔茨海默病(Alzheimer's disease,AD)等神经退行性疾病发病过程中具有重要的防御作用.大量的流行病学数据表明,非甾体类抗炎药能够降低AD发生的风险.DOCK2是炎症反应的重要调节因子,然而其在AD病理演变过程中所起的作用却并不十分清楚.本文从DOCK2介导神经炎症这一角度入手,就DOCK2与AD之间的关系进行综述.

  16. INSILICO MODELING AND DOCKING STUDIES OF NEW DELHI METALLO BETA LACTAMASE-1 (SUPER BUG

    Directory of Open Access Journals (Sweden)

    DR. JAYASREE GANUGAPATI,

    2011-03-01

    Full Text Available New Delhi Metallo Beta Lactamase-1 (NDM-1 is a novel beta -lactamase enzyme that is ubiquitously found in Escherichia coli. This enzyme belongs to a B1 subclass of Metallo Beta Lactamases and is known to induce resistance to standard intravenous antibiotics. The tertiary structure of NDM-1 was predicted using Modeller9v7, based on the structural homology of the x-ray crystallographic structures of VIM-2 & VIM- 4 (Verona imipenemase-2 & -4 proteins from Pseudomonas aeruginosa. Further refinement of the structure was done using the loop modeling. Docking Analysis of NDM-1 with flavonoids was then performed using, GOLD, Auto Dock and Argus Lab. The analysis of the results of all three docking softwares suggested that Quercetin may be a potential inhibitor of NDM-1. Further analysis in the wet labmay provide us more information regarding inhibiting of NDM-1.

  17. Discovery of Anti-SARS Coronavirus Drug Based on Molecular Docking and Database Screening

    Institute of Scientific and Technical Information of China (English)

    CHEN,Hai-Feng(陈海峰); YAO,Jian-Hua(姚建华); SUN,Jing(孙晶); LI,Qiang(李强); LI,Feng(李丰); FAN,Bo-Tao(范波涛); YUAN,Shen-Gang(袁身刚)

    2004-01-01

    The active site of 3CL proteinase (3CLpro) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CLpro of human coronavirus, then it was selected as the reference for molecular docking and database screening. The ligands from two databases were used to search potential lead structures with molecular docking. Several structures from natural products and ACD-SC databases were found to have lower binding free energy with 3CLpro than that of Ag7088. These structures have similar hydrophobicity to Ag7088. They have complementary electrostatic potential and hydrogen bond acceptor and donor with 3CLpro, showing that the strategy of anti-SARS drug design based on molecular docking and database screening is feasible.

  18. Active Wireline Heave Compensation for Ocean Drilling

    Science.gov (United States)

    Goldberg, D.; Liu, T.; Swain, K.; Furman, C.; Iturrino, G. J.

    2014-12-01

    The up-and-down heave motion of a ship causes a similar motion on any instruments tethered on wireline cable below it. If the amplitude of this motion is greater than a few tens of cm, significant discrepancy in the depth below the ship is introduced, causing uncertainty in the acquired data. Large and irregular cabled motions also increase the risk of damaging tethered instruments, particularly those with relatively delicate sensors. In 2005, Schlumberger and Deep Down, Inc built an active wireline heave compensator (AHC) system for use onboard the JOIDES Resolution to compensate for heave motion on wireline logging tools deployed in scientific drill holes. The goals for the new AHC system were to (1) design a reliable heave compensation system; and (2) devise a robust and quantitative methodology for routine assessment of compensation efficiency (CE) during wireline operations. Software programs were developed to monitor CE and the dynamics of logging tools in real-time, including system performance under variable parameters such as water depth, sea state, cable length, logging speed and direction. We present the CE results from the AHC system on the JOIDES Resolution during a 5-year period of recent IODP operations and compare the results to those from previous compensation systems deployed during ODP and IODP. Based on new data under heave conditions of ±0.2-2.0 m and water depths of 300-4,800 m in open holes, the system reduces 65-80% of downhole tool displacement under stationary conditions and 50-60% during normal logging operations. Moreover, down/up tool motion at low speeds (300-600 m/h) reduces the system's CE values by 15-20%, and logging down at higher speeds (1,000-1,200 m/h) reduces CE values by 55-65%. Furthermore, the system yields slightly lower CE values of 40-50% without tension feedback of the downhole cable while logging. These results indicate that the new system's compensation efficiency is comparable to or better than previous systems

  19. Differential regulation of synaptic vesicle tethering and docking by UNC-18 and TOM-1

    Directory of Open Access Journals (Sweden)

    Elena O Gracheva

    2010-10-01

    Full Text Available The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18, unc-64(syntaxin and tom-1(tomosyn. We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin

  20. Mutations in DOCK7 in individuals with epileptic encephalopathy and cortical blindness.

    Science.gov (United States)

    Perrault, Isabelle; Hamdan, Fadi F; Rio, Marlène; Capo-Chichi, José-Mario; Boddaert, Nathalie; Décarie, Jean-Claude; Maranda, Bruno; Nabbout, Rima; Sylvain, Michel; Lortie, Anne; Roux, Philippe P; Rossignol, Elsa; Gérard, Xavier; Barcia, Giulia; Berquin, Patrick; Munnich, Arnold; Rouleau, Guy A; Kaplan, Josseline; Rozet, Jean-Michel; Michaud, Jacques L

    2014-06-05

    Epileptic encephalopathies are increasingly thought to be of genetic origin, although the exact etiology remains uncertain in many cases. We describe here three girls from two nonconsanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. In individuals from each family, brain imaging also showed specific changes, including an abnormally marked pontobulbar sulcus and abnormal signals (T2 hyperintensities) and atrophy in the occipital lobe. Exome sequencing performed in the first family did not reveal any gene with rare homozygous variants shared by both affected siblings. It did, however, show one gene, DOCK7, with two rare heterozygous variants (c.2510delA [p.Asp837Alafs(∗)48] and c.3709C>T [p.Arg1237(∗)]) found in both affected sisters. Exome sequencing performed in the proband of the second family also showed the presence of two rare heterozygous variants (c.983C>G [p.Ser328(∗)] and c.6232G>T [p.Glu2078(∗)]) in DOCK7. Sanger sequencing confirmed that all three individuals are compound heterozygotes for these truncating mutations in DOCK7. These mutations have not been observed in public SNP databases and are predicted to abolish domains critical for DOCK7 function. DOCK7 codes for a Rac guanine nucleotide exchange factor that has been implicated in the genesis and polarization of newborn pyramidal neurons and in the morphological differentiation of GABAergic interneurons in the developing cortex. All together, these observations suggest that loss of DOCK7 function causes a syndromic form of epileptic encephalopathy by affecting multiple neuronal processes.

  1. PRESSURE COMPENSATION METHOD OF UNDERWATER HYDRAULIC SYSTEM WITH HYDRAULIC POWER UNIT BEING UNDER ATMOSPHERIC CIRCUMSTANCE AND PRESSURE COMPENSATED VALVE

    Institute of Scientific and Technical Information of China (English)

    Wang Qingfeng; Li Yanmin; Zhong Tianyu; Xu Guohua

    2005-01-01

    Based on the analysis of the-state-of-the-art of pressure compensation of underwater hydraulic systems (UHSs), a new method of pressure compensation of UHSs, whose hydraulic power unit is in the atmospheric circumstance, is proposed. And a pilot-operated relief valve with pressure compensation is realized. The pressure compensation precision is guaranteed by direct detection. Its dynamic performance and stability are improved by a dynamic feedback. Theoretical study, simulation and experiment show that the pilot-operated relief valve with pressure compensation has a fine property of tracking underwater ambient pressure and meet the requirement of underwater ambient pressure compensation.

  2. Designing A Nonlinear Integer Programming Model For A Cross-Dock By A Genetic Algorithm

    OpenAIRE

    Bahareh Vaisi; Reza Tavakkoli-Moghaddam

    2015-01-01

    Abstract This paper presents a non-linear integer programming model for a cross-dock problem that considers the total transportation cost of inbound and outbound trucks from an origin to a destination and the total cost of assigning strip and stack doors to trucks based on their number of trips and the distance between doors in cross-dock. In previous studies these two cost-based problems are modeled separately however it is more realistic and practical to use both of them as an integrated cr...

  3. Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

    Science.gov (United States)

    Balakumar, C; Lamba, P; Kishore, D Pran; Narayana, B Lakshmi; Rao, K Venkat; Rajwinder, K; Rao, A Raghuram; Shireesha, B; Narsaiah, B

    2010-11-01

    A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies.

  4. Accounting for large amplitude protein deformation during in silico macromolecular docking.

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-02-22

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  5. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Directory of Open Access Journals (Sweden)

    Chantal Prévost

    2011-02-01

    Full Text Available Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  6. Re-planning for compensator-based IMRT with original compensators.

    Science.gov (United States)

    Zhang, Geoffrey; Feygelman, Vladimir; Stevens, Craig; Li, Weiqi; Leuthold, Susan; Springett, Gregory; Hoffe, Sarah

    2011-01-01

    Compared with multileaf collimator (MLC)-based intensity-modulated radiotherapy (IMRT) for moving targets, compensator-based IMRT has advantages such as shorter beam-on time, fewer monitor units with potentially decreased secondary carcinogenesis risk, better optimization-to-deliverable dose conversion, and often better dose conformity. Some of the disadvantages include additional time for the compensators to be built and delivered, as well as extra cost. Patients undergoing treatment of abdominal cancers often experience weight loss. It would be necessary to account for this change in weight with a new plan and a second set of compensators. However, this would result in treatment delays and added costs. We have developed a method to re-plan the patient using the same set of compensators. Because the weight changes seen with the treatment of abdominal cancers are usually relatively small, a new 4D computed tomography (CT) acquired in the treatment position with markers on the original isocenter tattoos can be registered to the original planning scan. The contours of target volumes from the original scans are copied to the new scan after fusion. The original compensator set can be used together with a few field-in-field (FiF) beams defined by the MLC (or beams with cerrobend blocks for accelerators not equipped with a MLC). The weights of the beams with compensators are reduced so that the FiF or blocked beams can be optimized to mirror the original plan and dose distribution. Seven abdominal cancer cases are presented using this technique. The new plan on the new planning CT images usually has the same dosimetric quality as the original. The target coverage and dose uniformity are improved compared with the plan without FiF/block modification. Techniques combining additional FiF or blocked beams with the original compensators optimize the treatment plans when patients lose weight and save time and cost compared with generating plans with a new set of compensators.

  7. DrugScorePPI knowledge-based potentials used as scoring and objective function in protein-protein docking.

    Directory of Open Access Journals (Sweden)

    Dennis M Krüger

    Full Text Available The distance-dependent knowledge-based DrugScore(PPI potentials, previously developed for in silico alanine scanning and hot spot prediction on given structures of protein-protein complexes, are evaluated as a scoring and objective function for the structure prediction of protein-protein complexes. When applied for ranking "unbound perturbation" ("unbound docking" decoys generated by Baker and coworkers a 4-fold (1.5-fold enrichment of acceptable docking solutions in the top ranks compared to a random selection is found. When applied as an objective function in FRODOCK for bound protein-protein docking on 97 complexes of the ZDOCK benchmark 3.0, DrugScore(PPI/FRODOCK finds up to 10% (15% more high accuracy solutions in the top 1 (top 10 predictions than the original FRODOCK implementation. When used as an objective function for global unbound protein-protein docking, fair docking success rates are obtained, which improve by ∼ 2-fold to 18% (58% for an at least acceptable solution in the top 10 (top 100 predictions when performing knowledge-driven unbound docking. This suggests that DrugScore(PPI balances well several different types of interactions important for protein-protein recognition. The results are discussed in view of the influence of crystal packing and the type of protein-protein complex docked. Finally, a simple criterion is provided with which to estimate a priori if unbound docking with DrugScore(PPI/FRODOCK will be successful.

  8. 18 CFR 1304.206 - Requirements for community docks, piers, boathouses, or other water-use facilities.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Requirements for community docks, piers, boathouses, or other water-use facilities. 1304.206 Section 1304.206 Conservation of....206 Requirements for community docks, piers, boathouses, or other water-use facilities. (a)...

  9. Flexible CDOCKER: Development and application of a pseudo-explicit structure-based docking method within CHARMM.

    Science.gov (United States)

    Gagnon, Jessica K; Law, Sean M; Brooks, Charles L

    2016-03-30

    Protein-ligand docking is a commonly used method for lead identification and refinement. While traditional structure-based docking methods represent the receptor as a rigid body, recent developments have been moving toward the inclusion of protein flexibility. Proteins exist in an interconverting ensemble of conformational states, but effectively and efficiently searching the conformational space available to both the receptor and ligand remains a well-appreciated computational challenge. To this end, we have developed the Flexible CDOCKER method as an extension of the family of complete docking solutions available within CHARMM. This method integrates atomically detailed side chain flexibility with grid-based docking methods, maintaining efficiency while allowing the protein and ligand configurations to explore their conformational space simultaneously. This is in contrast to existing approaches that use induced-fit like sampling, such as Glide or Autodock, where the protein or the ligand space is sampled independently in an iterative fashion. Presented here are developments to the CHARMM docking methodology to incorporate receptor flexibility and improvements to the sampling protocol as demonstrated with re-docking trials on a subset of the CCDC/Astex set. These developments within CDOCKER achieve docking accuracy competitive with or exceeding the performance of other widely utilized docking programs.

  10. Approximation of the optimal compensator for a large space structure

    Science.gov (United States)

    Mackay, M. K.

    1983-01-01

    This paper considers the approximation of the optimal compensator for a Large Space Structure. The compensator is based upon a solution to the Linear Stochastic Quadratic Regulator problem. Colocation of sensors and actuators is assumed. A small gain analytical solution for the optimal compensator is obtained for a single input/single output system, i.e., certain terms in the compensator can be neglected for sufficiently small gain. The compensator is calculated in terms of the kernel to a Volterra integral operator using a Neumann series. The calculation of the compensator is based upon the C sub 0 semigroup for the infinite dimensional system. A finite dimensional approximation of the compensator is, therefore, obtained through analysis of the infinite dimensional compensator which is a compact operator.

  11. MTB-USDH Compensation Tracking System (MTB-CTS)

    Data.gov (United States)

    US Agency for International Development — MTB-USDH Compensation Tracking System: is the USDH Compensation Tracking System (MTB-CTS) to assist managers in monitoring their payroll costs for U.S. direct hires....

  12. Method for Analysis of an Offshore Heave Compensator

    Directory of Open Access Journals (Sweden)

    Gwi-Nam Kim

    2016-02-01

    Full Text Available A heave compensation system consists of a drill string compensator (DSC and an active heave compensator (AHC cylinder, which together produce control force over an oil pressure system suitable for transmission of considerable power and compensating for heaving motion of the hull during drilling work. In this study, a heave compensator of an oil pressure system was simulated to draw a conclusion, which was verified by comparison with the result of a test conducted using an actual miniature model. The compensation rate was 95%, based on which the dynamic behaviors of an actual-size heave compensator were presumed. Furthermore, the speed of each cylinder and the acceleration of heave can be determined and used to fabricate an actual-size heave compensator.

  13. Application of fuzzy logic-neural network based reinforcement learning to proximity and docking operations: Special approach/docking testcase results

    Science.gov (United States)

    Jani, Yashvant

    1993-01-01

    As part of the RICIS project, the reinforcement learning techniques developed at Ames Research Center are being applied to proximity and docking operations using the Shuttle and Solar Maximum Mission (SMM) satellite simulation. In utilizing these fuzzy learning techniques, we use the Approximate Reasoning based Intelligent Control (ARIC) architecture, and so we use these two terms interchangeably to imply the same. This activity is carried out in the Software Technology Laboratory utilizing the Orbital Operations Simulator (OOS) and programming/testing support from other contractor personnel. This report is the final deliverable D4 in our milestones and project activity. It provides the test results for the special testcase of approach/docking scenario for the shuttle and SMM satellite. Based on our experience and analysis with the attitude and translational controllers, we have modified the basic configuration of the reinforcement learning algorithm in ARIC. The shuttle translational controller and its implementation in ARIC is described in our deliverable D3. In order to simulate the final approach and docking operations, we have set-up this special testcase as described in section 2. The ARIC performance results for these operations are discussed in section 3 and conclusions are provided in section 4 along with the summary for the project.

  14. Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Sunker, Asma; Morsy, Heba; Al-Sheddi, Tarfa; Shamseldin, Hanan E; Adly, Nouran; Hashem, Mais; Alkuraya, Fowzan S

    2011-08-12

    Adams-Oliver syndrome (AOS) is defined by the combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD). It is usually inherited as an autosomal-dominant trait, but autosomal-recessive inheritance has also been documented. In an individual with autosomal-recessive AOS, we combined autozygome analysis with exome sequencing to identify a homozygous truncating mutation in dedicator of cytokinesis 6 gene (DOCK6) which encodes an atypical guanidine exchange factor (GEF) known to activate two members of the Rho GTPase family: Cdc42 and Rac1. Another homozygous truncating mutation was identified upon targeted sequencing of DOCK6 in an unrelated individual with AOS. Consistent with the established role of Cdc42 and Rac1 in the organization of the actin cytoskeleton, we demonstrate a cellular phenotype typical of a defective actin cytoskeleton in patient cells. These findings, combined with a Dock6 expression profile that is consistent with an AOS phenotype as well as the very recent demonstration of dominant mutations of ARHGAP31 in AOS, establish Cdc42 and Rac1 as key molecules in the pathogenesis of AOS and suggest that other regulators of these Rho GTPase proteins might be good candidates in the quest to define the genetic spectrum of this genetically heterogeneous condition.

  15. A General Theoretical Model of Enthalpy-EntropyCompensation

    Institute of Scientific and Technical Information of China (English)

    LIU,Lei; GUO, Qing-Xiang

    2001-01-01

    Enthalpy-entropy compensation remains a mystery in chemistry and biophysics.recent study suggested that the solventreorganization might constitute the physical orihin of the compensation, which was unforumstely not wisely applicable because compensation was also observeserved in solid phade reactions.In this study,a general theoretical model based upon strictmathematical deduction was presented,which indicated thatthe redistribution of the distinguishable subspecies might bethe physical origin of the enthalpy-intropy compensations in solvation and surface adsorption weue discussed.

  16. Tunable dispersion compensation using phase modulation in receiver part

    DEFF Research Database (Denmark)

    Siahlo, Andrei; Clausen, Anders; Oxenløwe, Leif Katsuo

    2004-01-01

    A novel method of tuneable dispersion compensation at which phase modulation is applied in the receiver part is proposed for OTDM systems. Compensation of dispersion of 3.2 ps/nm at 160 Gb/s OTDM transmission is demonstrated.......A novel method of tuneable dispersion compensation at which phase modulation is applied in the receiver part is proposed for OTDM systems. Compensation of dispersion of 3.2 ps/nm at 160 Gb/s OTDM transmission is demonstrated....

  17. Sales compensation governance: the last frontier of corporate reform.

    Science.gov (United States)

    Gundy, Peter R; Gaeta, Elizabeth C

    2004-01-01

    The area of sales compensation has remained relatively untouched by recent pressures for compensation reform. This article highlights some of the ways that sales organizations stumble in managing their compensation programs, and why it takes more than a simple tactical fix to address these problems effectively. The authors describe a more structured governance framework that not only identifies and resolves key sales compensation issues, but ultimately safeguards the effectiveness and financial integrity of the sales organization itself.

  18. Video Coding with Motion-Compensated Lifted Wavelet Transforms

    OpenAIRE

    Flierl, M.; Girod, B.

    2004-01-01

    This article explores the efficiency of motion-compensated three-dimensional transform coding, a compression scheme that employs a motion-compensated transform for a group of pictures. We investigate this coding scheme experimentally and theoretically. The practical coding scheme employs in temporal direction a wavelet decomposition with motion-compensated lifting steps. Further, we compare the experimental results to that of a predictive video codec with single-hypothesis motion compensation...

  19. The Pros and Cons of Performance-Based Compensation.

    Science.gov (United States)

    Solmon, Lewis C.; Podgursky, Michael

    This paper analyzes the current and historical criticism of performance-based compensation in K-12 education. It claims that new compensation methods are feasible and are necessary in order to attract and retain the best and the brightest into the teaching profession. The document outlines the objections to performance-based compensation, which in…

  20. 26 CFR 1.162-7 - Compensation for personal services.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Compensation for personal services. 1.162-7...-7 Compensation for personal services. (a) There may be included among the ordinary and necessary... compensation for personal services actually rendered. The test of deductibility in the case of...

  1. 39 CFR 3050.27 - Workers' Compensation Report.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Workers' Compensation Report. 3050.27 Section 3050.27 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL PERIODIC REPORTING § 3050.27 Workers' Compensation Report. The Workers' Compensation Report, including summary workpapers, shall be provided by...

  2. 20 CFR 404.1409 - Purposes of using compensation.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Purposes of using compensation. 404.1409 Section 404.1409 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND... the Railroad Retirement Program § 404.1409 Purposes of using compensation. Compensation which...

  3. 26 CFR 1.162-8 - Treatment of excessive compensation.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Treatment of excessive compensation. 1.162-8...-8 Treatment of excessive compensation. The income tax liability of the recipient in respect of an amount ostensibly paid to him as compensation, but not allowed to be deducted as such by the payor,...

  4. 7 CFR 625.8 - Compensation for easements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Compensation for easements. 625.8 Section 625.8..., DEPARTMENT OF AGRICULTURE WATER RESOURCES HEALTHY FORESTS RESERVE PROGRAM § 625.8 Compensation for easements... section. (d) Acceptance of offered easement compensation. (1) NRCS will not acquire any easement...

  5. 48 CFR 252.217-7004 - Job orders and compensation.

    Science.gov (United States)

    2010-10-01

    ... compensation. 252.217-7004 Section 252.217-7004 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.217-7004 Job orders and compensation. As prescribed in 217.7104(a), use the following clause: JOB ORDERS AND COMPENSATION (MAY 2006) (a) The Contracting Officer shall...

  6. 47 CFR 64.1300 - Payphone compensation obligation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Payphone compensation obligation. 64.1300... compensation obligation. (a) For purposes of this subpart, a Completing Carrier is a long distance carrier or... parties by contract. (c) The compensation obligation set forth herein shall not apply to calls...

  7. 76 FR 25273 - Listing Standards for Compensation Committees

    Science.gov (United States)

    2011-05-04

    ... COMMISSION 17 CFR Parts 229 and 240 RIN 3235-AK95 Listing Standards for Compensation Committees AGENCY... security of an issuer that is not in compliance with Section 10C's compensation committee and compensation... establish listing standards that, among other things, require each member of a listed issuer's...

  8. 47 CFR 51.711 - Symmetrical reciprocal compensation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Symmetrical reciprocal compensation. 51.711... (CONTINUED) INTERCONNECTION Reciprocal Compensation for Transport and Termination of Telecommunications Traffic § 51.711 Symmetrical reciprocal compensation. (a) Rates for transport and termination...

  9. 29 CFR 511.4 - Compensation of committee members.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Compensation of committee members. 511.4 Section 511.4... WAGE ORDER PROCEDURE FOR AMERICAN SAMOA § 511.4 Compensation of committee members. Each member of an industry committee will be allowed per diem compensation at the rate specified in Chapter 304 of...

  10. 77 FR 60581 - Compensation, Retirement Programs, and Related Benefits

    Science.gov (United States)

    2012-10-03

    ... shareholders on senior officer compensation.\\6\\ \\6\\ See 77 FR 3172 (Jan. 23, 2012). ] III. Comments and Our... rules on senior officer compensation disclosures and other related topics. \\11\\ See 75 FR 64728, Oct. 20...'' availability to those whose total compensation exceeded $50,000. See 51 FR 21336 (June 12, 1986)....

  11. 20 CFR 209.15 - Compensation reportable when paid.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Compensation reportable when paid. 209.15... RAILROAD EMPLOYERS' REPORTS AND RESPONSIBILITIES § 209.15 Compensation reportable when paid. (a) General. In preparing a report required under this part, an employer may report compensation in the...

  12. 47 CFR 64.1301 - Per-payphone compensation.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Per-payphone compensation. 64.1301 Section 64... compensation. (a) Interim access code and subscriber 800 calls. In the absence of a negotiated agreement to pay... on Remand in CC Docket No. 96-128, FCC 02-292, must pay default compensation to payphone...

  13. 20 CFR 404.1412 - Compensation quarters of coverage.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Compensation quarters of coverage. 404.1412... the Railroad Retirement Program § 404.1412 Compensation quarters of coverage. As used in this subpart, a compensation quarter of coverage is any quarter of coverage computed with respect to...

  14. 29 CFR 505.3 - Prevailing minimum compensation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Prevailing minimum compensation. 505.3 Section 505.3 Labor... HUMANITIES § 505.3 Prevailing minimum compensation. (a)(1) In the absence of an alternative determination...)(2) of this section, the prevailing minimum compensation required to be paid under the Act to...

  15. 50 CFR 600.245 - Council member compensation.

    Science.gov (United States)

    2010-10-01

    ... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Council Membership § 600.245 Council member compensation. (a) All voting Council members whose eligibility for compensation has... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Council member compensation....

  16. Reactive current compensation with hybrid circuit; Blindstromkompensation mit Hybridschaltung

    Energy Technology Data Exchange (ETDEWEB)

    Henning Mueller, Janitza

    2013-06-01

    Compensation systems for reactive currents have to reduce costs. However, at excessively enhanced harmonic loads compensation systems are quickly overloaded and even become cost drivers. Plants in reinforced construction and improved technology are required. During rapid load fluctuations, compensation systems can be controlled better with thyristor controllers instead of slow shooter.

  17. Temperature compensation of resonant cavities with a teflon post

    OpenAIRE

    1982-01-01

    The negative temperature coefficient of E for teflon is used to compensate the frequency drift of a metal cavity due to thermal expansion. An experimental X-band transmission resonator was compensated in this way with a 10 mm teflon post. The results are considered of great interest for the compensation of waveguide millimiter wave oscillators. Peer Reviewed

  18. 77 FR 38421 - Listing Standards for Compensation Committees

    Science.gov (United States)

    2012-06-27

    ... compensation policy will consist only of directors who are independent.'' \\17\\ In addition, Congress sought to... for Compensation Committees; Final Rule #0;#0;Federal Register / Vol. 77 , No. 124 / Wednesday, June... RIN 3235-AK95 Listing Standards for Compensation Committees AGENCY: Securities and Exchange...

  19. Relative Motion Compensation for Cargo Handling Operations -- Annotated Bibliography

    Science.gov (United States)

    1991-01-01

    4-6 Active Heave Compensation Systems on Board of Vessels and Offshore Rigs ............................................... 4...Herwig, "Active Heave Compensation Systems on Board of Vessels and Offshore Rigs," Marine Technology, pp. 59-61 (May 1986). Active heave compensation systems

  20. Vibration Compensation for Scanning Tunneling Microscope

    Institute of Scientific and Technical Information of China (English)

    LI Meng-chao; FU Xing; WEI Xiao-lei; HU Xiao-tang

    2003-01-01

    The influence of vibration is already one of main obstacles for improving the nano measuring accuracy.The techniques of anti-vibration,vibration isolation and vibration compensation become an important branch in nano measuring field.Starting with the research of sensitivity to vibration of scanning tunneling microscope(STM),the theory,techniques and realization methods of nano vibration sensor based on tunnel effect are initially investigated,followed by developing the experimental devices.The experiments of the vibration detection and vibration compensation are carried out.The experimental results show that vibration sensor based on tunnel effect is characterized by high sensitivity,good frequency characteristic and the same vibratory response characteristic consistent with STM.

  1. Zero energy buildings and mismatch compensation factors

    DEFF Research Database (Denmark)

    Lund, Henrik; Marszal, Anna Joanna; Heiselberg, Per

    2011-01-01

    This paper takes an overall energy system approach to analysing the mismatch problem of zero energy and zero emission buildings (ZEBs). The mismatch arises from hourly differences in energy production and consumption at the building level and results in the need for exchange of electricity via...... of the energy production unit. Based on historical data for the electricity supply area in western Denmark, this paper makes a first attempt to quantify mismatch compensation factors. The results indicate that such compensation factors are a little below one for buildings with photovoltaics (PV) and a little...... the public grid even though the building has an annual net-exchange of zero. This paper argues that, when looked upon from the viewpoint of the overall electricity supply system, a mismatch can be both negative and positive. Moreover, there are often both an element of levelling out mismatches between...

  2. Intonation and Compensation of Fretted String Instruments

    CERN Document Server

    Varieschi, Gabriele U

    2009-01-01

    In this paper we present mathematical models and we analyze the physics related to the problem of intonation of musical instruments such as guitars, mandolins and similar, i.e., we study how to produce perfectly in tune notes on these instruments. This analysis begins with the correct fret placement on the instrument fingerboard, following precise mathematical laws, but then it becomes increasingly complicated due to the geometrical deformation of the strings when these instruments are played, and also due to the inharmonic characteristics of the same strings. As a consequence of these factors, perfect intonation of all the notes on the instrument can never be achieved, but complex compensation procedures are introduced and studied to minimize the problem. To test the validity of these compensation procedures, we have performed extensive measurements using standard monochord sonometers and other basic acoustical devices, which confirm the correctness of our theoretical models. In particular, these experimenta...

  3. Power Compensation for ICRF Heating in EAST

    Science.gov (United States)

    Chen, Gen; Qin, Chengming; Mao, Yuzhou; Zhao, Yanping; Yuan, Shuai; Zhang, Xinjun

    2016-08-01

    The source system covering a working frequency range of 24 MHz to 70 MHz with a total maximum output power of 12 MW has already been fabricated for Ion Cyclotron Range of Frequency (ICRF) heating in EAST from 2012. There are two continuous wave (CW) antennas consisting of four launching elements each fed by a separate 1.5 MW transmitter. Due to the strong mutual coupling among the launching elements, the injection power for launching elements should be imbalance to keep the k‖ (parallel wave number) spectrum of the launcher symmetric for ICRF heating. Cross power induced by the mutual coupling will also induce many significant issues, such as an uncontrollable phase of currents in launching elements, high voltage standing wave ratio (VSWR), and impedance mismatching. It is necessary to develop a power compensation system for antennas to keep the power balance between the feed points. The power balance system consists of two significant parts: a decoupler and phase control. The decoupler helps to achieve ports isolation to make the differential phase controllable and compensate partly cross power. After that, the differential phase of 0 or π will keep the power balance of two feed points completely. The first power compensation system consisting of four decouplers was assembled and tested for the port B antenna at the working frequency of 35 MHz. With the application of the power compensation system, the power balance, phase feedback control, and voltage standing wave ratio (VSWR) had obviously been improved in the 2015 EAST campaign. supported by the National Magnetic Confinement Fusion Science Program of China (No. 2015GB101001) and National Natural Science Foundation of China (Nos. 11575237, 11375235, 11375236)

  4. Offset Error Compensation in Roundness Measurement

    Institute of Scientific and Technical Information of China (English)

    朱喜林; 史俊; 李晓梅

    2004-01-01

    This paper analyses three causes of offset error in roundness measurement and presents corresponding compensation methods.The causes of offset error include excursion error resulting from the deflection of the sensor's line of measurement from the rotational center in measurement (datum center), eccentricity error resulting from the variance between the workpiece's geometrical center and the rotational center, and tilt error resulting from the tilt between the workpiece's geometrical axes and the rotational centerline.

  5. Motivation and Politics in Executive Compensation.

    Science.gov (United States)

    1983-07-01

    59, ind found that CEO income (e.g., bonus, salary, and stock options ) was primarily related to sales rather than to profits. After testing for...executives are formally rewarded in terms of Iase salaries, bonuses, stock options , stock appreciation rights (SARs), performance achievement plans, and...restricted stock options . Stock options , stock appreciation rights, and restricted stock options involve compensation that can be exercised within

  6. Method of assembling a thermal expansion compensator

    Science.gov (United States)

    Determan, William (Inventor); Matejczyk, Daniel Edward (Inventor)

    2012-01-01

    A thermal expansion compensator is provided and includes a first electrode structure having a first surface, a second electrode structure having a second surface facing the first surface and an elastic element bonded to the first and second surfaces and including a conductive element by which the first and second electrode structures electrically and/or thermally communicate, the conductive element having a length that is not substantially longer than a distance between the first and second surfaces.

  7. An optimal fuzzy PID control approach for docking maneuver of two spacecraft: Orientational motion

    Directory of Open Access Journals (Sweden)

    A. Kosari

    2017-02-01

    Full Text Available This paper describes a scheme for a Fuzzy-Proportional Integral Derivative (FPID controller based on genetic algorithm (GA, in a docking maneuver of two spacecraft. The docking maneuver consists of two parts: translation and orientation. Euler’s gyroscopic equation is applied to obtain governing equations of orientational phase. Here, a designed fuzzy-PID controller for stabilization purpose of orientational phase of a docking maneuver is presented based on the Single Input Fuzzy Inference Motor (SIFIMs dynamically connected Preferrer Fuzzy Inference Motor (PFIM. This fuzzy-PID controller takes the error signal of Euler’s angles and the error of angular velocities of the chaser as its input items, and the driving force as its output. The parameters of the controller are ascertained by using a genetic algorithm. Conflicting objective functions (which their 3D pareto frontiers are obtained by Multi-objective Genetic Algorithm (MOGA are distance errors from the set point, angle errors from the set point, and control efforts. Optimization constraint is maximal of the momentum produced by momentum wheels. The result of optimum point demonstrates that the designed controller makes an efficient performance in the orientational phase of the chaser spacecraft. Compared to similar works, some of system parameters like settling time are improved and overshoot (as a critical parameter in docking maneuver is decreased.

  8. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment

    DEFF Research Database (Denmark)

    Kufareva, Irina; Katritch, Vsevolod; Biggin, Phil

    2014-01-01

    Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock asse...

  9. High-throughput Molecular Docking Now in Reach for a Wider Biochemical Community

    NARCIS (Netherlands)

    Balan, D.M.; Malinauskas, T.; Prins, J.C.P.; Moller, S.

    2012-01-01

    In silico molecular docking is used to predict how a small molecule, the ligand, interacts with a target protein, its receptor. Together with experimental methods like NMR or X-ray crystallography, industrial and academic groups use it for their investigation of compounds with the potential to modul

  10. Conceptual design of the hot cell facility universal docking station at ITER

    Energy Technology Data Exchange (ETDEWEB)

    Dammann, A., E-mail: alexis.dammann@iter.org [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Benchikhoune, M.; Friconneau, J.P.; Ivanov, V. [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Lemee, A. [SOGETI High Tech, 180 Rue Rene Descartes, 13851 Aix en Provence (France); Martins, J.P. [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Tamassy, G. [SOGETI High Tech, 180 Rue Rene Descartes, 13851 Aix en Provence (France)

    2011-10-15

    Between main shutdowns of the ITER machine, in-vessel components and Iter Remote Maintenance System (IRMS) are transferred between the Tokamak complex and the Hot Cell Facility using different types of sealed casks. Transfer Casks have different physical interfaces with the Vacuum Vessel, which need to be the same at the docking stations of the HCF. It means that in-vessel components and IRMS are cleaned in the same cells, which is in fact not convenient. Furthermore, logistic studies showed that the use rate of the cells is very inhomogeneous. In order to have dedicated cell for decontamination of Remote Handling tools, in order to increase the operability efficiency and to removes the hot cell docking operation from the critical path, the concept of a universal docking station has been investigated. Based on an existing design, the work was focused on a review of requirements, the re-design and the integration within the HCF layout. The universal docking station has been proposed and is now integrated in HCF design.

  11. Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using haptics.

    Science.gov (United States)

    Iakovou, Georgios; Hayward, Steven; Laycock, Stephen D

    2015-09-01

    Molecular docking systems model and simulate in silico the interactions of intermolecular binding. Haptics-assisted docking enables the user to interact with the simulation via their sense of touch but a stringent time constraint on the computation of forces is imposed due to the sensitivity of the human haptic system. To simulate high fidelity smooth and stable feedback the haptic feedback loop should run at rates of 500Hz to 1kHz. We present an adaptive force calculation approach that can be executed in parallel on a wide range of Graphics Processing Units (GPUs) for interactive haptics-assisted docking with wider applicability to molecular simulations. Prior to the interactive session either a regular grid or an octree is selected according to the available GPU memory to determine the set of interatomic interactions within a cutoff distance. The total force is then calculated from this set. The approach can achieve force updates in less than 2ms for molecular structures comprising hundreds of thousands of atoms each, with performance improvements of up to 90 times the speed of current CPU-based force calculation approaches used in interactive docking. Furthermore, it overcomes several computational limitations of previous approaches such as pre-computed force grids, and could potentially be used to model receptor flexibility at haptic refresh rates.

  12. 48 CFR 47.303-12 - Ex dock, pier, or warehouse, port of importation.

    Science.gov (United States)

    2010-10-01

    ... warehouse, port of importation. 47.303-12 Section 47.303-12 Federal Acquisition Regulations System FEDERAL..., pier, or warehouse, port of importation. (a) Explanation of delivery term. Ex dock, pier, or warehouse... in the warehouse at the specified port of importation. (b) Contractor responsibilities....

  13. Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.

    Science.gov (United States)

    Antony, Priya; Vijayan, Ranjit

    2015-01-01

    Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors.

  14. Evaluation of multiple protein docking structures using correctly predicted pairwise subunits

    Directory of Open Access Journals (Sweden)

    Esquivel-Rodríguez Juan

    2012-03-01

    Full Text Available Abstract Background Many functionally important proteins in a cell form complexes with multiple chains. Therefore, computational prediction of multiple protein complexes is an important task in bioinformatics. In the development of multiple protein docking methods, it is important to establish a metric for evaluating prediction results in a reasonable and practical fashion. However, since there are only few works done in developing methods for multiple protein docking, there is no study that investigates how accurate structural models of multiple protein complexes should be to allow scientists to gain biological insights. Methods We generated a series of predicted models (decoys of various accuracies by our multiple protein docking pipeline, Multi-LZerD, for three multi-chain complexes with 3, 4, and 6 chains. We analyzed the decoys in terms of the number of correctly predicted pair conformations in the decoys. Results and conclusion We found that pairs of chains with the correct mutual orientation exist even in the decoys with a large overall root mean square deviation (RMSD to the native. Therefore, in addition to a global structure similarity measure, such as the global RMSD, the quality of models for multiple chain complexes can be better evaluated by using the local measurement, the number of chain pairs with correct mutual orientation. We termed the fraction of correctly predicted pairs (RMSD at the interface of less than 4.0Å as fpair and propose to use it for evaluation of the accuracy of multiple protein docking.

  15. Discovery of potential cholesterol esterase inhibitors using in silico docking studies

    Directory of Open Access Journals (Sweden)

    Thirumalaisamy Sivashanmugam

    2013-08-01

    Full Text Available New drug discovery is considered broadly in terms of two kinds of investiga-tional activities such as exploration and exploitation. This study deals with the evaluation of the cholesterol esterase inhibitory activity of flavonoids apigenin, biochanin, curcumin, diosmetin, epipervilline, glycitein, okanin, rhamnazin and tangeritin using in silico docking studies. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. The results showed that all the selected flavonoids showed binding energy ranging between -7.08 kcal/mol to -5.64 kcal/mol when compared with that of the standard compound gallic acid (-4.11 kcal/mol. Intermolecular energy (-9.13 kcal/mol to -7.09 kcal/mol and inhibition constant (6.48 µM to 73.18 µM of the ligands also coincide with the binding energy. All the selected flavonoids contributed cholesterol esterase inhibitory activity, these molecular docking analyses could lead to the further develop-ment of potent cholesterol esterase inhibitors for the treatment of obesity.

  16. Assessing protein-ligand docking for the binding of organometallic compounds to proteins.

    Science.gov (United States)

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

    2014-01-30

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

  17. A Memetic Algorithm for the Vehicle Routing Problem with Cross Docking

    Directory of Open Access Journals (Sweden)

    Sanae Larioui

    2015-11-01

    Full Text Available In this paper we address the VRPCD, in which a set of homogeneous vehicles are used to transport products from the suppliers to customers via a cross-dock. The products can be consolidated at the cross-dock but cannot be stored for very long as the cross-dock does not have long-term inventory-holding capabilities. The objective of the VRPCD is to minimize the total traveled distance while respecting time window constraints of suppliers and customers and a time horizon for the whole transportation operation. Rummaging through all the work of literature on vehicle routing problems with cross-docking, there is no work that considers that customer will receive its requests from several suppliers; this will be the point of innovation of this work. A heuristic and a memetic algorithm are used to solve the problem. The proposed algorithms are implemented and tested on data sets involving up to 200 nodes (customers and suppliers. The first results show that the memetic algorithm can produce high quality solutions.

  18. The binding of cytochrome c to neuroglobin: A docking and surface plasmon resonance study

    DEFF Research Database (Denmark)

    Bønding, Signe Helbo; Henty, K.; Dingley, A.J.;

    2008-01-01

    It has recently been proposed that the role of neuroglobin in the protection of neurons from ischaemia induced cell death requires the formation of a transient complex with cytochrome c. No such complex has yet been isolated. Here, we present the results of soft docking calculations, which indica...

  19. Molecular Docking of Enzyme Inhibitors: A Computational Tool for Structure-Based Drug Design

    Science.gov (United States)

    Rudnitskaya, Aleksandra; Torok, Bela; Torok, Marianna

    2010-01-01

    Molecular docking is a frequently used method in structure-based rational drug design. It is used for evaluating the complex formation of small ligands with large biomolecules, predicting the strength of the bonding forces and finding the best geometrical arrangements. The major goal of this advanced undergraduate biochemistry laboratory exercise…

  20. Challenges, applications, and recent advances of protein-ligand docking in structure-based drug design.

    Science.gov (United States)

    Grinter, Sam Z; Zou, Xiaoqin

    2014-07-11

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