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Sample records for enhances docking accuracy

  1. Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism

    Directory of Open Access Journals (Sweden)

    Jurian Schuijers

    2018-04-01

    Full Text Available Summary: Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. : Schuijers et al. show that a conserved CTCF site at the promoter of the MYC oncogene plays an important role in enhancer-promoter looping with tumor-specific super-enhancers. Perturbation of this site provides a potential therapeutic vulnerability. Keywords: gene regulation, super-enhancers, chromosome structure, enhancer docking

  2. Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism.

    Science.gov (United States)

    Schuijers, Jurian; Manteiga, John Colonnese; Weintraub, Abraham Selby; Day, Daniel Sindt; Zamudio, Alicia Viridiana; Hnisz, Denes; Lee, Tong Ihn; Young, Richard Allen

    2018-04-10

    Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. An NMR-based scoring function improves the accuracy of binding pose predictions by docking by two orders of magnitude

    Energy Technology Data Exchange (ETDEWEB)

    Orts, Julien [EMBL, Structure and Computational Biology Unit (Germany); Bartoschek, Stefan [Industriepark Hoechst, Sanofi-Aventis Deutschland GmbH, R and D LGCR/Parallel Synthesis and Natural Products (Germany); Griesinger, Christian [Max Planck Institute for Biophysical Chemistry (Germany); Monecke, Peter [Industriepark Hoechst, Sanofi-Aventis Deutschland GmbH, R and D LGCR/Structure, Design and Informatics (Germany); Carlomagno, Teresa, E-mail: teresa.carlomagno@embl.de [EMBL, Structure and Computational Biology Unit (Germany)

    2012-01-15

    Low-affinity ligands can be efficiently optimized into high-affinity drug leads by structure based drug design when atomic-resolution structural information on the protein/ligand complexes is available. In this work we show that the use of a few, easily obtainable, experimental restraints improves the accuracy of the docking experiments by two orders of magnitude. The experimental data are measured in nuclear magnetic resonance spectra and consist of protein-mediated NOEs between two competitively binding ligands. The methodology can be widely applied as the data are readily obtained for low-affinity ligands in the presence of non-labelled receptor at low concentration. The experimental inter-ligand NOEs are efficiently used to filter and rank complex model structures that have been pre-selected by docking protocols. This approach dramatically reduces the degeneracy and inaccuracy of the chosen model in docking experiments, is robust with respect to inaccuracy of the structural model used to represent the free receptor and is suitable for high-throughput docking campaigns.

  4. Docking ligands into flexible and solvated macromolecules. 7. Impact of protein flexibility and water molecules on docking-based virtual screening accuracy.

    Science.gov (United States)

    Therrien, Eric; Weill, Nathanael; Tomberg, Anna; Corbeil, Christopher R; Lee, Devin; Moitessier, Nicolas

    2014-11-24

    The use of predictive computational methods in the drug discovery process is in a state of continual growth. Over the last two decades, an increasingly large number of docking tools have been developed to identify hits or optimize lead molecules through in-silico screening of chemical libraries to proteins. In recent years, the focus has been on implementing protein flexibility and water molecules. Our efforts led to the development of Fitted first reported in 2007 and further developed since then. In this study, we wished to evaluate the impact of protein flexibility and occurrence of water molecules on the accuracy of the Fitted docking program to discriminate active compounds from inactive compounds in virtual screening (VS) campaigns. For this purpose, a total of 171 proteins cocrystallized with small molecules representing 40 unique enzymes and receptors as well as sets of known ligands and decoys were selected from the Protein Data Bank (PDB) and the Directory of Useful Decoys (DUD), respectively. This study revealed that implementing displaceable crystallographic or computationally placed particle water molecules and protein flexibility can improve the enrichment in active compounds. In addition, an informed decision based on library diversity or research objectives (hit discovery vs lead optimization) on which implementation to use may lead to significant improvements.

  5. Accuracy and Metrological Reliability Enhancing of Thermoelectric Transducers

    Directory of Open Access Journals (Sweden)

    Bogdan Stadnyk

    2010-12-01

    Full Text Available This article is devoted to development and use of thermoelectric thermotransducers with an enhanced accuracy and metrological reliability. The actuality of a problem is stipulated. Investigating changes at typical external environments, the mechanisms of transformation function instability are considered; possibilities of thermodynamic presentation use are analyzed concerning a thermometric substance. The algorithm of thermotransducer instrumental errors’ minimization is developed.

  6. Enhancement of diffusers BSDF accuracy: spectral features effect

    NARCIS (Netherlands)

    Brug, H. van; Courrèges-Lacoste, G.B.; Otter, G.C.J.; Schaarsberg, J.G.; Delwart, S.; Del Bello, U.

    2006-01-01

    This paper reports the activities performed in the framework of the ESA contract 18432/04/NL/AR: Enhancement of diffusers BSDF Accuracy. This study was conducted to investigate properties of various diffusers. Diffusers are widely used in space instruments as part of the on-board absolute

  7. Multiple receptor conformers based molecular docking study of fluorine enhanced ethionamide with mycobacterium enoyl ACP reductase (InhA).

    Science.gov (United States)

    Khan, Akib Mahmud; Shawon, Jakaria; Halim, Mohammad A

    2017-10-01

    A major limitation in current molecular docking method is that of failure to account for receptor flexibility. Herein we report multiple receptor conformers based molecular docking as a practical alternative to account for the receptor flexibility. Multiple (forty) conformers of Mycobacterium Enoyl ACP Reductase (InhA) are generated from Molecular Dynamics simulation and twenty crystallographic structures of InhA bound to different inhibitors are obtained from the Protein Data Bank. Fluorine directed modifications are performed to currently available anti-tuberculosis drug ethionamide. The modified drugs are optimized using B3LYP 6-31G (d,p) level of theory. Dipole moment, frontier orbital gap and thermodynamical properties such as electronic energy, enthalpy and Gibbs free energy of these optimized drugs are investigated. These drugs are subsequently docked against the conformers of InhA. Molecular docking against multiple InhA conformations show variation in ligand binding affinity and suggest that Ser94, Gly96, Lys165 and Ile194 amino acids play critical role on strong drug-InhA interaction. Modified drug N1 showed greater binding affinity compared to EN in most conformations. Structure of PDB ID: 2NSD and snapshot conformer at 5.5ns show most favorable binding with N1 compared to other conformers. Fluorine participates in forming fluorine bonds and contributes significantly in increasing binding affinity. Our study reveal that addition of trifluoromethyl group explicitly shows promise in improving thermodynamic properties and in enhancing hydrogen bonding and non-bonded interactions. Molecular dynamics (MD) simulation show that EN and N1 remained in the binding pocket similar to the docked pose of EN-InhA and E1-InhA complexes and also suggested that InhA binds to its inhibitor in inhibitor-induced folding manner. ADMET calculations predict modified drugs to have improved pharmacokinetic properties. Our study concludes that multiple receptor conformers based

  8. Molecular docking.

    Science.gov (United States)

    Morris, Garrett M; Lim-Wilby, Marguerita

    2008-01-01

    Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

  9. Calibration of Robot Reference Frames for Enhanced Robot Positioning Accuracy

    OpenAIRE

    Cheng, Frank Shaopeng

    2008-01-01

    This chapter discussed the importance and methods of conducting robot workcell calibration for enhancing the accuracy of the robot TCP positions in industrial robot applications. It shows that the robot frame transformations define the robot geometric parameters such as joint position variables, link dimensions, and joint offsets in an industrial robot system. The D-H representation allows the robot designer to model the robot motion geometry with the four standard D-H parameters. The robot k...

  10. Evidence for enhanced interoceptive accuracy in professional musicians

    Directory of Open Access Journals (Sweden)

    Katharina eSchirmer-Mokwa

    2015-12-01

    Full Text Available Interoception is defined as the perceptual activity involved in the processing of internal bodily signals. While the ability of internal perception is considered a relatively stable trait, recent data suggest that learning to integrate multisensory information can modulate it. Making music is a uniquely rich multisensory experience that has shown to alter motor, sensory, and multimodal representations in the brain of musicians. We hypothesize that musical training also heightens interoceptive accuracy comparable to other perceptual modalities. Thirteen professional singers, twelve string players, and thirteen matched non-musicians were examined using a well-established heartbeat discrimination paradigm complemented by self-reported dispositional traits. Results revealed that both groups of musicians displayed higher interoceptive accuracy than non-musicians, whereas no differences were found between singers and string-players. Regression analyses showed that accumulated musical practice explained about 49% variation in heartbeat perception accuracy in singers but not in string-players. Psychometric data yielded a number of psychologically plausible inter-correlations in musicians related to performance anxiety. However, dispositional traits were not a confounding factor on heartbeat discrimination accuracy. Together, these data provide first evidence indicating that professional musicians show enhanced interoceptive accuracy compared to non-musicians. We argue that musical training largely accounted for this effect.

  11. A docking study of enhanced intracellular survival protein from Mycobacterium tuberculosis with human DUSP16/MKP-7

    International Nuclear Information System (INIS)

    Yoon, Hye-Jin; Kim, Kyoung Hoon; Yang, Jin Kuk; Suh, Se Won; Kim, Hyunsik; Jang, Soonmin

    2013-01-01

    A docking study of Mtb Eis with its substrate DUSP16/MKP-7 was performed. The docking model suggests dissociation of hexameric Mtb Eis into dimers or monomers. The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis, and one of its secreted effector proteins, called enhanced intracellular survival (Eis) protein, enhances its survival in macrophages. Mtb Eis activates JNK-specific dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7) through the acetylation on Lys55, thus inactivating JNK by dephosphorylation. Based on the recently reported crystal structure of Mtb Eis, a docking model for the binding of Mtb Eis to DUSP16/MKP-7 was generated. In the docking model, the substrate helix containing Lys55 of DUSP16/MKP-7 fits nicely into the active-site cleft of Mtb Eis; the twisted β-sheet of Eis domain II embraces the substrate helix from one side. Most importantly, the side-chain of Lys55 is inserted toward acetyl-CoA and the resulting distance is 4.6 Å between the NZ atom of Lys55 and the carbonyl carbon of the acetyl group in acetyl-CoA. The binding of Mtb Eis and DUSP16/MKP-7 is maintained by strong electrostatic interactions. The active-site cleft of Mtb Eis has a negatively charged surface formed by Asp25, Glu138, Asp286, Glu395 and the terminal carboxylic group of Phe396. In contrast, DUSP16/MKP-7 contains five basic residues, Lys52, Lys55, Arg56, Arg57 and Lys62, which point toward the negatively charged surface of the active-site pocket of Mtb Eis. Thus, the current docking model suggests that the binding of DUSP16/MKP-7 to Mtb Eis should be established by charge complementarity in addition to a very favorable geometric arrangement. The suggested mode of binding requires the dissociation of the hexameric Mtb Eis into dimers or monomers. This study may be useful for future studies aiming to develop inhibitors of Mtb Eis as a new anti-tuberculosis drug candidate

  12. A docking study of enhanced intracellular survival protein from Mycobacterium tuberculosis with human DUSP16/MKP-7

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hye-Jin, E-mail: yoonhj@snu.ac.kr; Kim, Kyoung Hoon [Seoul National University, Seoul 151-747 (Korea, Republic of); Yang, Jin Kuk [Soongsil University, Seoul 156-743 (Korea, Republic of); Suh, Se Won [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Hyunsik; Jang, Soonmin, E-mail: yoonhj@snu.ac.kr [Sejong University, Seoul 143-747 (Korea, Republic of)

    2013-11-01

    A docking study of Mtb Eis with its substrate DUSP16/MKP-7 was performed. The docking model suggests dissociation of hexameric Mtb Eis into dimers or monomers. The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis, and one of its secreted effector proteins, called enhanced intracellular survival (Eis) protein, enhances its survival in macrophages. Mtb Eis activates JNK-specific dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7) through the acetylation on Lys55, thus inactivating JNK by dephosphorylation. Based on the recently reported crystal structure of Mtb Eis, a docking model for the binding of Mtb Eis to DUSP16/MKP-7 was generated. In the docking model, the substrate helix containing Lys55 of DUSP16/MKP-7 fits nicely into the active-site cleft of Mtb Eis; the twisted β-sheet of Eis domain II embraces the substrate helix from one side. Most importantly, the side-chain of Lys55 is inserted toward acetyl-CoA and the resulting distance is 4.6 Å between the NZ atom of Lys55 and the carbonyl carbon of the acetyl group in acetyl-CoA. The binding of Mtb Eis and DUSP16/MKP-7 is maintained by strong electrostatic interactions. The active-site cleft of Mtb Eis has a negatively charged surface formed by Asp25, Glu138, Asp286, Glu395 and the terminal carboxylic group of Phe396. In contrast, DUSP16/MKP-7 contains five basic residues, Lys52, Lys55, Arg56, Arg57 and Lys62, which point toward the negatively charged surface of the active-site pocket of Mtb Eis. Thus, the current docking model suggests that the binding of DUSP16/MKP-7 to Mtb Eis should be established by charge complementarity in addition to a very favorable geometric arrangement. The suggested mode of binding requires the dissociation of the hexameric Mtb Eis into dimers or monomers. This study may be useful for future studies aiming to develop inhibitors of Mtb Eis as a new anti-tuberculosis drug candidate.

  13. Amide-linked Ethanolamine Conjugate of Gemfibrozil as a Profound HDL Enhancer: Design, Synthesis, Pharmacological Screening and Docking Study.

    Science.gov (United States)

    Rai, Himanshu; Dhaneshwar, Suneela S

    2015-01-01

    Elevated concentration of any or all types of lipids in the plasma including hypertriglyceridemia and hypercholesterolemia leads to atherosclerotic cardiovascular disease. Effective medication needs multiple drug therapy as recommended cholesterol and triglyceride levels are difficult to achieve by monotherapy and frequently require the use of more than one lipid-lowering medication. Gemfibrozil lowers plasma triglyceride-rich lipoproteins mainly VLDL and increases HDL. It is associated with short plasma half-life (1.5h) and GIT distress on long term use. In a study it was found that ethanolamine decreases serum cholesterol, especially VLDL cholesterol and LDL cholesterol in rats fed an HF/HC diet. In the present work, we thought of exploring the effect of co-drug of gemfibrozil with ethanolamine (GE-I) as a potential combination therapy for the management of mixed hyperlipidemia. Synthesis of GE-I was effected by CDI coupling. Structure was confirmed spectrally. Interestingly kinetic studies revealed that GE-I resisted chemical and enzymatic hydrolysis. In tritoninduced hyperlipidemia, significant lowering of serum lipid levels was observed. The hallmark of GEI was its profound effect on HDL level which was raised above the normal level by 15%. Docking study also supported modulatory effect of GE-I (docking score -7.012) on PPAR-α which was comparable to docking score of gemfibrozil (-9.432). These preliminary observations prompt us to consider GE-I as a novel, serendipitous, hybrid anti-hyperlipidemic new chemical entity which needs be studied extensively to prove it as an HDL enhancing anti-hyperlipidemic agent.

  14. 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.

  15. Enzymatic Activity Enhancement of Non-Covalent Modified Superoxide Dismutase and Molecular Docking Analysis

    Directory of Open Access Journals (Sweden)

    Fa-Jun Song

    2012-03-01

    Full Text Available The enzyme activity of superoxide dismutase was improved in the pyrogallol autoxidation system by about 27%, after interaction between hydroxypropyl-β-cyclo- dextrin and superoxide dismutase. Fluorescence spectrometry was used to study the interaction between hydroxypropyl-β-cyclodextrin and superoxide dismutase at different temperatures. By doing this, it can be found that these interactions increase fluorescence sensitivity. In the meantime, the synchronous fluorescence intensity revealed the interaction sites to be close to the tryptophan (Trp and tyrosine (Tyr residues of superoxide dismutase. Furthermore, molecular docking was applied to explore the binding mode between the ligands and the receptor. This suggested that HP-β-CD interacted with the B ring, G ring and the O ring and revealed that the lysine (Lys residues enter the nanocavity. It was concluded that the HP-β-CD caused specific conformational changes in SOD by non-covalent modification.

  16. Enhancing spoken connected-digit recognition accuracy by error ...

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    nition systems have gained acceptable accuracy levels, the accuracy of recognition of current connected ... bar code and ISBN1 library code to name a few. ..... Kopec G, Bush M 1985 Network-based connected-digit recognition. IEEE Trans.

  17. Enhancing lineup identification accuracy: two codes are better than one.

    Science.gov (United States)

    Melara, R D; DeWitt-Rickards, T S; O'Brien, T P

    1989-10-01

    Ways of improving identification accuracy were explored by comparing the conventional visual lineup with an auditory/visual lineup, one that paired color photographs with voice recordings. This bimodal lineup necessitated sequential presentation of lineup members; Experiment 1 showed that performance in sequential lineups was better than performance in traditional simultaneous lineups. In Experiments 2A and 2B unimodal and bimodal lineups were compared by using a multiple-lineup paradigm: Ss viewed 3 videotaped episodes depicting standard police procedures and were tested in 4 sequential lineups. Bimodal lineups were more diagnostic than either visual or auditory lineups alone. The bimodal lineup led to a 126% improvement in number of correct identifications over the conventional visual lineup, with no concomitant increase in number of false identifications. These results imply strongly that bimodal procedures should be adopted in real-world lineups. The nature of memorial processes underlying this bimodal advantage is discussed.

  18. Accuracy enhancement of point triangulation probes for linear displacement measurement

    Science.gov (United States)

    Kim, Kyung-Chan; Kim, Jong-Ahn; Oh, SeBaek; Kim, Soo Hyun; Kwak, Yoon Keun

    2000-03-01

    Point triangulation probes (PTBs) fall into a general category of noncontact height or displacement measurement devices. PTBs are widely used for their simple structure, high resolution, and long operating range. However, there are several factors that must be taken into account in order to obtain high accuracy and reliability; measurement errors from inclinations of an object surface, probe signal fluctuations generated by speckle effects, power variation of a light source, electronic noises, and so on. In this paper, we propose a novel signal processing algorithm, named as EASDF (expanded average square difference function), for a newly designed PTB which is composed of an incoherent source (LED), a line scan array detector, a specially selected diffuse reflecting surface, and several optical components. The EASDF, which is a modified correlation function, is able to calculate displacement between the probe and the object surface effectively even if there are inclinations, power fluctuations, and noises.

  19. Enhancement of Localization Accuracy in Cellular Networks via Cooperative AdHoc Links

    DEFF Research Database (Denmark)

    Lhomme, Edouard; Frattasi, Simone; Figueiras, Joao

    2006-01-01

    Positioning information enables new applications for cellular phones, personal communication systems, and specialized mobile radios. The network heterogeneity emerging in the fourth generation (4G) of mobile networks can be utilized for enhancements of the location estimation accuracy...

  20. Enhancement accuracy of approximated solutions of the nonlinear singular integral equations of Chew-Low type

    International Nuclear Information System (INIS)

    Zhidkov, E.P.; Nguen Mong; Khoromskij, B.N.

    1979-01-01

    The ways of enhancement of the accuracy of approximate solutions of the Chew-Low type equation are considered. Difference schemes are proposed which allow one to obtain solution expansion in degrees of lattice step. On the basis of the expansion by the Richardson method the refinement of approximated solutions is made. Besides, the iteration process is constructed which reduces immediately to the solution of enhanced accuracy. The efficiency of the methods proposed is illustrated by numerical examples

  1. 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.

  2. Protein docking prediction using predicted protein-protein interface.

    Science.gov (United States)

    Li, Bin; Kihara, Daisuke

    2012-01-10

    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. 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. 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.

  3. Rendezvous and docking tracker

    Science.gov (United States)

    Ray, Art J.; Ross, Susan E.; Deming, Douglas R.

    1986-01-01

    A conceptual solid-state rendezvous and docking tracker (RDT) has been devised for generating range and attitude data for a docking vehicle relative to a target vehicle. Emphasis is placed on the approach of the Orbiter to a link with the Space Station. Three laser illuminators ring the optical axis of the lens a directed toward retroreflectors on the target vehicle. Each retroreflector is equipped with a bandpass filter for a designated illumination frequency. Data are collected sequentially over a 20 deg field of view as the range closes to 100-1000 m. A fourth ranging retroreflector 0.3 m from center is employed during close-in maneuvers. The system provides tracking data on motions with 6 deg of freedom, and furnishes 500 msec updates (to be enhanced to 100 msec) to the operator at a computer console.

  4. Accuracy of nursing diagnosis "readiness for enhanced hope" in patients with chronic kidney disease.

    Science.gov (United States)

    Silva, Renan Alves; Melo, Geórgia Alcântara Alencar; Caetano, Joselany Áfio; Lopes, Marcos Venícios Oliveira; Butcher, Howard Karl; Silva, Viviane Martins da

    2017-07-06

    To analyse the accuracy of the nursing diagnosis readiness for enhanced hope in patients with chronic kidney disease. This is a cross-sectional study with 62 patients in the haemodialysis clinic conducted from August to November 2015. The Hearth Hope Scale was used to create definitions of the defining characteristics of the North American Nursing Diagnosis Association International. We analysed the measures of sensitivity, specificity, predictive value, likelihood ratio, and odds ratio of the defining characteristics of the diagnosis. Of the characteristics, 82.22% presented the diagnosis. The defining characteristics "Expresses the desire to enhance congruency of expectations with desires" and "Expresses the desire to enhance problem solving to meet goals" increased the chance of having the diagnosis by eleven and five, respectively. The characteristics, "Expresses desire to enhance congruency of expectations with desires" and "Expresses desire to enhance problem solving to meet goals" had good accuracy measures.

  5. Using the multi-objective optimization replica exchange Monte Carlo enhanced sampling method for protein-small molecule docking.

    Science.gov (United States)

    Wang, Hongrui; Liu, Hongwei; Cai, Leixin; Wang, Caixia; Lv, Qiang

    2017-07-10

    In this study, we extended the replica exchange Monte Carlo (REMC) sampling method to protein-small molecule docking conformational prediction using RosettaLigand. In contrast to the traditional Monte Carlo (MC) and REMC sampling methods, these methods use multi-objective optimization Pareto front information to facilitate the selection of replicas for exchange. The Pareto front information generated to select lower energy conformations as representative conformation structure replicas can facilitate the convergence of the available conformational space, including available near-native structures. Furthermore, our approach directly provides min-min scenario Pareto optimal solutions, as well as a hybrid of the min-min and max-min scenario Pareto optimal solutions with lower energy conformations for use as structure templates in the REMC sampling method. These methods were validated based on a thorough analysis of a benchmark data set containing 16 benchmark test cases. An in-depth comparison between MC, REMC, multi-objective optimization-REMC (MO-REMC), and hybrid MO-REMC (HMO-REMC) sampling methods was performed to illustrate the differences between the four conformational search strategies. Our findings demonstrate that the MO-REMC and HMO-REMC conformational sampling methods are powerful approaches for obtaining protein-small molecule docking conformational predictions based on the binding energy of complexes in RosettaLigand.

  6. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2015-11-01

    Full Text Available Olayide A Arodola, Mahmoud ES SolimanMolecular Modelling and Drug Design Lab, School of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South AfricaAbstract: Based on experimental data, the anticancer activity of nelfinavir (NFV, a US Food and Drug Administration (FDA-approved HIV-1 protease inhibitor (PI, was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90, a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 µM. Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively. Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602 played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding

  7. Comparison of Accuracy of Contrast Enhanced Computed Tomography with Accuracy of Non-Contrast Magnetic Resonance Imaging in Evaluation of Local Extension of Base of Tongue Malignancies

    Directory of Open Access Journals (Sweden)

    Ketan Rathod

    2018-01-01

    Full Text Available Diagnosis of base of tongue malignancy can be obtained through clinical examination and biopsy. Magnetic Resonance Imaging (MRI and Computed Tomography (CT are used to detect its local extension, nodal spread and distant metastases. The main aim of study was to compare the accuracy of MRI and contrast enhanced CT in determining the local extent of base of tongue malignancy. Twenty five patients, biopsy proven cases of squamous cell carcinoma of base of tongue were taken. 1.5 Tesla Magnetic Resonance Unit with T2 weighted axial, coronal image; T1 weighted axial, coronal image; and STIR (Short tau inversion recovery axial and coronal images were used. 16 slice Computed Tomography unit with non-contrast and contrast enhanced images were used. Accuracy of CT to detect midline crossing: 50%; accuracy of MRI to detect midline crossing: 100%; accuracy of CT to detect anterior extension: 92%; accuracy of MRI to detect anterior extension: 100%; accuracy of CT to detect tonsillar fossa invasion: 83%; accuracy of MRI to detect tonsillar fossa invasion: 100%; accuracy of CT to detect oro pharyngeal spread: 83%; accuracy of MRI to detect oro pharyngeal spread: 100%; accuracy of CT to detect bone involvement: 20%; accuracy of MRI to detect bone involvement: 100%. MRI proved to be a better investigation than CT, in terms of evaluation of depth of invasion, presence of bony involvement, extension to opposite side, anterior half of tongue, tonsillar fossa, floor of mouth or oropharynx.

  8. Direction of Arrival Estimation Accuracy Enhancement via Using Displacement Invariance Technique

    Directory of Open Access Journals (Sweden)

    Youssef Fayad

    2015-01-01

    Full Text Available A new algorithm for improving Direction of Arrival Estimation (DOAE accuracy has been carried out. Two contributions are introduced. First, Doppler frequency shift that resulted from the target movement is estimated using the displacement invariance technique (DIT. Second, the effect of Doppler frequency is modeled and incorporated into ESPRIT algorithm in order to increase the estimation accuracy. It is worth mentioning that the subspace approach has been employed into ESPRIT and DIT methods to reduce the computational complexity and the model’s nonlinearity effect. The DOAE accuracy has been verified by closed-form Cramér-Rao bound (CRB. The simulation results of the proposed algorithm are better than those of the previous estimation techniques leading to the estimator performance enhancement.

  9. Acute appendicitis: sensitivity, specificity and diagnostic accuracy of thin-section contrast-enhanced CT findings

    International Nuclear Information System (INIS)

    Lee, Ji Yon; Choi, Dong Il; Park, Hae Won; Lee, Young Rae; Kook, Shin Ho; Kwang, Hyon Joo; Kim, Seung Kwon; Chung, Eun Chul

    2002-01-01

    To assess the sensitivity, specificity, and diagnostic accuracy of individual contrast-enhanced helical CT findings of acute appendicitis. We retrospectively reviewed the appendiceal helical CT scans, obtained after intravenous contrast administration (abdomen; 7-mm collimation, abdominopelvic junction; 5-mm collimation), of 50 patients with surgically proven acute appendicitis and 112 with alternative diagnoses. The following parameters were analysed by three radiologists: enlarged appendix (>6 mm in diameter), appendiceal wall thickening, appendiceal wall enhancement, no identification of the appendix, appendicolith(s), (appendiceal) intraluminal air, abscess, lymphadenopathy, terminal ileal wall thickening, focal cecal apical thickening, focal colonic wall thickening, and segmental colonic wall thickening. The CT findings of acute appendicitis that statistically distinguished it from alternative diagnoses were an enlarged appendix (sensitivity; 92%, specificity; 93%, diagnostic accuracy; 93%), appendiceal wall thickening (for these three parameters: 68%, 96% and 88%, respectively), periappendiceal fat stranding (90%, 79%, 82%), appendiceal wall enhancement (72%, 86%, 82%), appendicolith (16%, 100%, 74%), and focal cecal apical thickening (14%, 100%, 74%) (for each, p<0305). On thin-section contrast-enhanced helical CT, an enlarged appendix and periappendiceal fat stranding were found in 90% or more patients with acute appendicitis. Appendiceal wall thickening and enhancement were alearly demonstrated and significant findings for diagnosis. Less common but specific findings include appendicolith, focal cecal apical thickening and intramural air, can also help us establish a diagnosis of acute appendicitis

  10. Diagnostic Accuracy of Dynamic Contrast Enhanced Magnetic Resonance Imaging in Characterizing Lung Masses

    Science.gov (United States)

    Inan, Nagihan; Arslan, Arzu; Donmez, Muhammed; Sarisoy, Hasan Tahsin

    2016-01-01

    Background Imaging plays a critical role not only in the detection, but also in the characterization of lung masses as benign or malignant. Objectives To determine the diagnostic accuracy of dynamic magnetic resonance imaging (MRI) in the differential diagnosis of benign and malignant lung masses. Patients and Methods Ninety-four masses were included in this prospective study. Five dynamic series of T1-weighted spoiled gradient echo (FFE) images were obtained, followed by a T1-weighted FFE sequence in the late phase (5th minutes). Contrast enhancement patterns in the early (25th second) and late (5th minute) phase images were evaluated. For the quantitative evaluation, signal intensity (SI)-time curves were obtained and the maximum relative enhancement, wash-in rate, and time-to-peak enhancement of masses in both groups were calculated. Results The early phase contrast enhancement patterns were homogeneous in 78.2% of the benign masses, while heterogeneous in 74.4% of the malignant tumors. On the late phase images, 70.8% of the benign masses showed homogeneous enhancement, while most of the malignant masses showed heterogeneous enhancement (82.4%). During the first pass, the maximum relative enhancement and wash-in rate values of malignant masses were significantly higher than those of the benign masses (P = 0.03 and 0.04, respectively). The cutoff value at 15% yielded a sensitivity of 85.4%, specificity of 61.2%, and positive predictive value of 68.7% for the maximum relative enhancement. Conclusion Contrast enhancement patterns and SI-time curve analysis of MRI are helpful in the differential diagnosis of benign and malignant lung masses. PMID:27703654

  11. EM Simulation Accuracy Enhancement for Broadband Modeling of On-Wafer Passive Components

    DEFF Research Database (Denmark)

    Johansen, Tom Keinicke; Jiang, Chenhui; Hadziabdic, Dzenan

    2007-01-01

    This paper describes methods for accuracy enhancement in broadband modeling of on-wafer passive components using electromagnetic (EM) simulation. It is shown that standard excitation schemes for integrated component simulation leads to poor correlation with on-wafer measurements beyond the lower...... GHz frequency range. We show that this is due to parasitic effects and higher-order modes caused by the excitation schemes. We propose a simple equivalent circuit for the parasitic effects in the well-known ground ring excitation scheme. An extended L-2L calibration method is shown to improve...

  12. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

    Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

  13. Diagnostic accuracy of segmental enhancement inversion for diagnosis of renal oncocytoma at biphasic contrast enhanced CT: systematic review

    International Nuclear Information System (INIS)

    Schieda, Nicola; McInnes, Matthew D.F.; Cao, Lilly

    2014-01-01

    To use systematic review to evaluate the diagnostic accuracy of segmental enhancement inversion (SEI) at contrast-enhanced biphasic multi-detector computed tomography (MDCT) for the diagnosis of renal oncocytoma. Several electronic databases were searched through October 2013. Two reviewers independently selected studies that met the inclusion criteria and extracted data. Study quality was assessed with the QUADAS-2 tool. The primary 2 x 2 data were investigated with forest plot and ROC plot of sensitivity and specificity. Four studies met the inclusion criteria (307 patients). Considerable heterogeneity between studies precluded meta-analysis. Two studies from the same group of investigators demonstrated reasonable diagnostic accuracy (sensitivity 59-80 % and specificity 87-99 %), while two others did not (sensitivity 0-6 %, specificity 93-100 %). Possible reasons for this include timing of biphasic MDCT and methods of interpretation but not size of lesion. SEI is a specific imaging finding of renal oncocytoma with highly variable sensitivity. This substantial heterogeneity across studies and between institutions suggests that further validation of this imaging finding is necessary prior to application in clinical practice. (orig.)

  14. Diagnostic accuracy of segmental enhancement inversion for diagnosis of renal oncocytoma at biphasic contrast enhanced CT: systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Schieda, Nicola; McInnes, Matthew D.F.; Cao, Lilly [Ottawa Hospital Research Institute, Department of Medical Imaging, Ottawa, ON (Canada)

    2014-06-15

    To use systematic review to evaluate the diagnostic accuracy of segmental enhancement inversion (SEI) at contrast-enhanced biphasic multi-detector computed tomography (MDCT) for the diagnosis of renal oncocytoma. Several electronic databases were searched through October 2013. Two reviewers independently selected studies that met the inclusion criteria and extracted data. Study quality was assessed with the QUADAS-2 tool. The primary 2 x 2 data were investigated with forest plot and ROC plot of sensitivity and specificity. Four studies met the inclusion criteria (307 patients). Considerable heterogeneity between studies precluded meta-analysis. Two studies from the same group of investigators demonstrated reasonable diagnostic accuracy (sensitivity 59-80 % and specificity 87-99 %), while two others did not (sensitivity 0-6 %, specificity 93-100 %). Possible reasons for this include timing of biphasic MDCT and methods of interpretation but not size of lesion. SEI is a specific imaging finding of renal oncocytoma with highly variable sensitivity. This substantial heterogeneity across studies and between institutions suggests that further validation of this imaging finding is necessary prior to application in clinical practice. (orig.)

  15. Contrast-enhanced spectral mammography improves diagnostic accuracy in the symptomatic setting.

    Science.gov (United States)

    Tennant, S L; James, J J; Cornford, E J; Chen, Y; Burrell, H C; Hamilton, L J; Girio-Fragkoulakis, C

    2016-11-01

    To assess the diagnostic accuracy of contrast-enhanced spectral mammography (CESM), and gauge its "added value" in the symptomatic setting. A retrospective multi-reader review of 100 consecutive CESM examinations was performed. Anonymised low-energy (LE) images were reviewed and given a score for malignancy. At least 3 weeks later, the entire examination (LE and recombined images) was reviewed. Histopathology data were obtained for all cases. Differences in performance were assessed using receiver operator characteristic (ROC) analysis. Sensitivity, specificity, and lesion size (versus MRI or histopathology) differences were calculated. Seventy-three percent of cases were malignant at final histology, 27% were benign following standard triple assessment. ROC analysis showed improved overall performance of CESM over LE alone, with area under the curve of 0.93 versus 0.83 (p<0.025). CESM showed increased sensitivity (95% versus 84%, p<0.025) and specificity (81% versus 63%, p<0.025) compared to LE alone, with all five readers showing improved accuracy. Tumour size estimation at CESM was significantly more accurate than LE alone, the latter tending to undersize lesions. In 75% of cases, CESM was deemed a useful or significant aid to diagnosis. CESM provides immediately available, clinically useful information in the symptomatic clinic in patients with suspicious palpable abnormalities. Radiologist sensitivity, specificity, and size accuracy for breast cancer detection and staging are all improved using CESM as the primary mammographic investigation. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  16. Enhancement of accuracy in shape sensing of surgical needles using optical frequency domain reflectometry in optical fibers.

    Science.gov (United States)

    Parent, Francois; Loranger, Sebastien; Mandal, Koushik Kanti; Iezzi, Victor Lambin; Lapointe, Jerome; Boisvert, Jean-Sébastien; Baiad, Mohamed Diaa; Kadoury, Samuel; Kashyap, Raman

    2017-04-01

    We demonstrate a novel approach to enhance the precision of surgical needle shape tracking based on distributed strain sensing using optical frequency domain reflectometry (OFDR). The precision enhancement is provided by using optical fibers with high scattering properties. Shape tracking of surgical tools using strain sensing properties of optical fibers has seen increased attention in recent years. Most of the investigations made in this field use fiber Bragg gratings (FBG), which can be used as discrete or quasi-distributed strain sensors. By using a truly distributed sensing approach (OFDR), preliminary results show that the attainable accuracy is comparable to accuracies reported in the literature using FBG sensors for tracking applications (~1mm). We propose a technique that enhanced our accuracy by 47% using UV exposed fibers, which have higher light scattering compared to un-exposed standard single mode fibers. Improving the experimental setup will enhance the accuracy provided by shape tracking using OFDR and will contribute significantly to clinical applications.

  17. An autonomous rendezvous and docking system using cruise missile technologies

    Science.gov (United States)

    Jones, Ruel Edwin

    1991-01-01

    In November 1990 the Autonomous Rendezvous & Docking (AR&D) system was first demonstrated for members of NASA's Strategic Avionics Technology Working Group. This simulation utilized prototype hardware from the Cruise Missile and Advanced Centaur Avionics systems. The object was to show that all the accuracy, reliability and operational requirements established for a space craft to dock with Space Station Freedom could be met by the proposed system. The rapid prototyping capabilities of the Advanced Avionics Systems Development Laboratory were used to evaluate the proposed system in a real time, hardware in the loop simulation of the rendezvous and docking reference mission. The simulation permits manual, supervised automatic and fully autonomous operations to be evaluated. It is also being upgraded to be able to test an Autonomous Approach and Landing (AA&L) system. The AA&L and AR&D systems are very similar. Both use inertial guidance and control systems supplemented by GPS. Both use an Image Processing System (IPS), for target recognition and tracking. The IPS includes a general purpose multiprocessor computer and a selected suite of sensors that will provide the required relative position and orientation data. Graphic displays can also be generated by the computer, providing the astronaut / operator with real-time guidance and navigation data with enhanced video or sensor imagery.

  18. Image accuracy and representational enhancement through low-level, multi-sensor integration techniques

    International Nuclear Information System (INIS)

    Baker, J.E.

    1993-05-01

    Multi-Sensor Integration (MSI) is the combining of data and information from more than one source in order to generate a more reliable and consistent representation of the environment. The need for MSI derives largely from basic ambiguities inherent in our current sensor imaging technologies. These ambiguities exist as long as the mapping from reality to image is not 1-to-1. That is, if different 44 realities'' lead to identical images, a single image cannot reveal the particular reality which was the truth. MSI techniques can be divided into three categories based on the relative information content of the original images with that of the desired representation: (1) ''detail enhancement,'' wherein the relative information content of the original images is less rich than the desired representation; (2) ''data enhancement,'' wherein the MSI techniques axe concerned with improving the accuracy of the data rather than either increasing or decreasing the level of detail; and (3) ''conceptual enhancement,'' wherein the image contains more detail than is desired, making it difficult to easily recognize objects of interest. In conceptual enhancement one must group pixels corresponding to the same conceptual object and thereby reduce the level of extraneous detail. This research focuses on data and conceptual enhancement algorithms. To be useful in many real-world applications, e.g., autonomous or teleoperated robotics, real-time feedback is critical. But, many MSI/image processing algorithms require significant processing time. This is especially true of feature extraction, object isolation, and object recognition algorithms due to their typical reliance on global or large neighborhood information. This research attempts to exploit the speed currently available in state-of-the-art digitizers and highly parallel processing systems by developing MSI algorithms based on pixel rather than global-level features

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

    Directory of Open Access Journals (Sweden)

    Rezaul Chowdhury

    Full Text Available 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.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.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: http

  20. Protein-Protein Docking with F2Dock 2.0 and GB-Rerank

    Science.gov (United States)

    Chowdhury, Rezaul; Rasheed, Muhibur; Keidel, Donald; Moussalem, Maysam; Olson, Arthur; Sanner, Michel; Bajaj, Chandrajit

    2013-01-01

    Motivation Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F2 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 F2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F2 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. F2 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 F2 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: http

  1. 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 examining economic results of four management and housing scenarios, and by discussing their consequences for animal welfare in the light of legal and ethical considerations. The four scenarios compared are: ‘Standard Docked’, a conventional housing scenario with tail docking meeting the recommendations...... for Danish production (0.7 m2/pig); ‘Standard Undocked’, which is the same as ‘Standard Docked’ but with no tail docking, ‘Efficient Undocked’ and ‘Enhanced Undocked’, which have increased solid floor area (0.9 and 1.0 m2/pig, respectively) provision of loose manipulable materials (100 and 200 g/straw per...

  2. Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: improved sensor performance with enhanced calibrations.

    Science.gov (United States)

    Leelarathna, Lalantha; English, Shane W; Thabit, Hood; Caldwell, Karen; Allen, Janet M; Kumareswaran, Kavita; Wilinska, Malgorzata E; Nodale, Marianna; Haidar, Ahmad; Evans, Mark L; Burnstein, Rowan; Hovorka, Roman

    2014-02-01

    Accurate real-time continuous glucose measurements may improve glucose control in the critical care unit. We evaluated the accuracy of the FreeStyle(®) Navigator(®) (Abbott Diabetes Care, Alameda, CA) subcutaneous continuous glucose monitoring (CGM) device in critically ill adults using two methods of calibration. In a randomized trial, paired CGM and reference glucose (hourly arterial blood glucose [ABG]) were collected over a 48-h period from 24 adults with critical illness (mean±SD age, 60±14 years; mean±SD body mass index, 29.6±9.3 kg/m(2); mean±SD Acute Physiology and Chronic Health Evaluation score, 12±4 [range, 6-19]) and hyperglycemia. In 12 subjects, the CGM device was calibrated at variable intervals of 1-6 h using ABG. In the other 12 subjects, the sensor was calibrated according to the manufacturer's instructions (1, 2, 10, and 24 h) using arterial blood and the built-in point-of-care glucometer. In total, 1,060 CGM-ABG pairs were analyzed over the glucose range from 4.3 to 18.8 mmol/L. Using enhanced calibration median (interquartile range) every 169 (122-213) min, the absolute relative deviation was lower (7.0% [3.5, 13.0] vs. 12.8% [6.3, 21.8], P<0.001), and the percentage of points in the Clarke error grid Zone A was higher (87.8% vs. 70.2%). Accuracy of the Navigator CGM device during critical illness was comparable to that observed in non-critical care settings. Further significant improvements in accuracy may be obtained by frequent calibrations with ABG measurements.

  3. PEPSI-Dock: a detailed data-driven protein–protein interaction potential accelerated by polar Fourier correlation

    OpenAIRE

    Neveu , Emilie; Ritchie , David; Popov , Petr; Grudinin , Sergei

    2016-01-01

    International audience; Motivation: Docking prediction algorithms aim to find the native conformation of a complex of proteins from knowledge of their unbound structures. They rely on a combination of sampling and scoring methods, adapted to different scales. Polynomial Expansion of Protein Structures and Interactions for Docking (PEPSI-Dock) improves the accuracy of the first stage of the docking pipeline , which will sharpen up the final predictions. Indeed, PEPSI-Dock benefits from the pre...

  4. Enhancing the Accuracy of Advanced High Temperature Mechanical Testing through Thermography

    Directory of Open Access Journals (Sweden)

    Jonathan Jones

    2018-03-01

    Full Text Available This paper describes the advantages and enhanced accuracy thermography provides to high temperature mechanical testing. This technique is not only used to monitor, but also to control test specimen temperatures where the infra-red technique enables accurate non-invasive control of rapid thermal cycling for non-metallic materials. Isothermal and dynamic waveforms are employed over a 200–800 °C temperature range to pre-oxidised and coated specimens to assess the capability of the technique. This application shows thermography to be accurate to within ±2 °C of thermocouples, a standardised measurement technique. This work demonstrates the superior visibility of test temperatures previously unobtainable by conventional thermocouples or even more modern pyrometers that thermography can deliver. As a result, the speed and accuracy of thermal profiling, thermal gradient measurements and cold/hot spot identification using the technique has increased significantly to the point where temperature can now be controlled by averaging over a specified area. The increased visibility of specimen temperatures has revealed additional unknown effects such as thermocouple shadowing, preferential crack tip heating within an induction coil, and, fundamental response time of individual measurement techniques which are investigated further.

  5. Enhancing the accuracy of subcutaneous glucose sensors: a real-time deconvolution-based approach.

    Science.gov (United States)

    Guerra, Stefania; Facchinetti, Andrea; Sparacino, Giovanni; Nicolao, Giuseppe De; Cobelli, Claudio

    2012-06-01

    Minimally invasive continuous glucose monitoring (CGM) sensors can greatly help diabetes management. Most of these sensors consist of a needle electrode, placed in the subcutaneous tissue, which measures an electrical current exploiting the glucose-oxidase principle. This current is then transformed to glucose levels after calibrating the sensor on the basis of one, or more, self-monitoring blood glucose (SMBG) samples. In this study, we design and test a real-time signal-enhancement module that, cascaded to the CGM device, improves the quality of its output by a proper postprocessing of the CGM signal. In fact, CGM sensors measure glucose in the interstitium rather than in the blood compartment. We show that this distortion can be compensated by means of a regularized deconvolution procedure relying on a linear regression model that can be updated whenever a pair of suitably sampled SMBG references is collected. Tests performed both on simulated and real data demonstrate a significant accuracy improvement of the CGM signal. Simulation studies also demonstrate the robustness of the method against departures from nominal conditions, such as temporal misplacement of the SMBG samples and uncertainty in the blood-to-interstitium glucose kinetic model. Thanks to its online capabilities, the proposed signal-enhancement algorithm can be used to improve the performance of CGM-based real-time systems such as the hypo/hyper glycemic alert generators or the artificial pancreas.

  6. Enhanced Positioning Algorithm of ARPS for Improving Accuracy and Expanding Service Coverage

    Directory of Open Access Journals (Sweden)

    Kyuman Lee

    2016-08-01

    Full Text Available The airborne relay-based positioning system (ARPS, which employs the relaying of navigation signals, was proposed as an alternative positioning system. However, the ARPS has limitations, such as relatively large vertical error and service restrictions, because firstly, the user position is estimated based on airborne relays that are located in one direction, and secondly, the positioning is processed using only relayed navigation signals. In this paper, we propose an enhanced positioning algorithm to improve the performance of the ARPS. The main idea of the enhanced algorithm is the adaptable use of either virtual or direct measurements of reference stations in the calculation process based on the structural features of the ARPS. Unlike the existing two-step algorithm for airborne relay and user positioning, the enhanced algorithm is divided into two cases based on whether the required number of navigation signals for user positioning is met. In the first case, where the number of signals is greater than four, the user first estimates the positions of the airborne relays and its own initial position. Then, the user position is re-estimated by integrating a virtual measurement of a reference station that is calculated using the initial estimated user position and known reference positions. To prevent performance degradation, the re-estimation is performed after determining its requirement through comparing the expected position errors. If the navigation signals are insufficient, such as when the user is outside of airborne relay coverage, the user position is estimated by additionally using direct signal measurements of the reference stations in place of absent relayed signals. The simulation results demonstrate that a higher accuracy level can be achieved because the user position is estimated based on the measurements of airborne relays and a ground station. Furthermore, the service coverage is expanded by using direct measurements of reference

  7. The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures

    Directory of Open Access Journals (Sweden)

    Alejandro Castro-Alvarez

    2017-01-01

    Full Text Available The accuracy of five docking programs at reproducing crystallographic structures of complexes of 8 macrolides and 12 related macrocyclic structures, all with their corresponding receptors, was evaluated. Self-docking calculations indicated excellent performance in all cases (mean RMSD values ≤ 1.0 and confirmed the speed of AutoDock Vina. Afterwards, the lowest-energy conformer of each molecule and all the conformers lying 0–10 kcal/mol above it (as given by Macrocycle, from MacroModel 10.0 were subjected to standard docking calculations. While each docking method has its own merits, the observed speed of the programs was as follows: Glide 6.6 > AutoDock Vina 1.1.2 > DOCK 6.5 >> AutoDock 4.2.6 > AutoDock 3.0.5. For most of the complexes, the five methods predicted quite correct poses of ligands at the binding sites, but the lower RMSD values for the poses of highest affinity were in the order: Glide 6.6 ≈ AutoDock Vina ≈ DOCK 6.5 > AutoDock 4.2.6 >> AutoDock 3.0.5. By choosing the poses closest to the crystal structure the order was: AutoDock Vina > Glide 6.6 ≈ DOCK 6.5 ≥ AutoDock 4.2.6 >> AutoDock 3.0.5. Re-scoring (AutoDock 4.2.6//AutoDock Vina, Amber Score and MM-GBSA improved the agreement between the calculated and experimental data. For all intents and purposes, these three methods are equally reliable.

  8. Clinical MR mammography. Impact of hormonal status on background enhancement and diagnostic accuracy

    International Nuclear Information System (INIS)

    Baltzer, Pascal Andreas Thomas; Dietzel, M.; Burmeister, H.; Pfleiderer, S.O.; Kaiser, W.A.; Vag, T.; Gajda, M.; Camara, O.

    2011-01-01

    Purpose: Hormonal stimulation can induce background enhancement (BE) in MR mammography (MRM). This fact has been assumed to decrease the accuracy of MRM. Consequently, this report investigates: 1. The prevalence of BE in postmenopausal vs. premenopausal women in correlation to hormonal cycle phase (CP). 2. The impact of hormonal status (HS) and BE on diagnostic accuracy. Materials and Methods: Consecutive patients over 22 months with complete HS information (week of CP or postmenopausal) were included in this prospective investigation. Exclusion criteria were any hormonal therapy, hysterectomy as well as cancer proven by biopsy. The standard of reference was histopathology. All MRM scans were acquired using the same protocol (1.5 T, dynamic T 1w GRE after 0.1 mmol/kg bw Gd-DTPA i. v.). Two radiologists rated all examinations in consensus according to BI-RADS. BE was defined as: 0 = missing, 1 = moderate, 2 = distinct. Results: 224 patients (150 postmenopausal, 74 premenopausal, 45 in the second week of CP) were included in this study (83 benign and 141 malignant findings). BE was more frequent in premenopausal women (p = 0.006), but did not differ between CP (p = 0.460). Neither HS nor BE had a significant impact on the diagnostic parameters of MRM (p ≥ 0.375). However, regarding BE, the relative number of false positive (FP) findings was highest (5 / 10; 50 %) in the distinct BE group. Regarding HS, 17 % more FP findings were observed in premenopausal women examined outside the second week of CP. Conclusion: In premenopausal women, HS leads to increased BE of breast tissue, independent of CP. Distinct BE and less pronounced, non-optimal CP may lead to an increased number of false positive findings. (orig.)

  9. Clinical MR mammography. Impact of hormonal status on background enhancement and diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Baltzer, Pascal Andreas Thomas; Dietzel, M.; Burmeister, H.; Pfleiderer, S.O.; Kaiser, W.A. [Jena Univ. (Germany). Inst. of Diagnostic and Interventional Radiology; Vag, T. [Klinikum Rechts der Isar (Germany). Dept. of Radiology; Gajda, M. [Jena Univ. (Germany). Inst. of Pathology; Camara, O. [Jena Univ. (Germany). Clinic of Gynaecology

    2011-05-15

    Purpose: Hormonal stimulation can induce background enhancement (BE) in MR mammography (MRM). This fact has been assumed to decrease the accuracy of MRM. Consequently, this report investigates: 1. The prevalence of BE in postmenopausal vs. premenopausal women in correlation to hormonal cycle phase (CP). 2. The impact of hormonal status (HS) and BE on diagnostic accuracy. Materials and Methods: Consecutive patients over 22 months with complete HS information (week of CP or postmenopausal) were included in this prospective investigation. Exclusion criteria were any hormonal therapy, hysterectomy as well as cancer proven by biopsy. The standard of reference was histopathology. All MRM scans were acquired using the same protocol (1.5 T, dynamic T 1w GRE after 0.1 mmol/kg bw Gd-DTPA i. v.). Two radiologists rated all examinations in consensus according to BI-RADS. BE was defined as: 0 = missing, 1 = moderate, 2 = distinct. Results: 224 patients (150 postmenopausal, 74 premenopausal, 45 in the second week of CP) were included in this study (83 benign and 141 malignant findings). BE was more frequent in premenopausal women (p = 0.006), but did not differ between CP (p = 0.460). Neither HS nor BE had a significant impact on the diagnostic parameters of MRM (p {>=} 0.375). However, regarding BE, the relative number of false positive (FP) findings was highest (5 / 10; 50 %) in the distinct BE group. Regarding HS, 17 % more FP findings were observed in premenopausal women examined outside the second week of CP. Conclusion: In premenopausal women, HS leads to increased BE of breast tissue, independent of CP. Distinct BE and less pronounced, non-optimal CP may lead to an increased number of false positive findings. (orig.)

  10. Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies.

    Science.gov (United States)

    Aldridge, Robert W; Shaji, Kunju; Hayward, Andrew C; Abubakar, Ibrahim

    2015-01-01

    The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets. EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters. Exact matching using NHS number between two datasets (containing 5931 and 1759 records) identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity 100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3, 100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review. With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance) then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for vulnerable

  11. Vehicle Position Estimation Based on Magnetic Markers: Enhanced Accuracy by Compensation of Time Delays

    Directory of Open Access Journals (Sweden)

    Yeun-Sub Byun

    2015-11-01

    Full Text Available The real-time recognition of absolute (or relative position and orientation on a network of roads is a core technology for fully automated or driving-assisted vehicles. This paper presents an empirical investigation of the design, implementation, and evaluation of a self-positioning system based on a magnetic marker reference sensing method for an autonomous vehicle. Specifically, the estimation accuracy of the magnetic sensing ruler (MSR in the up-to-date estimation of the actual position was successfully enhanced by compensating for time delays in signal processing when detecting the vertical magnetic field (VMF in an array of signals. In this study, the signal processing scheme was developed to minimize the effects of the distortion of measured signals when estimating the relative positional information based on magnetic signals obtained using the MSR. In other words, the center point in a 2D magnetic field contour plot corresponding to the actual position of magnetic markers was estimated by tracking the errors between pre-defined reference models and measured magnetic signals. The algorithm proposed in this study was validated by experimental measurements using a test vehicle on a pilot network of roads. From the results, the positioning error was found to be less than 0.04 m on average in an operational test.

  12. New generation of docking programs: Supercomputer validation of force fields and quantum-chemical methods for docking.

    Science.gov (United States)

    Sulimov, Alexey V; Kutov, Danil C; Katkova, Ekaterina V; Ilin, Ivan S; Sulimov, Vladimir B

    2017-11-01

    Discovery of new inhibitors of the protein associated with a given disease is the initial and most important stage of the whole process of the rational development of new pharmaceutical substances. New inhibitors block the active site of the target protein and the disease is cured. Computer-aided molecular modeling can considerably increase effectiveness of new inhibitors development. Reliable predictions of the target protein inhibition by a small molecule, ligand, is defined by the accuracy of docking programs. Such programs position a ligand in the target protein and estimate the protein-ligand binding energy. Positioning accuracy of modern docking programs is satisfactory. However, the accuracy of binding energy calculations is too low to predict good inhibitors. For effective application of docking programs to new inhibitors development the accuracy of binding energy calculations should be higher than 1kcal/mol. Reasons of limited accuracy of modern docking programs are discussed. One of the most important aspects limiting this accuracy is imperfection of protein-ligand energy calculations. Results of supercomputer validation of several force fields and quantum-chemical methods for docking are presented. The validation was performed by quasi-docking as follows. First, the low energy minima spectra of 16 protein-ligand complexes were found by exhaustive minima search in the MMFF94 force field. Second, energies of the lowest 8192 minima are recalculated with CHARMM force field and PM6-D3H4X and PM7 quantum-chemical methods for each complex. The analysis of minima energies reveals the docking positioning accuracies of the PM7 and PM6-D3H4X quantum-chemical methods and the CHARMM force field are close to one another and they are better than the positioning accuracy of the MMFF94 force field. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Contrast-enhanced spectral mammography based on a photon-counting detector: quantitative accuracy and radiation dose

    Science.gov (United States)

    Lee, Seungwan; Kang, Sooncheol; Eom, Jisoo

    2017-03-01

    Contrast-enhanced mammography has been used to demonstrate functional information about a breast tumor by injecting contrast agents. However, a conventional technique with a single exposure degrades the efficiency of tumor detection due to structure overlapping. Dual-energy techniques with energy-integrating detectors (EIDs) also cause an increase of radiation dose and an inaccuracy of material decomposition due to the limitations of EIDs. On the other hands, spectral mammography with photon-counting detectors (PCDs) is able to resolve the issues induced by the conventional technique and EIDs using their energy-discrimination capabilities. In this study, the contrast-enhanced spectral mammography based on a PCD was implemented by using a polychromatic dual-energy model, and the proposed technique was compared with the dual-energy technique with an EID in terms of quantitative accuracy and radiation dose. The results showed that the proposed technique improved the quantitative accuracy as well as reduced radiation dose comparing to the dual-energy technique with an EID. The quantitative accuracy of the contrast-enhanced spectral mammography based on a PCD was slightly improved as a function of radiation dose. Therefore, the contrast-enhanced spectral mammography based on a PCD is able to provide useful information for detecting breast tumors and improving diagnostic accuracy.

  14. Impact of intravascular enhancement, heart rate, and calcium score on diagnostic accuracy in multislice Computed Tomography coronary angiography

    International Nuclear Information System (INIS)

    Cademartiri, Filippo; Mollet, Nico R.; Kriestin, Gabriel P.; Runza, Giuseppe; Bartolotta, Tommaso Vincenzo; Galia, Massimo; Midiri, Massimo; Belgrano, Manuel; Pozzi Mucelli, Roberto

    2005-01-01

    Purpose. To assess the effect of intravascular enhancement, heart rate, and calcium score on diagnostic accuracy in the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). Materials and methods. One hundred patients (88 males; 59±11 years) with suspected coronary artery disease who had undergone conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA, with the following protocol: collimation 16x0.75 mm, gantry rotation time 420 ms, feed/rotation 2.8 mm, kV 120, mAs 400-500. The protocol for contrast material administration was 100 ml of Iodixanol 320 mgI/nl at 4 ml/s and the scan delay was defined with a bolus tracking technique. In all patients vascular enhancement was measured in the aortic root, and the left and the right coronary arteries. The average enhancement was used to divide the population in two groups of 50 patients each, one with lower enhancement (Low), and one with higher enhancement (High). In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (≥50% lumen reduction) was evaluated in vessels ≥2mm in diameter using quantitative CA as the reference standard. The differences in diagnostic accuracy were compared with a Chi-square test and a p [it

  15. Spacecraft rendezvous and docking

    DEFF Research Database (Denmark)

    Jørgensen, John Leif

    1999-01-01

    The phenomenons and problems encountered when a rendezvous manoeuvre, 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 analysed. So far, all solutions that has been brought into realization has...... 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...

  16. Accuracy-enhanced constitutive parameter identification using virtual fields method and special stereo-digital image correlation

    Science.gov (United States)

    Zhang, Zhongya; Pan, Bing; Grédiac, Michel; Song, Weidong

    2018-04-01

    The virtual fields method (VFM) is generally used with two-dimensional digital image correlation (2D-DIC) or grid method (GM) for identifying constitutive parameters. However, when small out-of-plane translation/rotation occurs to the test specimen, 2D-DIC and GM are prone to yield inaccurate measurements, which further lessen the accuracy of the parameter identification using VFM. In this work, an easy-to-implement but effective "special" stereo-DIC (SS-DIC) method is proposed for accuracy-enhanced VFM identification. The SS-DIC can not only deliver accurate deformation measurement without being affected by unavoidable out-of-plane movement/rotation of a test specimen, but can also ensure evenly distributed calculation data in space, which leads to simple data processing. Based on the accurate kinematics fields with evenly distributed measured points determined by SS-DIC method, constitutive parameters can be identified by VFM with enhanced accuracy. Uniaxial tensile tests of a perforated aluminum plate and pure shear tests of a prismatic aluminum specimen verified the effectiveness and accuracy of the proposed method. Experimental results show that the constitutive parameters identified by VFM using SS-DIC are more accurate and stable than those identified by VFM using 2D-DIC. It is suggested that the proposed SS-DIC can be used as a standard measuring tool for mechanical identification using VFM.

  17. Contrast-enhanced three-dimensional MR angiography of neck vessels: does dephasing effect alter diagnostic accuracy?

    International Nuclear Information System (INIS)

    Cosottini, M.; Calabrese, R.; Murri, L.; Puglioli, M.; Zampa, V.; Michelassi, M.C.; Ortori, S.; Bartolozzi, C.

    2003-01-01

    The aim of this study was to evaluate diagnostic accuracy of contrast-enhanced MRA (CEMRA) compared with digital subtraction angiography (DSA) in studying neck vessels of 48 patients. In three groups of patients, we used three MRA protocols differing for voxel size to assess if intravoxel dephasing effects could modify accuracy of CEMRA. Accuracy and correlation with DSA results were calculated in all patients and separately in the three groups. A qualitative analysis of the likeness between morphology of the stenosis in CEMRA and DSA images was also assessed. In all patients accuracy and agreement with DSA were 96% and k=0.85 in subclavian arteries, 96% and k=0.84 in vertebral artery, 97% and k=0.88 in common carotid arteries, and 94% and k=0.86 in internal carotid arteries. In the three groups accuracy and agreement with DSA did not show any significant difference. Qualitative analysis of CEMRA and DSA images revealed a better agreement in depicting the morphology of stenosis using a smaller voxel size. The CEMRA represents a powerful tool for the non-invasive evaluation of neck vessels. Overestimation trend of CEMRA is confirmed and the reduction of voxel size, decreasing the dephasing intravoxel effect, allows to have a better overlapping of stenosis morphology on CEMRA compared with DSA, but it does not yield diagnostic gain in the stenosis grading. (orig.)

  18. Accuracy of enhanced and unenhanced MRI in diagnosing scaphoid proximal pole avascular necrosis and predicting surgical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Fox, M.G. [University of Virginia, Department of Radiology and Medical Imaging, Charlottesville, VA (United States); Wang, D.T. [University of Virginia, Department of Radiology and Medical Imaging, Charlottesville, VA (United States); Medical College of Wisconsin, Milwaukee, WI (United States); Chhabra, A.B. [University of Virginia Health System, Department of Orthopedics, Charlottesville, VA (United States)

    2015-11-15

    Determine the sensitivity, specificity and accuracy of unenhanced and enhanced MRI in diagnosing scaphoid proximal pole (PP) avascular necrosis (AVN) and correlate whether MRI can help guide the selection of a vascularized or nonvascularized bone graft. The study was approved by the IRB. Two MSK radiologists independently performed a retrospective review of unenhanced and enhanced MRIs from 18 patients (16 males, 2 females; median age, 17.5 years) with scaphoid nonunions and surgery performed within 65 days of the MRI. AVN was diagnosed on the unenhanced MRI when a diffusely decreased T1-W signal was present in the PP and on the enhanced MRI when PP enhancement was less than distal pole enhancement. Surgical absence of PP bleeding was diagnostic of PP AVN. Postoperative osseous union (OU) was assessed with computed tomography and/or radiographs. Sensitivity, specificity and accuracy for PP AVN were 71, 82 and 78 % for unenhanced and 43, 82 and 67 % for enhanced MRI. Patients with PP AVN on unenhanced MRI had 86 % (6/7) OU; 100 % (5/5) OU with vascularized bone grafts and 50 % (1/2) OU with nonvascularized grafts. Patients with PP AVN on enhanced MRI had 80 % (4/5) OU; 100 % (3/3) OU with vascularized bone grafts and 50 % (1/2) OU with nonvascularized grafts. Patients with viable PP on unenhanced and enhanced MRI had 91 % (10/11) and 92 % (12/13) OU, respectively, all but one with nonvascularized graft. When PP AVN is evident on MRI, OU is best achieved with vascularized grafts. If PP AVN is absent, OU is successful with nonvascularized grafts. (orig.)

  19. Accuracy of enhanced and unenhanced MRI in diagnosing scaphoid proximal pole avascular necrosis and predicting surgical outcome

    International Nuclear Information System (INIS)

    Fox, M.G.; Wang, D.T.; Chhabra, A.B.

    2015-01-01

    Determine the sensitivity, specificity and accuracy of unenhanced and enhanced MRI in diagnosing scaphoid proximal pole (PP) avascular necrosis (AVN) and correlate whether MRI can help guide the selection of a vascularized or nonvascularized bone graft. The study was approved by the IRB. Two MSK radiologists independently performed a retrospective review of unenhanced and enhanced MRIs from 18 patients (16 males, 2 females; median age, 17.5 years) with scaphoid nonunions and surgery performed within 65 days of the MRI. AVN was diagnosed on the unenhanced MRI when a diffusely decreased T1-W signal was present in the PP and on the enhanced MRI when PP enhancement was less than distal pole enhancement. Surgical absence of PP bleeding was diagnostic of PP AVN. Postoperative osseous union (OU) was assessed with computed tomography and/or radiographs. Sensitivity, specificity and accuracy for PP AVN were 71, 82 and 78 % for unenhanced and 43, 82 and 67 % for enhanced MRI. Patients with PP AVN on unenhanced MRI had 86 % (6/7) OU; 100 % (5/5) OU with vascularized bone grafts and 50 % (1/2) OU with nonvascularized grafts. Patients with PP AVN on enhanced MRI had 80 % (4/5) OU; 100 % (3/3) OU with vascularized bone grafts and 50 % (1/2) OU with nonvascularized grafts. Patients with viable PP on unenhanced and enhanced MRI had 91 % (10/11) and 92 % (12/13) OU, respectively, all but one with nonvascularized graft. When PP AVN is evident on MRI, OU is best achieved with vascularized grafts. If PP AVN is absent, OU is successful with nonvascularized grafts. (orig.)

  20. Accuracy of enhanced and unenhanced MRI in diagnosing scaphoid proximal pole avascular necrosis and predicting surgical outcome.

    Science.gov (United States)

    Fox, M G; Wang, D T; Chhabra, A B

    2015-11-01

    Determine the sensitivity, specificity and accuracy of unenhanced and enhanced MRI in diagnosing scaphoid proximal pole (PP) avascular necrosis (AVN) and correlate whether MRI can help guide the selection of a vascularized or nonvascularized bone graft. The study was approved by the IRB. Two MSK radiologists independently performed a retrospective review of unenhanced and enhanced MRIs from 18 patients (16 males, 2 females; median age, 17.5 years) with scaphoid nonunions and surgery performed within 65 days of the MRI. AVN was diagnosed on the unenhanced MRI when a diffusely decreased T1-W signal was present in the PP and on the enhanced MRI when PP enhancement was less than distal pole enhancement. Surgical absence of PP bleeding was diagnostic of PP AVN. Postoperative osseous union (OU) was assessed with computed tomography and/or radiographs. Sensitivity, specificity and accuracy for PP AVN were 71, 82 and 78% for unenhanced and 43, 82 and 67% for enhanced MRI. Patients with PP AVN on unenhanced MRI had 86% (6/7) OU; 100% (5/5) OU with vascularized bone grafts and 50% (1/2) OU with nonvascularized grafts. Patients with PP AVN on enhanced MRI had 80% (4/5) OU; 100% (3/3) OU with vascularized bone grafts and 50% (1/2) OU with nonvascularized grafts. Patients with viable PP on unenhanced and enhanced MRI had 91% (10/11) and 92% (12/13) OU, respectively, all but one with nonvascularized graft. When PP AVN is evident on MRI, OU is best achieved with vascularized grafts. If PP AVN is absent, OU is successful with nonvascularized grafts.

  1. 75 FR 35953 - Enhancing Payment Accuracy Through a ``Do Not Pay List''

    Science.gov (United States)

    2010-06-23

    ... Payment Accuracy Through a ``Do Not Pay List'' Memorandum for the Heads of Executive Departments and... Management and Budget (OMB) in consultation with agencies, shall be collectively known as the ``Do Not Pay... process for determining whether the information provided on the ``Do Not Pay List'' is sufficient to stop...

  2. IRSeL-An approach to enhance continuity and accuracy of remotely sensed land cover data

    Science.gov (United States)

    Rathjens, H.; Dörnhöfer, K.; Oppelt, N.

    2014-09-01

    Land cover data gives the opportunity to study interactions between land cover status and environmental issues such as hydrologic processes, soil properties, or biodiversity. Land cover data often are based on classification of remote sensing data that seldom provides the requisite accuracy, spatial availability and temporal observational frequency for environmental studies. Thus, there is a high demand for accurate and spatio-temporal complete time series of land cover. In the past considerable research was undertaken to increase land cover classification accuracy, while less effort was spent on interpolation techniques. The purpose of this article is to present a space-time interpolation and revision approach for remotely sensed land cover data. The approach leverages special properties known for agricultural areas such as crop rotations or temporally static land cover classes. The newly developed IRSeL-tool (Interpolation and improvement of Remotely Sensed Land cover) corrects classification errors and interpolates missing land cover pixels. The easy-to-use tool solely requires an initial land cover data set. The IRSeL specific interpolation and revision technique, the data input requirements and data output structure are described in detail. A case study in an area around the city of Neumünster in Northern Germany from 2006 to 2012 was performed for IRSeL validation with initial land cover data sets (Landsat TM image classifications) for the years 2006, 2007, 2009, 2010 and 2011. The results of the case study showed that IRSeL performs well; including years with no classification data overall accuracy values for IRSeL interpolated pixels range from 0.63 to 0.81. IRSeL application significantly increases the accuracy of the land cover data; overall accuracy values rise 0.08 in average resulting in overall accuracy values of at least 0.86. Considering estimated reliabilities, the IRSeL tool provides a temporally and spatially completed and revised land cover

  3. Systolic Blood Pressure Accuracy Enhancement in the Electronic Palpation Method Using Pulse Waveform

    Science.gov (United States)

    2001-10-25

    adrenalin) or vasodilating (Nipride or Nitromex) medicines. Also painkillers and anesthetics (Oxanest, Diprivan, Fentanyl and Rapifen) may have affected...the measurements. It is hard to distinguish the effects of medication and assess their relation to blood pressure errors and pulse shapes...CONCLUSION During this study, 51 cardiac operated patients were measured to define the effects of arterial stiffening on the accuracy of the

  4. Enhancing Predictive Accuracy of Cardiac Autonomic Neuropathy Using Blood Biochemistry Features and Iterative Multitier Ensembles.

    Science.gov (United States)

    Abawajy, Jemal; Kelarev, Andrei; Chowdhury, Morshed U; Jelinek, Herbert F

    2016-01-01

    Blood biochemistry attributes form an important class of tests, routinely collected several times per year for many patients with diabetes. The objective of this study is to investigate the role of blood biochemistry for improving the predictive accuracy of the diagnosis of cardiac autonomic neuropathy (CAN) progression. Blood biochemistry contributes to CAN, and so it is a causative factor that can provide additional power for the diagnosis of CAN especially in the absence of a complete set of Ewing tests. We introduce automated iterative multitier ensembles (AIME) and investigate their performance in comparison to base classifiers and standard ensemble classifiers for blood biochemistry attributes. AIME incorporate diverse ensembles into several tiers simultaneously and combine them into one automatically generated integrated system so that one ensemble acts as an integral part of another ensemble. We carried out extensive experimental analysis using large datasets from the diabetes screening research initiative (DiScRi) project. The results of our experiments show that several blood biochemistry attributes can be used to supplement the Ewing battery for the detection of CAN in situations where one or more of the Ewing tests cannot be completed because of the individual difficulties faced by each patient in performing the tests. The results show that AIME provide higher accuracy as a multitier CAN classification paradigm. The best predictive accuracy of 99.57% has been obtained by the AIME combining decorate on top tier with bagging on middle tier based on random forest. Practitioners can use these findings to increase the accuracy of CAN diagnosis.

  5. A new source difference artificial neural network for enhanced positioning accuracy

    International Nuclear Information System (INIS)

    Bhatt, Deepak; Aggarwal, Priyanka; Devabhaktuni, Vijay; Bhattacharya, Prabir

    2012-01-01

    Integrated inertial navigation system (INS) and global positioning system (GPS) units provide reliable navigation solution compared to standalone INS or GPS. Traditional Kalman filter-based INS/GPS integration schemes have several inadequacies related to sensor error model and immunity to noise. Alternatively, multi-layer perceptron (MLP) neural networks with three layers have been implemented to improve the position accuracy of the integrated system. However, MLP neural networks show poor accuracy for low-cost INS because of the large inherent sensor errors. For the first time the paper demonstrates the use of knowledge-based source difference artificial neural network (SDANN) to improve navigation performance of low-cost sensor, with or without external aiding sources. Unlike the conventional MLP or artificial neural networks (ANN), the structure of SDANN consists of two MLP neural networks called the coarse model and the difference model. The coarse model learns the input–output data relationship whereas the difference model adds knowledge to the system and fine-tunes the coarse model output by learning the associated training or estimation error. Our proposed SDANN model illustrated a significant improvement in navigation accuracy of up to 81% over conventional MLP. The results demonstrate that the proposed SDANN method is effective for GPS/INS integration schemes using low-cost inertial sensors, with and without GPS

  6. Weight Multispectral Reconstruction Strategy for Enhanced Reconstruction Accuracy and Stability With Cerenkov Luminescence Tomography.

    Science.gov (United States)

    Hongbo Guo; Xiaowei He; Muhan Liu; Zeyu Zhang; Zhenhua Hu; Jie Tian

    2017-06-01

    Cerenkov luminescence tomography (CLT) provides a novel technique for 3-D noninvasive detection of radiopharmaceuticals in living subjects. However, because of the severe scattering of Cerenkov light, the reconstruction accuracy and stability of CLT is still unsatisfied. In this paper, a modified weight multispectral CLT (wmCLT) reconstruction strategy was developed which split the Cerenkov radiation spectrum into several sub-spectral bands and weighted the sub-spectral results to obtain the final result. To better evaluate the property of the wmCLT reconstruction strategy in terms of accuracy, stability and practicability, several numerical simulation experiments and in vivo experiments were conducted and the results obtained were compared with the traditional multispectral CLT (mCLT) and hybrid-spectral CLT (hCLT) reconstruction strategies. The numerical simulation results indicated that wmCLT strategy significantly improved the accuracy of Cerenkov source localization and intensity quantitation and exhibited good stability in suppressing noise in numerical simulation experiments. And the comparison of the results achieved from different in vivo experiments further indicated significant improvement of the wmCLT strategy in terms of the shape recovery of the bladder and the spatial resolution of imaging xenograft tumors. Overall the strategy reported here will facilitate the development of nuclear and optical molecular tomography in theoretical study.

  7. 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.

  8. Enhancing spatial detection accuracy for syndromic surveillance with street level incidence data

    Directory of Open Access Journals (Sweden)

    Alemi Farrokh

    2010-01-01

    Full Text Available Abstract Background The Department of Defense Military Health System operates a syndromic surveillance system that monitors medical records at more than 450 non-combat Military Treatment Facilities (MTF worldwide. The Electronic Surveillance System for Early Notification of Community-based Epidemics (ESSENCE uses both temporal and spatial algorithms to detect disease outbreaks. This study focuses on spatial detection and attempts to improve the effectiveness of the ESSENCE implementation of the spatial scan statistic by increasing the spatial resolution of incidence data from zip codes to street address level. Methods Influenza-Like Illness (ILI was used as a test syndrome to develop methods to improve the spatial accuracy of detected alerts. Simulated incident clusters of various sizes were superimposed on real ILI incidents from the 2008/2009 influenza season. Clusters were detected using the spatial scan statistic and their displacement from simulated loci was measured. Detected cluster size distributions were also evaluated for compliance with simulated cluster sizes. Results Relative to the ESSENCE zip code based method, clusters detected using street level incidents were displaced on average 65% less for 2 and 5 mile radius clusters and 31% less for 10 mile radius clusters. Detected cluster size distributions for the street address method were quasi normal and sizes tended to slightly exceed simulated radii. ESSENCE methods yielded fragmented distributions and had high rates of zero radius and oversized clusters. Conclusions Spatial detection accuracy improved notably with regard to both location and size when incidents were geocoded to street addresses rather than zip code centroids. Since street address geocoding success rates were only 73.5%, zip codes were still used for more than one quarter of ILI cases. Thus, further advances in spatial detection accuracy are dependant on systematic improvements in the collection of individual

  9. Physician involvement enhances coding accuracy to ensure national standards: an initiative to improve awareness among new junior trainees.

    Science.gov (United States)

    Nallasivan, S; Gillott, T; Kamath, S; Blow, L; Goddard, V

    2011-06-01

    Record Keeping Standards is a development led by the Royal College of Physicians of London (RCP) Health Informatics Unit and funded by the National Health Service (NHS) Connecting for Health. A supplementary report produced by the RCP makes a number of recommendations based on a study held at an acute hospital trust. We audited the medical notes and coding to assess the accuracy, documentation by the junior doctors and also to correlate our findings with the RCP audit. Northern Lincolnshire & Goole Hospitals NHS Foundation Trust has 114,000 'finished consultant episodes' per year. A total of 100 consecutive medical (50) and rheumatology (50) discharges from Diana Princess of Wales Hospital from August-October 2009 were reviewed. The results showed an improvement in coding accuracy (10% errors), comparable to the RCP audit but with 5% documentation errors. Physician involvement needs enhancing to improve the effectiveness and to ensure clinical safety.

  10. DARC 2.0: Improved Docking and Virtual Screening at Protein Interaction Sites.

    Directory of Open Access Journals (Sweden)

    Ragul Gowthaman

    Full Text Available Over the past decade, protein-protein interactions have emerged as attractive but challenging targets for therapeutic intervention using small molecules. Due to the relatively flat surfaces that typify protein interaction sites, modern virtual screening tools developed for optimal performance against "traditional" protein targets perform less well when applied instead at protein interaction sites. Previously, we described a docking method specifically catered to the shallow binding modes characteristic of small-molecule inhibitors of protein interaction sites. This method, called DARC (Docking Approach using Ray Casting, operates by comparing the topography of the protein surface when "viewed" from a vantage point inside the protein against the topography of a bound ligand when "viewed" from the same vantage point. Here, we present five key enhancements to DARC. First, we use multiple vantage points to more accurately determine protein-ligand surface complementarity. Second, we describe a new scheme for rapidly determining optimal weights in the DARC scoring function. Third, we incorporate sampling of ligand conformers "on-the-fly" during docking. Fourth, we move beyond simple shape complementarity and introduce a term in the scoring function to capture electrostatic complementarity. Finally, we adjust the control flow in our GPU implementation of DARC to achieve greater speedup of these calculations. At each step of this study, we evaluate the performance of DARC in a "pose recapitulation" experiment: predicting the binding mode of 25 inhibitors each solved in complex with its distinct target protein (a protein interaction site. Whereas the previous version of DARC docked only one of these inhibitors to within 2 Å RMSD of its position in the crystal structure, the newer version achieves this level of accuracy for 12 of the 25 complexes, corresponding to a statistically significant performance improvement (p < 0.001. Collectively then, we find

  11. Analysis of the Accuracy of Beidou Combined Orbit Determination Enhanced by LEO and ISL

    Directory of Open Access Journals (Sweden)

    FENG Laiping

    2017-05-01

    Full Text Available In order to improve the precision of BeiDou orbit determination under the conditions of regional ground monitoring station and make good use of increasingly rich on-board data and upcoming ISL technology, a method of BeiDou precision orbit determination is proposed which combines the use of ground monitoring stations data, low earth orbit satellite(LEOs data and Inter-Satellite Link(ISL data. The effects of assisting data of LEOs and ISL on the precision orbit determination of navigation satellite are discussed. Simulation analysis is carried out mainly from the number of LEOs, orbit slot configuration and ISL. The results show that the orbit precision of BeiDou will greatly improve about 73% with a small number of LEOs, while improvement of clock bias is not remarkable; the uniform orbit slot configuration of the same number of LEOs has a modest effect on the accuracy of combined orbit determination; compared with LEOs, the increase of ISL will significantly improve the accuracy of orbit determination with a higher efficiency.

  12. Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission.

    Science.gov (United States)

    Su, Bo; Ji, Yun-Song; Sun, Xu-lu; Liu, Xiang-Hua; Chen, Zhe-Yu

    2014-01-17

    Appropriate mitochondrial transport and distribution are essential for neurons because of the high energy and Ca(2+) buffering requirements at synapses. Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating synaptic transmission and plasticity. However, whether and how BDNF can regulate mitochondrial transport and distribution are still unclear. Here, we find that in cultured hippocampal neurons, application of BDNF for 15 min decreased the percentage of moving mitochondria in axons, a process dependent on the activation of the TrkB receptor and its downstream PI3K and phospholipase-Cγ signaling pathways. Moreover, the BDNF-induced mitochondrial stopping requires the activation of transient receptor potential canonical 3 and 6 (TRPC3 and TRPC6) channels and elevated intracellular Ca(2+) levels. The Ca(2+) sensor Miro1 plays an important role in this process. Finally, the BDNF-induced mitochondrial stopping leads to the accumulation of more mitochondria at presynaptic sites. Mutant Miro1 lacking the ability to bind Ca(2+) prevents BDNF-induced mitochondrial presynaptic accumulation and synaptic transmission, suggesting that Miro1-mediated mitochondrial motility is involved in BDNF-induced mitochondrial presynaptic docking and neurotransmission. Together, these data suggest that mitochondrial transport and distribution play essential roles in BDNF-mediated synaptic transmission.

  13. Assessment of an alanine EPR dosimetry technique with enhanced precision and accuracy

    CERN Document Server

    Hayes, R B; Wieser, A; Romanyukha, A A; Hardy, B L; Barrus, J K

    2000-01-01

    Dose reconstruction in the course of a series of blind tests demonstrated that an accuracy of 10 mGy for low doses and 1% for high doses can be achieved using EPR spectroscopy. This was accomplished using a combination of methodologies including polynomial filtration of the EPR spectrum, dosimeter rotation during scanning, use of an EPR standard fixed into the resonator and subtraction of all nonradiogenic signals. Doses were reconstructed over the range of 0.01-1000 Gy using this compound spectral EPR analysis. This EPR technique, being equally applicable to fractionated doses (such as those delivered during multiple radiotherapy treatments), was verified to exhibit dose reciprocity. Irradiated alanine dosimeters which were stored exhibited compound spectral EPR signal fading of ca 3% over 9 months. All error estimates given in this paper are given at the 1 standard deviation level and unless otherwise specified do not account for uncertainties in source calibration.

  14. Distributed Secondary Control for DC Microgrid Applications with Enhanced Current Sharing Accuracy

    DEFF Research Database (Denmark)

    Lu, Xiaonan; Guerrero, Josep M.; Sun, Kai

    2013-01-01

    With the consideration of line resistances in a dc microgrid, the current sharing accuracy is lowered down, since the dc output voltage cannot be exactly the same for different interfacing converters. Meanwhile, the dc bus voltage deviation is involved by using droop control. In this paper...... control diagram is accomplished and the requirement of distributed configuration in a microgrid is satisfied. The experimental validation based on a 2×2.2 kW prototype was implemented to demonstrate the proposed approach......., a distributed secondary control method is proposed. Droop control is employed as the primary control method for load current sharing. Meanwhile, the dc output voltage and current in each module is transferred to the others by the low bandwidth communication (LBC) network. Average voltage and current controllers...

  15. Assessment of an alanine EPR dosimetry technique with enhanced precision and accuracy

    International Nuclear Information System (INIS)

    Hayes, Robert B.; Haskell, E.H.; Wieser, Albrecht; Romanyukha, Alexander A.; Hardy, Byron L.; Barrus, Jeffrey K.

    2000-01-01

    Dose reconstruction in the course of a series of blind tests demonstrated that an accuracy of 10 mGy for low doses and 1% for high doses can be achieved using EPR spectroscopy. This was accomplished using a combination of methodologies including polynomial filtration of the EPR spectrum, dosimeter rotation during scanning, use of an EPR standard fixed into the resonator and subtraction of all nonradiogenic signals. Doses were reconstructed over the range of 0.01-1000 Gy using this compound spectral EPR analysis. This EPR technique, being equally applicable to fractionated doses (such as those delivered during multiple radiotherapy treatments), was verified to exhibit dose reciprocity. Irradiated alanine dosimeters which were stored exhibited compound spectral EPR signal fading of ca 3% over 9 months. All error estimates given in this paper are given at the 1 standard deviation level and unless otherwise specified do not account for uncertainties in source calibration

  16. Accuracy Enhancements for Positioning of Mobile Devices in Wireless Communication Networks

    DEFF Research Database (Denmark)

    Figueiras, Joao

    of the physical length of the communication links. Since these solutions do not require integration of additional hardware into the mobile nodes, they are cheap and simple to implement. As a price to pay, accuracy is typically lower in comparison to dedicated positioning systems. Thus, an important challenge...... communication among users, cooperative positioning strategies aim at localizing devices as a group and not as individuals. In order to reach this goal it is necessary to combine measurements from two domains: device-to-device links and cellular links. Since this combination of information......Positioning of mobile devices in wireless communication networks is nowadays being intensively investigated due to the combined benefit of location information and communication. Typical solutions for such scenario rely on robust algorithms that estimate position from indirect measurements...

  17. Diagnostic Accuracy of Ultrasound, Contrast-enhanced CT, and Conventional MRI for Differentiating Leiomyoma From Leiomyosarcoma.

    Science.gov (United States)

    Gaetke-Udager, Kara; McLean, Karen; Sciallis, Andrew P; Alves, Timothy; Maturen, Katherine E; Mervak, Benjamin M; Moore, Andreea G; Wasnik, Ashish P; Erba, Jake; Davenport, Matthew S

    2016-10-01

    This study aimed to determine whether uterine leiomyoma can be distinguished from uterine leiomyosarcoma on ultrasound (US), computed tomography (CT), and/or magnetic resonance imaging (MRI) without diffusion-weighted imaging. Institutional review board approval was obtained and informed consent was waived for this Health Insurance Portability and Accountability Act-compliant retrospective case-control diagnostic accuracy study. All subjects with resected uterine leiomyosarcoma diagnosed over a 17-year period (1998-2014) at a single institution for whom pre-resection US (n = 10), CT (n = 11), or MRI (n = 7) was available were matched by tumor size and imaging modality with 28 subjects with resected uterine leiomyoma. Six blinded radiologists (three attendings, three residents) assigned 5-point Likert scores for the following features: (1) margins, (2) necrosis, (3) hemorrhage, (4) vascularity, (5) calcifications, (6) heterogeneity, and (7) likelihood of malignancy (primary end point). Mean suspicion scores were calculated and receiver operating characteristic curves were generated. The ability of individual morphologic features to predict malignancy was assessed with logistic regression. Mean suspicion scores were 2.5 ± 1.2 (attendings) and 2.4 ± 1.3 (residents) for leiomyoma, and 2.7 ± 1.3 (attendings) and 2.7 ± 1.4 (residents) for leiomyosarcoma. The areas under the receiver operating characteristic curves (range: 0.330-0.685) were not significantly different from chance, either overall (P = .36-.88) or by any modality (P = .28-.96), for any reader. Reader experience had no effect on diagnostic accuracy. No morphologic parameter was significantly predictive of malignancy (P = .10-.97). Uterine leiomyoma cannot be differentiated accurately from leiomyosarcoma on US, CT, or MRI without diffusion-weighted imaging. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  18. Accuracy enhancement of laser induced breakdown spectra using permittivity and size optimized plasma confinement rings.

    Science.gov (United States)

    Li, An; Guo, Shuai; Wazir, Nasrullah; Chai, Ke; Liang, Liang; Zhang, Min; Hao, Yan; Nan, Pengfei; Liu, Ruibin

    2017-10-30

    The inevitable problems in laser induced breakdown spectroscopy are matrix effect and statistical fluctuation of the spectral signal, which can be partly avoided by utilizing a proper confined unit. The dependences of spectral signal enhancement on relative permittivity were studied by varying materials to confine the plasma, which include polytetrafluoroethylene(PTFE), nylon/dacron, silicagel, and nitrile-butadiene rubber (NBR) with the relative permittivity 2.2, ~3.3, 3.6, 8~13, 15~22. We found that higher relative permittivity rings induce stronger enhancement ability, which restricts the energy dissipation of plasma better and due to the reflected electromagnetic wave from the wall of different materials, the electromagnetic field of plasma can be well confined and makes the distribution of plasma more orderly. The spectral intensities of the characteristic lines Si I 243.5 nm and Si I 263.1 nm increased approximately 2 times with relative permittivity values from 2.2 to ~20. The size dependent enhancement of PTFE was further checked and the maximum gain was realized by using a confinement ring with a diameter size of 5 mm and a height of 3 mm (D5mmH3mm), and the rings with D2mmH1mm and D3mmH2mm also show higher enhancement factor. In view of peak shift, peak lost and accidental peaks in the obtained spectra were properly treated in data progressing; the spectral fluctuation decreased drastically for various materials with different relative permittivities as confined units, which means the core of plasma is stabilized, attributing to the confinement effect. Furthermore, the quantitative analysis in coal shows wonderful results-the prediction fitting coefficient R 2 reaches 0.98 for ash and 0.99 for both volatile and carbon.

  19. Remote docking apparatus

    International Nuclear Information System (INIS)

    Dent, T.H.; Sumpman, W.C.; Wilhelm, J.J.

    1981-01-01

    The remote docking apparatus comprises a support plate with locking devices mounted thereon. The locking devices are capable of being inserted into tubular members for suspending the support plate therefrom. A vertical member is attached to the support plate with an attachment mechanism attached to the vertical member. A remote access manipulator is capable of being attached to the attachment mechanism so that the vertical member can position the remote access manipulator so that the remote access manipulator can be initially attached to the tubular members in a well defined manner

  20. A non-docking intraoperative electron beam applicator system

    International Nuclear Information System (INIS)

    Palta, J.R.; Suntharalingam, N.

    1989-01-01

    A non-docking intraoperative radiation therapy electron beam applicator system for a linear accelerator has been designed to minimize the mechanical, electrical, and tumor visualization problems associated with a docking system. A number of technical innovations have been used in the design of this system. These include: (a) a new intraoperative radiation therapy cone design that gives a better dose uniformity in the treatment volume at all depths; (b) a collimation system which reduces the leakage radiation dose to tissues outside the intraoperative radiation therapy cone; (c) a non-docking system with a translational accuracy of 2 mm and a rotational accuracy of 0.5 degrees; and (d) a rigid clamping system for the cones. A comprehensive set of dosimetric characteristics of the intraoperative radiation therapy applicator system is presented

  1. 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.

  2. Diagnostic accuracy and tolerability of contrast enhanced CT colonoscopy in symptomatic patients with increased risk for colorectal cancer

    International Nuclear Information System (INIS)

    Ozsunar, Yelda; Coskun, Guelten; Delibas, Naciye; Uz, Burcin; Yuekselen, Vahit

    2009-01-01

    Objective: We compared the accuracy and tolerability of intravenous contrast enhanced spiral computed tomography colonography (CTC) and optical colonoscopy (OC) for the detection of colorectal neoplasia in symptomatic patients for colorectal neoplasia. Methods: A prospective study was performed in 48 patients with symptomatic patients with increased risk for colorectal cancer. Spiral CTC was performed in supine and prone positions after colonic cleansing. The axial, 2D MPR and virtual endoluminal views were analyzed. Results of spiral CTC were compared with OC which was done within 15 days. The psychometric tolerance test was asked to be performed for both CTC and colonoscopy after the procedure. Results: Ten lesions in 9 of 48 patients were found in CTC and confirmed with OC. Two masses and eight polyps, consisted of 1 tubulovillous, 1 tubular, 2 villous adenoma, 4 adenomatous polyp, 4 adenocarcinoma, were identified. Lesion prevalence was 21%. Sensitivity, specificity, accuracy, positive and negative predictive values were found 100%, 87%, 89%, 67% and 100%, respectively. Psychometric tolerance test showed that CTC significantly more comfortable comparing with OC (p = 0.00). CTC was the preferred method in 37% while OC was preferred in 6% of patients. In both techniques, the most unpleasant part was bowel cleansing. Conclusion: Contrast enhanced CTC is a highly accurate method in detecting colorectal lesions. Since the technique was found to be more comfortable and less time consuming compare to OE, it may be preferable in management of symptomatic patients with increased risk for colorectal cancer.

  3. Remote handling dynamical modelling: assessment on new approach to enhance positioning accuracy with heavy load manipulation

    International Nuclear Information System (INIS)

    Gagarina-Sasia, T.; David, O.; Dubus, G.; Perrot, Y.; Riwain, A.

    2007-01-01

    In vessel maintenance work in Fusion Tokamak will be carried out with help several sets of robotic devices. Heavy loads handling in constrained space is identified by all players of the RH community as a key-issue in the latest Fusion Tokamak facilities. To deal with high-level dexterity tasks, high payload to mass ratio and limited operating space, RH equipment designers can only propose systems whose mechanical flexibility is no longer negligible and need to be taken into account in the control scheme. Traditional approaches where control system only includes a linear model of deformation of the structure leads to poor positioning accuracy. Uncontrolled or under evaluated errors could be damaging for in-vessel components during maintenance operations in the Tokamak facility. To address the control of complex flexible systems, we will investigate the use of specific mechanical software that combines both finite element and kinematical joints analyses, with a strong-coupled formulation, to perform system dynamics simulations. This procedure will be applied on a single axis mock up robotic joint with highly flexible structure. A comparison of experimental results with the traditional linear approach and the specified software model will be carried out. Benefits introduced by this new approach will finally be assessed in view of RH design or specification in the field of RH in Fusion Tokamak scale such as ITER. (orig.)

  4. A novel approach to enhance the accuracy of vibration control of Frames

    Directory of Open Access Journals (Sweden)

    Toloue Iraj

    2018-01-01

    Full Text Available All structures built within known seismically active regions are typically designed to endure earthquake forces. Despite advances in earthquake resistant structures, it can be inferred from hindsight that no structure is entirely immune to damage from earthquakes. Active vibration control systems, unlike the traditional methods which enlarge beams and columns, are highly effective countermeasures to reduce the effects of earthquake loading on a structure. It requires fast computation of nonlinear structural analysis in near time and has historically demanded advanced programming hosted on powerful computers. This research aims to develop a new approach for active vibration control of frames, which is applicable over both elastic and plastic material behavior. In this study, the Force Analogy Method (FAM, which is based on Hook’s Law is further extended using the Timoshenko element which considers shear deformations to increase the reliability and accuracy of the controller. The proposed algorithm is applied to a 2D portal frame equipped with linear actuator, which is designed based on full state Linear Quadratic Regulator (LQR. For comparison purposes, the portal frame is analysed by both the Euler Bernoulli and Timoshenko element respectively. The results clearly demonstrate the superiority of the Timoshenko element over Euler Bernoulli for application in nonlinear analysis.

  5. Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy.

    Science.gov (United States)

    Cantarero, Gabriela; Spampinato, Danny; Reis, Janine; Ajagbe, Loni; Thompson, Tziporah; Kulkarni, Kopal; Celnik, Pablo

    2015-02-18

    The cerebellum is involved in the update of motor commands during error-dependent learning. Transcranial direct current stimulation (tDCS), a form of noninvasive brain stimulation, has been shown to increase cerebellar excitability and improve learning in motor adaptation tasks. Although cerebellar involvement has been clearly demonstrated in adaptation paradigms, a type of task that heavily relies on error-dependent motor learning mechanisms, its role during motor skill learning, a behavior that likely involves error-dependent as well as reinforcement and strategic mechanisms, is not completely understood. Here, in humans, we delivered cerebellar tDCS to modulate its activity during novel motor skill training over the course of 3 d and assessed gains during training (on-line effects), between days (off-line effects), and overall improvement. We found that excitatory anodal tDCS applied over the cerebellum increased skill learning relative to sham and cathodal tDCS specifically by increasing on-line rather than off-line learning. Moreover, the larger skill improvement in the anodal group was predominantly mediated by reductions in error rate rather than changes in movement time. These results have important implications for using cerebellar tDCS as an intervention to speed up motor skill acquisition and to improve motor skill accuracy, as well as to further our understanding of cerebellar function. Copyright © 2015 the authors 0270-6474/15/353285-06$15.00/0.

  6. A novel approach to enhance the accuracy of vibration control of Frames

    Science.gov (United States)

    Toloue, Iraj; Shahir Liew, Mohd; Harahap, I. S. H.; Lee, H. E.

    2018-03-01

    All structures built within known seismically active regions are typically designed to endure earthquake forces. Despite advances in earthquake resistant structures, it can be inferred from hindsight that no structure is entirely immune to damage from earthquakes. Active vibration control systems, unlike the traditional methods which enlarge beams and columns, are highly effective countermeasures to reduce the effects of earthquake loading on a structure. It requires fast computation of nonlinear structural analysis in near time and has historically demanded advanced programming hosted on powerful computers. This research aims to develop a new approach for active vibration control of frames, which is applicable over both elastic and plastic material behavior. In this study, the Force Analogy Method (FAM), which is based on Hook's Law is further extended using the Timoshenko element which considers shear deformations to increase the reliability and accuracy of the controller. The proposed algorithm is applied to a 2D portal frame equipped with linear actuator, which is designed based on full state Linear Quadratic Regulator (LQR). For comparison purposes, the portal frame is analysed by both the Euler Bernoulli and Timoshenko element respectively. The results clearly demonstrate the superiority of the Timoshenko element over Euler Bernoulli for application in nonlinear analysis.

  7. Accuracy and role of contrast-enhanced CT in diagnosis and surgical planning in 88 soft tissue tumours of extremities

    International Nuclear Information System (INIS)

    Verga, Lucia; Robiati, Sara; De Marchi, Armanda; Martorano, Domenico; Faletti, Carlo; Brach del Prever, Elena Maria; Linari, Alessandra; Boffano, Michele; Piana, Raimondo

    2016-01-01

    Soft tissue tumours (STT) require accurate diagnosis in order to identify potential malignancies. Preoperative planning is fundamental to avoid inadequate treatments. The role of contrast-enhanced computed tomography (CT) for local staging remains incompletely assessed. Aims of the study were to evaluate CT accuracy in discriminating active from aggressive tumours compared to histology and evaluate the role of CT angiography (CTA) in surgical planning. This retrospective cohort series of 88 cases from 1200 patients (7 %) was locally studied by contrast-enhanced CT and CTA in a referral centre: 74 malignant tumours, 14 benign lesions. Contrast-enhancement patterns and relationship of the mass with major vessels and bone were compared with histology on surgically excised samples. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were evaluated in discriminating active from aggressive tumours. Sensitivity in differentiating aggressive tumours from active lesions was 89 %, specificity 84 %, PPV 90 %, NPV 82 %. The relationship between mass and major vessels/bone was fundamental for surgical strategy respectively in 40 % and in 58 % of malignant tumours. Contrast-enhanced CT and CTA are effective in differentiating aggressive masses from active lesions in soft tissue and in depicting the relationship between tumour and adjacent bones and major vessels. (orig.)

  8. Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS.

    Science.gov (United States)

    Schellhaas, Barbara; Görtz, Ruediger S; Pfeifer, Lukas; Kielisch, Christian; Neurath, Markus F; Strobel, Deike

    2017-09-01

    A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases.For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared.Histology, CE-computed tomography and CE-MRI served as reference standards. The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; pdiagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the diagnosis of HCC with CEUS. Washout should not be a necessary prerequisite for the diagnosis of definite HCC. CEUS-LI-RADS in its current version is inferior to ESCULAP for the noninvasive diagnosis of HCC

  9. Process planning and accuracy distribution of marine power plant modularization

    Directory of Open Access Journals (Sweden)

    ZHANG Jinguo

    2018-02-01

    Full Text Available [Objectives] Modular shipbuilding can shorten the cycle of design and construction, lower production costs and improve the quality of products, but higher shipbuilding capabilities are required, especially for the installation of power plants. Because of such characteristics of modular shipbuilding as the high precision of docking links, long size equipment installation chain and quantitative docking interfaces, docking installation is very difficult due to high docking deviation and low accuracy of docking installation, leading to the abnormal vibration of equipment. In order to solve this problem, [Methods] on the basis of domestic shipbuilding capability, numerical calculation methods are used to analyze the accuracy distribution of modular installation. [Results] The results show that the accuracy distribution of different docking links is reasonable and feasible, and the setting of adjusting allowance matches the requirements of shipbuilding. [Conclusions] This method provides a reference for the modular construction of marine power plants.

  10. AggieSat: Autonomous Rendezvous and Docking Technology Demonstrator, Phase I

    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...

  11. The accuracy and utility of contrast-enhanced MR angiography for localization of spinal dural arteriovenous fistulas: the Toronto experience

    Energy Technology Data Exchange (ETDEWEB)

    Lindenholz, Arjen [University Medical Center Groningen, Department of Neurosurgery AB71, PO Box 30001, Groningen (Netherlands); Toronto Western Hospital, Department of Medical Imaging, Division of Neuroradiology, Toronto, ON (Canada); TerBrugge, Karel G.; Farb, Richard I. [Toronto Western Hospital, Department of Medical Imaging, Division of Neuroradiology, Toronto, ON (Canada); Dijk, J.M.C. van [University Medical Center Groningen, Department of Neurosurgery AB71, PO Box 30001, Groningen (Netherlands)

    2014-11-15

    The purpose of this study was to determine the accuracy and utility of contrast-enhanced MR angiography (CE-MRA) in spinal dural arteriovenous fistulas (SDAVF). A retrospective analysis from 1999-2012 identified 70 patients clinically suspected of harboring a SDAVF. Each patient underwent consecutive conventional MR-imaging, CE-MRA, and digital subtraction angiography (DSA). The presence or absence of serpentine flow voids, T2-weighted hyperintensity, and cord enhancement were evaluated, as well as location of the fistula as predicted by CE-MRA. DSA was used as the reference standard. Of the 70 cases, 53 were determined to be a SDAVF, 10 cases were shown to be other forms of vascular malformation, and 7 were DSA-negative. On MRI, all reported cases of SDAVF showed serpentine flow voids (100 %). T2-weighted hyperintensity was seen in 48 of 50 cases (96 %), extending to the conus in 41 of 48 cases (85 %). Cord enhancement was seen in 38 of 41 cases (93 %). CE-MRA correctly localized the SDAVF in 43 of the 53 cases (81 %). CE-MRA is a useful non-invasive examination for the detection and localization of SDAVF. CE-MRA facilitates but does not replace DSA as confirmation of location, fistula type, and arterial detail, which are required before treatment. (orig.)

  12. Emergence of realism: Enhanced visual artistry and high accuracy of visual numerosity representation after left prefrontal damage.

    Science.gov (United States)

    Takahata, Keisuke; Saito, Fumie; Muramatsu, Taro; Yamada, Makiko; Shirahase, Joichiro; Tabuchi, Hajime; Suhara, Tetsuya; Mimura, Masaru; Kato, Motoichiro

    2014-05-01

    Over the last two decades, evidence of enhancement of drawing and painting skills due to focal prefrontal damage has accumulated. It is of special interest that most artworks created by such patients were highly realistic ones, but the mechanism underlying this phenomenon remains to be understood. Our hypothesis is that enhanced tendency of realism was associated with accuracy of visual numerosity representation, which has been shown to be mediated predominantly by right parietal functions. Here, we report a case of left prefrontal stroke, where the patient showed enhancement of artistic skills of realistic painting after the onset of brain damage. We investigated cognitive, functional and esthetic characteristics of the patient׳s visual artistry and visual numerosity representation. Neuropsychological tests revealed impaired executive function after the stroke. Despite that, the patient׳s visual artistry related to realism was rather promoted across the onset of brain damage as demonstrated by blind evaluation of the paintings by professional art reviewers. On visual numerical cognition tasks, the patient showed higher performance in comparison with age-matched healthy controls. These results paralleled increased perfusion in the right parietal cortex including the precuneus and intraparietal sulcus. Our data provide new insight into mechanisms underlying change in artistic style due to focal prefrontal lesion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Diagnostic accuracy of dynamic contrast-enhanced MR imaging of renal masses with rapid-acquisition spin-echo technique

    International Nuclear Information System (INIS)

    Eilenberg, S.S.; Lee, J.K.T.; Brown, J.J.; Heiken, J.P.; Mirowitz, S.A.

    1990-01-01

    This paper compares the diagnostic accuracy of Gd-DTPA-enhanced rapid-acquisition spin-echo (RASE) imaging with standard spin-echo techniques for detecting renal cysts and solid renal neoplasms. RASE imaging combines a short TR (275 msec)/short TE (10 msec), single excitation pulse sequence with half-Fourier data sampling. Eighteen patients with CT evidence of renal masses were first evaluated with standard T1-and T2-weighted SE sequences. Pre- and serial postcontrast (Cd-DTPA, 0.1 mmol./kg) RASE sequences were then performed during suspended respiration. A final set of postcontrast images was obtained with the standard T1-weighted SE sequence. Each set of MR images was first reviewed separately (ie, T1, T2, pre- and post-contrast RASE, etc)

  14. The feasibility and accuracy of enhanced MR pulmonary perfusion imaging in evaluating therapeutic effect of pulmonary embolism

    International Nuclear Information System (INIS)

    Wang Nana; Lv Biao; Zhao Zhaoqi; Huang Xiaoyong; Lu Dongxu; Mi Hongzhi; Yu Weiyong

    2010-01-01

    Objective: To investigate the feasibility and accuracy of enhanced magnetic resonance pulmonary perfusion imaging (MRPP) in the diagnosis and follow-up of pulmonary embolism (PE). Methods: Sixty patients suspected of PE underwent MRPP. Twenty-seven patients also underwent radionuclide perfusion imaging. 22 patients repeated MRPP examination after 3 day to 1 month antieoagulation or thrombolytic therapy. The feasibility and accuracy of MRPP in the diagnosis and follow-up of PE were evaluated according to the transformation rate of signal (TROS), time-signal curve and some parameters of main pulmonary artery (such as peak value of flow, mean flow velocity and flow rate). The t test and rank sum test were used for the statistics. Results: MRPP showed a high agreement with radionuclide perfusion imaging. TROS was (2.86 ± 2.48) vs(6.72 ± 2.54) (t=3.370, P 0.05). Conclusion: MRPP shows a high agreement with radionuclide perfusion imaging and is a useful method for the diagnosis and follow-up of PE. (authors)

  15. An algorithm to correct saturated mass spectrometry ion abundances for enhanced quantitation and mass accuracy in omic studies

    Energy Technology Data Exchange (ETDEWEB)

    Bilbao, Aivett; Gibbons, Bryson C.; Slysz, Gordon W.; Crowell, Kevin L.; Monroe, Matthew E.; Ibrahim, Yehia M.; Smith, Richard D.; Payne, Samuel H.; Baker, Erin S.

    2018-04-01

    The mass accuracy and peak intensity of ions detected by mass spectrometry (MS) measurements are essential to facilitate compound identification and quantitation. However, high concentration species can easily cause problems if their ion intensities reach beyond the limits of the detection system, leading to distorted and non-ideal detector response (e.g. saturation), and largely precluding the calculation of accurate m/z and intensity values. Here we present an open source computational method to correct peaks above a defined intensity (saturated) threshold determined by the MS instrumentation such as the analog-to-digital converters or time-to-digital converters used in conjunction with time-of-flight MS. In this method, the isotopic envelope for each observed ion above the saturation threshold is compared to its expected theoretical isotopic distribution. The most intense isotopic peak for which saturation does not occur is then utilized to re-calculate the precursor m/z and correct the intensity, resulting in both higher mass accuracy and greater dynamic range. The benefits of this approach were evaluated with proteomic and lipidomic datasets of varying complexities. After correcting the high concentration species, reduced mass errors and enhanced dynamic range were observed for both simple and complex omic samples. Specifically, the mass error dropped by more than 50% in most cases with highly saturated species and dynamic range increased by 1-2 orders of magnitude for peptides in a blood serum sample.

  16. Accuracy of contrast-enhanced dual-energy MDCT for the assessment of iodine uptake in renal lesions.

    Science.gov (United States)

    Mileto, Achille; Marin, Daniele; Ramirez-Giraldo, Juan Carlos; Scribano, Emanuele; Krauss, Bernhard; Mazziotti, Silvio; Ascenti, Giorgio

    2014-05-01

    The objective of our study was to assess the accuracy of iodine-related attenuation and iodine quantification as imaging biomarkers of iodine uptake in renal lesions on a single-phase nephrographic image with dual-energy MDCT. Fifty-nine patients (41 men, 18 women; age range, 28-84 years) with 80 renal lesions underwent contrast-enhanced dual-energy CT during the nephrographic phase of enhancement. Renal lesions were characterized as enhancing or nonenhancing on color-coded iodine overlay maps using iodine-related attenuation (in Hounsfield units) and iodine quantification (in milligrams per milliliter). For iodine-related attenuation the iodine uptake thresholds of 15 and 20 HU were tested; a threshold of 0.5 mg/mL was used for iodine quantification. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of iodine-related attenuation and iodine quantification were calculated from chi-square tests of contingency with histopathology or imaging follow-up as the reference standard. The 95% CIs were calculated from binomial expression. Differences in sensitivity and specificity were assessed by means of McNemar analysis. A significant difference in sensitivity and specificity was found between iodine-related attenuation with the thresholds of 15 HU (sensitivity, 91.4%; specificity, 93.3%; PPV, 91.4%; NPV, 93.3%) and 20 HU (sensitivity, 77.1%; specificity, 100%; PPV, 100%; NPV, 84.9%) (p = 0.008) and between iodine quantification (sensitivity, 100%; specificity, 97.7%; PPV, 97.2%; NPV, 100%) and iodine-related attenuation with a threshold of 20 HU (p = 0.004). No significant difference in sensitivity and specificity was found between iodine quantification and iodine-related attenuation with a threshold of 15 HU. Contrast-enhanced dual-energy MDCT with iodine-related attenuation and iodine quantification allows accurate evaluation of iodine uptake in renal lesions on a single-phase nephrographic image.

  17. Improved accuracy of quantitative parameter estimates in dynamic contrast-enhanced CT study with low temporal resolution

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Mo, E-mail: Sunmo.Kim@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Hospital/University Health Network, Toronto, Ontario M5G 2M9 (Canada); Haider, Masoom A. [Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Medical Imaging, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Jaffray, David A. [Radiation Medicine Program, Princess Margaret Hospital/University Health Network, Toronto, Ontario M5G 2M9, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Yeung, Ivan W. T. [Radiation Medicine Program, Princess Margaret Hospital/University Health Network, Toronto, Ontario M5G 2M9 (Canada); Department of Medical Physics, Stronach Regional Cancer Centre, Southlake Regional Health Centre, Newmarket, Ontario L3Y 2P9 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada)

    2016-01-15

    Purpose: A previously proposed method to reduce radiation dose to patient in dynamic contrast-enhanced (DCE) CT is enhanced by principal component analysis (PCA) filtering which improves the signal-to-noise ratio (SNR) of time-concentration curves in the DCE-CT study. The efficacy of the combined method to maintain the accuracy of kinetic parameter estimates at low temporal resolution is investigated with pixel-by-pixel kinetic analysis of DCE-CT data. Methods: The method is based on DCE-CT scanning performed with low temporal resolution to reduce the radiation dose to the patient. The arterial input function (AIF) with high temporal resolution can be generated with a coarsely sampled AIF through a previously published method of AIF estimation. To increase the SNR of time-concentration curves (tissue curves), first, a region-of-interest is segmented into squares composed of 3 × 3 pixels in size. Subsequently, the PCA filtering combined with a fraction of residual information criterion is applied to all the segmented squares for further improvement of their SNRs. The proposed method was applied to each DCE-CT data set of a cohort of 14 patients at varying levels of down-sampling. The kinetic analyses using the modified Tofts’ model and singular value decomposition method, then, were carried out for each of the down-sampling schemes between the intervals from 2 to 15 s. The results were compared with analyses done with the measured data in high temporal resolution (i.e., original scanning frequency) as the reference. Results: The patients’ AIFs were estimated to high accuracy based on the 11 orthonormal bases of arterial impulse responses established in the previous paper. In addition, noise in the images was effectively reduced by using five principal components of the tissue curves for filtering. Kinetic analyses using the proposed method showed superior results compared to those with down-sampling alone; they were able to maintain the accuracy in the

  18. Fast, accurate, and reliable molecular docking with QuickVina 2.

    Science.gov (United States)

    Alhossary, Amr; Handoko, Stephanus Daniel; Mu, Yuguang; Kwoh, Chee-Keong

    2015-07-01

    The need for efficient molecular docking tools for high-throughput screening is growing alongside the rapid growth of drug-fragment databases. AutoDock Vina ('Vina') is a widely used docking tool with parallelization for speed. QuickVina ('QVina 1') then further enhanced the speed via a heuristics, requiring high exhaustiveness. With low exhaustiveness, its accuracy was compromised. We present in this article the latest version of QuickVina ('QVina 2') that inherits both the speed of QVina 1 and the reliability of the original Vina. We tested the efficacy of QVina 2 on the core set of PDBbind 2014. With the default exhaustiveness level of Vina (i.e. 8), a maximum of 20.49-fold and an average of 2.30-fold acceleration with a correlation coefficient of 0.967 for the first mode and 0.911 for the sum of all modes were attained over the original Vina. A tendency for higher acceleration with increased number of rotatable bonds as the design variables was observed. On the accuracy, Vina wins over QVina 2 on 30% of the data with average energy difference of only 0.58 kcal/mol. On the same dataset, GOLD produced RMSD smaller than 2 Å on 56.9% of the data while QVina 2 attained 63.1%. The C++ source code of QVina 2 is available at (www.qvina.org). aalhossary@pmail.ntu.edu.sg Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Multi-structure docking analysis of BACE1 crystal structures and non-peptidic ligands.

    Science.gov (United States)

    Haghighijoo, Zahra; Hemmateenejad, Bahram; Edraki, Najmeh; Miri, Ramin; Emami, Saeed

    2017-09-01

    In order to design novel non-peptidic inhibitors of BACE1, many research groups have attempted using computational studies including docking analyses. Since there are too many 3D structures for BACE1 in the protein database, the selection of suitable crystal structures is a key prerequisite for the successful application of molecular docking. We employed a multi-structure docking protocol. In which 615 ligands' structures were docked into 150 BACE1 structures. The large number of the resultant docking scores were post-processed by different data analysis methods including exploratory data analysis, regression analysis and discriminant analysis. It was found that using one crystal structure for docking did not result in high accuracy for predicting activity of the BACE1 inhibitors. Instead, using of the multi-structural docking scores, post-processed by chemometrics methods arrived to highly accurate predictive models. In this regards, the PDB accession codes of 4B70, 4DVF and 2WEZ could discriminate between active and inactive compounds, with higher accuracy. Clustering of the BACE1 structures based on principal component analysis of the crystallographic structures the revealed that the discriminant structures are in the center of the clusters. Thus, these structures can be selected as predominant crystal structures for docking studies of non-peptidic BACE1 inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Evaluation of the Accuracy of NASS/CDS Delta-V Estimates from the Enhanced WinSmash Algorithm

    Science.gov (United States)

    Hampton, Carolyn E.; Gabler, Hampton C.

    2010-01-01

    The National Automotive Sampling System / Crashworthiness Data System (NASS/CDS) uses the WinSmash program to reconstruct changes in vehicle velocity for real world crashes. Vehicle change in velocity, or delta-V, is a measure of crash severity and a predictor of injury risk. Earlier studies have demonstrated that WinSmash 2.42 underestimated the delta-V by 23% on average with the use of categorical stiffness values for vehicles identified as a source of error. An enhanced version of WinSmash, WinSmash 2008, was developed to employ vehicle specific stiffness values whenever possible. A total of 478 General Motors vehicles equipped with event data recorders (EDRs) and involved in real-world crashes were collected from years 2000 – 2008 of the NASS/CDS database and the delta-V was computed using the enhanced WinSmash. All vehicles were involved in frontal impacts. The enhanced reconstruction algorithm reduced the underestimation of delta-V from 23% to 13% on average for all vehicles. Delta-V estimates for cars only were greatly improved but still understated by 16% on average. Less than 5% error in delta-V was observed for pickup trucks and utility vehicles. The amount of structural overlap for the vehicle and investigator confidence in the reconstruction continued to have an effect on accuracy. No difference in average delta-V was observed when using either updated categorical stiffness values or vehicle specific stiffness values. The changes in WinSmash delta-Vs have important policy implications for NHTSA as the NASS/CDS delta-Vs are the basis for traffic and safety regulations as well as the speeds for vehicular crash testing and costs/benefits analyses. PMID:21050607

  1. 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.

  2. Diagnostic accuracy of contrast-enhanced ultrasound in differentiating benign and malignant focal liver lesions: a retrospective study

    International Nuclear Information System (INIS)

    Ooi, Chin-Chin; Low, Su-Chong Albert; Lim, Sze-Ying; Bakar, Rafidah Abu; Lo, Richard Hoau-Gong; Schneider-Kolsky, Michal; Lombardo, Paul

    2010-01-01

    Full text: Purpose: The purpose of this study was to access the diagnostic accuracy of our early experience with contrast-enhanced ultrasound (CEUS) in the characterisation of focal liver lesions (FLLs) using histopathology, contrastenhanced computed tomography (CT), magnetic resonance imaging (MRI) or other imaging follow-up as the standard of reference. Materials and Methods: Seventy-three patients with 82 FLLs who underwent liver CEUS from January 2006 to December 2008 were retrospectively reviewed. CEUS was performed with up to 4.8 mL of SonoVue (Bracco, Milan, Italy) using a low mechanical index mode. The CEUS findings were compared with histopathology, or where histopathology was not available, clinical and imaging follow-up over at least 12 months was used as the standard of reference. Results: Of the 82 FLLs, 50 were malignant and 32 were benign at final diagnosis. CEUS correctly identified 43 malignant FLLs, with final diagnosis confirmed by histopathology in 13 lesions and clinico-radiological follow-up in 30 lesions. Twenty-nine lesions were correctly identified as benign on CEUS, with all these lesions confirmed on c1inico-radiological follow-up. CEUS demonstrated a sensitivity of 86.0% and a specificity of 90.6% in the characterisation of liver lesions as malignant, with an overall accuracy of 87.8% (P< 0.05). Conclusion: Our early experience has shown that CEUS can be accurate in differentiating malignant from benign FLLs and may become a useful first-line imaging tool where CT or MRI are not available or contra-indicated.

  3. SKATE: a docking program that decouples systematic sampling from scoring.

    Science.gov (United States)

    Feng, Jianwen A; Marshall, Garland R

    2010-11-15

    SKATE is a docking prototype that decouples systematic sampling from scoring. This novel approach removes any interdependence between sampling and scoring functions to achieve better sampling and, thus, improves docking accuracy. SKATE systematically samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. Efficient systematic sampling is achieved by pruning the combinatorial tree using aggregate assembly, discriminant analysis, adaptive sampling, radial sampling, and clustering. Because systematic sampling is decoupled from scoring, the poses generated by SKATE can be ranked by any published, or in-house, scoring function. To test the performance of SKATE, ligands from the Asetex/CDCC set, the Surflex set, and the Vertex set, a total of 266 complexes, were redocked to their respective receptors. The results show that SKATE was able to sample poses within 2 A RMSD of the native structure for 98, 95, and 98% of the cases in the Astex/CDCC, Surflex, and Vertex sets, respectively. Cross-docking accuracy of SKATE was also assessed by docking 10 ligands to thymidine kinase and 73 ligands to cyclin-dependent kinase. 2010 Wiley Periodicals, Inc.

  4. Improved Harmony Search Algorithm for Truck Scheduling Problem in Multiple-Door Cross-Docking Systems

    Directory of Open Access Journals (Sweden)

    Zhanzhong Wang

    2018-01-01

    Full Text Available The key of realizing the cross docking is to design the joint of inbound trucks and outbound trucks, so a proper sequence of trucks will make the cross-docking system much more efficient and need less makespan. A cross-docking system is proposed with multiple receiving and shipping dock doors. The objective is to find the best door assignments and the sequences of trucks in the principle of products distribution to minimize the total makespan of cross docking. To solve the problem that is regarded as a mixed integer linear programming (MILP model, three metaheuristics, namely, harmony search (HS, improved harmony search (IHS, and genetic algorithm (GA, are proposed. Furthermore, the fixed parameters are optimized by Taguchi experiments to improve the accuracy of solutions further. Finally, several numerical examples are put forward to evaluate the performances of proposed algorithms.

  5. Enhanced systems for measuring and monitoring REDD+: Opportunities to improve the accuracy of emission factor and activity data in Indonesia

    Science.gov (United States)

    Solichin

    The importance of accurate measurement of forest biomass in Indonesia has been growing ever since climate change mitigation schemes, particularly the reduction of emissions from deforestation and forest degradation scheme (known as REDD+), were constitutionally accepted by the government of Indonesia. The need for an accurate system of historical and actual forest monitoring has also become more pronounced, as such a system would afford a better understanding of the role of forests in climate change and allow for the quantification of the impact of activities implemented to reduce greenhouse gas emissions. The aim of this study was to enhance the accuracy of estimations of carbon stocks and to monitor emissions in tropical forests. The research encompassed various scales (from trees and stands to landscape-sized scales) and a wide range of aspects, from evaluation and development of allometric equations to exploration of the potential of existing forest inventory databases and evaluation of cutting-edge technology for non-destructive sampling and accurate forest biomass mapping over large areas. In this study, I explored whether accuracy--especially regarding the identification and reduction of bias--of forest aboveground biomass (AGB) estimates in Indonesia could be improved through (1) development and refinement of allometric equations for major forest types, (2) integration of existing large forest inventory datasets, (3) assessing nondestructive sampling techniques for tree AGB measurement, and (4) landscape-scale mapping of AGB and forest cover using lidar. This thesis provides essential foundations to improve the estimation of forest AGB at tree scale through development of new AGB equations for several major forest types in Indonesia. I successfully developed new allometric equations using large datasets from various forest types that enable us to estimate tree aboveground biomass for both forest type specific and generic equations. My models outperformed

  6. Enhanced Load Power Sharing Accuracy in Droop-Controlled DC Microgrids with Both Mesh and Radial Configurations

    Directory of Open Access Journals (Sweden)

    Yiqi Liu

    2015-04-01

    Full Text Available The rational power sharing among different interface converters should be determined by the converter capacity. In order to guarantee that each converter operates at the ideal condition, considering the radial and mesh configuration, a modified strategy for load power sharing accuracy enhancement in droop-controlled DC microgrid is proposed in this paper. Two compensating terms which include averaging output power control and averaging DC voltage control of neighboring converters are employed. Since only the information of the neighboring converter is used, the complexity of the communication network can be reduced. The rational distribution of load power for different line resistance conditions is realized by using modified droop control that can be regarded as a distributed approach. Low bandwidth communication is used for exchanging sampled information between different converters. The feasibility and effectiveness of the proposed method for different network configurations and line resistances under different communication delay is analyzed in detail. Simulation results derived from a DC microgrid with three converters is implemented in MATLAB/Simulink to verify the proposed approach. Experimental results from a 3 × 10 kW prototype also show the performance of the proposed modified droop control scheme.

  7. Accuracy Enhancement with Processing Error Prediction and Compensation of a CNC Flame Cutting Machine Used in Spatial Surface Operating Conditions

    Directory of Open Access Journals (Sweden)

    Shenghai Hu

    2017-04-01

    Full Text Available This study deals with the precision performance of the CNC flame-cutting machine used in spatial surface operating conditions and presents an accuracy enhancement method based on processing error modeling prediction and real-time compensation. Machining coordinate systems and transformation matrix models were established for the CNC flame processing system considering both geometric errors and thermal deformation effects. Meanwhile, prediction and compensation models were constructed related to the actual cutting situation. Focusing on the thermal deformation elements, finite element analysis was used to measure the testing data of thermal errors, the grey system theory was applied to optimize the key thermal points, and related thermal dynamics models were carried out to achieve high-precision prediction values. Comparison experiments between the proposed method and the teaching method were conducted on the processing system after performing calibration. The results showed that the proposed method is valid and the cutting quality could be improved by more than 30% relative to the teaching method. Furthermore, the proposed method can be used under any working condition by making a few adjustments to the prediction and compensation models.

  8. Radiofrequency ablation of renal tumours: diagnostic accuracy of contrast-enhanced ultrasound for early detection of residual tumour

    International Nuclear Information System (INIS)

    Hoeffel, Christine; Pousset, Maud; Elie, Caroline; Timsit, Marc-Olivier; Mejean, Arnaud; Merran, Samuel; Tranquart, Francois; Khairoune, Ahmed; Helenon, Olivier; Correas, Jean-Michel; Joly, Dominique; Richard, Stephane

    2010-01-01

    To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in the early detection of residual tumour after radiofrequency ablation (RFA) of renal tumours. Patients referred to our institution for RFA of renal tumours prospectively underwent CEUS and computed tomography (CT) or magnetic resonance imaging (MRI) before, within 1 day and 6 weeks after treatment. Identification of residual tumour was assessed by three blinded radiologists. Reference standard was CT/MRI performed at least 1 year after RFA. A total of 66 renal tumours in 43 patients (median age 62 years; range 44-71.5) were studied. Inter-reader agreement (κ value) was 0.84 for CEUS. Prevalence of residual disease was 19%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), respectively, were as follows: 64% [confidence interval (CI) 39-84], 98% [CI 91-100], 82% [CI 52-95] and 92% [CI 83-97] on 24-h CEUS; 79% [CI 52-92], 100% [CI 94-100], 100% [CI 74-100] and 95% [CI 87-100] on 6-week CEUS; 79% [CI 52-92], 95% [CI 86-98], 79% [CI 52-92] and 95% [CI 86-98] on 24-h CT/MRI; and 100% [CI 72-100], 98% [CI 90-100], 91% [CI 62-98] and 100% [CI 93-100] on 6-week CT/MRI. CEUS has high specificity for the early diagnosis of residual tumour after renal RFA. (orig.)

  9. An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics.

    Science.gov (United States)

    Armen, Roger S; Chen, Jianhan; Brooks, Charles L

    2009-10-13

    Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and "noise" that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds.

  10. CT-docking patient stretcher

    International Nuclear Information System (INIS)

    Mirvis, S.E.; Owens, E.; Maslyn, J.; Rizutto, M.

    1990-01-01

    This paper assesses the use of a patient stretcher that directly docks to a CT scanner for acutely injured and/or critically ill patients. The stretcher permits performance of radiography and acts as a platform for critical care monitoring and patient support devices. During a 1-year period, the prototype CT-docking stretcher was used for 35 patients sustaining acute trauma and 25 patients from critical care units. Observations were elicited from physicians, nurses and technologists concerning the advantages or disadvantages of the docking stretcher. Advantages of the CT-docking stretcher included time saved in moving patients to the CT table from the admitting/emergency ward, transfer of critically ill patients onto the stretcher in the controlled environment of the intensive care unit rather than the CT suite, increasing CT throughput by direct docking of the patient stretcher to the CT scanner rather than manual transfer of complex support and monitoring devices with the patient, decreased risk associated with physical movement of patients with potentially unstable spinal injuries or unstable physiologic status, and decrease in potential for injury to medical personnel performing patient transfer

  11. Dry dock gate stability modelling

    Science.gov (United States)

    Oktoberty; Widiyanto; Sasono, E. J.; Pramono, S.; Wandono, A. T.

    2018-03-01

    The development of marine transportation needs in Indonesia increasingly opens national shipyard business opportunities to provide shipbuilding services to the shipbuilding vessels. That emphasizes the stability of prime. The ship's decking door becomes an integral part of the efficient place and the specification of the use of the asset of its operational ease. This study aims to test the stability of Dry Dock gate with the length of 35.4 meters using Maxsurf and Hydromax in analyzing the calculation were in its assessment using interval per 500 mm length so that it can get detail data toward longitudinal and transverse such as studying Ship planning in general. The test result shows dry dock gate meets IMO standard with ballast construction containing 54% and 68% and using fix ballast can produce GMt 1,924 m, tide height 11,357m. The GMt value indicates dry dick gate can be stable and firmly erect at the base of the mouth dry dock. When empty ballast produces GMt 0.996 which means dry dock date is stable, but can easily be torn down. The condition can be used during dry dock gate treatment.

  12. "Flexible Ligand Docking Studies of Matrix Metalloproteinase Inhibitors Using Lamarckian Genetic Algorithm "

    Directory of Open Access Journals (Sweden)

    lOrkideh Ghorban Dadrass

    2004-06-01

    Full Text Available As important therapeutic drug targets, matrix metalloproteinases (MMPs have recently attracted great interest in the search for potent and selective inhibitors using computer-aided molecular modelling and docking techniques. Availability of more than 60 X-ray crystal structures or NMR solution structures related to MMPs in Protein Data Bank (PDB of which more than half of them are in complex with various MMP inhibitors (MMPIs, provides a great opportunity for docking studies. In this study AutoDock 3.0.5 along with its LGA algorithm were used for automated flexible ligand docking of 32 MMPI-MMP complexes and docking accuracy and reliability of the estimated inhibition constants were evaluated. Twenty-six out of 32 docks had RMSD less than 3.0 Å which is considered as well-docked, however, for the most of the cases (15 out of 27, predicted pKi values were considerably overestimated in comparison to experimental values. To improve pKi prediction regarding MMPI-MMP complexes, inclusion of at least one such a complex in calibration of empirical free energy function in the next release of AutoDock is highly recommended.

  13. 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 .

  14. 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

  15. Development of real-time core monitoring system models with accuracy-enhanced neural network and its application

    International Nuclear Information System (INIS)

    Koo, Bon Hyun

    1994-02-01

    In a complicated system like pressurized water reactor, a number of key safety parameters need to be selected to represent the reactor systems safety. It could be more effective for the reactor safety to make the key safety parameters in real-time available directly to the reactor operator. Direct representation of key safety parameters is also desirable in the view of reactor core design since it could reduce unnecessary margins for various components of uncertainties. In this thesis, real-time core monitoring system models have been developed with use of artificial neural networks for the prediction of nuclear hot channel factor (HCF) and core departure from nucleate boiling ratio (DNBR) which are known to be the fundamental core safety parameters for pressurized water reactors. Artificial neural network algorithm, has been shown to be successful for the conservative and accurate prediction of the HCF and DNBR. For the development of system models, training patterns were generated using the FLAIR and COBRAIV-i computer codes for the HCF and DNBR. The selected input variables were the core power, reactor coolant flow, temperature, pressure, power distribution, boron concentration, and rod position. The developed system models could replace the existing core monitoring systems and then afford a better efficiency by using the additional margin which otherwise needs to be reserved for various unidentified uncertainties. Several variations of the neural network technique have been proposed and compared based on numerical experiments. The neural network can be augmented by use of a functional link to improve the performance of the network model. The functional link is found to be very effective especially when the relationship between the input parameters and the output parameters is overly complicated such as in the core HCF and DNBR. For the further enhancement of DNBR accuracy, two-fold weight sets were used. The coarse weight set can provide a quick and

  16. NASA Docking System (NDS) Technical Integration Meeting

    Science.gov (United States)

    Lewis, James L.

    2010-01-01

    This slide presentation reviews the NASA Docking System (NDS) as NASA's implementation of the International Docking System Standard (IDSS). The goals of the NDS, is to build on proven technologies previously demonstrated in flight and to advance the state of the art of docking systems by incorporating Low Impact Docking System (LIDS) technology into the NDS. A Hardware Demonstration was included in the meeting, and there was discussion about software, NDS major system interfaces, integration information, schedule, and future upgrades.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Igor V. Oferkin

    2015-01-01

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

  19. Spent fuel canister docking station

    International Nuclear Information System (INIS)

    Suikki, M.

    2006-01-01

    The working report for the spent fuel canister docking station presents a design for the operation and structure of the docking equipment located in the fuel handling cell for the spent fuel in the encapsulation plant. The report contains a description of the basic requirements for the docking station equipment and their implementation, the operation of the equipment, maintenance and a cost estimate. In the designing of the equipment all the problems related with the operation have been solved at the level of principle, nevertheless, detailed designing and the selection of final components have not yet been carried out. In case of defects and failures, solutions have been considered for postulated problems, and furthermore, the entire equipment was gone through by the means of systematic risk analysis (PFMEA). During the docking station designing we came across with needs to influence the structure of the actual disposal canister for spent nuclear fuel, too. Proposed changes for the structure of the steel lid fastening screw were included in the report. The report also contains a description of installation with the fuel handling cell structures. The purpose of the docking station for the fuel handling cell is to position and to seal the disposal canister for spent nuclear fuel into a penetration located on the cell floor and to provide suitable means for executing the loading of the disposal canister and the changing of atmosphere. The designed docking station consists of a docking ring, a covering hatch, a protective cone and an atmosphere-changing cap as well as the vacuum technology pertaining to the changing of atmosphere and the inert gas system. As far as the solutions are concerned, we have arrived at rather simple structures and most of the actuators of the system are situated outside of the actual fuel handling cell. When necessary, the equipment can also be used for the dismantling of a faulty disposal canister, cut from its upper end by machining. The

  20. Using grey intensity adjustment strategy to enhance the measurement accuracy of digital image correlation considering the effect of intensity saturation

    Science.gov (United States)

    Li, Bang-Jian; Wang, Quan-Bao; Duan, Deng-Ping; Chen, Ji-An

    2018-05-01

    Intensity saturation can cause decorrelation phenomenon and decrease the measurement accuracy in digital image correlation (DIC). In the paper, the grey intensity adjustment strategy is proposed to improve the measurement accuracy of DIC considering the effect of intensity saturation. First, the grey intensity adjustment strategy is described in detail, which can recover the truncated grey intensities of the saturated pixels and reduce the decorrelation phenomenon. The simulated speckle patterns are then employed to demonstrate the efficacy of the proposed strategy, which indicates that the displacement accuracy can be improved by about 40% by the proposed strategy. Finally, the true experimental image is used to show the feasibility of the proposed strategy, which indicates that the displacement accuracy can be increased by about 10% by the proposed strategy.

  1. The effects of noise reduction, sharpening, enhancement, and image magnification on diagnostic accuracy of a photostimulable phosphor system in the detection of non-cavitated approximal dental caries

    International Nuclear Information System (INIS)

    Kajan, Zahra Dalili; Davalloo, Reza Tayefeh; Tavangar, Mayam; Valizade, Fatemeh

    2015-01-01

    Contrast, sharpness, enhancement, and density can be changed in digital systems. The important question is to what extent the changes in these variables affect the accuracy of caries detection. Forty eight extracted human posterior teeth with healthy or proximal caries surfaces were imaged using a photostimulable phosphor (PSP) sensor. All original images were processed using a six-step method: (1) applying 'Sharpening 2' and 'Noise Reduction' processing options to the original images; (2) applying the 'Magnification 1:3' option to the image obtained in the first step; (3) enhancing the original images by using the 'Diagonal/' option; (4) reviewing the changes brought about by the third step of image processing and then, applying 'Magnification 1:3'; (5) applying 'Sharpening UM' to the original images; and (6) analyzing the changes brought about by the fifth step of image processing, and finally, applying 'Magnification 1:3.' Three observers evaluated the images. The tooth sections were evaluated histologically as the gold standard. The diagnostic accuracy of the observers was compared using a chi-squared test. The accuracy levels irrespective of the image processing method ranged from weak (18.8%) to intermediate (54.2%), but the highest accuracy was achieved at the sixth image processing step. The overall diagnostic accuracy level showed a statistically significant difference (p=0.0001). This study shows that the application of 'Sharpening UM' along with the 'Magnification 1:3' processing option improved the diagnostic accuracy and the observer agreement more effectively than the other processing procedures.

  2. The effects of noise reduction, sharpening, enhancement, and image magnification on diagnostic accuracy of a photostimulable phosphor system in the detection of non-cavitated approximal dental caries

    Energy Technology Data Exchange (ETDEWEB)

    Kajan, Zahra Dalili; Davalloo, Reza Tayefeh; Tavangar, Mayam; Valizade, Fatemeh [Faculty of Dentistry, Guilan University of Medical Sciences, Rasht (Iran, Islamic Republic of)

    2015-06-15

    Contrast, sharpness, enhancement, and density can be changed in digital systems. The important question is to what extent the changes in these variables affect the accuracy of caries detection. Forty eight extracted human posterior teeth with healthy or proximal caries surfaces were imaged using a photostimulable phosphor (PSP) sensor. All original images were processed using a six-step method: (1) applying 'Sharpening 2' and 'Noise Reduction' processing options to the original images; (2) applying the 'Magnification 1:3' option to the image obtained in the first step; (3) enhancing the original images by using the 'Diagonal/' option; (4) reviewing the changes brought about by the third step of image processing and then, applying 'Magnification 1:3'; (5) applying 'Sharpening UM' to the original images; and (6) analyzing the changes brought about by the fifth step of image processing, and finally, applying 'Magnification 1:3.' Three observers evaluated the images. The tooth sections were evaluated histologically as the gold standard. The diagnostic accuracy of the observers was compared using a chi-squared test. The accuracy levels irrespective of the image processing method ranged from weak (18.8%) to intermediate (54.2%), but the highest accuracy was achieved at the sixth image processing step. The overall diagnostic accuracy level showed a statistically significant difference (p=0.0001). This study shows that the application of 'Sharpening UM' along with the 'Magnification 1:3' processing option improved the diagnostic accuracy and the observer agreement more effectively than the other processing procedures.

  3. Diagnostic accuracy of fracture detection in suspected non-accidental injury: the effect of edge enhancement and digital display on observer performance

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, A.C. [Department of Radiology, Great Ormond Street Hospital for Children, London (United Kingdom) and Institute of Child Health, London (United Kingdom)]. E-mail: amaka.offiah@gosh.nhs.uk; Moon, L. [Department of Radiology, Great Ormond Street Hospital for Children, London (United Kingdom); Hall, C.M. [Department of Radiology, Great Ormond Street Hospital for Children, London (United Kingdom); Todd-Pokropek, A. [Department of Medical Physics and Bioengineering, University College London, London (United Kingdom)

    2006-02-15

    AIM: To compare the effect of varying degrees of edge enhancement and method of digital image display on fracture detection in suspected non-accidental injury (NAI). MATERIALS AND METHODS: Fifty radiographs from post-mortem skeletal surveys in 13 children with suspected NAI were selected. Images were obtained using a Fuji 5000R computed radiography system. Hard copies were printed with edge enhancement factors 0, 0.5 and 1.2. Images (edge enhancement 0.5) were also displayed on a 1K{sup 2} monitor. Six observers independently evaluated all 200 images for the presence of abnormality. Observers also scored each image for visualization of soft tissues, visualization of trabecular markings and overall image quality. The paired Student's t-test and location receiver operating curve (ROC) analysis were used to compare quality scores and diagnostic accuracy of each display method. Individual and pooled true-positive rates (sensitivity) were determined. For the purposes of ROC analysis, histology was taken as the gold standard. RESULTS: There was no difference in duration of hard and soft-copy reading sessions (p=0.76). After image manipulation soft-copy radiographs scored significantly better for image quality than hard copy (p<0.0001). Pooled observer sensitivity (at a specificity of 90%) was below 50% for all display methods. Diagnostic accuracy varied significantly between observers. Diagnostic accuracy of individual observers was not affected by display method. CONCLUSION: In suspected NAI, diagnostic accuracy of fracture detection is generally low. Diagnostic accuracy appears to be affected more by observer-related factors than by the method of digital image display.

  4. 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.

  5. 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.

  6. 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.

  7. Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms.

    Science.gov (United States)

    Sulimov, Alexey V; Zheltkov, Dmitry A; Oferkin, Igor V; Kutov, Danil C; Katkova, Ekaterina V; Tyrtyshnikov, Eugene E; Sulimov, Vladimir B

    2017-01-01

    We present the novel docking algorithm based on the Tensor Train decomposition and the TT-Cross global optimization. The algorithm is applied to the docking problem with flexible ligand and moveable protein atoms. The energy of the protein-ligand complex is calculated in the frame of the MMFF94 force field in vacuum. The grid of precalculated energy potentials of probe ligand atoms in the field of the target protein atoms is not used. The energy of the protein-ligand complex for any given configuration is computed directly with the MMFF94 force field without any fitting parameters. The conformation space of the system coordinates is formed by translations and rotations of the ligand as a whole, by the ligand torsions and also by Cartesian coordinates of the selected target protein atoms. Mobility of protein and ligand atoms is taken into account in the docking process simultaneously and equally. The algorithm is realized in the novel parallel docking SOL-P program and results of its performance for a set of 30 protein-ligand complexes are presented. Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms. It is shown that mobility of the protein atoms improves docking positioning accuracy. The SOL-P program is able to perform docking of a flexible ligand into the active site of the target protein with several dozens of protein moveable atoms: the native crystallized ligand pose is correctly found as the global energy minimum in the search space with 157 dimensions using 4700 CPU ∗ h at the Lomonosov supercomputer.

  8. Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

    Science.gov (United States)

    Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

    2012-06-01

    To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

  9. Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts.

    Science.gov (United States)

    Mori, Miki; Akashi-Tanaka, Sadako; Suzuki, Satoko; Daniels, Murasaki Ikeda; Watanabe, Chie; Hirose, Masanori; Nakamura, Seigo

    2017-01-01

    Contrast-enhanced spectral mammography to compare clinical efficacy of contrast-enhanced spectral mammography (CESM) and conventional digital mammography (MMG) with histopathology as gold standard in dense breasts. A total of 143 breasts of 72 women who underwent CESM and MMG between 2011 and 2014 at Showa University Hospital were analyzed. 129 (90.2 %) of 143 breasts revealed dense breasts on MMG. 58 (40.6 %) of 143 breasts were diagnosed with breast cancer at histopathology. The remaining 85 breasts were diagnosed with benign findings after image assessments and/or core needle biopsy. CESM revealed 8 false-negative cases among 58 breast cancer cases (sensitivity 86.2 %) and 5 false-positive cases (specificity 94.1 %). Accuracy was 90.9 %. Conventional MMG was assessed true positive in 31 of 58 breast cancer cases (sensitivity 53.4 %) and false positive in 12 cases (specificity 85.9 %). Accuracy was 72.7 %. Sensitivity (p < 0.001), specificity (p = 0.016) and accuracy (p < 0.001) were significantly higher on CESM compared to MMG. MMG missed malignancy in 27 breasts. Of these, 25 were dense breasts. Of these 25, 20 (80.0 %) breasts were positive on CESM. These findings suggest that CESM offers superior clinical performance compared to MMG. Use of CESM may decrease false negatives especially for women with dense breasts.

  10. Plasticity of the Binding Site of Renin: Optimized Selection of Protein Structures for Ensemble Docking.

    Science.gov (United States)

    Strecker, Claas; Meyer, Bernd

    2018-05-02

    Protein flexibility poses a major challenge to docking of potential ligands in that the binding site can adopt different shapes. Docking algorithms usually keep the protein rigid and only allow the ligand to be treated as flexible. However, a wrong assessment of the shape of the binding pocket can prevent a ligand from adapting a correct pose. Ensemble docking is a simple yet promising method to solve this problem: Ligands are docked into multiple structures, and the results are subsequently merged. Selection of protein structures is a significant factor for this approach. In this work we perform a comprehensive and comparative study evaluating the impact of structure selection on ensemble docking. We perform ensemble docking with several crystal structures and with structures derived from molecular dynamics simulations of renin, an attractive target for antihypertensive drugs. Here, 500 ns of MD simulations revealed binding site shapes not found in any available crystal structure. We evaluate the importance of structure selection for ensemble docking by comparing binding pose prediction, ability to rank actives above nonactives (screening utility), and scoring accuracy. As a result, for ensemble definition k-means clustering appears to be better suited than hierarchical clustering with average linkage. The best performing ensemble consists of four crystal structures and is able to reproduce the native ligand poses better than any individual crystal structure. Moreover this ensemble outperforms 88% of all individual crystal structures in terms of screening utility as well as scoring accuracy. Similarly, ensembles of MD-derived structures perform on average better than 75% of any individual crystal structure in terms of scoring accuracy at all inspected ensembles sizes.

  11. Diagnostic accuracy of {sup 18}F-FDG PET/CT compared with that of contrast-enhanced MRI of the breast at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Magometschnigg, Heinrich F.; Baltzer, Pascal A.; Fueger, Barbara; Helbich, Thomas H.; Weber, Michael [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Vienna (Austria); Karanikas, Georgios [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Dubsky, Peter [Medical University of Vienna, Department of Surgery, Vienna (Austria); Rudas, Margaretha [Medical University of Vienna, Department of Pathology, Vienna (Austria); Pinker, Katja [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Vienna (Austria); Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York (United States)

    2015-10-15

    To compare the diagnostic accuracy of prone {sup 18}F-FDG PET/CT with that of contrast-enhanced MRI (CE-MRI) at 3 T in suspicious breast lesions. To evaluate the influence of tumour size on diagnostic accuracy and the use of maximum standardized uptake value (SUV{sub MAX}) thresholds to differentiate malignant from benign breast lesions. A total of 172 consecutive patients with an imaging abnormality were included in this IRB-approved prospective study. All patients underwent {sup 18}F-FDG PET/CT and CE-MRI of the breast at 3 T in the prone position. Two reader teams independently evaluated the likelihood of malignancy as determined by {sup 18}F-FDG PET/CT and CE-MRI independently. {sup 18}F-FDG PET/CT data were qualitatively evaluated by visual interpretation. Quantitative assessment was performed by calculation of SUV{sub MAX}. Sensitivity, specificity, diagnostic accuracy, area under the curve and interreader agreement were calculated for all lesions and for lesions <10 mm. Histopathology was used as the standard of reference. There were 132 malignant and 40 benign lesions; 23 lesions (13.4 %) were <10 mm. Both {sup 18}F-FDG PET/CT and CE-MRI achieved an overall diagnostic accuracy of 93 %. There were no significant differences in sensitivity (p = 0.125), specificity (p = 0.344) or diagnostic accuracy (p = 1). For lesions <10 mm, diagnostic accuracy deteriorated to 91 % with both {sup 18}F-FDG PET/CT and CE-MRI. Although no significant difference was found for lesions <10 mm, CE-MRI at 3 T seemed to be more sensitive but less specific than {sup 18}F-FDG PET/CT. Interreader agreement was excellent (κ = 0.85 and κ = 0.92). SUV{sub MAX} threshold was not helpful in differentiating benign from malignant lesions. {sup 18}F-FDG PET/CT and CE-MRI at 3 T showed equal diagnostic accuracies in breast cancer diagnosis. For lesions <10 mm, diagnostic accuracy deteriorated, but was equal for {sup 18}F-FDG PET/CT and CE-MRI at 3 T. For lesions <10 mm, CE-MRI at 3 T seemed

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

    Directory of Open Access Journals (Sweden)

    Hongjian Li

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Cellulase enzyme: Homology modeling, binding site identification and molecular docking

    Science.gov (United States)

    Selvam, K.; Senbagam, D.; Selvankumar, T.; Sudhakar, C.; Kamala-Kannan, S.; Senthilkumar, B.; Govarthanan, M.

    2017-12-01

    Cellulase is an enzyme that degrades the linear polysaccharide like cellulose into glucose by breaking the β-1,4- glycosidic bonds. These enzymes are the third largest enzymes with a great potential towards the ethanol production and play a vital role in degrading the biomass. The production of ethanol depends upon the ability of the cellulose to utilize the wide range of substrates. In this study, the 3D structure of cellulase from Acinetobacter sp. was modeled by using Modeler 9v9 and validated by Ramachandran plot. The accuracy of the predicted 3D structure was checked using Ramachandran plot analysis showed that 81.1% in the favored region, compatibility of an atomic model (3D) with amino acid sequence (1D) for the model was observed as 78.21% and 49.395% for Verify 3D and ERRAT at SAVES server. As the binding efficacy with the substrate might suggests the choice of the substrate as carbon and nitrogen sources, the cellobiose, cellotetraose, cellotetriose and laminaribiose were employed in the docking studies. The docking of cellobiose, cellotetraose, cellotetriose and laminaribiose with cellulase exhibited the binding energy of -6.1523 kJ/mol, -7.8759 kJ/mol,-6.1590 kJ/mol and -6.7185 kJ/mol, respectively. These docking studies revealed that cellulase has the greater potential towards the cellotetraose as a substrate for the high yield of ethanol.

  15. Performance enhancement of low-cost, high-accuracy, state estimation for vehicle collision prevention system using ANFIS

    Science.gov (United States)

    Saadeddin, Kamal; Abdel-Hafez, Mamoun F.; Jaradat, Mohammad A.; Jarrah, Mohammad Amin

    2013-12-01

    In this paper, a low-cost navigation system that fuses the measurements of the inertial navigation system (INS) and the global positioning system (GPS) receiver is developed. First, the system's dynamics are obtained based on a vehicle's kinematic model. Second, the INS and GPS measurements are fused using an extended Kalman filter (EKF) approach. Subsequently, an artificial intelligence based approach for the fusion of INS/GPS measurements is developed based on an Input-Delayed Adaptive Neuro-Fuzzy Inference System (IDANFIS). Experimental tests are conducted to demonstrate the performance of the two sensor fusion approaches. It is found that the use of the proposed IDANFIS approach achieves a reduction in the integration development time and an improvement in the estimation accuracy of the vehicle's position and velocity compared to the EKF based approach.

  16. 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.

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

    Science.gov (United States)

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

    2017-07-01

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

  18. Application of Numerical Optimization Methods to Perform Molecular Docking on Graphics Processing Units

    Directory of Open Access Journals (Sweden)

    M. A. Farkov

    2014-01-01

    Full Text Available An analysis of numerical optimization methods for solving a problem of molecular docking has been performed. Some additional requirements for optimization methods according to GPU architecture features were specified. A promising method for implementation on GPU was selected. Its implementation was described and performance and accuracy tests were performed.

  19. Diagnostic accuracy of gadoxetic acid-enhanced MR for small hypervascular hepatocellular carcinoma and the concordance rate of Liver Imaging Reporting and Data System (LI-RADS).

    Science.gov (United States)

    Bae, Jae Seok; Kim, Jung Hoon; Yu, Mi Hye; Lee, Dong Ho; Kim, Hyo-Cheol; Chung, Jin Wook; Han, Joon Koo

    2017-01-01

    To assess diagnostic accuracy of gadoxetic acid-enhanced MR for small hypervascular hepatocellular carcinoma (HCC) detected by C-arm CT and concordance rate of Liver Imaging Reporting and Data System (LI-RADS). In this retrospective study, we recruited 4,544 patients suspected of having HCC underwent C-arm CT from November 2008 to May 2013. Among these patients, gadoxetic acid-enhanced MR was performed in 167 patients with HCC (n = 379; 257 > 1 cm, 122 ≤ 1 cm). HCC was confirmed by MR, CT, or follow-up images. Two radiologists graded likelihood of HCC and assessed MR features. Jackknife alternative free-response receiver operating characteristic (JAFROC) analysis was performed. All HCCs were evaluated concordance rate of LI-RADS. Mean JAFROC figure of merit for large (>1-cm) HCC was 0.948, while that for small HCC was 0.787 with fair agreement (κ = 0.409). Mean sensitivity and positive predictive value (PPV) were 91% and 90% for large HCC versus 63.0% and 79% for small HCC, respectively. Seventeen of 122 small HCCs (13.9%) were not visible on MR. Among 379 HCCs, 99 met LR-5, and 259 met LR-4. Common features for small HCC included arterial enhancement (81.9%), hepatobiliary phase hypointensity (80.3%), and delayed washout (72.9%). Diagnostic accuracy of gadoxetic acid-enhanced MR imaging for small, hypervascular HCCs (Mean figure of merit = 0.787) was still low compared with large HCC (Mean figure of merit = 0.948). LR-5 and LR-4 covered 94% (358/379) of the HCCs.

  20. Diagnostic accuracy of contrast enhanced ultrasound in patients with blunt abdominal trauma presenting to the emergency department: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Zhongheng; Hong, Yucai; Liu, Ning; Chen, Yuhao

    2017-06-30

    We aimed to investigate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in evaluating blunt abdominal trauma for patients presenting to the emergency department. Electronic search of Scopus and Pubmed was performed from inception to September 2016. Human studies investigating the diagnostic accuracy of CEUS in identifying abdominal solid organ injuries were included. Risk of bias was assessed using the QUADAS tool. A total of 10 studies were included in the study and 9 of them were included for meta-analysis. The log(DOR) values ranged from 3.80 (95% CI: 2.81-4.79) to 8.52 (95% CI: 4.58-12.47) in component studies. The combined log(DOR) was 6.56 (95% CI: 5.66-7.45). The Cochran's Q was 11.265 (p = 0.793 with 16 degrees of freedom), and the Higgins' I 2 was 0%. The CEUS had a sensitivity of 0.981 (95% CI: 0.868-0.950) and a false positive rate of 0.018 (95% CI: 0.010-0.032) for identifying parenchymal injuries, with an AUC of 0.984. CEUS performed at emergency department had good diagnostic accuracy in identifying abdominal solid organ injuries. CEUS can be recommended in monitoring solid organ injuries, especially for patients managed with non-operative strategy.

  1. Diagnostic accuracy of C-arm CT during selective transcatheter angiography for hepatocellular carcinoma: comparison with intravenous contrast-enhanced, biphasic, dynamic MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Higashihara, Hiroki; Osuga, Keigo; Onishi, Hiromitsu; Nakamoto, Atsushi; Tsuboyama, Takahiro; Maeda, Noboru; Hori, Masatoshi; Kim, Tonsok; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Suita, Osaka (Japan)

    2012-04-15

    This study was aimed to compare the accuracy, sensitivity, and positive predictive value of C-arm CT (CACT) during selective transcatheter angiography with those of multidetector CT (MDCT) in the detection of hepatocellular carcinoma (HCC). In this prospective study, 30 patients (mean age, 73 years) with unresectable HCC were examined with CACT before chemoembolisation. Images of a combination of CACT during arterial portography (CACTAP) and dual-phase CACT during hepatic arteriography (CACTHA) was obtained and images of intravenous contrast-enhanced, biphasic, dynamic, MDCT was also obtained beforehand. Three blinded observers independently reviewed CACT and MDCT. Diagnostic accuracy was evaluated by the alternative free-response receiver operating characteristic (AFROC) method. Sensitivities and positive predictive values (PPV) were analyzed with the paired t-test. In the mean area under the AFROC curve (Az), there was no significant difference between MDCT and CACT (MDCT, mean Az value, 0.83; CACT, 0.85, respectively) (P = 0.32). There was also no significant difference between the two techniques in sensitivity (MDCT, mean 0.65; CACT, 0.60) and PPV (MDCT, mean 0.98; CACT, 0.97) (P = 0.40, P = 0.68, respectively). The diagnostic accuracy of CACT was equivalent to that of biphasic CT in the diagnosis of HCC. (orig.)

  2. Vision Based Navigation for Autonomous Cooperative Docking of CubeSats

    Science.gov (United States)

    Pirat, Camille; Ankersen, Finn; Walker, Roger; Gass, Volker

    2018-05-01

    A realistic rendezvous and docking navigation solution applicable to CubeSats is investigated. The scalability analysis of the ESA Autonomous Transfer Vehicle Guidance, Navigation & Control (GNC) performances and the Russian docking system, shows that the docking of two CubeSats would require a lateral control performance of the order of 1 cm. Line of sight constraints and multipath effects affecting Global Navigation Satellite System (GNSS) measurements in close proximity prevent the use of this sensor for the final approach. This consideration and the high control accuracy requirement led to the use of vision sensors for the final 10 m of the rendezvous and docking sequence. A single monocular camera on the chaser satellite and various sets of Light-Emitting Diodes (LEDs) on the target vehicle ensure the observability of the system throughout the approach trajectory. The simple and novel formulation of the measurement equations allows differentiating unambiguously rotations from translations between the target and chaser docking port and allows a navigation performance better than 1 mm at docking. Furthermore, the non-linear measurement equations can be solved in order to provide an analytic navigation solution. This solution can be used to monitor the navigation filter solution and ensure its stability, adding an extra layer of robustness for autonomous rendezvous and docking. The navigation filter initialization is addressed in detail. The proposed method is able to differentiate LEDs signals from Sun reflections as demonstrated by experimental data. The navigation filter uses a comprehensive linearised coupled rotation/translation dynamics, describing the chaser to target docking port motion. The handover, between GNSS and vision sensor measurements, is assessed. The performances of the navigation function along the approach trajectory is discussed.

  3. Diagnostic accuracy of magnetic resonance, computed tomography and contrast enhanced ultrasound in radiological multimodality assessment of peribiliary liver metastases.

    Directory of Open Access Journals (Sweden)

    Vincenza Granata

    Full Text Available We compared diagnostic performance of Magnetic Resonance (MR, Computed Tomography (CT and Ultrasound (US with (CEUS and without contrast medium to identify peribiliary metastasis.We identified 35 subjects with histological proven peribiliary metastases who underwent CEUS, CT and MR study. Four radiologists evaluated the presence of peribiliary lesions, using a 4-point confidence scale. Echogenicity, density and T1-Weigthed (T1-W, T2-W and Diffusion Weighted Imaging (DWI signal intensity as well as the enhancement pattern during contrast studies on CEUS, CT and MR so as hepatobiliary-phase on MRI was assessed.All lesions were detected by MR. CT detected 8 lesions, while US/CEUS detected one lesion. According to the site of the lesion, respect to the bile duct and hepatic parenchyma: 19 (54.3% were periductal, 15 (42.8% were intra-periductal and 1 (2.8% was periductal-intrahepatic. According to the confidence scale MRI had the best diagnostic performance to assess the lesion. CT obtained lower diagnostic performance. There was no significant difference in MR signal intensity and contrast enhancement among all metastases (p>0.05. There was no significant difference in CT density and contrast enhancement among all metastases (p>0.05.MRI is the method of choice for biliary tract tumors but it does not allow a correct differential diagnosis among different histological types of metastasis. The presence of biliary tree dilatation without hepatic lesions on CT and US/CEUS study may be an indirect sign of peribiliary metastases and for this reason the patient should be evaluated by MRI.

  4. Enhancing the accuracy of GPS point positioning by converting the single frequency data to dual frequency data

    Directory of Open Access Journals (Sweden)

    Aly M. El-naggar

    2011-09-01

    Full Text Available The global positioning system (GPS has been used to support a wide variety of applications, such as high-accuracy positioning and navigation. Differential GPS techniques can largely eliminate common-mode errors between the reference and the rover GPS stations resulting from ionospheric and tropospheric refraction and delays, satellite and receiver clock biases, and orbital errors [1]. The ionospheric delay in the propagation of global positioning system (GPS signals is one of the main sources of error in GPS precise positioning and navigation. A dual-frequency GPS receiver can eliminate (to the first order the ionospheric delay through a linear combination of the L1 and L2 observations [2]. The most significant effect of ionospheric delay appear in case of using single frequency data. In this paper the single frequency data of concerned station are converted to dual frequency data by employing dual frequency data from 11 regional GPS stations distributed around it. Total electron content (TEC was calculated at every GPS station to produce the mathematical model of TEC which is a function of latitude (Φ and longitude (λ. By using this mathematical model the values of TEC and L2 can be predicted at the single frequency GPS station for each satellite, after that the comparison between predicted and observation values of TEC and L2 was performed. The estimation method and test results of the proposed method indicates that the difference between predicted and observation values is very small.

  5. Accuracy Enhancement of Raman Spectroscopy Using Complementary Laser-Induced Breakdown Spectroscopy (LIBS) with Geologically Mixed Samples.

    Science.gov (United States)

    Choi, Soojin; Kim, Dongyoung; Yang, Junho; Yoh, Jack J

    2017-04-01

    Quantitative Raman analysis was carried out with geologically mixed samples that have various matrices. In order to compensate the matrix effect in Raman shift, laser-induced breakdown spectroscopy (LIBS) analysis was performed. Raman spectroscopy revealed the geological materials contained in the mixed samples. However, the analysis of a mixture containing different matrices was inaccurate due to the weak signal of the Raman shift, interference, and the strong matrix effect. On the other hand, the LIBS quantitative analysis of atomic carbon and calcium in mixed samples showed high accuracy. In the case of the calcite and gypsum mixture, the coefficient of determination of atomic carbon using LIBS was 0.99, while the signal using Raman was less than 0.9. Therefore, the geological composition of the mixed samples is first obtained using Raman and the LIBS-based quantitative analysis is then applied to the Raman outcome in order to construct highly accurate univariate calibration curves. The study also focuses on a method to overcome matrix effects through the two complementary spectroscopic techniques of Raman spectroscopy and LIBS.

  6. Combined FVTD/PSTD Schemes with Enhanced Spectral Accuracy for the Design of Large-Scale EMC Applications

    Directory of Open Access Journals (Sweden)

    N. V. Kantartzis

    2012-10-01

    Full Text Available A generalized conformal time-domain method with adjustable spectral accuracy is introduced in this paper for the consistent analysis of large-scale electromagnetic compatibility problems. The novel 3-D hybrid schemes blend a stencil-optimized finite-volume time-domain and a multimodal Fourier-Chebyshev pseudo-spectral time-domain algorithm that split the overall space into smaller and flexible areas. A key asset is that both techniques are updated independently and interconnected by robust boundary conditions. Also, combining a family of spatial derivative approximators with controllable precision in general curvilinear coordinates, the proposed method launches a conformal field flux formulation to derive electromagnetic quantities in regions with fine details. For advanced grid reliability at dissimilar media interfaces, dispersion-reduced adaptive operators, which assign the proper weights to each spatial increment, are developed. So, the resulting discretization yields highly rigorous and computationally affordable simulations, devoid of lattice errors. Numerical results, addressing detailed comparisons of various realistic applications with reference or measurement data verify our methodology and reveal its significant applicability.

  7. Image quality and diagnostic accuracy of unenhanced SSFP MR angiography compared with conventional contrast-enhanced MR angiography for the assessment of thoracic aortic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Krishnam, Mayil S. [University of California, Cardiovascular and Thoracic Imaging, UCI Medical Center, Irvine, CA (United States); Tomasian, Anderanik; Malik, Sachin; Ruehm, Stefan G. [University of California at Los Angeles, Department of Radiological Sciences, Ronald Reagan Medical Center, Los Angeles, CA (United States); Desphande, Vibhas; Laub, Gerhard [Siemens Medical Solutions, Los Angeles, CA (United States)

    2010-06-15

    The purpose of this study was to determine the image quality and diagnostic accuracy of three-dimensional (3D) unenhanced steady state free precession (SSFP) magnetic resonance angiography (MRA) for the evaluation of thoracic aortic diseases. Fifty consecutive patients with known or suspected thoracic aortic disease underwent free-breathing ECG-gated unenhanced SSFP MRA with non-selective radiofrequency excitation and contrast-enhanced (CE) MRA of the thorax at 1.5 T. Two readers independently evaluated the two datasets for image quality in the aortic root, ascending aorta, aortic arch, descending aorta, and origins of supra-aortic arteries, and for abnormal findings. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined for both datasets. Sensitivity, specificity, and diagnostic accuracy of unenhanced SSFP MRA for the diagnosis of aortic abnormalities were determined. Abnormal aortic findings, including aneurysm (n = 47), coarctation (n = 14), dissection (n = 12), aortic graft (n = 6), intramural hematoma (n = 11), mural thrombus in the aortic arch (n = 1), and penetrating aortic ulcer (n = 9), were confidently detected on both datasets. Sensitivity, specificity, and diagnostic accuracy of SSFP MRA for the detection of aortic disease were 100% with CE-MRA serving as a reference standard. Image quality of the aortic root was significantly higher on SSFP MRA (P < 0.001) with no significant difference for other aortic segments (P > 0.05). SNR and CNR values were higher for all segments on SSFP MRA (P < 0.01). Our results suggest that free-breathing navigator-gated 3D SSFP MRA with non-selective radiofrequency excitation is a promising technique that provides high image quality and diagnostic accuracy for the assessment of thoracic aortic disease without the need for intravenous contrast material. (orig.)

  8. Image quality and diagnostic accuracy of unenhanced SSFP MR angiography compared with conventional contrast-enhanced MR angiography for the assessment of thoracic aortic diseases

    International Nuclear Information System (INIS)

    Krishnam, Mayil S.; Tomasian, Anderanik; Malik, Sachin; Ruehm, Stefan G.; Desphande, Vibhas; Laub, Gerhard

    2010-01-01

    The purpose of this study was to determine the image quality and diagnostic accuracy of three-dimensional (3D) unenhanced steady state free precession (SSFP) magnetic resonance angiography (MRA) for the evaluation of thoracic aortic diseases. Fifty consecutive patients with known or suspected thoracic aortic disease underwent free-breathing ECG-gated unenhanced SSFP MRA with non-selective radiofrequency excitation and contrast-enhanced (CE) MRA of the thorax at 1.5 T. Two readers independently evaluated the two datasets for image quality in the aortic root, ascending aorta, aortic arch, descending aorta, and origins of supra-aortic arteries, and for abnormal findings. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined for both datasets. Sensitivity, specificity, and diagnostic accuracy of unenhanced SSFP MRA for the diagnosis of aortic abnormalities were determined. Abnormal aortic findings, including aneurysm (n = 47), coarctation (n = 14), dissection (n = 12), aortic graft (n = 6), intramural hematoma (n = 11), mural thrombus in the aortic arch (n = 1), and penetrating aortic ulcer (n = 9), were confidently detected on both datasets. Sensitivity, specificity, and diagnostic accuracy of SSFP MRA for the detection of aortic disease were 100% with CE-MRA serving as a reference standard. Image quality of the aortic root was significantly higher on SSFP MRA (P 0.05). SNR and CNR values were higher for all segments on SSFP MRA (P < 0.01). Our results suggest that free-breathing navigator-gated 3D SSFP MRA with non-selective radiofrequency excitation is a promising technique that provides high image quality and diagnostic accuracy for the assessment of thoracic aortic disease without the need for intravenous contrast material. (orig.)

  9. 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.

  10. 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.

  11. Tin-filter enhanced dual-energy-CT: image quality and accuracy of CT numbers in virtual noncontrast imaging.

    Science.gov (United States)

    Kaufmann, Sascha; Sauter, Alexander; Spira, Daniel; Gatidis, Sergios; Ketelsen, Dominik; Heuschmid, Martin; Claussen, Claus D; Thomas, Christoph

    2013-05-01

    To measure and compare the objective image quality of true noncontrast (TNC) images with virtual noncontrast (VNC) images acquired by tin-filter-enhanced, dual-source, dual-energy computed tomography (DECT) of upper abdomen. Sixty-three patients received unenhanced abdominal CT and enhanced abdominal DECT (100/140 kV with tin filter) in portal-venous phase. VNC images were calculated from the DECT datasets using commercially available software. The mean attenuation of relevant tissues and image quality were compared between the TNC and VNC images. Image quality was rated objectively by measuring image noise and the sharpness of object edges using custom-designed software. Measurements were compared using Student two-tailed t-test. Correlation coefficients for tissue attenuation measurements between TNC and VNC were calculated and the relative deviations were illustrated using Bland-Altman plots. Mean attenuation differences between TNC and VNC (HUTNC - HUVNC) image sets were as follows: right liver lobe -4.94 Hounsfield units (HU), left liver lobe -3.29 HU, vena cava -2.19 HU, spleen -7.46 HU, pancreas 1.29 HU, fat -11.14 HU, aorta 1.29 HU, bone marrow 36.83 HU (all P VNC and TNC series were observed for liver, vena portae, kidneys, pancreas, muscle and bone marrow (Pearson's correlation coefficient ≥0.75). Mean image noise was significantly higher in TNC images (P VNC and TNC images (P = .19). The Hounsfield units in VNC images closely resemble TNC images in the majority of the organs of the upper abdomen (kidneys, liver, pancreas). In spleen and fat, Hounsfield numbers in VNC images are tend to be higher than in TNC images. VNC images show a low image noise and satisfactory edge sharpness. Other criteria of image quality and the depiction of certain lesions need to be evaluated additionally. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

  12. Diagnostic accuracy of contrast-enhanced ultrasound in assessing the therapeutic response to radio frequency ablation for liver tumors: systematic review and meta-analysis.

    Science.gov (United States)

    Xuan, Min; Zhou, Fengsheng; Ding, Yan; Zhu, Qiaoying; Dong, Ji; Zhou, Hao; Cheng, Jun; Jiang, Xiao; Wu, Pengxi

    2018-04-01

    To review the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) used to detect residual or recurrent liver tumors after radiofrequency ablation (RFA). This technique uses contrast-enhanced computer tomography or/and contrast-enhanced magnetic resonance imaging as the gold standard of investigation. MEDLINE, EMBASE, and COCHRANE were systematically searched for all potentially eligible studies comparing CEUS with the reference standard that follows RFA. Risk of bias and applicability concerns were addressed by adopting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled point estimates for sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) with 95% CI were computed before plotting the sROC (summary receiver operating characteristic) curve. Meta-regression and subgroup analysis were used to identify the source of the heterogeneity that was detected. Publication bias was evaluated using Deeks' funnel plot asymmetry test. Ten eligible studies on 1162 lesions that occurred between 2001 and 2016 were included in the final analysis. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable. The pooled sensitivity and specificity of CEUS in detecting residual or recurrent liver tumors had the following values: 0.90 (95% CI 0.85-0.94) and 1.00 (95% CI 0.99-1.00), respectively. Overall DOR was 420.10 (95% CI 142.30-1240.20). The sources of heterogeneity could not be precisely identified by meta-regression or subgroup analysis. No evidence of publication bias was found. This study confirmed that CEUS exhibits high sensitivity and specificity in assessing therapeutic responses to RFA for liver tumors.

  13. Effects of wood preservative leachates from docks

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, P.H.; Van Dolah, R.F.; Bobo, M.Y.; Mathews, T.D. [South Carolina Marine Resources Research Inst., Charleston, SC (United States)

    1994-12-31

    Recent evidence indicates that the wood preservative commonly used in dock pilings (chromated copper arsenate or CCA) is highly toxic to several estuarine organisms in laboratory experiments. Increasing demand for residential docks prompted a field study intended to complement these earlier laboratory investigations. Objectives of the study were to: (1) examine concentrations of Cu, Cr, and As in sediments and oysters from intertidal locations in several creeks with and without high densities of docks; (2) examine the bioaccumulation of wood preservative leachates by laboratory-reared oysters transferred to field sites near and distant from newly constructed docks; and (3) investigate the acute toxicity of wood preservative leachates for several species of estuarine fishes and invertebrates exposed to these compounds in the field. Preliminary results indicate that sediment concentrations of all three metals were well below ER-L levels reported by Long and Morgan at all but one dock site. In an ancillary study, 24h LC{sub 50} bioassays were performed using rotifers (Brachionus plicatilis) which were exposed to pore water from sediments in creeks with and without docks. Toxicities of bulk sediments from the same sites were examined using Microtox which measures decreases in bioluminescence of marine bacteria (Photobacterium phosphoreum) as a function of sediment concentration. Neither the rotifer nor the Microtox bioassays showed any significant differences in toxicity between creeks with and without docks.

  14. Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease

    Energy Technology Data Exchange (ETDEWEB)

    Punwani, Shonit; Taylor, Stuart A.; Halligan, Steve [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospital, Department of Radiology, London (United Kingdom); Cheung, King Kenneth; Skipper, Nicholas [University College London, Centre for Medical Imaging, London (United Kingdom); Bell, Nichola; Humphries, Paul D. [University College London Hospital, Department of Radiology, London (United Kingdom); Bainbridge, Alan [University College London, Department of Medical Physics and Bioengineering, London (United Kingdom); Groves, Ashley M.; Hain, Sharon F.; Ben-Haim, Simona [University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Shankar, Ananth; Daw, Stephen [University College London Hospital, Department of Paediatrics, London (United Kingdom)

    2013-08-15

    Accurate assessment of splenic disease is important for staging Hodgkin lymphoma. The purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease. Thirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error. Seven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI. T2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement. (orig.)

  15. Enhanced accuracy of the microwave field strength measurement in a CW-EPR by pulsed modulation technique

    Science.gov (United States)

    Rakvin, B.; Carić, D.; Kveder, M.

    2018-02-01

    The microwave magnetic field strength, B1, in the cavity of a conventional continuous wave electron paramagnetic resonance, CW-EPR, spectrometer was measured by employing modulation sidebands, MS, in the EPR spectrum. MS spectrum in CW-EPR is produced by applying the modulation frequency, ωrf, which exceeds the linewidth, δB, given in frequency units. An amplitude-modulated CW-EPR, AM-CW-EPR, was selected as detection method. Theoretical description of AM-CW-EPR spectrum was modified by adding Bloch-Siegert-like shift obtained by taking into account the cumulative effect of the non-resonant interactions between the driving fields and the spin system. This approach enables to enhance the precision of B1 measurement. In order to increase the sensitivity of the method when saturation effects, due to higher intensity of B1, decrease the resolution of AM-CW-EPR spectrum, detection at the second harmonic of CW-EPR has been employed.

  16. Enhanced accuracy of the microwave field strength measurement in a CW-EPR by pulsed modulation technique.

    Science.gov (United States)

    Rakvin, B; Carić, D; Kveder, M

    2018-02-01

    The microwave magnetic field strength, B 1 , in the cavity of a conventional continuous wave electron paramagnetic resonance, CW-EPR, spectrometer was measured by employing modulation sidebands, MS, in the EPR spectrum. MS spectrum in CW-EPR is produced by applying the modulation frequency, ω rf , which exceeds the linewidth, δB, given in frequency units. An amplitude-modulated CW-EPR, AM-CW-EPR, was selected as detection method. Theoretical description of AM-CW-EPR spectrum was modified by adding Bloch-Siegert-like shift obtained by taking into account the cumulative effect of the non-resonant interactions between the driving fields and the spin system. This approach enables to enhance the precision of B 1 measurement. In order to increase the sensitivity of the method when saturation effects, due to higher intensity of B 1 , decrease the resolution of AM-CW-EPR spectrum, detection at the second harmonic of CW-EPR has been employed. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Dynamic contrast-enhanced MRI improves accuracy for detecting focal splenic involvement in children and adolescents with Hodgkin disease

    International Nuclear Information System (INIS)

    Punwani, Shonit; Taylor, Stuart A.; Halligan, Steve; Cheung, King Kenneth; Skipper, Nicholas; Bell, Nichola; Humphries, Paul D.; Bainbridge, Alan; Groves, Ashley M.; Hain, Sharon F.; Ben-Haim, Simona; Shankar, Ananth; Daw, Stephen

    2013-01-01

    Accurate assessment of splenic disease is important for staging Hodgkin lymphoma. The purpose of this study was to assess T2-weighted imaging with and without dynamic contrast-enhanced (DCE) MRI for evaluation of splenic Hodgkin disease. Thirty-one children with Hodgkin lymphoma underwent whole-body T2-weighted MRI with supplementary DCE splenic imaging, and whole-body PET-CT before and following chemotherapy. Two experienced nuclear medicine physicians derived a PET-CT reference standard for splenic disease, augmented by follow-up imaging. Unaware of the PET-CT, two experienced radiologists independently evaluated MRI exercising a locked sequential read paradigm (T2-weighted then DCE review) and recorded the presence/absence of splenic disease at each stage. Performance of each radiologist was determined prior to and following review of DCE-MRI. Incorrect MRI findings were ascribed to reader (lesion present on MRI but missed by reader) or technical (lesion not present on MRI) error. Seven children had splenic disease. Sensitivity/specificity of both radiologists for the detection of splenic involvement using T2-weighted images alone was 57%/100% and increased to 100%/100% with DCE-MRI. There were three instances of technical error on T2-weighted imaging; all lesions were visible on DCE-MRI. T2-weighted imaging when complemented by DCE-MRI imaging may improve evaluation of Hodgkin disease splenic involvement. (orig.)

  18. Detection of PCT and urinary β2 -MG enhances the accuracy for localization diagnosing pediatric urinary tract infection.

    Science.gov (United States)

    Fang, Jian; Luan, Jiangwei; Zhu, Gaohong; Qi, Chang; Wang, Dandan

    2017-09-01

    The purpose of this article was to investigate whether the combination of urinary beta 2 microglobulin (urinary β 2 -MG) and procalcitonin (PCT) diagnosis could enhance the localization diagnostic precision of pediatric urinary tract infection comparing with single diagnosis. A study was conducted in the Nephrology Department of Wuhan women and children's health care centre. This study incorporated 85 participants, including 35 children who were diagnosed as upper urinary tract infection (UUTI) with the symptom of fever and 50 children who conducted lower urinary tract infection (LUTI). Levels of PCT and urinary β 2 -MG in both UUTI and LUTI patients were measured and compared. The level of PCT and β 2 -MG were both significantly higher in UUTI group compared with in LUTI group. AUC of urinary β 2 -MG ROC (sensitivity of 71.4%, specificity of 90.0%) was significantly smaller than that of PCT ROC (sensitivity of 77.1%, specificity of 96.0%) in the single diagnosis. Although in the combined diagnosis, the sensitivity and specificity increased to 88.6% and 98%, respectively. Both PCT and β 2 -MG could be used to localize the UTI. Introducing urinary β 2 -MG into PCT diagnosis could increase the sensitivity and specificity of UTI lesion diagnosis in clinical practice. © 2016 The Authors Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

  19. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  20. Vehicle routing with cross-docking

    DEFF Research Database (Denmark)

    Wen, Min; Larsen, Jesper; Clausen, Jens

    2009-01-01

    a set of homogeneous vehicles are used to transport orders from the suppliers to the corresponding customers via a cross-dock. The orders can be consolidated at the cross-dock but cannot be stored for very long because the cross-dock does not have long-term inventory-holding capabilities. The objective...... of the VRPCD is to minimize the total travel time while respecting time window constraints at the nodes and a time horizon for the whole transportation operation. In this paper, a mixed integer programming formulation for the VRPCD is proposed. A tabu search heuristic is embedded within an adaptive memory...... values) within very short computational time....

  1. 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.

  2. Enhancing the calculation accuracy of performance characteristics of power-generating units by correcting general measurands based on matching energy balances

    Science.gov (United States)

    Shchinnikov, P. A.; Safronov, A. V.

    2014-12-01

    General principles of a procedure for matching energy balances of thermal power plants (TPPs), whose use enhances the accuracy of information-measuring systems (IMSs) during calculations of performance characteristics (PCs), are stated. To do this, there is the possibility for changing values of measured and calculated variables within intervals determined by measurement errors and regulations. An example of matching energy balances of the thermal power plants with a T-180 turbine is made. The proposed procedure allows one to reduce the divergence of balance equations by 3-4 times. It is shown also that the equipment operation mode affects the profit deficiency. Dependences for the divergence of energy balances on the deviation of input parameters and calculated data for the fuel economy before and after matching energy balances are represented.

  3. Enhancing predictive accuracy and reproducibility in clinical evaluation research: Commentary on the special section of the Journal of Evaluation in Clinical Practice.

    Science.gov (United States)

    Bryant, Fred B

    2016-12-01

    This paper introduces a special section of the current issue of the Journal of Evaluation in Clinical Practice that includes a set of 6 empirical articles showcasing a versatile, new machine-learning statistical method, known as optimal data (or discriminant) analysis (ODA), specifically designed to produce statistical models that maximize predictive accuracy. As this set of papers clearly illustrates, ODA offers numerous important advantages over traditional statistical methods-advantages that enhance the validity and reproducibility of statistical conclusions in empirical research. This issue of the journal also includes a review of a recently published book that provides a comprehensive introduction to the logic, theory, and application of ODA in empirical research. It is argued that researchers have much to gain by using ODA to analyze their data. © 2016 John Wiley & Sons, Ltd.

  4. Accuracy of the Enhanced Liver Fibrosis Test vs Fibrotest, Elastography and Indirect Markers in Detection of Advanced Fibrosis in Patients with Alcoholic Liver Disease

    DEFF Research Database (Denmark)

    Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang

    2018-01-01

    BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2......-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal...... significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P=.521 and .004 for comparison with ELF). Adding a serum marker to transient elastography...

  5. Endometrial cancer with cervical stromal invasion: diagnostic accuracy of diffusion-weighted and dynamic contrast enhanced MR imaging at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gigin; Lu, Hsin-Ying [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Medical Imaging and Intervention, Institute for Radiological Research, Guishan, Taoyuan (China); Chang Gung Memorial Hospital at Linkou, Clinical Phenome Center, Guishan, Taoyuan (China); Huang, Yu-Ting; Lin, Yu-Chun; Ng, Shu-Hang; Ng, Koon-Kwan [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Medical Imaging and Intervention, Institute for Radiological Research, Guishan, Taoyuan (China); Chao, Angel; Lai, Chyong-Huey [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Obstetrics and Gynecology and Gynecologic Cancer Research Center, Guishan, Taoyuan (China); Yang, Lan-Yan [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Clinical Trial Center, Guishan, Taoyuan (China); Wu, Ren-Chin [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Pathology, Guishan, Taoyuan (China)

    2017-05-15

    To compare the diagnostic accuracy of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for detecting cervical stromal invasion in endometrial cancer. Eighty-three consecutive women with endometrial cancer underwent preoperative evaluation in a 3-T unit, including T2-weighted, DW (b = 0 and 1000 s/mm{sup 2}), and DCE MR imaging. Two radiologists independently assessed presence of cervical stromal invasion, with histopathological reference as gold standard. For assessing cervical stromal invasion, the diagnostic accuracy, sensitivity, and specificity, respectively for Reader 1/Reader 2, were as follows: DW MR imaging - 95.2 %/91.6 %, 91.7 %/100 %, and 95.8 %/90.1 %; DCE MR imaging - 91.6 %/88 %, 58.3 %/50 %, and 97.2 %/94.4 %. The diagnostic performance of DW MR imaging (Reader 1: areas under the receiver operating characteristic curve (AUC) = 0.98; Reader 2: AUC = 0.97) was significantly higher than that of DCE MR imaging (p = 0.009 for Reader 2) or T2-weighted MR imaging (Reader 1: p = 0.006; Reader 2: p = 0.013). Patients with cervical stromal invasion showed a significantly greater canal width (p < 0.0001) and myometrial invasion extent (p = 0.006). DW MR imaging has superior diagnostic performance compared with DCE MR imaging in the detection of cervical stromal invasion. (orig.)

  6. Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Rajaram, Smitha [Unit of Academic Radiology, University of Sheffield, Sheffield (United Kingdom); Academic Unit of Radiology, C Floor, Royal Hallamshire Hospital, Sheffield (United Kingdom); Swift, Andrew J.; Wild, Jim M. [Unit of Academic Radiology, University of Sheffield, Sheffield (United Kingdom); Sheffield Cardiovascular Biomedical Research Unit, Sheffield (United Kingdom); Capener, David; Telfer, Adam [Unit of Academic Radiology, University of Sheffield, Sheffield (United Kingdom); Davies, Christine; Hill, Catherine [Sheffield Teaching Hospitals Trust, Department of Radiology, Sheffield (United Kingdom); Condliffe, Robin; Elliot, Charles; Kiely, David G. [Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (United Kingdom); Sheffield Cardiovascular Biomedical Research Unit, Sheffield (United Kingdom); Hurdman, Judith [Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (United Kingdom)

    2012-02-15

    To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) and the added benefit of unenhanced proton MR angiography compared with CT pulmonary angiography (CTPA) in patients with chronic thromboembolic disease (CTE). A 2 year retrospective study of 53 patients with chronic thromboembolic pulmonary hypertension who underwent CTPA and MRI for suspected pulmonary hypertension and a control group of 36 patients with no CT evidence of pulmonary embolism. The MRI was evaluated for CTE and the combined diagnostic accuracy of ce-MRA and unenhanced proton MRA was determined. CE-MRA generated lung perfusion maps were also assessed. The overall sensitivity and specificity of CE-MRA in diagnosing proximal and distal CTE were 98% and 94%, respectively. The sensitivity improved from 50% to 88% for central vessel disease when CE-MRA images were analysed with unenhanced proton MRA. The CE-MRA identified more stenoses (29/18), post-stenosis dilatation (23/7) and occlusions (37/29) compared with CTPA. The CE-MRA perfusion images showed a sensitivity of 92% for diagnosing CTE. CE-MRA has high sensitivity and specificity for diagnosing CTE. The sensitivity of CE-MRA for visualisation of adherent central and lobar thrombus significantly improves with the addition of unenhanced proton MRA which delineates the vessel wall. (orig.)

  7. Effects of x-ray and CT image enhancements on the robustness and accuracy of a rigid 3D/2D image registration

    International Nuclear Information System (INIS)

    Kim, Jinkoo; Yin Fangfang; Zhao Yang; Kim, Jae Ho

    2005-01-01

    A rigid body three-dimensional/two-dimensional (3D/2D) registration method has been implemented using mutual information, gradient ascent, and 3D texturemap-based digitally reconstructed radiographs. Nine combinations of commonly used x-ray and computed tomography (CT) image enhancement methods, including window leveling, histogram equalization, and adaptive histogram equalization, were examined to assess their effects on accuracy and robustness of the registration method. From a set of experiments using an anthropomorphic chest phantom, we were able to draw several conclusions. First, the CT and x-ray preprocessing combination with the widest attraction range was the one that linearly stretched the histograms onto the entire display range on both CT and x-ray images. The average attraction ranges of this combination were 71.3 mm and 61.3 deg in the translation and rotation dimensions, respectively, and the average errors were 0.12 deg and 0.47 mm. Second, the combination of the CT image with tissue and bone information and the x-ray images with adaptive histogram equalization also showed subvoxel accuracy, especially the best in the translation dimensions. However, its attraction ranges were the smallest among the examined combinations (on average 36 mm and 19 deg). Last the bone-only information on the CT image did not show convergency property to the correct registration

  8. Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension

    International Nuclear Information System (INIS)

    Rajaram, Smitha; Swift, Andrew J.; Wild, Jim M.; Capener, David; Telfer, Adam; Davies, Christine; Hill, Catherine; Condliffe, Robin; Elliot, Charles; Kiely, David G.; Hurdman, Judith

    2012-01-01

    To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) and the added benefit of unenhanced proton MR angiography compared with CT pulmonary angiography (CTPA) in patients with chronic thromboembolic disease (CTE). A 2 year retrospective study of 53 patients with chronic thromboembolic pulmonary hypertension who underwent CTPA and MRI for suspected pulmonary hypertension and a control group of 36 patients with no CT evidence of pulmonary embolism. The MRI was evaluated for CTE and the combined diagnostic accuracy of ce-MRA and unenhanced proton MRA was determined. CE-MRA generated lung perfusion maps were also assessed. The overall sensitivity and specificity of CE-MRA in diagnosing proximal and distal CTE were 98% and 94%, respectively. The sensitivity improved from 50% to 88% for central vessel disease when CE-MRA images were analysed with unenhanced proton MRA. The CE-MRA identified more stenoses (29/18), post-stenosis dilatation (23/7) and occlusions (37/29) compared with CTPA. The CE-MRA perfusion images showed a sensitivity of 92% for diagnosing CTE. CE-MRA has high sensitivity and specificity for diagnosing CTE. The sensitivity of CE-MRA for visualisation of adherent central and lobar thrombus significantly improves with the addition of unenhanced proton MRA which delineates the vessel wall. (orig.)

  9. Design and Preliminary Testing of the International Docking Adapter's Peripheral Docking Target

    Science.gov (United States)

    Foster, Christopher W.; Blaschak, Johnathan; Eldridge, Erin A.; Brazzel, Jack P.; Spehar, Peter T.

    2015-01-01

    The International Docking Adapter's Peripheral Docking Target (PDT) was designed to allow a docking spacecraft to judge its alignment relative to the docking system. The PDT was designed to be compatible with relative sensors using visible cameras, thermal imagers, or Light Detection and Ranging (LIDAR) technologies. The conceptual design team tested prototype designs and materials to determine the contrast requirements for the features. This paper will discuss the design of the PDT, the methodology and results of the tests, and the conclusions pertaining to PDT design that were drawn from testing.

  10. Combined Docking with Classical Force Field and Quantum Chemical Semiempirical Method PM7

    Directory of Open Access Journals (Sweden)

    A. V. Sulimov

    2017-01-01

    Full Text Available Results of the combined use of the classical force field and the recent quantum chemical PM7 method for docking are presented. Initially the gridless docking of a flexible low molecular weight ligand into the rigid target protein is performed with the energy function calculated in the MMFF94 force field with implicit water solvent in the PCM model. Among several hundred thousand local minima, which are found in the docking procedure, about eight thousand lowest energy minima are chosen and then energies of these minima are recalculated with the recent quantum chemical semiempirical PM7 method. This procedure is applied to 16 test complexes with different proteins and ligands. For almost all test complexes such energy recalculation results in the global energy minimum configuration corresponding to the ligand pose near the native ligand position in the crystalized protein-ligand complex. A significant improvement of the ligand positioning accuracy comparing with MMFF94 energy calculations is demonstrated.

  11. Combined Docking with Classical Force Field and Quantum Chemical Semiempirical Method PM7.

    Science.gov (United States)

    Sulimov, A V; Kutov, D C; Katkova, E V; Sulimov, V B

    2017-01-01

    Results of the combined use of the classical force field and the recent quantum chemical PM7 method for docking are presented. Initially the gridless docking of a flexible low molecular weight ligand into the rigid target protein is performed with the energy function calculated in the MMFF94 force field with implicit water solvent in the PCM model. Among several hundred thousand local minima, which are found in the docking procedure, about eight thousand lowest energy minima are chosen and then energies of these minima are recalculated with the recent quantum chemical semiempirical PM7 method. This procedure is applied to 16 test complexes with different proteins and ligands. For almost all test complexes such energy recalculation results in the global energy minimum configuration corresponding to the ligand pose near the native ligand position in the crystalized protein-ligand complex. A significant improvement of the ligand positioning accuracy comparing with MMFF94 energy calculations is demonstrated.

  12. α-Synuclein may cross-bridge v-SNARE and acidic phospholipids to facilitate SNARE-dependent vesicle docking.

    Science.gov (United States)

    Lou, Xiaochu; Kim, Jaewook; Hawk, Brenden J; Shin, Yeon-Kyun

    2017-06-06

    Misfolded α-synuclein (A-syn) is widely recognized as the primal cause of neurodegenerative diseases including Parkinson's disease and dementia with Lewy bodies. The normal cellular function of A-syn has, however, been elusive. There is evidence that A-syn plays multiple roles in the exocytotic pathway in the neuron, but the underlying molecular mechanisms are unclear. A-syn has been known to interact with negatively charged phospholipids and with vesicle SNARE protein VAMP2. Using single-vesicle docking/fusion assays, we find that A-syn promotes SNARE-dependent vesicles docking significantly at 2.5 µM. When phosphatidylserine (PS) is removed from t-SNARE-bearing vesicles, the docking enhancement by A-syn disappears and A-syn instead acts as an inhibitor for docking. In contrast, subtraction of PS from the v-SNARE-carrying vesicles enhances vesicle docking even further. Moreover, when we truncate the C-terminal 45 residues of A-syn that participates in interacting with VAMP2, the promotion of vesicle docking is abrogated. Thus, the results suggest that the A-syn's interaction with v-SNARE through its C-terminal tail and its concurrent interaction with PS in trans through its amphipathic N-terminal domain facilitate SNARE complex formation, whereby A-syn aids SNARE-dependent vesicle docking. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  13. Dockomatic - automated ligand creation and docking.

    Science.gov (United States)

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

    2010-11-08

    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. 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. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  14. 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.

  15. Automated docking screens: a feasibility study.

    Science.gov (United States)

    Irwin, John J; Shoichet, Brian K; Mysinger, Michael M; Huang, Niu; Colizzi, Francesco; Wassam, Pascal; Cao, Yiqun

    2009-09-24

    Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 A rmsd 50-60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 A rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org .

  16. Enhancement of diffusers BRDF accuracy

    Science.gov (United States)

    Otter, Gerard; Bazalgette Courrèges-Lacoste, Gregory; van Brug, Hedser; Schaarsberg, Jos Groote; Delwart, Steven; del Bello, Umberto

    2017-11-01

    This paper reports the result of an ESA study conducted at TNO to investigate properties of various diffusers. Diffusers are widely used in space instruments as part of the on-board absolute calibration. Knowledge of the behaviour of the diffuser is therefore most important. From measurements of launched instruments in-orbit it has been discovered that when a diffuser is used in the vacuum of space the BRDF can change with respect to the one in ambient conditions. This is called the air/vacuum effect and has been simulated in this study by measuring the BRDF in a laboratory in ambient as well as vacuum conditions. Another studied effect is related to the design parameters of the optical system and the scattering properties of the diffuser. The effect is called Spectral Features and is a noise like structure superimposed on the diffuser BRDF. Modern space spectrometers, which have high spectral resolution and/or a small field of view (high spatial resolution) are suffering from this effect. The choice of diffuser can be very critical with respect to the required absolute radiometric calibration of an instrument. Even if the Spectral Features are small it can influence the error budget of the retrieval algorithms for the level 2 products. in this presentation diffuser trade-off results are presented and the Spectral Features model applied to the optical configuration of the MERIS instrument is compared to in-flight measurements of MERIS.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...

  18. Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking

    Directory of Open Access Journals (Sweden)

    Qian Yang

    2017-10-01

    Full Text Available Background: Low-intensity ultrasound (LIUS was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders.Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS.Results: Our data revealed following interesting findings: (1 LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2 LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells, MSCs (mesenchymal stem cells, B1-B cells and Treg (regulatory T cells; (3 LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4 LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5 Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6 LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways.Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair.

  19. Docking screens: right for the right reasons?

    Science.gov (United States)

    Kolb, Peter; Irwin, John J

    2009-01-01

    Whereas docking screens have emerged as the most practical way to use protein structure for ligand discovery, an inconsistent track record raises questions about how well docking actually works. In its favor, a growing number of publications report the successful discovery of new ligands, often supported by experimental affinity data and controls for artifacts. Few reports, however, actually test the underlying structural hypotheses that docking makes. To be successful and not just lucky, prospective docking must not only rank a true ligand among the top scoring compounds, it must also correctly orient the ligand so the score it receives is biophysically sound. If the correct binding pose is not predicted, a skeptic might well infer that the discovery was serendipitous. Surveying over 15 years of the docking literature, we were surprised to discover how rarely sufficient evidence is presented to establish whether docking actually worked for the right reasons. The paucity of experimental tests of theoretically predicted poses undermines confidence in a technique that has otherwise become widely accepted. Of course, solving a crystal structure is not always possible, and even when it is, it can be a lot of work, and is not readily accessible to all groups. Even when a structure can be determined, investigators may prefer to gloss over an erroneous structural prediction to better focus on their discovery. Still, the absence of a direct test of theory by experiment is a loss for method developers seeking to understand and improve docking methods. We hope this review will motivate investigators to solve structures and compare them with their predictions whenever possible, to advance the field.

  20. DockQ: A Quality Measure for Protein-Protein Docking Models.

    Directory of Open Access Journals (Sweden)

    Sankar Basu

    Full Text Available The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10Å might still qualify as 'acceptable' with a descent Fnat (>0.50 and iRMS (<3.0Å. This is also the reason why the so called CAPRI criteria for assessing the quality of docking models is defined by applying various ad-hoc cutoffs on these measures to classify a docking model into the four classes: Incorrect, Acceptable, Medium, or High quality. This classification has been useful in CAPRI, but since models are grouped in only four bins it is also rather limiting, making it difficult to rank models, correlate with scoring functions or use it as target function in machine learning algorithms. Here, we present DockQ, a continuous protein-protein docking model quality measure derived by combining Fnat, LRMS, and iRMS to a single score in the range [0, 1] that can be used to assess the quality of protein docking models. By using DockQ on CAPRI models it is possible to almost completely reproduce the original CAPRI classification into Incorrect, Acceptable, Medium and High quality. An average PPV of 94% at 90% Recall demonstrating that there is no need to apply predefined ad-hoc cutoffs to classify docking models. Since DockQ recapitulates the CAPRI classification almost perfectly, it can be viewed as a higher resolution version of the CAPRI classification, making it possible to estimate model quality in a more quantitative way using Z-scores or sum of top ranked models, which has been so valuable for the CASP community. The possibility to directly correlate a quality measure to a scoring function has been crucial for the development of scoring functions for

  1. Accuracy in the quantification of chemical exchange saturation transfer (CEST) and relayed nuclear Overhauser enhancement (rNOE) saturation transfer effects.

    Science.gov (United States)

    Zhang, Xiao-Yong; Wang, Feng; Li, Hua; Xu, Junzhong; Gochberg, Daniel F; Gore, John C; Zu, Zhongliang

    2017-07-01

    Accurate quantification of chemical exchange saturation transfer (CEST) effects, including dipole-dipole mediated relayed nuclear Overhauser enhancement (rNOE) saturation transfer, is important for applications and studies of molecular concentration and transfer rate (and thereby pH or temperature). Although several quantification methods, such as Lorentzian difference (LD) analysis, multiple-pool Lorentzian fits, and the three-point method, have been extensively used in several preclinical and clinical applications, the accuracy of these methods has not been evaluated. Here we simulated multiple-pool Z spectra containing the pools that contribute to the main CEST and rNOE saturation transfer signals in the brain, numerically fit them using the different methods, and then compared their derived CEST metrics with the known solute concentrations and exchange rates. Our results show that the LD analysis overestimates contributions from amide proton transfer (APT) and intermediate exchanging amine protons; the three-point method significantly underestimates both APT and rNOE saturation transfer at -3.5 ppm (NOE(-3.5)). The multiple-pool Lorentzian fit is more accurate than the other two methods, but only at lower irradiation powers (≤1 μT at 9.4 T) within the range of our simulations. At higher irradiation powers, this method is also inaccurate because of the presence of a fast exchanging CEST signal that has a non-Lorentzian lineshape. Quantitative parameters derived from in vivo images of rodent brain tumor obtained using an irradiation power of 1 μT were also compared. Our results demonstrate that all three quantification methods show similar contrasts between tumor and contralateral normal tissue for both APT and the NOE(-3.5). However, the quantified values of the three methods are significantly different. Our work provides insight into the fitting accuracy obtainable in a complex tissue model and provides guidelines for evaluating other newly developed

  2. goGPS: open source software for enhancing the accuracy of low-cost receivers by single-frequency relative kinematic positioning

    International Nuclear Information System (INIS)

    Realini, Eugenio; Reguzzoni, Mirko

    2013-01-01

    goGPS is a free and open source satellite positioning software package aiming to provide a collaborative platform for research and teaching purposes. It was first published in 2009 and since then several related projects are on-going. Its objective is the investigation of strategies for enhancing the accuracy of low-cost single-frequency GPS receivers, mainly by relative positioning with respect to a base station and by a tailored extended Kalman filter working directly on code and phase observations. In this paper, the positioning algorithms implemented in goGPS are presented, emphasizing the modularity of the software design; two specific strategies to support the navigation with low-cost receivers are also proposed and discussed, namely an empirical observation weighting function calibrated on the receiver signal-to-noise ratio and the inclusion of height information from a digital terrain model as an additional observation in the Kalman filter. The former is crucial when working with high-sensitivity receivers, while the latter can significantly improve the positioning in the vertical direction. The overall goGPS positioning accuracy is assessed by comparison with a dual-frequency receiver and with the positioning computed by a standard low-cost receiver. The benefits of the calibrated weighting function and the digital terrain model are investigated by an experiment in a dense urban environment. It comes out that the use of goGPS and low-cost receivers leads to results comparable with those obtained by higher level receivers; goGPS has good performances also in a dense urban environment, where its additional features play an important role. (paper)

  3. 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.

  4. Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

    Science.gov (United States)

    Thiele, Maja; Madsen, Bjørn Stæhr; Hansen, Janne Fuglsang; Detlefsen, Sönke; Antonsen, Steen; Krag, Aleksander

    2018-04-01

    Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for

  5. DockQ: A Quality Measure for Protein-Protein Docking Models

    Science.gov (United States)

    Basu, Sankar

    2016-01-01

    The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10Å) might still qualify as 'acceptable' with a descent Fnat (>0.50) and iRMS (iRMS to a single score in the range [0, 1] that can be used to assess the quality of protein docking models. By using DockQ on CAPRI models it is possible to almost completely reproduce the original CAPRI classification into Incorrect, Acceptable, Medium and High quality. An average PPV of 94% at 90% Recall demonstrating that there is no need to apply predefined ad-hoc cutoffs to classify docking models. Since DockQ recapitulates the CAPRI classification almost perfectly, it can be viewed as a higher resolution version of the CAPRI classification, making it possible to estimate model quality in a more quantitative way using Z-scores or sum of top ranked models, which has been so valuable for the CASP community. The possibility to directly correlate a quality measure to a scoring function has been crucial for the development of scoring functions for protein structure prediction, and DockQ should be useful in a similar development in the protein docking field. DockQ is available at http://github.com/bjornwallner/DockQ/ PMID:27560519

  6. Solvated protein-DNA docking using HADDOCK

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marc van; Visscher, Koen M.; Kastritis, Panagiotis L.; Bonvin, Alexandre M. J. J., E-mail: a.m.j.j.bonvin@uu.nl [Utrecht University, Bijvoet Center for Biomolecular Research, Faculty of Science-Chemistry (Netherlands)

    2013-05-15

    Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein-DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein-DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein-DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein-DNA complexes.

  7. Solvated protein–DNA docking using HADDOCK

    International Nuclear Information System (INIS)

    Dijk, Marc van; Visscher, Koen M.; Kastritis, Panagiotis L.; Bonvin, Alexandre M. J. J.

    2013-01-01

    Interfacial water molecules play an important role in many aspects of protein–DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the docking of protein–DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein–DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein–DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein–DNA complexes.

  8. Rendezvous and Docking for Space Exploration

    Science.gov (United States)

    Machula, M. F.; Crain, T.; Sandhoo, G. S.

    2005-01-01

    To achieve the exploration goals, new approaches to exploration are being envisioned that include robotic networks, modular systems, pre-positioned propellants and in-space assembly in Earth orbit, Lunar orbit and other locations around the cosmos. A fundamental requirement for rendezvous and docking to accomplish in-space assembly exists in each of these locations. While existing systems and technologies can accomplish rendezvous and docking in low earth orbit, and rendezvous and docking with crewed systems has been successfully accomplished in low lunar orbit, our capability must extend toward autonomous rendezvous and docking. To meet the needs of the exploration vision in-space assembly requiring both crewed and uncrewed vehicles will be an integral part of the exploration architecture. This paper focuses on the intelligent application of autonomous rendezvous and docking technologies to meet the needs of that architecture. It also describes key technology investments that will increase the exploration program's ability to ensure mission success, regardless of whether the rendezvous are fully automated or have humans in the loop.

  9. Electro-optical rendezvous and docking sensors

    Science.gov (United States)

    Tubbs, David J.; Kesler, Lynn O.; Sirko, Robert J.

    1991-01-01

    Electro-optical sensors provide unique and critical functionality for space missions requiring rendezvous, docking, and berthing. McDonnell Douglas is developing a complete rendezvous and docking system for both manned and unmanned missions. This paper examines our sensor development and the systems and missions which benefit from rendezvous and docking sensors. Simulation results quantifying system performance improvements in key areas are given, with associated sensor performance requirements. A brief review of NASA-funded development activities and the current performance of electro-optical sensors for space applications is given. We will also describe current activities at McDonnell Douglas for a fully functional demonstration to address specific NASA mission needs.

  10. AnchorDock: Blind and Flexible Anchor-Driven Peptide Docking.

    Science.gov (United States)

    Ben-Shimon, Avraham; Niv, Masha Y

    2015-05-05

    The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. SAMPL4 & DOCK3.7: lessons for automated docking procedures

    Science.gov (United States)

    Coleman, Ryan G.; Sterling, Teague; Weiss, Dahlia R.

    2014-03-01

    The SAMPL4 challenges were used to test current automated methods for solvation energy, virtual screening, pose and affinity prediction of the molecular docking pipeline DOCK 3.7. Additionally, first-order models of binding affinity were proposed as milestones for any method predicting binding affinity. Several important discoveries about the molecular docking software were made during the challenge: (1) Solvation energies of ligands were five-fold worse than any other method used in SAMPL4, including methods that were similarly fast, (2) HIV Integrase is a challenging target, but automated docking on the correct allosteric site performed well in terms of virtual screening and pose prediction (compared to other methods) but affinity prediction, as expected, was very poor, (3) Molecular docking grid sizes can be very important, serious errors were discovered with default settings that have been adjusted for all future work. Overall, lessons from SAMPL4 suggest many changes to molecular docking tools, not just DOCK 3.7, that could improve the state of the art. Future difficulties and projects will be discussed.

  12. Post processing of protein-compound docking for fragment-based drug discovery (FBDD): in-silico structure-based drug screening and ligand-binding pose prediction.

    Science.gov (United States)

    Fukunishi, Yoshifumi

    2010-01-01

    For fragment-based drug development, both hit (active) compound prediction and docking-pose (protein-ligand complex structure) prediction of the hit compound are important, since chemical modification (fragment linking, fragment evolution) subsequent to the hit discovery must be performed based on the protein-ligand complex structure. However, the naïve protein-compound docking calculation shows poor accuracy in terms of docking-pose prediction. Thus, post-processing of the protein-compound docking is necessary. Recently, several methods for the post-processing of protein-compound docking have been proposed. In FBDD, the compounds are smaller than those for conventional drug screening. This makes it difficult to perform the protein-compound docking calculation. A method to avoid this problem has been reported. Protein-ligand binding free energy estimation is useful to reduce the procedures involved in the chemical modification of the hit fragment. Several prediction methods have been proposed for high-accuracy estimation of protein-ligand binding free energy. This paper summarizes the various computational methods proposed for docking-pose prediction and their usefulness in FBDD.

  13. Proximity Operations and Docking Sensor Development

    Science.gov (United States)

    Howard, Richard T.; Bryan, Thomas C.; Brewster, Linda L.; Lee, James E.

    2009-01-01

    The Next Generation Advanced Video Guidance Sensor (NGAVGS) has been under development for the last three years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in spot mode out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. 12 Parts obsolescence issues prevent the construction of more AVGS units, and the next generation sensor was updated to allow it to support the CEV and COTS programs. The flight proven AR&D sensor has been redesigned to update parts and add additional capabilities for CEV and COTS with the development of the Next Generation AVGS at the Marshall Space Flight Center. The obsolete imager and processor are being replaced with new radiation tolerant parts. In addition, new capabilities include greater sensor range, auto ranging capability, and real-time video output. This paper presents some sensor hardware trades, use of highly integrated laser components, and addresses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It also discusses approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements

  14. 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.

  15. Differential Regulation of Synaptic Vesicle Tethering and Docking by UNC-18 and TOM-1.

    Science.gov (United States)

    Gracheva, Elena O; Maryon, Ed B; Berthelot-Grosjean, Martine; Richmond, Janet E

    2010-01-01

    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 25 nm 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.

  16. 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

  17. A Novel Docking System for Modular Self-Reconfigurable Robots

    Directory of Open Access Journals (Sweden)

    Tan Zhang

    2017-10-01

    Full Text Available Existing self-reconfigurable robots achieve connections and disconnections by a separate drive of the docking system. In this paper, we present a new docking system with which the connections and disconnections are driven by locomotion actuators, without the need for a separate drive, which reduces the weight and the complexity of the modules. This self-reconfigurable robot consists of two types of fundamental modules, i.e., active and passive modules. By the docking system, two types of connections are formed with the fundamental modules, and the docking and undocking actions are achieved through simple control with less sensory feedback. This paper describes the design of the robotic modules, the docking system, the docking process, and the docking force analysis. An experiment is performed to demonstrate the self-reconfigurable robot with the docking system.

  18. 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.

  19. Multibody dynamical modeling for spacecraft docking process with spring-damper buffering device: A new validation approach

    Science.gov (United States)

    Daneshjou, Kamran; Alibakhshi, Reza

    2018-01-01

    In the current manuscript, the process of spacecraft docking, as one of the main risky operations in an on-orbit servicing mission, is modeled based on unconstrained multibody dynamics. The spring-damper buffering device is utilized here in the docking probe-cone system for micro-satellites. Owing to the impact occurs inevitably during docking process and the motion characteristics of multibody systems are remarkably affected by this phenomenon, a continuous contact force model needs to be considered. Spring-damper buffering device, keeping the spacecraft stable in an orbit when impact occurs, connects a base (cylinder) inserted in the chaser satellite and the end of docking probe. Furthermore, by considering a revolute joint equipped with torsional shock absorber, between base and chaser satellite, the docking probe can experience both translational and rotational motions simultaneously. Although spacecraft docking process accompanied by the buffering mechanisms may be modeled by constrained multibody dynamics, this paper deals with a simple and efficient formulation to eliminate the surplus generalized coordinates and solve the impact docking problem based on unconstrained Lagrangian mechanics. By an example problem, first, model verification is accomplished by comparing the computed results with those recently reported in the literature. Second, according to a new alternative validation approach, which is based on constrained multibody problem, the accuracy of presented model can be also evaluated. This proposed verification approach can be applied to indirectly solve the constrained multibody problems by minimum required effort. The time history of impact force, the influence of system flexibility and physical interaction between shock absorber and penetration depth caused by impact are the issues followed in this paper. Third, the MATLAB/SIMULINK multibody dynamic analysis software will be applied to build impact docking model to validate computed results and

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

    NARCIS (Netherlands)

    de Vries, S.J.|info:eu-repo/dai/nl/304837717; van Dijk, M.|info:eu-repo/dai/nl/325811113; Bonvin, A.M.J.J.|info:eu-repo/dai/nl/113691238

    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

  1. CovalentDock Cloud: a web server for automated covalent docking.

    Science.gov (United States)

    Ouyang, Xuchang; Zhou, Shuo; Ge, Zemei; Li, Runtao; Kwoh, Chee Keong

    2013-07-01

    Covalent binding is an important mechanism for many drugs to gain its function. We developed a computational algorithm to model this chemical event and extended it to a web server, the CovalentDock Cloud, to make it accessible directly online without any local installation and configuration. It provides a simple yet user-friendly web interface to perform covalent docking experiments and analysis online. The web server accepts the structures of both the ligand and the receptor uploaded by the user or retrieved from online databases with valid access id. It identifies the potential covalent binding patterns, carries out the covalent docking experiments and provides visualization of the result for user analysis. This web server is free and open to all users at http://docking.sce.ntu.edu.sg/.

  2. 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...

  3. Compodock, a new device for sterile docking

    NARCIS (Netherlands)

    van der Meer, P. F.; Biekart, F. T.; Pietersz, R. N.; Rebers, S. P.; Reesink, H. W.

    2000-01-01

    BACKGROUND: A new device for sterile docking, the Compodock (Fresenius NPBI Transfusion Technology), was developed for connecting PVC tubing for medical use while maintaining sterility. STUDY DESIGN AND METHODS: Sterility of the connections was assessed by welding tubing with a heavy exterior

  4. Solvated protein-DNA docking using HADDOCK

    NARCIS (Netherlands)

    van Dijk, Marc; Visscher, Koen M; Bonvin, Alexandre M.J.J; Kastritis, Panagiotis L.

    2013-01-01

    Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that allows explicit inclusion of water molecules in the

  5. Operator learning effects in teleoperated rendezvous & docking

    Science.gov (United States)

    Wilde, M.; Harder, J.; Purschke, R.

    Teleoperation of spacecraft proximity operations and docking requires delicate timing and coordination of spacecraft maneuvers. Experience has shown that human operators show large performance fluctuations in these areas, which are a major factor to be addressed in operator training. In order to allow the quantification of the impact of these human fluctuations on control system performance and the human perception of this performance, a learning curve study was conducted with teleoperated final approach and docking scenarios. Over a period of ten experiment days, three test participants were tasked with repeatedly completing a set of three training scenarios. The scenarios were designed to contain different combinations of the major elements of any final approach and docking situation, and to feature an increasing difficulty level. The individual difficulty levels for the three operators furthermore differed in the level of operator support functions available in their human-machine interfaces. Operator performance in the test scenarios were evaluated in the fields approach success and precision, docking safety, and approach efficiency by a combination of recorded maneuver data and questionnaires. The results show that operator experience and the associated learning curves increase operator performance substantially, regardless of the support system used. The paper also shows that the fluctuations in operator performance and self-perception are substantial between as well as within experiment days, and must be reckoned with in teleoperation system design and mission planning.

  6. AnchorDock for Blind Flexible Docking of Peptides to Proteins.

    Science.gov (United States)

    Slutzki, Michal; Ben-Shimon, Avraham; Niv, Masha Y

    2017-01-01

    Due to increasing interest in peptides as signaling modulators and drug candidates, several methods for peptide docking to their target proteins are under active development. The "blind" docking problem, where the peptide-binding site on the protein surface is unknown, presents one of the current challenges in the field. AnchorDock protocol was developed by Ben-Shimon and Niv to address this challenge.This protocol narrows the docking search to the most relevant parts of the conformational space. This is achieved by pre-folding the free peptide and by computationally detecting anchoring spots on the surface of the unbound protein. Multiple flexible simulated annealing molecular dynamics (SAMD) simulations are subsequently carried out, starting from pre-folded peptide conformations, constrained to the various precomputed anchoring spots.Here, AnchorDock is demonstrated using two known protein-peptide complexes. A PDZ-peptide complex provides a relatively easy case due to the relatively small size of the protein, and a typical peptide conformation and binding region; a more challenging example is a complex between USP7 N-term and a p53-derived peptide, where the protein is larger, and the peptide conformation and a binding site are generally assumed to be unknown. AnchorDock returned native-like solutions ranked first and third for the PDZ and USP7 complexes, respectively. We describe the procedure step by step and discuss possible modifications where applicable.

  7. Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline.

    Science.gov (United States)

    Fan, Xueping; Labrador, Juan Pablo; Hing, Huey; Bashaw, Greg J

    2003-09-25

    Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Here we present evidence that the SH3-SH2 adaptor protein Dreadlocks (Dock), the p21-activated serine-threonine kinase (Pak), and the Rac1/Rac2/Mtl small GTPases can function during Robo repulsion. Loss-of-function and genetic interaction experiments suggest that limiting the function of Dock, Pak, or Rac partially disrupts Robo repulsion. In addition, Dock can directly bind to Robo's cytoplasmic domain, and the association of Dock and Robo is enhanced by stimulation with Slit. Furthermore, Slit stimulation can recruit a complex of Dock and Pak to the Robo receptor and trigger an increase in Rac1 activity. These results provide a direct physical link between the Robo receptor and an important cytoskeletal regulatory protein complex and suggest that Rac can function in both attractive and repulsive axon guidance.

  8. PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

    Science.gov (United States)

    Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

    2016-04-07

    Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

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

    OpenAIRE

    Marco Zucca; Pietro Giuseppe Crespi; Nicola Longarini

    2017-01-01

    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 ...

  10. Linear Actuator System for the NASA Docking System

    Science.gov (United States)

    Dick, Brandon N.; Oesch, Christopher; Rupp, Timothy W.

    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. 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.

  11. PEPSI-Dock: a detailed data-driven protein-protein interaction potential accelerated by polar Fourier correlation.

    Science.gov (United States)

    Neveu, Emilie; Ritchie, David W; Popov, Petr; Grudinin, Sergei

    2016-09-01

    Docking prediction algorithms aim to find the native conformation of a complex of proteins from knowledge of their unbound structures. They rely on a combination of sampling and scoring methods, adapted to different scales. Polynomial Expansion of Protein Structures and Interactions for Docking (PEPSI-Dock) improves the accuracy of the first stage of the docking pipeline, which will sharpen up the final predictions. Indeed, PEPSI-Dock benefits from the precision of a very detailed data-driven model of the binding free energy used with a global and exhaustive rigid-body search space. As well as being accurate, our computations are among the fastest by virtue of the sparse representation of the pre-computed potentials and FFT-accelerated sampling techniques. Overall, this is the first demonstration of a FFT-accelerated docking method coupled with an arbitrary-shaped distance-dependent interaction potential. First, we present a novel learning process to compute data-driven distant-dependent pairwise potentials, adapted from our previous method used for rescoring of putative protein-protein binding poses. The potential coefficients are learned by combining machine-learning techniques with physically interpretable descriptors. Then, we describe the integration of the deduced potentials into a FFT-accelerated spherical sampling provided by the Hex library. Overall, on a training set of 163 heterodimers, PEPSI-Dock achieves a success rate of 91% mid-quality predictions in the top-10 solutions. On a subset of the protein docking benchmark v5, it achieves 44.4% mid-quality predictions in the top-10 solutions when starting from bound structures and 20.5% when starting from unbound structures. The method runs in 5-15 min on a modern laptop and can easily be extended to other types of interactions. https://team.inria.fr/nano-d/software/PEPSI-Dock sergei.grudinin@inria.fr. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e

  12. Assessment of Spatial Navigation and Docking Performance During Simulated Rover Tasks

    Science.gov (United States)

    Wood, S. J.; Dean, S. L.; De Dios, Y. E.; Moore, S. T.

    2010-01-01

    INTRODUCTION: Following long-duration exploration transits, pressurized rovers will enhance surface mobility to explore multiple sites across Mars and other planetary bodies. Multiple rovers with docking capabilities are envisioned to expand the range of exploration. However, adaptive changes in sensorimotor and cognitive function may impair the crew s ability to safely navigate and perform docking tasks shortly after transition to the new gravitoinertial environment. The primary goal of this investigation is to quantify post-flight decrements in spatial navigation and docking performance during a rover simulation. METHODS: Eight crewmembers returning from the International Space Station will be tested on a motion simulator during four pre-flight and three post-flight sessions over the first 8 days following landing. The rover simulation consists of a serial presentation of discrete tasks to be completed within a scheduled 10 min block. The tasks are based on navigating around a Martian outpost spread over a 970 sq m terrain. Each task is subdivided into three components to be performed as quickly and accurately as possible: (1) Perspective taking: Subjects use a joystick to indicate direction of target after presentation of a map detailing current orientation and location of the rover with the task to be performed. (2) Navigation: Subjects drive the rover to the desired location while avoiding obstacles. (3) Docking: Fine positioning of the rover is required to dock with another object or align a camera view. Overall operator proficiency will be based on how many tasks the crewmember can complete during the 10 min time block. EXPECTED RESULTS: Functionally relevant testing early post-flight will develop evidence regarding the limitations to early surface operations and what countermeasures are needed. This approach can be easily adapted to a wide variety of simulated vehicle designs to provide sensorimotor assessments for other operational and civilian populations.

  13. 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

    % (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...

  14. Diagnostic accuracy of virtual non-contrast enhanced dual-energy CT for diagnosis of adrenal adenoma: A systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Connolly, Michael J.; McInnes, Matthew D.F.; Schieda, Nicola [University of Ottawa Department of Radiology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON (United States); El-Khodary, Mohamed [McMaster University Department of Radiology, Hamilton, ON (Canada); McGrath, Trevor A. [University of Ottawa, Faculty of Medicine, Ottawa, Ontario (Canada)

    2017-10-15

    To compare the diagnostic accuracy of dual-energy (DE) virtual non-contrast computed tomography (vNCT) to non-contrast CT (NCT) for the diagnosis of adrenal adenomas. Search of multiple databases and grey literature was performed. Two reviewers independently applied inclusion criteria and extracted data. Risk of bias was assessed using QUADAS-2. Summary estimates of diagnostic accuracy were generated and sources of heterogeneity were assessed. Five studies (170 patients; 192 adrenal masses) were included for diagnostic accuracy assessment; all used dual-source dual-energy CT. Pooled sensitivity for adrenal adenoma on vNCT was 54% (95% CI: 47-62%). Pooled sensitivity for NCT was 57% (95% CI: 45-69%). Pooling of specificity was not performed since no false positives were reported. There was a trend for overestimation of HU density on vNCT as compared to NCT which appeared related to contrast timing. Potential sources of bias were seen regarding the index test and reference standard for the included studies. Potential sources of heterogeneity between studies were seen in adenoma prevalence and intravenous contrast timing. vNCT images generated from dual-energy CT demonstrated comparable sensitivity to NCT for the diagnosis of adenomas; however the included studies are heterogeneous and at high risk for some types of bias. (orig.)

  15. Multilevel Parallelization of AutoDock 4.2

    Directory of Open Access Journals (Sweden)

    Norgan Andrew P

    2011-04-01

    Full Text Available Abstract Background Virtual (computational screening is an increasingly important tool for drug discovery. AutoDock is a popular open-source application for performing molecular docking, the prediction of ligand-receptor interactions. AutoDock is a serial application, though several previous efforts have parallelized various aspects of the program. In this paper, we report on a multi-level parallelization of AutoDock 4.2 (mpAD4. Results Using MPI and OpenMP, AutoDock 4.2 was parallelized for use on MPI-enabled systems and to multithread the execution of individual docking jobs. In addition, code was implemented to reduce input/output (I/O traffic by reusing grid maps at each node from docking to docking. Performance of mpAD4 was examined on two multiprocessor computers. Conclusions Using MPI with OpenMP multithreading, mpAD4 scales with near linearity on the multiprocessor systems tested. In situations where I/O is limiting, reuse of grid maps reduces both system I/O and overall screening time. Multithreading of AutoDock's Lamarkian Genetic Algorithm with OpenMP increases the speed of execution of individual docking jobs, and when combined with MPI parallelization can significantly reduce the execution time of virtual screens. This work is significant in that mpAD4 speeds the execution of certain molecular docking workloads and allows the user to optimize the degree of system-level (MPI and node-level (OpenMP parallelization to best fit both workloads and computational resources.

  16. Multilevel Parallelization of AutoDock 4.2.

    Science.gov (United States)

    Norgan, Andrew P; Coffman, Paul K; Kocher, Jean-Pierre A; Katzmann, David J; Sosa, Carlos P

    2011-04-28

    Virtual (computational) screening is an increasingly important tool for drug discovery. AutoDock is a popular open-source application for performing molecular docking, the prediction of ligand-receptor interactions. AutoDock is a serial application, though several previous efforts have parallelized various aspects of the program. In this paper, we report on a multi-level parallelization of AutoDock 4.2 (mpAD4). Using MPI and OpenMP, AutoDock 4.2 was parallelized for use on MPI-enabled systems and to multithread the execution of individual docking jobs. In addition, code was implemented to reduce input/output (I/O) traffic by reusing grid maps at each node from docking to docking. Performance of mpAD4 was examined on two multiprocessor computers. Using MPI with OpenMP multithreading, mpAD4 scales with near linearity on the multiprocessor systems tested. In situations where I/O is limiting, reuse of grid maps reduces both system I/O and overall screening time. Multithreading of AutoDock's Lamarkian Genetic Algorithm with OpenMP increases the speed of execution of individual docking jobs, and when combined with MPI parallelization can significantly reduce the execution time of virtual screens. This work is significant in that mpAD4 speeds the execution of certain molecular docking workloads and allows the user to optimize the degree of system-level (MPI) and node-level (OpenMP) parallelization to best fit both workloads and computational resources.

  17. Enhancing Docking and Manipulation Capability for Microgravity Robotic Free Flyers

    Data.gov (United States)

    National Aeronautics and Space Administration — The risks and challenges of the space environment have logically led to proposals to use robots to perform tasks for efficiency and safety reasons. Robotic free...

  18. 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...

  19. QuickVina: accelerating AutoDock Vina using gradient-based heuristics for global optimization.

    Science.gov (United States)

    Handoko, Stephanus Daniel; Ouyang, Xuchang; Su, Chinh Tran To; Kwoh, Chee Keong; Ong, Yew Soon

    2012-01-01

    Predicting binding between macromolecule and small molecule is a crucial phase in the field of rational drug design. AutoDock Vina, one of the most widely used docking software released in 2009, uses an empirical scoring function to evaluate the binding affinity between the molecules and employs the iterated local search global optimizer for global optimization, achieving a significantly improved speed and better accuracy of the binding mode prediction compared its predecessor, AutoDock 4. In this paper, we propose further improvement in the local search algorithm of Vina by heuristically preventing some intermediate points from undergoing local search. Our improved version of Vina-dubbed QVina-achieved a maximum acceleration of about 25 times with the average speed-up of 8.34 times compared to the original Vina when tested on a set of 231 protein-ligand complexes while maintaining the optimal scores mostly identical. Using our heuristics, larger number of different ligands can be quickly screened against a given receptor within the same time frame.

  20. Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase.

    Science.gov (United States)

    Iman, Maryam; Khansefid, Zeynab; Davood, Asghar

    2016-01-01

    Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme.

  1. CLUB-MARTINI: Selecting Favourable Interactions amongst Available Candidates, a Coarse-Grained Simulation Approach to Scoring Docking Decoys.

    Directory of Open Access Journals (Sweden)

    Qingzhen Hou

    Full Text Available Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in which proteins interact. In a recent study, we successfully applied coarse-grained molecular dynamics simulations to measure binding free energy for two protein complexes with similar accuracy to full-atomistic simulation, but 500-fold less time consuming. Here, we investigate the efficacy of this approach as a scoring method to identify stable binding conformations from thousands of docking decoys produced by protein docking programs. To test our method, we first applied it to calculate binding free energies of all protein conformations in a CAPRI (Critical Assessment of PRedicted Interactions benchmark dataset, which included over 19000 protein docking solutions for 15 benchmark targets. Based on the binding free energies, we ranked all docking solutions to select the near-native binding modes under the assumption that the native-solutions have lowest binding free energies. In our top 100 ranked structures, for the 'easy' targets that have many near-native conformations, we obtain a strong enrichment of acceptable or better quality structures; for the 'hard' targets without near-native decoys, our method is still able to retain structures which have native binding contacts. Moreover, in our top 10 selections, CLUB-MARTINI shows a comparable performance when compared with other state-of-the-art docking scoring functions. As a proof of concept, CLUB-MARTINI performs remarkably well for many targets and is able to pinpoint near-native binding modes in the top selections. To the best of our knowledge, this is the first time interaction free energy calculated from MD simulations have been used to rank docking solutions at a large scale.

  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. DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0.

    Science.gov (United States)

    Jiang, Xiaohui; Kumar, Kamal; Hu, Xin; Wallqvist, Anders; Reifman, Jaques

    2008-09-08

    Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS) to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability. To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs. The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.

  4. DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0

    Directory of Open Access Journals (Sweden)

    Wallqvist Anders

    2008-09-01

    Full Text Available Abstract Background Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability. Implementation To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs. Conclusion The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.

  5. Molecular Dynamics and Docking of Biphenyl: A Potential ...

    African Journals Online (AJOL)

    Results: Molecular docking by FireDock web server showed that biPhe-43 and Trp-43-mutated CD4 inhibited the binding of ... In a 5ns MD simulation, biPhe-43 and Trp-43 mutated CD4 .... 'unbound' MD on UMHPC Linux Cluster SGIAltix.

  6. Diagnostic Accuracy of Detecting Hashimoto's Thyroiditis in Thyroid Cancer Patients Who Underwent Thyroid Surgery: Comparison of Ultrasonography, Positron Emission Tomography/CT, Contrast Enhanced CT, and Anti-Thyroid Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Gyun; Lee, Tae Hyun; Park, Dong Hee; Nam, Sang Been [Dept. of Radiology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2012-11-15

    To compare the diagnostic accuracy of ultrasonography (US), F18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), contrast enhanced CT (CECT), serum anti-thyroid antibody for detecting Hashimoto's thyroiditis in thyroid cancer patients who underwent neck surgery. A total of 150 patients with suspicious for thyroid cancer, who had previously undergone US guided needle aspiration of thyroid, were evaluated with the use of US, PET/CT, CECT and serum anti-thyroid antibody. The four studies were performed within two months before neck surgery. Hashimoto's thyroiditis was confirmed by histopathological results. The diagnostic accuracy of US, PET/CT, CECT and serum anti-thyroid antibody were calculated statistically. Hashimoto's thyroiditis was diagnosed in 51 out of the 150 patients, following neck surgery. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US were 76.5%, 92.9%, 84.8%, 88.5%, and 87.3%, respectively. The corresponding values of PET/CT were 37.3%, 96.0%, 82.6%, 74.8%, and 76.0%, and CECT were 62.7%, 89.9%, 76.2%, 82.4%, and 80.7%, and serum anti-thyroid antibody level were 90.2%, 93.9%, 88.5%, 94.9%, and 92.7%, respectively. McNemar test revealed significant difference among PET/CT and others, but no significant differences among US, CECT and serum anti-thyroid antibody. Overall, serum anti-thyroid antibody showed most accurate diagnostic performance. In detecting Hashimoto's thyroiditis, serum anti-thyroid antibody showed higher diagnostic accuracy than others. US also showed relatively high diagnostic accuracy.

  7. Diagnostic Accuracy of Detecting Hashimoto's Thyroiditis in Thyroid Cancer Patients Who Underwent Thyroid Surgery: Comparison of Ultrasonography, Positron Emission Tomography/CT, Contrast Enhanced CT, and Anti-Thyroid Antibody

    International Nuclear Information System (INIS)

    Kim, Young Gyun; Lee, Tae Hyun; Park, Dong Hee; Nam, Sang Been

    2012-01-01

    To compare the diagnostic accuracy of ultrasonography (US), F18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), contrast enhanced CT (CECT), serum anti-thyroid antibody for detecting Hashimoto's thyroiditis in thyroid cancer patients who underwent neck surgery. A total of 150 patients with suspicious for thyroid cancer, who had previously undergone US guided needle aspiration of thyroid, were evaluated with the use of US, PET/CT, CECT and serum anti-thyroid antibody. The four studies were performed within two months before neck surgery. Hashimoto's thyroiditis was confirmed by histopathological results. The diagnostic accuracy of US, PET/CT, CECT and serum anti-thyroid antibody were calculated statistically. Hashimoto's thyroiditis was diagnosed in 51 out of the 150 patients, following neck surgery. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US were 76.5%, 92.9%, 84.8%, 88.5%, and 87.3%, respectively. The corresponding values of PET/CT were 37.3%, 96.0%, 82.6%, 74.8%, and 76.0%, and CECT were 62.7%, 89.9%, 76.2%, 82.4%, and 80.7%, and serum anti-thyroid antibody level were 90.2%, 93.9%, 88.5%, 94.9%, and 92.7%, respectively. McNemar test revealed significant difference among PET/CT and others, but no significant differences among US, CECT and serum anti-thyroid antibody. Overall, serum anti-thyroid antibody showed most accurate diagnostic performance. In detecting Hashimoto's thyroiditis, serum anti-thyroid antibody showed higher diagnostic accuracy than others. US also showed relatively high diagnostic accuracy.

  8. Autonomous Docking Based on Infrared System for Electric Vehicle Charging in Urban Areas

    Science.gov (United States)

    Pérez, Joshué; Nashashibi, Fawzi; Lefaudeux, Benjamin; Resende, Paulo; Pollard, Evangeline

    2013-01-01

    Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris. PMID:23429581

  9. Autonomous docking based on infrared system for electric vehicle charging in urban areas.

    Science.gov (United States)

    Pérez, Joshué; Nashashibi, Fawzi; Lefaudeux, Benjamin; Resende, Paulo; Pollard, Evangeline

    2013-02-21

    Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris.

  10. Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

    Directory of Open Access Journals (Sweden)

    Yiming Xu

    2017-11-01

    Full Text Available Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

  11. Autonomous Docking Based on Infrared System for Electric Vehicle Charging in Urban Areas

    Directory of Open Access Journals (Sweden)

    Joshué Pérez

    2013-02-01

    Full Text Available Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris.

  12. Diagnostic accuracy of unenhanced, contrast-enhanced perfusion and angiographic MRI sequences for pulmonary embolism diagnosis: results of independent sequence readings

    Energy Technology Data Exchange (ETDEWEB)

    Revel, Marie Pierre [Hopital Europeen Georges Pompidou, APHP, Departments of Radiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); Hotel-Dieu, Service de Radiologie, Paris (France); Sanchez, Olivier; Meyer, Guy [Hopital Europeen Georges Pompidou, APHP, Respiratory and intensive care and, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); INSERM Unite 765, Paris (France); Lefort, Catherine; Couchon, Sophie; Hernigou, Anne; Frija, Guy [Hopital Europeen Georges Pompidou, APHP, Departments of Radiology, Paris (France); Niarra, Ralph [Hopital Europeen Georges Pompidou, APHP, Clinical Epidemiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); Chatellier, Gilles [Hopital Europeen Georges Pompidou, APHP, Clinical Epidemiology, Paris (France); Universite Paris Descartes Sorbonne Paris Cite, Paris (France); INSERM CIC-EC E4, Paris (France)

    2013-09-15

    To independently evaluate unenhanced, contrast-enhanced perfusion and angiographic MR sequences for pulmonary embolism (PE) diagnosis. Prospective investigation, including 274 patients who underwent perfusion, unenhanced 2D steady-state-free-precession (SSFP) and contrast-enhanced 3D angiographic MR sequences on a 1.5-T unit, in addition to CTA (CT angiography). Two independent readers evaluated each sequence independently in random order. Sensitivity, specificity, predictive values and inter-reader agreement were calculated for each sequence, excluding sequences judged inconclusive. Sensitivity was also calculated according to PE location. Contrast-enhanced angiographic sequences showed the highest sensitivity (82.9 and 89.7 %, reader 1 and reader 2, respectively), specificity (98.5 and 100 %) and agreement (kappa value 0.77). Unenhanced angiographic sequences, although less sensitive overall (68.7 and 76.4 %), were sensitive for the detection of proximal PE (92.7 and 100 %) and showed high specificity (96.1 and 99.1 %) and good agreement (kappa value 0.62). Perfusion sequences showed lower sensitivity (75.0 and 79.3 %), specificity (84.8 and 89.7 %) and agreement (kappa value 0.51), and a negative predictive value of 84.8 % at best. Compared with contrast-enhanced angiographic sequences, unenhanced sequences demonstrate lower sensitivity, except for proximal PE, but high specificity and agreement. The negative predictive value of perfusion sequences was insufficient to safely rule out PE. (orig.)

  13. An Improved Droop Control Method for DC Microgrids Based on Low Bandwidth Communication with DC Bus Voltage Restoration and Enhanced Current Sharing Accuracy

    DEFF Research Database (Denmark)

    Lu, Xiaonan; Guerrero, Josep M.; Sun, Kai

    2014-01-01

    Droop control is the basic control method for load current sharing in dc microgrid applications. The conventional dc droop control method is realized by linearly reducing the dc output voltage as the output current increases. This method has two limitations. First, with the consideration of line...... resistance in a droop-controlled dc microgrid, since the output voltage of each converter cannot be exactly the same, the output current sharing accuracy is degraded. Second, the DC bus voltage deviation increases with the load due to the droop action. In this paper, in order to improve the performance......, and the LBC system is only used for changing the values of the dc voltage and current. Hence, a decentralized control scheme is accomplished. The simulation test based on Matlab/Simulink and the experimental validation based on a 2×2.2 kW prototype were implemented to demonstrate the proposed approach....

  14. A cognitive-motor intervention using a dance video game to enhance foot placement accuracy and gait under dual task conditions in older adults: a randomized controlled trial.

    Science.gov (United States)

    Pichierri, Giuseppe; Murer, Kurt; de Bruin, Eling D

    2012-12-14

    Computer-based interventions have demonstrated consistent positive effects on various physical abilities in older adults. This study aims to compare two training groups that achieve similar amounts of strength and balance exercise where one group receives an intervention that includes additional dance video gaming. The aim is to investigate the different effects of the training programs on physical and psychological parameters in older adults. Thirty-one participants (mean age ± SD: 86.2 ± 4.6 years), residents of two Swiss hostels for the aged, were randomly assigned to either the dance group (n = 15) or the control group (n = 16). The dance group absolved a twelve-week cognitive-motor exercise program twice weekly that comprised progressive strength and balance training supplemented with additional dance video gaming. The control group performed only the strength and balance exercises during this period. Outcome measures were foot placement accuracy, gait performance under single and dual task conditions, and falls efficacy. After the intervention between-group comparison revealed significant differences for gait velocity (U = 26, P = .041, r = .45) and for single support time (U = 24, P = .029, r = .48) during the fast walking dual task condition in favor of the dance group. No significant between-group differences were observed either in the foot placement accuracy test or in falls efficacy. There was a significant interaction in favor of the dance video game group for improvements in step time. Significant improved fast walking performance under dual task conditions (velocity, double support time, step length) was observed for the dance video game group only. These findings suggest that in older adults a cognitive-motor intervention may result in more improved gait under dual task conditions in comparison to a traditional strength and balance exercise program. This trial has been registered under ISRCTN05350123 (www.controlled-trials.com)

  15. In silico molecular modeling of neuraminidase enzyme H1N1 avian influenza virus and docking with zanamivir ligands

    Directory of Open Access Journals (Sweden)

    Muthiyan Ramachandran

    2012-12-01

    Full Text Available Objective: Neuraminidase is an enzyme aspartic protease that is essential for the life cycle of H1N1. Methods: Constructed a model of Neuraminidase enzyme the 3D structure as template using with Modeller software. The Neuraminidase enzyme model was predicted and validated by Procheck, What check, Errat, Verify-3D and AutoDock web server for reliability. Results: The Modeller homology-modeling algorithm was demonstrated excellent accuracy in blind predictions. The Neuraminidase enzyme model built with little, 35% identity could be accurate enough to be successfully used in receptor based rational drug design. The closest homologue with the highest sequence identity 100% was selected. Zanamivir drug and analogues were retrieved from PubChem database, as well as subjected to docking interaction with Neuraminidase enzyme used AutoDock programme. Based on the root mean square deviation and lowest binding energy values the best docking orientation was selected. The better lowest binding energy value -6.91 was selected of CID_25209232. Conclusions: This study will be used in broad screening of inhibitors of the protein. However, further implemented experimental and clinical verification is needed to establishment these analogues as drug.

  16. A cognitive-motor intervention using a dance video game to enhance foot placement accuracy and gait under dual task conditions in older adults: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Pichierri Giuseppe

    2012-12-01

    Full Text Available Abstract Background Computer-based interventions have demonstrated consistent positive effects on various physical abilities in older adults. This study aims to compare two training groups that achieve similar amounts of strength and balance exercise where one group receives an intervention that includes additional dance video gaming. The aim is to investigate the different effects of the training programs on physical and psychological parameters in older adults. Methods Thirty-one participants (mean age ± SD: 86.2 ± 4.6 years, residents of two Swiss hostels for the aged, were randomly assigned to either the dance group (n = 15 or the control group (n = 16. The dance group absolved a twelve-week cognitive-motor exercise program twice weekly that comprised progressive strength and balance training supplemented with additional dance video gaming. The control group performed only the strength and balance exercises during this period. Outcome measures were foot placement accuracy, gait performance under single and dual task conditions, and falls efficacy. Results After the intervention between-group comparison revealed significant differences for gait velocity (U = 26, P = .041, r = .45 and for single support time (U = 24, P = .029, r = .48 during the fast walking dual task condition in favor of the dance group. No significant between-group differences were observed either in the foot placement accuracy test or in falls efficacy. Conclusions There was a significant interaction in favor of the dance video game group for improvements in step time. Significant improved fast walking performance under dual task conditions (velocity, double support time, step length was observed for the dance video game group only. These findings suggest that in older adults a cognitive-motor intervention may result in more improved gait under dual task conditions in comparison to a traditional strength and balance exercise program

  17. Dynamic Docking: A Paradigm Shift in Computational Drug Discovery

    Directory of Open Access Journals (Sweden)

    Dario Gioia

    2017-11-01

    Full Text Available Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking. Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress.

  18. Enhancement of the spectral selectivity of complex samples by measuring them in a frozen state at low temperatures in order to improve accuracy for quantitative analysis. Part II. Determination of viscosity for lube base oils using Raman spectroscopy.

    Science.gov (United States)

    Kim, Mooeung; Chung, Hoeil

    2013-03-07

    The use of selectivity-enhanced Raman spectra of lube base oil (LBO) samples achieved by the spectral collection under frozen conditions at low temperatures was effective for improving accuracy for the determination of the kinematic viscosity at 40 °C (KV@40). A collection of Raman spectra from samples cooled around -160 °C provided the most accurate measurement of KV@40. Components of the LBO samples were mainly long-chain hydrocarbons with molecular structures that were deformable when these were frozen, and the different structural deformabilities of the components enhanced spectral selectivity among the samples. To study the structural variation of components according to the change of sample temperature from cryogenic to ambient condition, n-heptadecane and pristane (2,6,10,14-tetramethylpentadecane) were selected as representative components of LBO samples, and their temperature-induced spectral features as well as the corresponding spectral loadings were investigated. A two-dimensional (2D) correlation analysis was also employed to explain the origin for the improved accuracy. The asynchronous 2D correlation pattern was simplest at the optimal temperature, indicating the occurrence of distinct and selective spectral variations, which enabled the variation of KV@40 of LBO samples to be more accurately assessed.

  19. Enhancing the discrimination accuracy between metastases, gliomas and meningiomas on brain MRI by volumetric textural features and ensemble pattern recognition methods.

    Science.gov (United States)

    Georgiadis, Pantelis; Cavouras, Dionisis; Kalatzis, Ioannis; Glotsos, Dimitris; Athanasiadis, Emmanouil; Kostopoulos, Spiros; Sifaki, Koralia; Malamas, Menelaos; Nikiforidis, George; Solomou, Ekaterini

    2009-01-01

    Three-dimensional (3D) texture analysis of volumetric brain magnetic resonance (MR) images has been identified as an important indicator for discriminating among different brain pathologies. The purpose of this study was to evaluate the efficiency of 3D textural features using a pattern recognition system in the task of discriminating benign, malignant and metastatic brain tissues on T1 postcontrast MR imaging (MRI) series. The dataset consisted of 67 brain MRI series obtained from patients with verified and untreated intracranial tumors. The pattern recognition system was designed as an ensemble classification scheme employing a support vector machine classifier, specially modified in order to integrate the least squares features transformation logic in its kernel function. The latter, in conjunction with using 3D textural features, enabled boosting up the performance of the system in discriminating metastatic, malignant and benign brain tumors with 77.14%, 89.19% and 93.33% accuracy, respectively. The method was evaluated using an external cross-validation process; thus, results might be considered indicative of the generalization performance of the system to "unseen" cases. The proposed system might be used as an assisting tool for brain tumor characterization on volumetric MRI series.

  20. Molecular docking study of Papaver alkaloids to some alkaloid receptors

    Directory of Open Access Journals (Sweden)

    A. Nofallah

    2017-11-01

    Full Text Available Background and objectives: More than 40 different alkaloids have been obtained from opium the most important of which are morphine, codeine, papaverine, noscapine and tabaine. Opioid alkaloids produce analgesia by affecting areas of the brain that have peptides with pharmacological pseudo-opioid properties. These alkaloids show important effects on some intracellular peptides like mu, delta, and kappa receptors. Therefore, studying the effects of these alkaloids on different receptors is essential. Methods: Molecular docking is a well-known method in exploring the protein-ligand interactions. In this research, five important alkaloids were docked to crystal structure of human mu opioid receptor (4DKL, human delta opioid receptor (4EJ4 and human kappa opioid receptor (4DJH which were retrieved from protein databank. The 3D-structures of alkaloids were drawn by chembiooffice2010 and minimized with hyperchem package and submitted to molecular docking utilizing autodock-vina. Flexibility of the proteins was considered. The docking studies were performed to compare the affinity of these five alkaloids to the mentioned receptors. Results: We computationally docked each alkaloid compound onto each receptor structure and estimated their binding affinity based on dock scores. Dock score is a criteria including binding energy which utilized here for prediction and comparison of the binding affinities. Binding interactions of the docked alkaloids in receptor pockets were also visually inspected and compared. Conclusion: In this approach, using docking study as a computational method provided a valuable insight of opioid receptor pocket structures which would be essential to design more efficient drugs in pain managements and addiction treatments.

  1. 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.

  2. Imaging Flash Lidar for Safe Landing on Solar System Bodies and Spacecraft Rendezvous and Docking

    Science.gov (United States)

    Amzajerdian, Farzin; Roback, Vincent E.; Bulyshev, Alexander E.; Brewster, Paul F.; Carrion, William A; Pierrottet, Diego F.; Hines, Glenn D.; Petway, Larry B.; Barnes, Bruce W.; Noe, Anna M.

    2015-01-01

    NASA has been pursuing flash lidar technology for autonomous, safe landing on solar system bodies and for automated rendezvous and docking. During the final stages of the landing from about 1 kilometer to 500 meters above the ground, the flash lidar can generate 3-Dimensional images of the terrain to identify hazardous features such as craters, rocks, and steep slopes. The onboard flight computer can then use the 3-D map of terrain to guide the vehicle to a safe location. As an automated rendezvous and docking sensor, the flash lidar can provide relative range, velocity, and bearing from an approaching spacecraft to another spacecraft or a space station. NASA Langley Research Center has developed and demonstrated a flash lidar sensor system capable of generating 16,000 pixels range images with 7 centimeters precision, at 20 Hertz frame rate, from a maximum slant range of 1800 m from the target area. This paper describes the lidar instrument and presents the results of recent flight tests onboard a rocket-propelled free-flyer vehicle (Morpheus) built by NASA Johnson Space Center. The flights were conducted at a simulated lunar terrain site, consisting of realistic hazard features and designated landing areas, built at NASA Kennedy Space Center specifically for this demonstration test. This paper also provides an overview of the plan for continued advancement of the flash lidar technology aimed at enhancing its performance to meet both landing and automated rendezvous and docking applications.

  3. A new scoring function for protein-protein docking that identifies native structures with unprecedented accuracy

    DEFF Research Database (Denmark)

    Moreira, Irina S.; da Silva Martins, João Miguel; Coimbra, João T.S.

    2015-01-01

    . It incorporates alanine scanning mutagenesis experimental data that need to be obtained a priori. The scoring scheme works by matching the computational and the experimental alanine scanning mutagenesis results. The size of the trial P-P interface area is also taken into account. We show that the method ranks...

  4. Enhancement of precision and accuracy by Monte-Carlo simulation of a well-type pressurized ionization chamber used in radionuclide metrology

    International Nuclear Information System (INIS)

    Kryeziu, D.

    2006-09-01

    The aim of this work was to test and validate the Monte-Carlo (MC) ionization chamber simulation method in calculating the activity of radioactive solutions. This is required when no or not sufficient experimental calibration figures are available as well as to improve the accuracy of activity measurements for other radionuclides. Well-type or 4π γ ISOCAL IV ionization chambers (IC) are widely used in many national standard laboratories around the world. As secondary standard measuring systems these radionuclide calibrators serve to maintain measurement consistency checks and to ensure the quality of standards disseminated to users for a wide range of radionuclide where many of them are with special interest in nuclear medicine as well as in different applications on radionuclide metrology. For the studied radionuclides the calibration figures (efficiencies) and their respective volume correction factors are determined by using the PENELOPE MC computer code system. The ISOCAL IV IC filled with nitrogen gas at approximately 1 MPa is simulated. The simulated models of the chamber are designed by means of reduced quadric equation and applying the appropriate mathematical transformations. The simulations are done for various container geometries of the standard solution which take forms of: i) sealed Jena glass 5 ml PTB standard ampoule, ii) 10 ml (P6) vial and iii) 10 R Schott Type 1+ vial. Simulation of the ISOCAL IV IC is explained. The effect of density variation of the nitrogen filling gas on the sensitivity of the chamber is investigated. The code is also used to examine the effects of using lead and copper shields as well as to evaluate the sensitivity of the chamber to electrons and positrons. Validation of the Monte-Carlo simulation method has been proved by comparing the Monte-Carlo simulation calculated and experimental calibration figures available from the National Physical Laboratory (NPL) England which are deduced from the absolute activity

  5. Synthesis and molecular docking of pyrimidine incorporated novel ...

    Indian Academy of Sciences (India)

    APOORVA MISRA

    2018-03-09

    Mar 9, 2018 ... aDepartment of Chemistry, Banasthali Vidyapith, Banasthali, Rajasthan 304 022, India ... serotonin 5-HT6 receptor antagonist,22 hepatitis-A virus ..... Molecular docking structure and ligand protein binding sites of MTX- (a) ...

  6. Molecular Docking Study on Galantamine Derivatives as Cholinesterase Inhibitors.

    Science.gov (United States)

    Atanasova, Mariyana; Yordanov, Nikola; Dimitrov, Ivan; Berkov, Strahil; Doytchinova, Irini

    2015-06-01

    A training set of 22 synthetic galantamine derivatives binding to acetylcholinesterase was docked by GOLD and the protocol was optimized in terms of scoring function, rigidity/flexibility of the binding site, presence/absence of a water molecule inside and radius of the binding site. A moderate correlation was found between the affinities of compounds expressed as pIC50 values and their docking scores. The optimized docking protocol was validated by an external test set of 11 natural galantamine derivatives and the correlation coefficient between the docking scores and the pIC50 values was 0.800. The derived relationship was used to analyze the interactions between galantamine derivatives and AChE. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Synthesis, docking and anticancer activity studies of D-proline ...

    Indian Academy of Sciences (India)

    D-proline-incorporated wainunuamide — a cyclic octapeptide was synthesized and characterized ... Cyclic octapeptide; molecular docking; solution phase synthesis; anticancer activity ..... dynamics and their binding affinities, using free energy.

  8. Passive, Failure-Tolerant Docking and Undocking with Articulated Magnets

    Data.gov (United States)

    National Aeronautics and Space Administration — Current spacecraft docking relies on active movement (e.g. thrusters) to close the gap between participants, and to separate them when undocking. I intend to develop...

  9. Synthesis, in vitro anti-inflammatory activity and molecular docking ...

    Indian Academy of Sciences (India)

    alkyl and heterocyclic alkyl moieties were synthesized, characterized and subsequently evaluated for ... Docking studies with these compounds against cyclooxygenase-2 receptor ...... thiadiazole derivatives as possible anti-tubercular agents.

  10. Optimal Rendezvous and Docking Simulator for Elliptical Orbits, Phase I

    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...

  11. Molecular docking studies on rocaglamide, a traditional Chinese ...

    African Journals Online (AJOL)

    Keywords: Periodontitis, Inflammation, Rocaglamide, Molecular docking, Lamarckian ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, ... chronic, bacterial infection-associated auto- .... The binding pocket in this case.

  12. Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

    Science.gov (United States)

    Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

    2017-01-01

    To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

  13. Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study

    Directory of Open Access Journals (Sweden)

    Filipe Ramos Barra

    Full Text Available Abstract Objective: To assess the feasibility of contrast-enhanced spectral mammography (CESM of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC. Materials and methods: In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM. We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. Results: The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively. The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886. The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598. Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88. Conclusion: CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

  14. Collecting wrappers, labels, and packages to enhance accuracy of food records among children 2-8 years in the Pacific region: Children's Healthy Living Program (CHL).

    Science.gov (United States)

    Yonemori, Kim M; Ennis, Tui; Novotny, Rachel; Fialkowski, Marie K; Ettienne, Reynolette; Wilkens, Lynne R; Leon Guerrero, Rachael T; Bersamin, Andrea; Coleman, Patricia; Li, Fenfang; Boushey, Carol J

    2017-12-01

    The aim was to describe differences in dietary outcomes based on the provision of food wrappers, labels or packages (WLP) to complement data from dietary records (DR) among children from the US Affiliated Pacific. The WLP were intended to aid food coding. Since WLP can be associated with ultra-processed foods, one might expect differences in sodium, sugar, and other added ingredients to emerge. Dietary intakes of children (2-8 y) in Alaska, Hawai'i, Commonwealth of the Northern Mariana Islands, and Guam were collected using parent/caregiver completed 2-day DR. Parents were encouraged to collect WLP associated with the child's intake. Trained staff entered data from the DRs including the WLP when available using PacTrac3, a web application. Of the 1,868 DRs collected and entered at the time of this report, 498 (27%) included WLP. After adjusting for confounders (sex, age, location, education, food assistance), the DRs with WLP had significantly higher amounts of energy (kcal), total fat, saturated fat, added sugar, and sodium. These results suggest the inclusion of WLP enhanced the dietary intake data. The intake of energy, fat, added sugar and sodium derived from processed foods and foods consumed outside the home was better captured in children who had WLP.

  15. Exponential Repulsion Improves Structural Predictability of Molecular Docking

    Czech Academy of Sciences Publication Activity Database

    Bazgier, Václav; Berka, K.; Otyepka, M.; Banáš, P.

    2016-01-01

    Roč. 37, č. 28 (2016), s. 2485-2494 ISSN 0192-8651 Institutional support: RVO:61389030 Keywords : cyclin-dependent kinases * structure-based design * scoring functions * cdk2 inhibitors * force-field * ligand interactions * drug discovery * purine * potent * protein-kinase-2 * molecular docking * dock 6.6 * drug design * cyclin-dependent kinase 2 * directory of decoys Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.229, year: 2016

  16. 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.

  17. A primer on wood as dock construction material

    Science.gov (United States)

    Stan Lebow

    2007-01-01

    To be a successful marina owner and operator, it’s important to understand all the facets of one’s facility, including the intricacies of one part of the marina that most boaters take for granted: the docks. When it comes to dock construction, marinas have a wide-range of materials to choose from, with one of the most commonly used materials being preservative-treated...

  18. Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis▿ †

    Science.gov (United States)

    Feske, Marsha; Nudelman, Rodolfo J.; Medina, Miguel; Lew, Justin; Singh, Manisha; Couturier, Jacob; Graviss, Edward A.; Lewis, Dorothy E.

    2008-01-01

    Children and immunocompromised adults are at an increased risk of tuberculosis (TB), but diagnosis is more challenging. Recently developed gamma interferon (IFN-γ) release assays provide increased sensitivity and specificity for diagnosis of latent TB, but their use is not FDA approved in immunocompromised or pediatric populations. Both populations have reduced numbers of T cells, which are major producers of IFN-γ. Interleukin 7 (IL-7), a survival cytokine, stabilizes IFN-γ message and increases protein production. IL-7 was added to antigen-stimulated lymphocytes to improve IFN-γ responses as measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Antigens used were tetanus toxoid (n = 10), p24 (from human immunodeficiency virus [HIV], n = 9), and TB peptides (n = 15). Keyhole limpet hemocyanin was used as a negative control, and phytohemagglutinin was the positive control. IL-7 improved antigen-specific responses to all antigens tested including tetanus toxoid, HIV type 1 p24, and TB peptides (ESAT-6 and CFP-10) with up to a 14-fold increase (mean = 3.8), as measured by ELISA. Increased IFN-γ responses from controls, HIV-positive patients, and TB patients were statistically significant, with P values of <0.05, 0.01, and 0.05, respectively. ELISPOT assay results confirmed ELISA findings (P values of <0.01, 0.02, and 0.03, respectively), with a strong correlation between the two tests (R2 = 0.82 to 0.99). Based on average background levels, IL-7 increased detection of IFN-γ by 39% compared to the level with antigen alone. Increased production of IFN-γ induced by IL-7 improves sensitivity of ELISA and ELISPOT assays for all antigens tested. Further enhancement of IFN-γ-based assays might improve TB diagnosis in those populations at highest risk for TB. PMID:18753334

  19. Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy

    International Nuclear Information System (INIS)

    Yilmaz, E.; Akkoclu, A.; Degirmenci, B.; Cooper, R.A.; Sengun, B.; Gulcu, A.; Osma, E.; Ucan, E.S.

    2005-01-01

    AIM: The aim of this study was to correlate findings of perfusion magnetic resonance imaging (MRI) and perfusion scintigraphy in cases where there was a suspicion of abnormal pulmonary vasculature, and to evaluate the usefulness of MRI in the detection of perfusion deficits of the lung. METHODS: In all, 17 patients with suspected abnormality of the pulmonary vasculature underwent dynamic contrast-enhanced MRI. T1-weighted 3D fast-field echo pulse sequences were obtained (TR/TE 3.3/1.58 ms; flip angle 30 deg ; slice thickness 12 to 15 mm). The dynamic study was acquired in the coronal plane following administration of 0.1 mmol/kg gadopentetate dimeglumine. A total of 8 to 10 sections repeated 20 to 25 times at intervals of 1 s were performed. Perfusion lung scintigraphy was carried out a maximum of 48 h before the MR examination in all cases. Two radiologists, who were blinded to the clinical data and results of other imaging methods, reviewed all coronal sections. MR perfusion images were independently assessed in terms of segmental or lobar perfusion defects in the 85 lobes of the 17 individuals, and the findings were compared with the results of scintigraphy. RESULTS: Of the 17 patients, 8 were found to have pulmonary emboli, 2 chronic obstructive pulmonary disease with emphysema, 2 bullous emphysema, 2 Takayasu arteritis and 1 had a hypoplastic pulmonary artery. Pulmonary perfusion was completely normal in 2 cases. In 35 lobes, perfusion defects were detected using both methods, in 4 with MR alone and in 9 only with scintigraphy. There was good agreement between MRI and scintigraphy findings (kappa=0.695). CONCLUSION: Pulmonary perfusion MRI is a new alternative to scintigraphy in the evaluation of pulmonary perfusion for various lung disorders. In addition, this technique allows measurement and quantification of pulmonary perfusion abnormalities

  20. Demonstration of automated proximity and docking technologies

    Science.gov (United States)

    Anderson, Robert L.; Tsugawa, Roy K.; Bryan, Thomas C.

    An autodock was demonstrated using straightforward techniques and real sensor hardware. A simulation testbed was established and validated. The sensor design was refined with improved optical performance and image processing noise mitigation techniques, and the sensor is ready for production from off-the-shelf components. The autonomous spacecraft architecture is defined. The areas of sensors, docking hardware, propulsion, and avionics are included in the design. The Guidance Navigation and Control architecture and requirements are developed. Modular structures suitable for automated control are used. The spacecraft system manager functions including configuration, resource, and redundancy management are defined. The requirements for autonomous spacecraft executive are defined. High level decisionmaking, mission planning, and mission contingency recovery are a part of this. The next step is to do flight demonstrations. After the presentation the following question was asked. How do you define validation? There are two components to validation definition: software simulation with formal and vigorous validation, and hardware and facility performance validated with respect to software already validated against analytical profile.

  1. Combination of scoring schemes for protein docking

    Directory of Open Access Journals (Sweden)

    Schomburg Dietmar

    2007-08-01

    Full Text Available Abstract Background Docking algorithms are developed to predict in which orientation two proteins are likely to bind under natural conditions. The currently used methods usually consist of a sampling step followed by a scoring step. We developed a weighted geometric correlation based on optimised atom specific weighting factors and combined them with our previously published amino acid specific scoring and with a comprehensive SVM-based scoring function. Results The scoring with the atom specific weighting factors yields better results than the amino acid specific scoring. In combination with SVM-based scoring functions the percentage of complexes for which a near native structure can be predicted within the top 100 ranks increased from 14% with the geometric scoring to 54% with the combination of all scoring functions. Especially for the enzyme-inhibitor complexes the results of the ranking are excellent. For half of these complexes a near-native structure can be predicted within the first 10 proposed structures and for more than 86% of all enzyme-inhibitor complexes within the first 50 predicted structures. Conclusion We were able to develop a combination of different scoring schemes which considers a series of previously described and some new scoring criteria yielding a remarkable improvement of prediction quality.

  2. Reactive Path Planning Approach for Docking Robots in Unknown Environment

    Directory of Open Access Journals (Sweden)

    Peng Cui

    2017-01-01

    Full Text Available Autonomous robots need to be recharged and exchange information with the host through docking in the long-distance tasks. Therefore, feasible path is required in the docking process to guide the robot and adjust its pose. However, when there are unknown obstacles in the work area, it becomes difficult to determine the feasible path for docking. This paper presents a reactive path planning approach named Dubins-APF (DAPF to solve the path planning problem for docking in unknown environment with obstacles. In this proposed approach the Dubins curves are combined with the designed obstacle avoidance potential field to plan the feasible path. Firstly, an initial path is planned and followed according to the configurations of the robot and the docking station. Then when the followed path is evaluated to be infeasible, the intermediate configuration is calculated as well as the replanned path based on the obstacle avoidance potential field. The robot will be navigated to the docking station with proper pose eventually via the DAPF approach. The proposed DAPF approach is efficient and does not require the prior knowledge about the environment. Simulation results are given to validate the effectiveness and feasibility of the proposed approach.

  3. Grid heterogeneity in in-silico experiments: an exploration of drug screening using DOCK on cloud environments.

    Science.gov (United States)

    Yim, Wen-Wai; Chien, Shu; Kusumoto, Yasuyuki; Date, Susumu; Haga, Jason

    2010-01-01

    Large-scale in-silico screening is a necessary part of drug discovery and Grid computing is one answer to this demand. A disadvantage of using Grid computing is the heterogeneous computational environments characteristic of a Grid. In our study, we have found that for the molecular docking simulation program DOCK, different clusters within a Grid organization can yield inconsistent results. Because DOCK in-silico virtual screening (VS) is currently used to help select chemical compounds to test with in-vitro experiments, such differences have little effect on the validity of using virtual screening before subsequent steps in the drug discovery process. However, it is difficult to predict whether the accumulation of these discrepancies over sequentially repeated VS experiments will significantly alter the results if VS is used as the primary means for identifying potential drugs. Moreover, such discrepancies may be unacceptable for other applications requiring more stringent thresholds. This highlights the need for establishing a more complete solution to provide the best scientific accuracy when executing an application across Grids. One possible solution to platform heterogeneity in DOCK performance explored in our study involved the use of virtual machines as a layer of abstraction. This study investigated the feasibility and practicality of using virtual machine and recent cloud computing technologies in a biological research application. We examined the differences and variations of DOCK VS variables, across a Grid environment composed of different clusters, with and without virtualization. The uniform computer environment provided by virtual machines eliminated inconsistent DOCK VS results caused by heterogeneous clusters, however, the execution time for the DOCK VS increased. In our particular experiments, overhead costs were found to be an average of 41% and 2% in execution time for two different clusters, while the actual magnitudes of the execution time

  4. Impact of arterial input function selection on the accuracy of dynamic contrast-enhanced MRI quantitative analysis for the diagnosis of clinically significant prostate cancer.

    Science.gov (United States)

    Azahaf, Mustapha; Haberley, Marc; Betrouni, Nacim; Ernst, Olivier; Behal, Hélène; Duhamel, Alain; Ouzzane, Adil; Puech, Philippe

    2016-03-01

    Using a limited temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) dataset to assess the impact of the arterial input function (AIF) choice on the transfer constant (K(trans) ) to distinguish prostate carcinoma (PCa) from benign tissue. Thirty-eight patients with clinically important peripheral PCa (≥0.5 cc) were retrospectively studied. These patients underwent 1.5T multiparametric prostate MR with PCa and benign regions of interest (ROIs) selected using a visual registration with morphometric reconstruction obtained from radical prostatectomy. Using three pharmacokinetic (PK) analysis software programs, the mean K(trans) of ROIs was computed using three AIFs: an individual AIF (Ind-AIF) and two literature population average AIFs of Weinmann (W-AIF) and of Fritz-Hansen (FH-AIF). A pairwise comparison of the area under the receiver operating characteristic curves (AUROCC) obtained with different AIFs was performed. AUROCCs obtained with W-AIF (ranging from 0.801 to 0.843) were significantly higher than FH-AIF (ranging from 0.698 to 0.780, 0.002 ≤ P ≤ 0.045) and similar to or higher than Ind-AIF (ranging from 0.591 to 0.839, 0.014 ≤ P ≤ 0.9). Ind-AIF and FH-AIF provided similar AUROCC (0.34 ≤ P ≤ 0.81). The pairwise correlation of K(trans) values was moderate to very strong when comparing W-AIF with FH-AIF (the Spearman's correlation coefficients [SCCs] ranged from 0.55 to 0.93) and very weak to moderate when comparing W-AIF with Ind-AIF (the SCCs ranged from 0.018 to 0.59) or FH-AIF with Ind-AIF (the SCCs ranged from 0.30 to 0.51). W-AIF yielded a higher performance than FH-AIF and a similar or higher performance than Ind-AIF in distinguishing PCa from benign tissue. © 2015 Wiley Periodicals, Inc.

  5. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  6. Social Power Increases Interoceptive Accuracy

    Directory of Open Access Journals (Sweden)

    Mehrad Moeini-Jazani

    2017-08-01

    Full Text Available Building on recent psychological research showing that power increases self-focused attention, we propose that having power increases accuracy in perception of bodily signals, a phenomenon known as interoceptive accuracy. Consistent with our proposition, participants in a high-power experimental condition outperformed those in the control and low-power conditions in the Schandry heartbeat-detection task. We demonstrate that the effect of power on interoceptive accuracy is not explained by participants’ physiological arousal, affective state, or general intention for accuracy. Rather, consistent with our reasoning that experiencing power shifts attentional resources inward, we show that the effect of power on interoceptive accuracy is dependent on individuals’ chronic tendency to focus on their internal sensations. Moreover, we demonstrate that individuals’ chronic sense of power also predicts interoceptive accuracy similar to, and independent of, how their situationally induced feeling of power does. We therefore provide further support on the relation between power and enhanced perception of bodily signals. Our findings offer a novel perspective–a psychophysiological account–on how power might affect judgments and behavior. We highlight and discuss some of these intriguing possibilities for future research.

  7. Orion Handling Qualities During ISS Rendezvous and Docking

    Science.gov (United States)

    Hart, Jeremy J.; Stephens, J. P.; Spehar, P.; Bilimoria, K.; Foster, C.; Gonzalex, R.; Sullivan, K.; Jackson, B.; Brazzel, J.; Hart, J.

    2011-01-01

    The Orion spacecraft was designed to rendezvous with multiple vehicles in low earth orbit (LEO) and beyond. To perform the required rendezvous and docking task, Orion must provide enough control authority to perform coarse translational maneuvers while maintaining precision to perform the delicate docking corrections. While Orion has autonomous docking capabilities, it is expected that final approach and docking operations with the International Space Station (ISS) will initially be performed in a manual mode. A series of evaluations was conducted by NASA and Lockheed Martin at the Johnson Space Center to determine the handling qualities (HQ) of the Orion spacecraft during different docking and rendezvous conditions using the Cooper-Harper scale. This paper will address the specifics of the handling qualities methodology, vehicle configuration, scenarios flown, data collection tools, and subject ratings and comments. The initial Orion HQ assessment examined Orion docking to the ISS. This scenario demonstrates the Translational Hand Controller (THC) handling qualities of Orion. During this initial assessment, two different scenarios were evaluated. The first was a nominal docking approach to a stable ISS, with Orion initializing with relative position dispersions and a closing rate of approximately 0.1 ft/sec. The second docking scenario was identical to the first, except the attitude motion of the ISS was modeled to simulate a stress case ( 1 degree deadband per axis and 0.01 deg/sec rate deadband per axis). For both scenarios, subjects started each run on final approach at a docking port-to-port range of 20 ft. Subjects used the THC in pulse mode with cues from the docking camera image, window views, and range and range rate data displayed on the Orion display units. As in the actual design, the attitude of the Orion vehicle was held by the automated flight control system at 0.5 degree deadband per axis. Several error sources were modeled including Reaction

  8. 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.

  9. Protein-protein docking with dynamic residue protonation states.

    Directory of Open Access Journals (Sweden)

    Krishna Praneeth Kilambi

    2014-12-01

    Full Text Available Protein-protein interactions depend on a host of environmental factors. Local pH conditions influence the interactions through the protonation states of the ionizable residues that can change upon binding. In this work, we present a pH-sensitive docking approach, pHDock, that can sample side-chain protonation states of five ionizable residues (Asp, Glu, His, Tyr, Lys on-the-fly during the docking simulation. pHDock produces successful local docking funnels in approximately half (79/161 the protein complexes, including 19 cases where standard RosettaDock fails. pHDock also performs better than the two control cases comprising docking at pH 7.0 or using fixed, predetermined protonation states. On average, the top-ranked pHDock structures have lower interface RMSDs and recover more native interface residue-residue contacts and hydrogen bonds compared to RosettaDock. Addition of backbone flexibility using a computationally-generated conformational ensemble further improves native contact and hydrogen bond recovery in the top-ranked structures. Although pHDock is designed to improve docking, it also successfully predicts a large pH-dependent binding affinity change in the Fc-FcRn complex, suggesting that it can be exploited to improve affinity predictions. The approaches in the study contribute to the goal of structural simulations of whole-cell protein-protein interactions including all the environmental factors, and they can be further expanded for pH-sensitive protein design.

  10. Improving Docking Performance Using Negative Image-Based Rescoring.

    Science.gov (United States)

    Kurkinen, Sami T; Niinivehmas, Sanna; Ahinko, Mira; Lätti, Sakari; Pentikäinen, Olli T; Postila, Pekka A

    2018-01-01

    Despite the large computational costs of molecular docking, the default scoring functions are often unable to recognize the active hits from the inactive molecules in large-scale virtual screening experiments. Thus, even though a correct binding pose might be sampled during the docking, the active compound or its biologically relevant pose is not necessarily given high enough score to arouse the attention. Various rescoring and post-processing approaches have emerged for improving the docking performance. Here, it is shown that the very early enrichment (number of actives scored higher than 1% of the highest ranked decoys) can be improved on average 2.5-fold or even 8.7-fold by comparing the docking-based ligand conformers directly against the target protein's cavity shape and electrostatics. The similarity comparison of the conformers is performed without geometry optimization against the negative image of the target protein's ligand-binding cavity using the negative image-based (NIB) screening protocol. The viability of the NIB rescoring or the R-NiB, pioneered in this study, was tested with 11 target proteins using benchmark libraries. By focusing on the shape/electrostatics complementarity of the ligand-receptor association, the R-NiB is able to improve the early enrichment of docking essentially without adding to the computing cost. By implementing consensus scoring, in which the R-NiB and the original docking scoring are weighted for optimal outcome, the early enrichment is improved to a level that facilitates effective drug discovery. Moreover, the use of equal weight from the original docking scoring and the R-NiB scoring improves the yield in most cases.

  11. Accuracy in Optical Information Processing

    Science.gov (United States)

    Timucin, Dogan Aslan

    Low computational accuracy is an important obstacle for optical processors which blocks their way to becoming a practical reality and a serious challenger for classical computing paradigms. This research presents a comprehensive solution approach to the problem of accuracy enhancement in discrete analog optical information processing systems. Statistical analysis of a generic three-plane optical processor is carried out first, taking into account the effects of diffraction, interchannel crosstalk, and background radiation. Noise sources included in the analysis are photon, excitation, and emission fluctuations in the source array, transmission and polarization fluctuations in the modulator, and photoelectron, gain, dark, shot, and thermal noise in the detector array. Means and mutual coherence and probability density functions are derived for both optical and electrical output signals. Next, statistical models for a number of popular optoelectronic devices are studied. Specific devices considered here are light-emitting and laser diode sources, an ideal noiseless modulator and a Gaussian random-amplitude-transmittance modulator, p-i-n and avalanche photodiode detectors followed by electronic postprocessing, and ideal free-space geometrical -optics propagation and single-lens imaging systems. Output signal statistics are determined for various interesting device combinations by inserting these models into the general formalism. Finally, based on these special-case output statistics, results on accuracy limitations and enhancement in optical processors are presented. Here, starting with the formulation of the accuracy enhancement problem as (1) an optimal detection problem and (2) as a parameter estimation problem, the potential accuracy improvements achievable via the classical multiple-hypothesis -testing and maximum likelihood and Bayesian parameter estimation methods are demonstrated. Merits of using proper normalizing transforms which can potentially stabilize

  12. Arbitrary protein−protein docking targets biologically relevant interfaces

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2012-05-01

    Full Text Available Abstract Background Protein-protein recognition is of fundamental importance in the vast majority of biological processes. However, it has already been demonstrated that it is very hard to distinguish true complexes from false complexes in so-called cross-docking experiments, where binary protein complexes are separated and the isolated proteins are all docked against each other and scored. Does this result, at least in part, reflect a physical reality? False complexes could reflect possible nonspecific or weak associations. Results In this paper, we investigate the twilight zone of protein-protein interactions, building on an interesting outcome of cross-docking experiments: false complexes seem to favor residues from the true interaction site, suggesting that randomly chosen partners dock in a non-random fashion on protein surfaces. Here, we carry out arbitrary docking of a non-redundant data set of 198 proteins, with more than 300 randomly chosen "probe" proteins. We investigate the tendency of arbitrary partners to aggregate at localized regions of the protein surfaces, the shape and compositional bias of the generated interfaces, and the potential of this property to predict biologically relevant binding sites. We show that the non-random localization of arbitrary partners after protein-protein docking is a generic feature of protein structures. The interfaces generated in this way are not systematically planar or curved, but tend to be closer than average to the center of the proteins. These results can be used to predict biological interfaces with an AUC value up to 0.69 alone, and 0.72 when used in combination with evolutionary information. An appropriate choice of random partners and number of docking models make this method computationally practical. It is also noted that nonspecific interfaces can point to alternate interaction sites in the case of proteins with multiple interfaces. We illustrate the usefulness of arbitrary docking

  13. Arbitrary protein−protein docking targets biologically relevant interfaces

    International Nuclear Information System (INIS)

    Martin, Juliette; Lavery, Richard

    2012-01-01

    Protein-protein recognition is of fundamental importance in the vast majority of biological processes. However, it has already been demonstrated that it is very hard to distinguish true complexes from false complexes in so-called cross-docking experiments, where binary protein complexes are separated and the isolated proteins are all docked against each other and scored. Does this result, at least in part, reflect a physical reality? False complexes could reflect possible nonspecific or weak associations. In this paper, we investigate the twilight zone of protein-protein interactions, building on an interesting outcome of cross-docking experiments: false complexes seem to favor residues from the true interaction site, suggesting that randomly chosen partners dock in a non-random fashion on protein surfaces. Here, we carry out arbitrary docking of a non-redundant data set of 198 proteins, with more than 300 randomly chosen "probe" proteins. We investigate the tendency of arbitrary partners to aggregate at localized regions of the protein surfaces, the shape and compositional bias of the generated interfaces, and the potential of this property to predict biologically relevant binding sites. We show that the non-random localization of arbitrary partners after protein-protein docking is a generic feature of protein structures. The interfaces generated in this way are not systematically planar or curved, but tend to be closer than average to the center of the proteins. These results can be used to predict biological interfaces with an AUC value up to 0.69 alone, and 0.72 when used in combination with evolutionary information. An appropriate choice of random partners and number of docking models make this method computationally practical. It is also noted that nonspecific interfaces can point to alternate interaction sites in the case of proteins with multiple interfaces. We illustrate the usefulness of arbitrary docking using PEBP (Phosphatidylethanolamine binding

  14. 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.

  15. Inspection by docking of nuclear-powered ship 'Mutsu'

    International Nuclear Information System (INIS)

    1989-01-01

    Japan Atomic Energy Research Institute carried out the docking and inspection of the nuclear-powered ship 'Mutsu' at Sekinehama Port, Mutsu City, Aomori Prefecture, from the middle of June to late in July, 1989. In this inspection, the Mutsu was mounted on a floating dock off the coast, the dock was towed by tugboats into the port and moored at the pier, and after completing the works in the dock, the dock was towed to the outside of the port, and the Mutsu was launched. The Mutsu was built as a nuclear power experiment ship, and length 130 m, breadth 19 m, depth 13.2 m, design draft at full load 6.9 m, 8242 GT. One PWR of 36 MWt and one steam turbine of 10000 ps are installed, and velocity is 16.5 knots. In September, 1974, after the first criticality, the leak of radioactivity occurred. The repair of shield and general inspection on safety were carried out in Sasebo Shipyard from August, 1980 to August, 1982. Thereafter, the Mutsu stayed in Ominato, but in January, 1988, after the completion of Sekinehama Port, the Mutsu was brought there. The Sekinehama Port, the test and inspection of the Mutsu carried out so far and the plan of hereafter are reported. (K.I.)

  16. GPU acceleration of Dock6's Amber scoring computation.

    Science.gov (United States)

    Yang, Hailong; Zhou, Qiongqiong; Li, Bo; Wang, Yongjian; Luan, Zhongzhi; Qian, Depei; Li, Hanlu

    2010-01-01

    Dressing the problem of virtual screening is a long-term goal in the drug discovery field, which if properly solved, can significantly shorten new drugs' R&D cycle. The scoring functionality that evaluates the fitness of the docking result is one of the major challenges in virtual screening. In general, scoring functionality in docking requires a large amount of floating-point calculations, which usually takes several weeks or even months to be finished. This time-consuming procedure is unacceptable, especially when highly fatal and infectious virus arises such as SARS and H1N1, which forces the scoring task to be done in a limited time. This paper presents how to leverage the computational power of GPU to accelerate Dock6's (http://dock.compbio.ucsf.edu/DOCK_6/) Amber (J. Comput. Chem. 25: 1157-1174, 2004) scoring with NVIDIA CUDA (NVIDIA Corporation Technical Staff, Compute Unified Device Architecture - Programming Guide, NVIDIA Corporation, 2008) (Compute Unified Device Architecture) platform. We also discuss many factors that will greatly influence the performance after porting the Amber scoring to GPU, including thread management, data transfer, and divergence hidden. Our experiments show that the GPU-accelerated Amber scoring achieves a 6.5× speedup with respect to the original version running on AMD dual-core CPU for the same problem size. This acceleration makes the Amber scoring more competitive and efficient for large-scale virtual screening problems.

  17. 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

    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...... that effects of this management routine are more persistent than earlier suggested, and suggesting that docking length may influence the post-surgical behaviour of piglets. By use of the present sites of injection and dosages, neither local anaesthetic nor NSAID had marked effects on post-surgical behavioural......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...

  18. The Accuracy Enhancing Effect of Biasing Cues

    NARCIS (Netherlands)

    W. Vanhouche (Wouter); S.M.J. van Osselaer (Stijn)

    2009-01-01

    textabstractExtrinsic cues such as price and irrelevant attributes have been shown to bias consumers’ product judgments. Results in this article replicate those findings in pretrial judgments but show that such biasing cues can improve quality judgments at a later point in time. Initially biasing

  19. Enhancing the Classification Accuracy of IP Geolocation

    Science.gov (United States)

    2013-10-01

    accurately identify the geographic location of Internet devices has signficant implications for online- advertisers, application developers , network...Real Media, Comedy Central, Netflix and Spotify) and target advertising (e.g., Google). More re- cently, IP geolocation techniques have been deployed...distance to delay function and how they triangulate the position of the target. Statistical Geolocation [14] develops a joint probability density

  20. Accounting for Intraligand Interactions in Flexible Ligand Docking with a PMF-Based Scoring Function.

    Science.gov (United States)

    Lizunov, A Y; Gonchar, A L; Zaitseva, N I; Zosimov, V V

    2015-10-26

    We analyzed the frequency with which intraligand contacts occurred in a set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 , 742 - 755 .]. Our analysis showed that flexible ligands often form intraligand hydrophobic contacts, while intraligand hydrogen bonds are rare. The test set was also thoroughly investigated and classified. We suggest a universal method for enhancement of a scoring function based on a potential of mean force (PMF-based score) by adding a term accounting for intraligand interactions. The method was implemented via in-house developed program, utilizing an Algo_score scoring function [ Ramensky et al. Proteins: Struct., Funct., Genet. 2007 , 69 , 349 - 357 .] based on the Tarasov-Muryshev PMF [ Muryshev et al. J. Comput.-Aided Mol. Des. 2003 , 17 , 597 - 605 .]. The enhancement of the scoring function was shown to significantly improve the docking and scoring quality for flexible ligands in the test set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 , 742 - 755 .]. We then investigated the correlation of the docking results with two parameters of intraligand interactions estimation. These parameters are the weight of intraligand interactions and the minimum number of bonds between the ligand atoms required to take their interaction into account.

  1. Space Shuttle Program (SSP) Dual Docked Operations (DDO)

    Science.gov (United States)

    Sills, Joel W., Jr.; Bruno, Erica E.

    2016-01-01

    This document describes the concept definition, studies, and analysis results generated by the Space Shuttle Program (SSP), International Space Station (ISS) Program (ISSP), and Mission Operations Directorate for implementing Dual Docked Operations (DDO) during mated Orbiter/ISS missions. This work was performed over a number of years. Due to the ever increasing visiting vehicle traffic to and from the ISS, it became apparent to both the ISSP and the SSP that there would arise occasions where conflicts between a visiting vehicle docking and/or undocking could overlap with a planned Space Shuttle launch and/or during docked operations. This potential conflict provided the genesis for evaluating risk mitigations to gain maximum flexibility for managing potential visiting vehicle traffic to and from the ISS and to maximize launch and landing opportunities for all visiting vehicles.

  2. Protein-Protein Docking in Drug Design and Discovery.

    Science.gov (United States)

    Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

    2018-01-01

    Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

  3. Behaviour of tail-docked lambs tested in isolation

    Directory of Open Access Journals (Sweden)

    Marchewka Joanna

    2016-12-01

    Full Text Available The aims of the current study were to detect behavioural indicators of pain of tail-docked sheep tested in isolation and to determine the relationship between behaviour and the pain levels to which they were exposed. Twenty-four female lambs, randomly assigned to four pens, had their tail docked with a rubber ring (TD; n = 6 without pain control procedures, TD with anaesthesia (TDA; n = 6 or TD with anaesthesia and analgesia (TDAA; n = 6. Additionally, six lambs handled but without tail docking or application of pain relief measures were used as the control (C. On the day prior (Day –1 to the TD and on days 1, 3 and 5 post-procedure, each lamb was individually removed from its group and underwent a 2.5 min open field test in a separate pen. Frequencies of behaviours such as rest, running, standing, walking and exploring were directly observed. Frequencies of exploratory climbs (ECs and abrupt climbs (ACs over the testing pen’s walls were video-recorded. Data were analysed using generalised linear mixed models with repeated measurements, including treatment and day as fixed effects and behaviour on Day –1 as a linear covariate. Control and TDAA lambs stood more frequently than TD lambs. TD lambs performed significantly more ACs compared to all other treatment groups. No other treatment effects were detected. A day effect was detected for all behaviours, while the EC frequency was highest for all tail-docked lambs on Day 5. Findings suggest that standing, ACs and ECs could be used as potential indicators of pain in isolated tail-docked lambs. However, differences in ECs between treatments only appeared 3 d after tail docking.

  4. Parallel Evolutionary Optimization Algorithms for Peptide-Protein Docking

    Science.gov (United States)

    Poluyan, Sergey; Ershov, Nikolay

    2018-02-01

    In this study we examine the possibility of using evolutionary optimization algorithms in protein-peptide docking. We present the main assumptions that reduce the docking problem to a continuous global optimization problem and provide a way of using evolutionary optimization algorithms. The Rosetta all-atom force field was used for structural representation and energy scoring. We describe the parallelization scheme and MPI/OpenMP realization of the considered algorithms. We demonstrate the efficiency and the performance for some algorithms which were applied to a set of benchmark tests.

  5. 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.

  6. Automatic design of decision-tree induction algorithms tailored to flexible-receptor docking data.

    Science.gov (United States)

    Barros, Rodrigo C; Winck, Ana T; Machado, Karina S; Basgalupp, Márcio P; de Carvalho, André C P L F; Ruiz, Duncan D; de Souza, Osmar Norberto

    2012-11-21

    This paper addresses the prediction of the free energy of binding of a drug candidate with enzyme InhA associated with Mycobacterium tuberculosis. This problem is found within rational drug design, where interactions between drug candidates and target proteins are verified through molecular docking simulations. In this application, it is important not only to correctly predict the free energy of binding, but also to provide a comprehensible model that could be validated by a domain specialist. Decision-tree induction algorithms have been successfully used in drug-design related applications, specially considering that decision trees are simple to understand, interpret, and validate. There are several decision-tree induction algorithms available for general-use, but each one has a bias that makes it more suitable for a particular data distribution. In this article, we propose and investigate the automatic design of decision-tree induction algorithms tailored to particular drug-enzyme binding data sets. We investigate the performance of our new method for evaluating binding conformations of different drug candidates to InhA, and we analyze our findings with respect to decision tree accuracy, comprehensibility, and biological relevance. The empirical analysis indicates that our method is capable of automatically generating decision-tree induction algorithms that significantly outperform the traditional C4.5 algorithm with respect to both accuracy and comprehensibility. In addition, we provide the biological interpretation of the rules generated by our approach, reinforcing the importance of comprehensible predictive models in this particular bioinformatics application. We conclude that automatically designing a decision-tree algorithm tailored to molecular docking data is a promising alternative for the prediction of the free energy from the binding of a drug candidate with a flexible-receptor.

  7. 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

  8. Identification of Phytochemicals Targeting c-Met Kinase Domain using Consensus Docking and Molecular Dynamics Simulation Studies.

    Science.gov (United States)

    Aliebrahimi, Shima; Montasser Kouhsari, Shideh; Ostad, Seyed Nasser; Arab, Seyed Shahriar; Karami, Leila

    2018-06-01

    c-Met receptor tyrosine kinase is a proto-oncogene whose aberrant activation is attributed to a lower rate of survival in most cancers. Natural product-derived inhibitors known as "fourth generation inhibitors" constitute more than 60% of anticancer drugs. Furthermore, consensus docking approach has recently been introduced to augment docking accuracy and reduce false positives during a virtual screening. In order to obtain novel small-molecule Met inhibitors, consensus docking approach was performed using Autodock Vina and Autodock 4.2 to virtual screen Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database against active and inactive conformation of c-Met kinase domain structure. Two hit molecules that were in line with drug-likeness criteria, desired docking score, and binding pose were subjected to molecular dynamics simulations to elucidate intermolecular contacts in protein-ligand complexes. Analysis of molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area studies showed that ZINC08234189 is a plausible inhibitor for the active state of c-Met, whereas ZINC03871891 may be more effective toward active c-Met kinase domain compared to the inactive form due to higher binding energy. Our analysis showed that both the hit molecules formed hydrogen bonds with key residues of the hinge region (P1158, M1160) in the active form, which is a hallmark of kinase domain inhibitors. Considering the pivotal role of HGF/c-Met signaling in carcinogenesis, our results propose ZINC08234189 and ZINC03871891 as the therapeutic options to surmount Met-dependent cancers.

  9. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment

    KAUST Repository

    Lensink, Marc F.

    2016-04-28

    We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. © 2016 Wiley Periodicals, Inc.

  10. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment

    KAUST Repository

    Lensink, Marc F.; Velankar, Sameer; Kryshtafovych, Andriy; Huang, Shen-You; Schneidman-Duhovny, Dina; Sali, Andrej; Segura, Joan; Fernandez-Fuentes, Narcis; Viswanath, Shruthi; Elber, Ron; Grudinin, Sergei; Popov, Petr; Neveu, Emilie; Lee, Hasup; Baek, Minkyung; Park, Sangwoo; Heo, Lim; Rie Lee, Gyu; Seok, Chaok; Qin, Sanbo; Zhou, Huan-Xiang; Ritchie, David W.; Maigret, Bernard; Devignes, Marie-Dominique; Ghoorah, Anisah; Torchala, Mieczyslaw; Chaleil, Raphaë l A.G.; Bates, Paul A.; Ben-Zeev, Efrat; Eisenstein, Miriam; Negi, Surendra S.; Weng, Zhiping; Vreven, Thom; Pierce, Brian G.; Borrman, Tyler M.; Yu, Jinchao; Ochsenbein, Franç oise; Guerois, Raphaë l; Vangone, Anna; Rodrigues, Joã o P.G.L.M.; van Zundert, Gydo; Nellen, Mehdi; Xue, Li; Karaca, Ezgi; Melquiond, Adrien S.J.; Visscher, Koen; Kastritis, Panagiotis L.; Bonvin, Alexandre M.J.J.; Xu, Xianjin; Qiu, Liming; Yan, Chengfei; Li, Jilong; Ma, Zhiwei; Cheng, Jianlin; Zou, Xiaoqin; Shen, Yang; Peterson, Lenna X.; Kim, Hyung-Rae; Roy, Amit; Han, Xusi; Esquivel-Rodriguez, Juan; Kihara, Daisuke; Yu, Xiaofeng; Bruce, Neil J.; Fuller, Jonathan C.; Wade, Rebecca C.; Anishchenko, Ivan; Kundrotas, Petras J.; Vakser, Ilya A.; Imai, Kenichiro; Yamada, Kazunori; Oda, Toshiyuki; Nakamura, Tsukasa; Tomii, Kentaro; Pallara, Chiara; Romero-Durana, Miguel; Jimé nez-Garcí a, Brian; Moal, Iain H.; Fé rnandez-Recio, Juan; Joung, Jong Young; Kim, Jong Yun; Joo, Keehyoung; Lee, Jooyoung; Kozakov, Dima; Vajda, Sandor; Mottarella, Scott; Hall, David R.; Beglov, Dmitri; Mamonov, Artem; Xia, Bing; Bohnuud, Tanggis; Del Carpio, Carlos A.; Ichiishi, Eichiro; Marze, Nicholas; Kuroda, Daisuke; Roy Burman, Shourya S.; Gray, Jeffrey J.; Chermak, Edrisse; Cavallo, Luigi; Oliva, Romina; Tovchigrechko, Andrey; Wodak, Shoshana J.

    2016-01-01

    We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. © 2016 Wiley Periodicals, Inc.

  11. Cytopathologist-performed and ultrasound-guided fine needle aspiration cytology enhances diagnostic accuracy and avoids pitfalls: An overview of 20 years of personal experience with a selection of didactic cases.

    Science.gov (United States)

    Paksoy, Nadir; Ozbek, Busra

    2018-01-01

    Over the last few decades, fine needle aspiration cytology (FNA) has emerged as a SAFE (Simple, Accurate, Fast, Economical) diagnostic tool based on the morphologic evaluation of cells. The first and most important step in obtaining accurate results from FNA is to procure sufficient and representative material from the lesion and to appropriately transfer this material to the laboratory. Unfortunately, the most important aspect of this task occurs beyond the control of the cytopathologist, a key reason for obtaining unsatisfactory results with FNA. There is growing interest in the field of cytology in "cytopathologist-performed ultrasound (US)-guided FNA," which has been reported to yield accurate results. The first author has been applying FNA in his own private cytopathology practice with a radiologist and under the guidance of US for more than 20 years. This study retrospectively reviews the utility of this practice. We present a selection of didactic examples under different headings that highlight the application of FNA by a cytopathologist, accompanied by US, under the guidance of a radiologist, in the form of an "outpatient FNA clinic." The use of this technique enhances diagnostic accuracy and prevents pitfalls. The highlights of each case are also outlined as "take-home messages."

  12. Target Price Accuracy

    Directory of Open Access Journals (Sweden)

    Alexander G. Kerl

    2011-04-01

    Full Text Available This study analyzes the accuracy of forecasted target prices within analysts’ reports. We compute a measure for target price forecast accuracy that evaluates the ability of analysts to exactly forecast the ex-ante (unknown 12-month stock price. Furthermore, we determine factors that explain this accuracy. Target price accuracy is negatively related to analyst-specific optimism and stock-specific risk (measured by volatility and price-to-book ratio. However, target price accuracy is positively related to the level of detail of each report, company size and the reputation of the investment bank. The potential conflicts of interests between an analyst and a covered company do not bias forecast accuracy.

  13. Solvated protein-protein docking using Kyte-Doolittle-based water preferences

    NARCIS (Netherlands)

    Kastritis, P.; Visscher, K.M.; van Dijk, A.D.J.; Bonvin, A.M.J.J.

    2013-01-01

    HADDOCK is one of the few docking programs that can explicitly account for water molecules in the docking process. Its solvated docking protocol starts from hydrated molecules and a fraction of the resulting interfacial waters is subsequently removed in a biased Monte Carlo procedure based on

  14. Solvated protein-protein docking using Kyte-Doolittle-based water preferences

    NARCIS (Netherlands)

    Kastritis, Panagiotis L.; Visscher, Koen M.; van Dijk, Aalt D.J.; Bonvin, Alexandre M.J.J.

    HADDOCK is one of the few docking programs that can explicitly account for water molecules in the docking process. Its solvated docking protocol starts from hydrated molecules and a fraction of the resulting interfacial waters is subsequently removed in a biased Monte Carlo procedure based on

  15. More tail lesions among undocked than tail docked pigs in a conventional herd

    DEFF Research Database (Denmark)

    Lahrmann, H. P.; Busch, M. E.; D'Eath, R. B.

    2017-01-01

    The vast majority of piglets reared in the European Union (EU) and worldwide is tail docked to reduce the risk of being tail bitten, even though EU animal welfare legislation bans routine tail docking. Many conventional herds experience low levels of tail biting among tail docked pigs, however...

  16. China Accomplished Its First Space Rendezvous and Docking

    Institute of Scientific and Technical Information of China (English)

    Chen Xiaoli

    2011-01-01

    At 1:36 am on November 3,China's Shenzhou 8 unmanned spaceship and Tiangong 1 space lab spacecraft accomplished the country's first space docking procedure and coupling in space at more than 343km above Earth's surface,marking a great leap in China's space program.

  17. Complete cDNA sequence coding for human docking protein

    Energy Technology Data Exchange (ETDEWEB)

    Hortsch, M; Labeit, S; Meyer, D I

    1988-01-11

    Docking protein (DP, or SRP receptor) is a rough endoplasmic reticulum (ER)-associated protein essential for the targeting and translocation of nascent polypeptides across this membrane. It specifically interacts with a cytoplasmic ribonucleoprotein complex, the signal recognition particle (SRP). The nucleotide sequence of cDNA encoding the entire human DP and its deduced amino acid sequence are given.

  18. Synthesis, biological evaluation and molecular docking studies of ...

    African Journals Online (AJOL)

    Synthesis, biological evaluation and molecular docking studies of Mannich bases derived from 1, 3, 4-oxadiazole- 2-thiones as potential urease inhibitors. ... Mannich bases (5-17) were subjected to in silico screening as urease inhibitors, using crystal structure of urease (Protein Data Bank ID: 5FSE) as a model enzyme.

  19. 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.

  20. Optimization of Spacecraft Rendezvous and Docking using Interval Analysis

    NARCIS (Netherlands)

    Van Kampen, E.; Chu, Q.P.; Mulder, J.A.

    2010-01-01

    This paper applies interval optimization to the fixed-time multiple impulse rendezvous and docking problem. Current methods for solving this type of optimization problem include for example genetic algorithms and gradient based optimization. Unlike these methods, interval methods can guarantee that

  1. Molecular Dynamics and Docking of Biphenyl: A Potential ...

    African Journals Online (AJOL)

    Purpose: To develop a new drug that inhibits viral attachment and entry for the treatment of HIV/AIDS patients. Methods: Two Protein Databank (PDB) crystal structures of HIV-1 gp120-CD4 complexes, namely, 1RZK and 1G9N, were mutated at amino acid position 43 to a biphenylalanine (biPhe-43) residue. FireDock web ...

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

    DEFF Research Database (Denmark)

    Petersen, Hanne Løhmann; Røpke, Stefan

    2011-01-01

    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...

  3. Synthesis, anti-microbial activity and molecular docking studies on ...

    Indian Academy of Sciences (India)

    Molecular structures of triazolylcoumarins 1–8. method and are ... organic layer was washed with water (100 mL) and sat- ... (0.5mmol) in a mixture of THF and water (1:1) solution. ..... for docking studies with the target DNA gyrase B (PDB.

  4. Synthesis and molecular docking of new hydrazones derived from ...

    African Journals Online (AJOL)

    Synthesis and molecular docking of new hydrazones derived from ethyl isonipecotate and their biological activities. A Munir, Aziz-ur Rehman, M.A. Abbasi, S.Z. Siddiqui, A Nasir, S.G. Khan, S Rasool, S.A.A. Shah ...

  5. Tail docking in dogs: can attitude change be achieved?

    Science.gov (United States)

    Bennett, P; Perini, E

    2003-05-01

    The debate about tail docking in domestic dogs continues to rage in many developed countries and attitudes expressed by different community groups remain diametrically opposed. Veterinary associations and welfare organisations typically want the practice banned, while many breeders and pure-bred dog associations just as vigorously oppose the introduction of anti-docking legislation. In recent years, much data have been accumulated concerning the welfare implications of tail docking. A recent evaluation of this literature suggests that the practice has little to recommend it and that, in the absence of reasonable case-by-case justification, it may constitute an unacceptable abuse of a sentient species. Given this situation, it is difficult to understand why many canine interest groups, presumably representing those people who care most about the welfare of companion dogs, should continue to hold such strong attitudes in favour of tail docking. In this review we attempt to explain why different community groups might espouse strong but opposing attitudes, despite having access to the same information. We argue that the theory of cognitive dissonance, popular among social psychologists, may provide a useful framework within which to understand, and attempt to alter, attitudes that persist even though they appear contrary to available empirical evidence.

  6. 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.

  7. 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.

  8. Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a.

    Science.gov (United States)

    Deplazes, Evelyne; Davies, Josephine; Bonvin, Alexandre M J J; King, Glenn F; Mark, Alan E

    2016-01-25

    Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining experimental information with restraint-driven docking approaches. Using the complex formed by the venom peptide PcTx1 and the acid sensing ion channel (ASIC) 1a as a case study, we have examined the effect of different combinations of restraints and input structures on the statistical likelihood of (a) correctly predicting the structure of the binding interface and (b) the ability to predict which residues are involved in specific pairwise peptide-channel interactions. For this, we have analyzed over 200,000 water-refined docked structures obtained with various amounts and types of restraints of the peptide-channel complex predicted using the docking program HADDOCK. We found that increasing the number of restraints or even the use of pairwise interaction data resulted in only a modest improvement in the likelihood of finding a structure within a given accuracy. This suggests that shape complementarity and the force field make a large contribution to the accuracy of the predicted structure. The results also showed that there are large variations in the accuracy of the predicted structure depending on the precise combination of residues used as restraints. Finally, we reflect on the limitations of relying on geometric criteria such as root-mean square deviations to assess the accuracy of docking procedures. We propose that in addition to currently used measures, the likelihood of finding a structure within a given level of accuracy should be also used to evaluate docking methods.

  9. An integrated autonomous rendezvous and docking system architecture using Centaur modern avionics

    Science.gov (United States)

    Nelson, Kurt

    1991-01-01

    The avionics system for the Centaur upper stage is in the process of being modernized with the current state-of-the-art in strapdown inertial guidance equipment. This equipment includes an integrated flight control processor with a ring laser gyro based inertial guidance system. This inertial navigation unit (INU) uses two MIL-STD-1750A processors and communicates over the MIL-STD-1553B data bus. Commands are translated into load activation through a Remote Control Unit (RCU) which incorporates the use of solid state relays. Also, a programmable data acquisition system replaces separate multiplexer and signal conditioning units. This modern avionics suite is currently being enhanced through independent research and development programs to provide autonomous rendezvous and docking capability using advanced cruise missile image processing technology and integrated GPS navigational aids. A system concept was developed to combine these technologies in order to achieve a fully autonomous rendezvous, docking, and autoland capability. The current system architecture and the evolution of this architecture using advanced modular avionics concepts being pursued for the National Launch System are discussed.

  10. Spectrofluoremetric and molecular docking study on the interaction of bisdemethoxycurcumin with bovine β-casein nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mehranfar, Fahimeh [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Bordbar, Abdol-Khalegh, E-mail: bordbar@chem.ui.ac.ir [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Keyhanfar, Mehrnaz; Behbahani, Mandana [Faculty of Advanced Sciences and Technologies, Department of Biotechnology, University of Isfahan, Isfahan, 81746-73441 (Iran, Islamic Republic of)

    2013-11-15

    The interaction of bisdemethoxycurcumin (BDMC), as one of the main active component of turmeric (Curcuma longa L.), with bovine β-casein nanoparticle, as an efficient drug carrier system, was investigated using steady-state fluorescence spectroscopy and molecular docking calculations. Results of fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations suggested that BDMC bind to the hydrophobic core of β-casein via formation of 3 hydrogen bonds and several vander Waals contacts that represented the encapsulation of BDMC in β-casein micelle nanoparticles. The binding parameters including number of substantive binding sites and the binding constants were evaluated by fluorescence quenching method. Additionally, the cytotoxicity of free BDMC and BDMC-β-casein complex in human breast cancer cell line MCF7 was evaluated in vitro. The study revealed the higher cytotoxic effects of encapsulated BDMC on MCF7 cells compared to equal dose of free BDMC. -- Highlights: • BDMC binds to the hydrophobic core of β-casein. • The effective encapsulation of BDMC in β-casein micelle nanoparticles was shown. • Enhanced cytotoxicity was observed for encapsulated BDMC in β-casein nanoparticles.

  11. The Design of New HIV-IN Tethered Bifunctional Inhibitors using Multiple Microdomain Targeted Docking.

    Science.gov (United States)

    Ciubotaru, Mihai; Musat, Mihaela Georgiana; Surleac, Marius; Ionita, Elena; Petrescu, Andrei Jose; Abele, Edgars; Abele, Ramona

    2018-04-05

    Currently used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes, changes these viral enzymes which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome of the host T lymphocyte, highlighting its main functional and structural features to be subjected to inhibitory action. From a functional and structural perspective we present all classes of HIV-IN inhibitors with their most representative candidates. For each chosen compound we also explain its mechanism of IN inhibition. We use the recently resolved cryo EM IN tetramer intasome DNA complex [1] onto which we dock various reference IN inhibitory chemical scaffolds such as to target adjacent functional IN domains. Pairing compounds with complementary activity, which dock in the vicinity of a IN structural microdomain, we design bifunctional new drugs which may not only be more resilient to IN mutations but also may be more potent inhibitors than their original counterparts. In the end of our review we propose synthesis pathways to link such paired compounds with enhanced synergistic IN inhibitory effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Spectrofluoremetric and molecular docking study on the interaction of bisdemethoxycurcumin with bovine β-casein nanoparticles

    International Nuclear Information System (INIS)

    Mehranfar, Fahimeh; Bordbar, Abdol-Khalegh; Keyhanfar, Mehrnaz; Behbahani, Mandana

    2013-01-01

    The interaction of bisdemethoxycurcumin (BDMC), as one of the main active component of turmeric (Curcuma longa L.), with bovine β-casein nanoparticle, as an efficient drug carrier system, was investigated using steady-state fluorescence spectroscopy and molecular docking calculations. Results of fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations suggested that BDMC bind to the hydrophobic core of β-casein via formation of 3 hydrogen bonds and several vander Waals contacts that represented the encapsulation of BDMC in β-casein micelle nanoparticles. The binding parameters including number of substantive binding sites and the binding constants were evaluated by fluorescence quenching method. Additionally, the cytotoxicity of free BDMC and BDMC-β-casein complex in human breast cancer cell line MCF7 was evaluated in vitro. The study revealed the higher cytotoxic effects of encapsulated BDMC on MCF7 cells compared to equal dose of free BDMC. -- Highlights: • BDMC binds to the hydrophobic core of β-casein. • The effective encapsulation of BDMC in β-casein micelle nanoparticles was shown. • Enhanced cytotoxicity was observed for encapsulated BDMC in β-casein nanoparticles

  13. Re-docking scheme for generating near-native protein complexes by assembling residue interaction fingerprints.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Uchikoga

    Full Text Available Interaction profile method is a useful method for processing rigid-body docking. After the docking process, the resulting set of docking poses could be classified by calculating similarities among them using these interaction profiles to search for near-native poses. However, there are some cases where the near-native poses are not included in this set of docking poses even when the bound-state structures are used. Therefore, we have developed a method for generating near-native docking poses by introducing a re-docking process. We devised a method for calculating the profile of interaction fingerprints by assembling protein complexes after determining certain core-protein complexes. For our analysis, we used 44 bound-state protein complexes selected from the ZDOCK benchmark dataset ver. 2.0, including some protein pairs none of which generated near-native poses in the docking process. Consequently, after the re-docking process we obtained profiles of interaction fingerprints, some of which yielded near-native poses. The re-docking process involved searching for possible docking poses in a restricted area using the profile of interaction fingerprints. If the profile includes interactions identical to those in the native complex, we obtained near-native docking poses. Accordingly, near-native poses were obtained for all bound-state protein complexes examined here. Application of interaction fingerprints to the re-docking process yielded structures with more native interactions, even when a docking pose, obtained following the initial docking process, contained only a small number of native amino acid interactions. Thus, utilization of the profile of interaction fingerprints in the re-docking process yielded more near-native poses.

  14. Re-docking scheme for generating near-native protein complexes by assembling residue interaction fingerprints.

    Science.gov (United States)

    Uchikoga, Nobuyuki; Matsuzaki, Yuri; Ohue, Masahito; Hirokawa, Takatsugu; Akiyama, Yutaka

    2013-01-01

    Interaction profile method is a useful method for processing rigid-body docking. After the docking process, the resulting set of docking poses could be classified by calculating similarities among them using these interaction profiles to search for near-native poses. However, there are some cases where the near-native poses are not included in this set of docking poses even when the bound-state structures are used. Therefore, we have developed a method for generating near-native docking poses by introducing a re-docking process. We devised a method for calculating the profile of interaction fingerprints by assembling protein complexes after determining certain core-protein complexes. For our analysis, we used 44 bound-state protein complexes selected from the ZDOCK benchmark dataset ver. 2.0, including some protein pairs none of which generated near-native poses in the docking process. Consequently, after the re-docking process we obtained profiles of interaction fingerprints, some of which yielded near-native poses. The re-docking process involved searching for possible docking poses in a restricted area using the profile of interaction fingerprints. If the profile includes interactions identical to those in the native complex, we obtained near-native docking poses. Accordingly, near-native poses were obtained for all bound-state protein complexes examined here. Application of interaction fingerprints to the re-docking process yielded structures with more native interactions, even when a docking pose, obtained following the initial docking process, contained only a small number of native amino acid interactions. Thus, utilization of the profile of interaction fingerprints in the re-docking process yielded more near-native poses.

  15. 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

  16. Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Olusola Olalekan Elekofehinti

    2018-06-01

    Full Text Available Visfatin (Nicotinamide phosphoribosyltransferase is an adipokine implicated in mediating insulin resistance and exhibiting insulin mimetic effect and therefore represents a druggable target for diabetes therapy. About 3,844 peroxisome proliferator activated receptor gamma (PPARγ agonists documented in Chembl database were docked with PPARγ and those with binding energy of >−9 kcal/mol having experimental EC50 of 0.1 to 1 nM were selected. The candidate compounds (27 were thereafter docked with visfatin (PDB ID: 4WQ6 using AutodockVina out of which eight compounds that ranked highest in binding energy (when compared with the co-crystallized ligand of visfatin: 3TQ were selected. Compound 25 exhibited favorable ligand-protein molecular interaction and respected Lipinski’s rule of five and interestingly from the absorption, distribution, metabolism and excretion (ADME-Toxicity analysis the compound have enhanced pharmacological properties than the current ligand of visfatin. Keywords: Nicotinamide phosphoribosyltransferase, Visfatin molecular docking, Type 2 diabetes, Adipokines

  17. Rational design of methicillin resistance staphylococcus aureus inhibitors through 3D-QSAR, molecular docking and molecular dynamics simulations.

    Science.gov (United States)

    Ballu, Srilata; Itteboina, Ramesh; Sivan, Sree Kanth; Manga, Vijjulatha

    2018-04-01

    Staphylococcus aureus is a gram positive bacterium. It is the leading cause of skin and respiratory infections, osteomyelitis, Ritter's disease, endocarditis, and bacteraemia in the developed world. We employed combined studies of 3D QSAR, molecular docking which are validated by molecular dynamics simulations and in silico ADME prediction have been performed on Isothiazoloquinolones inhibitors against methicillin resistance Staphylococcus aureus. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study was applied using comparative molecular field analysis (CoMFA) with Q 2 of 0.578, R 2 of 0.988, and comparative molecular similarity indices analysis (CoMSIA) with Q 2 of 0.554, R 2 of 0.975. The predictive ability of these model was determined using a test set of molecules that gave acceptable predictive correlation (r 2 Pred) values 0.55 and 0.57 of CoMFA and CoMSIA respectively. Docking, simulations were employed to position the inhibitors into protein active site to find out the most probable binding mode and most reliable conformations. Developed models and Docking methods provide guidance to design molecules with enhanced activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Diagnosing Eyewitness Accuracy

    OpenAIRE

    Russ, Andrew

    2015-01-01

    Eyewitnesses frequently mistake innocent people for the perpetrator of an observed crime. Such misidentifications have led to the wrongful convictions of many people. Despite this, no reliable method yet exists to determine eyewitness accuracy. This thesis explored two new experimental methods for this purpose. Chapter 2 investigated whether repetition priming can measure prior exposure to a target and compared this with observers’ explicit eyewitness accuracy. Across three experiments slower...

  19. MM-ISMSA: An Ultrafast and Accurate Scoring Function for Protein-Protein Docking.

    Science.gov (United States)

    Klett, Javier; Núñez-Salgado, Alfonso; Dos Santos, Helena G; Cortés-Cabrera, Álvaro; Perona, Almudena; Gil-Redondo, Rubén; Abia, David; Gago, Federico; Morreale, Antonio

    2012-09-11

    An ultrafast and accurate scoring function for protein-protein docking is presented. It includes (1) a molecular mechanics (MM) part based on a 12-6 Lennard-Jones potential; (2) an electrostatic component based on an implicit solvent model (ISM) with individual desolvation penalties for each partner in the protein-protein complex plus a hydrogen bonding term; and (3) a surface area (SA) contribution to account for the loss of water contacts upon protein-protein complex formation. The accuracy and performance of the scoring function, termed MM-ISMSA, have been assessed by (1) comparing the total binding energies, the electrostatic term, and its components (charge-charge and individual desolvation energies), as well as the per residue contributions, to results obtained with well-established methods such as APBSA or MM-PB(GB)SA for a set of 1242 decoy protein-protein complexes and (2) testing its ability to recognize the docking solution closest to the experimental structure as that providing the most favorable total binding energy. For this purpose, a test set consisting of 15 protein-protein complexes with known 3D structure mixed with 10 decoys for each complex was used. The correlation between the values afforded by MM-ISMSA and those from the other methods is quite remarkable (r(2) ∼ 0.9), and only 0.2-5.0 s (depending on the number of residues) are spent on a single calculation including an all vs all pairwise energy decomposition. On the other hand, MM-ISMSA correctly identifies the best docking solution as that closest to the experimental structure in 80% of the cases. Finally, MM-ISMSA can process molecular dynamics trajectories and reports the results as averaged values with their standard deviations. MM-ISMSA has been implemented as a plugin to the widely used molecular graphics program PyMOL, although it can also be executed in command-line mode. MM-ISMSA is distributed free of charge to nonprofit organizations.

  20. Sensor-based automated docking of large waste canisters

    International Nuclear Information System (INIS)

    Drotning, W.D.

    1990-01-01

    Sensor-based programmable robots have the potential to speed up remote manipulation operations while protecting operators from exposure to radiation. Conventional master/slave manipulators have proven to be very slow in performing precision remote operations. In addition, inadvertent collisions of remotely manipulated objects with their environment increase the hazards associated with remote handling. This paper describes the development of a robotic system for the sensor-based automated remote manipulation and precision docking of large payloads. Computer vision and proximity sensing are used to control the precision docking of a large object with a passive target cavity. Specifically, a container of nuclear spent fuel on a transport vehicle is mated with an emplacement door on a vertical storage borehole at a waste repository

  1. Rigid Body Energy Minimization on Manifolds for Molecular Docking.

    Science.gov (United States)

    Mirzaei, Hanieh; Beglov, Dmitri; Paschalidis, Ioannis Ch; Vajda, Sandor; Vakili, Pirooz; Kozakov, Dima

    2012-11-13

    Virtually all docking methods include some local continuous minimization of an energy/scoring function in order to remove steric clashes and obtain more reliable energy values. In this paper, we describe an efficient rigid-body optimization algorithm that, compared to the most widely used algorithms, converges approximately an order of magnitude faster to conformations with equal or slightly lower energy. The space of rigid body transformations is a nonlinear manifold, namely, a space which locally resembles a Euclidean space. We use a canonical parametrization of the manifold, called the exponential parametrization, to map the Euclidean tangent space of the manifold onto the manifold itself. Thus, we locally transform the rigid body optimization to an optimization over a Euclidean space where basic optimization algorithms are applicable. Compared to commonly used methods, this formulation substantially reduces the dimension of the search space. As a result, it requires far fewer costly function and gradient evaluations and leads to a more efficient algorithm. We have selected the LBFGS quasi-Newton method for local optimization since it uses only gradient information to obtain second order information about the energy function and avoids the far more costly direct Hessian evaluations. Two applications, one in protein-protein docking, and the other in protein-small molecular interactions, as part of macromolecular docking protocols are presented. The code is available to the community under open source license, and with minimal effort can be incorporated into any molecular modeling package.

  2. Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B

    Science.gov (United States)

    Verma, Neelam; Mittal, Minakshi; Verma, Raman kumar

    2008-01-01

    Protein Tyrosine Phosphatases (PTPs) that function as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin resistant disease states. Reducing Protein Tyrosine Phosphatase1B (PTP1B) abundance not only enhances insulin sensitivity and improves glucose metabolism but also protects against obesity induced by high fat feeding. PTP1B inhibitors such as Formylchromone derivatives, 1, 2-Naphthoquinone derivatives and Oxalyl aryl amino benzoic derivatives may eventually find an important clinical role as insulin sensitizers in the management of Type-II Diabetes and metabolic syndrome. We have carried out docking of modified oxalyl aryl amino benzoic acid derivatives into three dimensional structure of PTP1B using BioMed CAChe 6.1. These compounds exhibit good selectivity for PTP1B over most of phosphatases in selectivity panel such as SHP-2, LAR, CD45 and TCPTP found in literature. This series of compounds identified the amino acid residues such as Gly220 and Arg221 are important for achieving specificity via H-bonding interactions. Lipophilic side chain of methionine in modified oxalyl aryl amino benzoic acid derivative [1b (a2, b2, c1, d)] lies in closer vicinity of hydrophobic region of protein consisted of Meth258 and Phe52 in comparison to active ligand. Docking Score in [1b (a2, b2, c1, d)] is -131.740Kcal/mol much better than active ligand score -98.584Kcal/mol. This information can be exploited to design PTP1B specific inhibitors. PMID:19238234

  3. DOCK8 is critical for the survival and function of NKT cells.

    Science.gov (United States)

    Crawford, Greg; Enders, Anselm; Gileadi, Uzi; Stankovic, Sanda; Zhang, Qian; Lambe, Teresa; Crockford, Tanya L; Lockstone, Helen E; Freeman, Alexandra; Arkwright, Peter D; Smart, Joanne M; Ma, Cindy S; Tangye, Stuart G; Goodnow, Christopher C; Cerundolo, Vincenzo; Godfrey, Dale I; Su, Helen C; Randall, Katrina L; Cornall, Richard J

    2013-09-19

    Patients with the dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome suffer from recurrent viral and bacterial infections, hyper-immunoglobulin E levels, eczema, and greater susceptibility to cancer. Because natural killer T (NKT) cells have been implicated in these diseases, we asked if these cells were affected by DOCK8 deficiency. Using a mouse model, we found that DOCK8 deficiency resulted in impaired NKT cell development, principally affecting the formation and survival of long-lived, differentiated NKT cells. In the thymus, DOCK8-deficient mice lack a terminally differentiated subset of NK1.1(+) NKT cells expressing the integrin CD103, whereas in the liver, DOCK8-deficient NKT cells express reduced levels of the prosurvival factor B-cell lymphoma 2 and the integrin lymphocyte function-associated antigen 1. Although the initial NKT cell response to antigen is intact in the absence of DOCK8, their ongoing proliferative and cytokine responses are impaired. Importantly, a similar defect in NKT cell numbers was detected in DOCK8-deficient humans, highlighting the relevance of the mouse model. In conclusion, our data demonstrate that DOCK8 is required for the development and survival of mature NKT cells, consistent with the idea that DOCK8 mediates survival signals within a specialized niche. Accordingly, impaired NKT cell numbers and function are likely to contribute to the susceptibility of DOCK8-deficient patients to recurrent infections and malignant disease.

  4. DOCK8 is critical for the survival and function of NKT cells

    Science.gov (United States)

    Crawford, Greg; Enders, Anselm; Gileadi, Uzi; Stankovic, Sanda; Zhang, Qian; Lambe, Teresa; Crockford, Tanya L.; Lockstone, Helen E.; Freeman, Alexandra; Arkwright, Peter D.; Smart, Joanne M.; Ma, Cindy S.; Tangye, Stuart G.; Goodnow, Christopher C.; Cerundolo, Vincenzo; Godfrey, Dale I.; Su, Helen C.; Randall, Katrina L.

    2013-01-01

    Patients with the dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome suffer from recurrent viral and bacterial infections, hyper–immunoglobulin E levels, eczema, and greater susceptibility to cancer. Because natural killer T (NKT) cells have been implicated in these diseases, we asked if these cells were affected by DOCK8 deficiency. Using a mouse model, we found that DOCK8 deficiency resulted in impaired NKT cell development, principally affecting the formation and survival of long-lived, differentiated NKT cells. In the thymus, DOCK8-deficient mice lack a terminally differentiated subset of NK1.1+ NKT cells expressing the integrin CD103, whereas in the liver, DOCK8-deficient NKT cells express reduced levels of the prosurvival factor B-cell lymphoma 2 and the integrin lymphocyte function-associated antigen 1. Although the initial NKT cell response to antigen is intact in the absence of DOCK8, their ongoing proliferative and cytokine responses are impaired. Importantly, a similar defect in NKT cell numbers was detected in DOCK8-deficient humans, highlighting the relevance of the mouse model. In conclusion, our data demonstrate that DOCK8 is required for the development and survival of mature NKT cells, consistent with the idea that DOCK8 mediates survival signals within a specialized niche. Accordingly, impaired NKT cell numbers and function are likely to contribute to the susceptibility of DOCK8-deficient patients to recurrent infections and malignant disease. PMID:23929855

  5. Overlay accuracy fundamentals

    Science.gov (United States)

    Kandel, Daniel; Levinski, Vladimir; Sapiens, Noam; Cohen, Guy; Amit, Eran; Klein, Dana; Vakshtein, Irina

    2012-03-01

    Currently, the performance of overlay metrology is evaluated mainly based on random error contributions such as precision and TIS variability. With the expected shrinkage of the overlay metrology budget to DBO (1st order diffraction based overlay). It is demonstrated that the sensitivity of DBO to overlay mark asymmetry is larger than the sensitivity of imaging overlay. Finally, we show that a recently developed measurement quality metric serves as a valuable tool for improving overlay metrology accuracy. Simulation results demonstrate that the accuracy of imaging overlay can be improved significantly by recipe setup optimized using the quality metric. We conclude that imaging overlay metrology, complemented by appropriate use of measurement quality metric, results in optimal overlay accuracy.

  6. 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.

  7. Like a glove: do the dimensions of male adanal suckers and tritonymphal female docking papillae correlate in the Proctophyllodidae (Astigmata: Analgoidea)?

    OpenAIRE

    Byers , K.A.; Proctor , H.C.

    2014-01-01

    International audience; Precopulatory guarding of tritonymphal females by adult males is common in feather mites (Acari: Astigmata). Within the Proctophyllodidae (Astigmata: Analgoidea), some genera possess morphological features in both sexes that have been suggested to enhance male attachment. One such structure in tritonymphal females is the development of a pair of fleshy lobe-like docking papillae, while males possess a pair of ventral adanal suckers that are proposed to fit over top of ...

  8. Improving shuffler assay accuracy

    International Nuclear Information System (INIS)

    Rinard, P.M.

    1995-01-01

    Drums of uranium waste should be disposed of in an economical and environmentally sound manner. The most accurate possible assays of the uranium masses in the drums are required for proper disposal. The accuracies of assays from a shuffler are affected by the type of matrix material in the drums. Non-hydrogenous matrices have little effect on neutron transport and accuracies are very good. If self-shielding is known to be a minor problem, good accuracies are also obtained with hydrogenous matrices when a polyethylene sleeve is placed around the drums. But for those cases where self-shielding may be a problem, matrices are hydrogenous, and uranium distributions are non-uniform throughout the drums, the accuracies are degraded. They can be greatly improved by determining the distributions of the uranium and then applying correction factors based on the distributions. This paper describes a technique for determining uranium distributions by using the neutron count rates in detector banks around the waste drum and solving a set of overdetermined linear equations. Other approaches were studied to determine the distributions and are described briefly. Implementation of this correction is anticipated on an existing shuffler next year

  9. Structural and dynamical aspects of Streptococcus gordonii FabH through molecular docking and MD simulations.

    Science.gov (United States)

    Shamim, Amen; Abbasi, Sumra Wajid; Azam, Syed Sikander

    2015-07-01

    β-Ketoacyl-ACP-synthase III (FabH or KAS III) has become an attractive target for the development of new antibacterial agents which can overcome the multidrug resistance. Unraveling the fatty acid biosynthesis (FAB) metabolic pathway and understanding structural coordinates of FabH will provide valuable insights to target Streptococcus gordonii for curing oral infection. In this study, we designed inhibitors against therapeutic target FabH, in order to block the FAB pathway. As compared to other targets, FabH has more interactions with other proteins, located on the leading strand with higher codon adaptation index value and associated with lipid metabolism category of COG. Current study aims to gain in silico insights into the structural and dynamical aspect of S. gordonii FabH via molecular docking and molecular dynamics (MD) simulations. The FabH protein is catalytically active in dimerization while it can lock in monomeric state. Current study highlights two residues Pro88 and Leu315 that are close to each other by dimerization. The active site of FabH is composed of the catalytic triad formed by residues Cys112, His249, and Asn279 in which Cys112 is involved in acetyl transfer, while His249 and Asn279 play an active role in decarboxylation. Docking analysis revealed that among the studied compounds, methyl-CoA disulfide has highest GOLD score (82.75), binding affinity (-11 kcal/mol) and exhibited consistently better interactions. During MD simulations, the FabH structure remained stable with the average RMSD value of 1.7 Å and 1.6 Å for undocked protein and docked complex, respectively. Further, crucial hydrogen bonding of the conserved catalytic triad for exhibiting high affinity between the FabH protein and ligand is observed by RDF analysis. The MD simulation results clearly demonstrated that binding of the inhibitor with S. gordonii FabH enhanced the structure and stabilized the dimeric FabH protein. Therefore, the inhibitor has the potential to become

  10. Biallelic loss-of-function variants in DOCK3 cause muscle hypotonia, ataxia, and intellectual disability.

    Science.gov (United States)

    Helbig, K L; Mroske, C; Moorthy, D; Sajan, S A; Velinov, M

    2017-10-01

    DOCK3 encodes the dedicator of cytokinesis 3 protein, a member of the DOCK180 family of proteins that are characterized by guanine-nucleotide exchange factor activity. DOCK3 is expressed exclusively in the central nervous system and plays an important role in axonal outgrowth and cytoskeleton reorganization. Dock3 knockout mice exhibit motor deficiencies with abnormal ataxic gait and impaired learning. We report 2 siblings with biallelic loss-of-function variants in DOCK3. Diagnostic whole-exome sequencing (WES) and chromosomal microarray were performed on a proband with severe developmental disability, hypotonia, and ataxic gait. Testing was also performed on the proband's similarly affected brother. A paternally inherited 458 kb deletion in chromosomal region 3p21.2 disrupting the DOCK3 gene was identified in both affected siblings. WES identified a nonsense variant c.382C>G (p.Gln128*) in the DOCK3 gene (NM_004947) on the maternal allele in both siblings. Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. We show that complete DOCK3 deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development. © 2017 The Authors. Clinical Genetics published by John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Combining self- and cross-docking as benchmark tools: the performance of DockBench in the D3R Grand Challenge 2

    Science.gov (United States)

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

    2018-01-01

    Molecular docking is a powerful tool in the field of computer-aided molecular design. In particular, it is the technique of choice for the prediction of a ligand pose within its target binding site. A multitude of docking methods is available nowadays, whose performance may vary depending on the data set. Therefore, some non-trivial choices should be made before starting a docking simulation. In the same framework, the selection of the target structure to use could be challenging, since the number of available experimental structures is increasing. Both issues have been explored within this work. The pose prediction of a pool of 36 compounds provided by D3R Grand Challenge 2 organizers was preceded by a pipeline to choose the best protein/docking-method couple for each blind ligand. An integrated benchmark approach including ligand shape comparison and cross-docking evaluations was implemented inside our DockBench software. The results are encouraging and show that bringing attention to the choice of the docking simulation fundamental components improves the results of the binding mode predictions.

  12. Experimental, molecular docking investigations and bioavailability study on the inclusion complexes of finasteride and cyclodextrins

    Directory of Open Access Journals (Sweden)

    Mady FM

    2017-06-01

    Full Text Available Fatma M Mady,1,2 Usama Farghaly Aly2 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Taibah University, Medina, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt Abstract: Finasteride (FIN is a Class II candidate of the Biopharmaceutics Classification System (BCS. The lipophilic cavity of cyclodextrins (CyDs enables it to construct a non-covalent inclusion complex with different insoluble drugs. Only β-cyclodextrin (β-CyD and hydroxypropyl-β-CyD (HP-β-CyD have been previously examined with FIN. This study aimed to investigate the consistence of FIN with different kinds of β-CyDs, including dimethyl-β-cyclodextrin (DM-β-CyD, carboxymethyl-β-cyclodextrin (CM-β-CyD, HP-β-CyD, sulfobutyl ether-β-cyclodextrin (SBE-β-CyD, and β-CyD, by the coprecipitation method. The resultant inclusion systems were characterized by differential scanning calorimetry, infrared spectroscopy, X-ray diffractometry, and dissolution studies. Moreover, molecular docking for the selected inclusion systems was carried out to explore the suitable arrangements of FIN in the cavity of β-CyD or its derivatives. The results suggested that the DM-β-CyD inclusion system gave the higher complexation efficiency for improvement in solubility of FIN and hence enhancement of its bioavailability. Pharmacokinetic parameters displayed a higher absorption rate and higher area under the curve of the FIN/DM-β-CyD inclusion complex when compared with the drug alone, which indicates an improvement in the absorption and bioavailability of FIN in the DM-β-CyD inclusion system. Keywords: finasteride, cyclodextrins, molecular docking, pharmacokinetics, bioavailability

  13. 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.

  14. Geoid undulation accuracy

    Science.gov (United States)

    Rapp, Richard H.

    1993-01-01

    The determination of the geoid and equipotential surface of the Earth's gravity field, has long been of interest to geodesists and oceanographers. The geoid provides a surface to which the actual ocean surface can be compared with the differences implying information on the circulation patterns of the oceans. For use in oceanographic applications the geoid is ideally needed to a high accuracy and to a high resolution. There are applications that require geoid undulation information to an accuracy of +/- 10 cm with a resolution of 50 km. We are far from this goal today but substantial improvement in geoid determination has been made. In 1979 the cumulative geoid undulation error to spherical harmonic degree 20 was +/- 1.4 m for the GEM10 potential coefficient model. Today the corresponding value has been reduced to +/- 25 cm for GEM-T3 or +/- 11 cm for the OSU91A model. Similar improvements are noted by harmonic degree (wave-length) and in resolution. Potential coefficient models now exist to degree 360 based on a combination of data types. This paper discusses the accuracy changes that have taken place in the past 12 years in the determination of geoid undulations.

  15. Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors.

    Science.gov (United States)

    Raveh, Barak; London, Nir; Zimmerman, Lior; Schueler-Furman, Ora

    2011-04-29

    Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions. © 2011 Raveh et al.

  16. [Screen potential CYP450 2E1 inhibitors from Chinese herbal medicine based on support vector regression and molecular docking method].

    Science.gov (United States)

    Chen, Xi; Lu, Fang; Jiang, Lu-di; Cai, Yi-Lian; Li, Gong-Yu; Zhang, Yan-Ling

    2016-07-01

    Inhibition of cytochrome P450 (CYP450) enzymes is the most common reasons for drug interactions, so the study on early prediction of CYPs inhibitors can help to decrease the incidence of adverse reactions caused by drug interactions.CYP450 2E1(CYP2E1), as a key role in drug metabolism process, has broad spectrum of drug metabolism substrate. In this study, 32 CYP2E1 inhibitors were collected for the construction of support vector regression (SVR) model. The test set data were used to verify CYP2E1 quantitative models and obtain the optimal prediction model of CYP2E1 inhibitor. Meanwhile, one molecular docking program, CDOCKER, was utilized to analyze the interaction pattern between positive compounds and active pocket to establish the optimal screening model of CYP2E1 inhibitors.SVR model and molecular docking prediction model were combined to screen traditional Chinese medicine database (TCMD), which could improve the calculation efficiency and prediction accuracy. 6 376 traditional Chinese medicine (TCM) compounds predicted by SVR model were obtained, and in further verification by using molecular docking model, 247 TCM compounds with potential inhibitory activities against CYP2E1 were finally retained. Some of them have been verified by experiments. The results demonstrated that this study could provide guidance for the virtual screening of CYP450 inhibitors and the prediction of CYPs-mediated DDIs, and also provide references for clinical rational drug use. Copyright© by the Chinese Pharmaceutical Association.

  17. Structure and Sequence Search on Aptamer-Protein Docking

    Science.gov (United States)

    Xiao, Jiajie; Bonin, Keith; Guthold, Martin; Salsbury, Freddie

    2015-03-01

    Interactions between proteins and deoxyribonucleic acid (DNA) play a significant role in the living systems, especially through gene regulation. However, short nucleic acids sequences (aptamers) with specific binding affinity to specific proteins exhibit clinical potential as therapeutics. Our capillary and gel electrophoresis selection experiments show that specific sequences of aptamers can be selected that bind specific proteins. Computationally, given the experimentally-determined structure and sequence of a thrombin-binding aptamer, we can successfully dock the aptamer onto thrombin in agreement with experimental structures of the complex. In order to further study the conformational flexibility of this thrombin-binding aptamer and to potentially develop a predictive computational model of aptamer-binding, we use GPU-enabled molecular dynamics simulations to both examine the conformational flexibility of the aptamer in the absence of binding to thrombin, and to determine our ability to fold an aptamer. This study should help further de-novo predictions of aptamer sequences by enabling the study of structural and sequence-dependent effects on aptamer-protein docking specificity.

  18. Waste Isolation Pilot Plant TruDock crane system analysis

    International Nuclear Information System (INIS)

    Morris, B.C.; Carter, M.

    1996-10-01

    The WIPP TruDock crane system located in the Waste Handling Building was identified in the WIPP Safety Analysis Report (SAR), November 1995, as a potential accident concern due to failures which could result in a dropped load. The objective of this analysis is to evaluate the frequency of failure of the TruDock crane system resulting in a dropped load and subsequent loss of primary containment, i.e. drum failure. The frequency of dropped loads was estimated to be 9.81E-03/year or approximately one every 102 years (or, for the 25% contingency, 7.36E-03/year or approximately one every 136 years). The dominant accident contributor was the failure of the cable/hook assemblies, based on failure data obtained from NUREG-0612, as analyzed by PLG, Inc. The WIPP crane system undergoes a rigorous test and maintenance program, crane operation is discontinued following any abnormality, and the crane operator and load spotter are required to be trained in safe crane operation, therefore it is felt that the WIPP crane performance will exceed the data presented in NUREG-0612 and the estimated failure frequency is felt to be conservative

  19. Gab Docking Proteins in Cardiovascular Disease, Cancer, and Inflammation

    Directory of Open Access Journals (Sweden)

    Yoshikazu Nakaoka

    2013-01-01

    Full Text Available The docking proteins of the Grb2-associated binder (Gab family have emerged as crucial signaling compartments in metazoans. In mammals, the Gab proteins, consisting of Gab1, Gab2, and Gab3, are involved in the amplification and integration of signal transduction evoked by a variety of extracellular stimuli, including growth factors, cytokines, antigens, and other molecules. Gab proteins lack the enzymatic activity themselves; however, when phosphorylated on tyrosine residues, they provide binding sites for multiple Src homology-2 (SH2 domain-containing proteins, such as SH2-containing protein tyrosine phosphatase 2 (SHP2, phosphatidylinositol 3-kinase regulatory subunit p85, phospholipase Cγ, Crk, and GC-GAP. Through these interactions, the Gab proteins transduce signals from activated receptors into pathways with distinct biological functions, thereby contributing to signal diversification. They are known to play crucial roles in numerous physiological processes through their associations with SHP2 and p85. In addition, abnormal Gab protein signaling has been linked to human diseases including cancer, cardiovascular disease, and inflammatory disorders. In this paper, we provide an overview of the structure, effector functions, and regulation of the Gab docking proteins, with a special focus on their associations with cardiovascular disease, cancer, and inflammation.

  20. Sex differences in accuracy and precision when judging time to arrival: data from two Internet studies.

    Science.gov (United States)

    Sanders, Geoff; Sinclair, Kamila

    2011-12-01

    We report two Internet studies that investigated sex differences in the accuracy and precision of judging time to arrival. We used accuracy to mean the ability to match the actual time to arrival and precision to mean the consistency with which each participant made their judgments. Our task was presented as a computer game in which a toy UFO moved obliquely towards the participant through a virtual three-dimensional space on route to a docking station. The UFO disappeared before docking and participants pressed their space bar at the precise moment they thought the UFO would have docked. Study 1 showed it was possible to conduct quantitative studies of spatiotemporal judgments in virtual reality via the Internet and confirmed reports that men are more accurate because women underestimate, but found no difference in precision measured as intra-participant variation. Study 2 repeated Study 1 with five additional presentations of one condition to provide a better measure of precision. Again, men were more accurate than women but there were no sex differences in precision. However, within the coincidence-anticipation timing (CAT) literature, of those studies that report sex differences, a majority found that males are both more accurate and more precise than females. Noting that many CAT studies report no sex differences, we discuss appropriate interpretations of such null findings. While acknowledging that CAT performance may be influenced by experience we suggest that the sex difference may have originated among our ancestors with the evolutionary selection of men for hunting and women for gathering.

  1. QSAR, molecular docking studies of thiophene and imidazopyridine derivatives as polo-like kinase 1 inhibitors

    Science.gov (United States)

    Cao, Shandong

    2012-08-01

    The purpose of the present study was to develop in silico models allowing for a reliable prediction of polo-like kinase inhibitors based on a large diverse dataset of 136 compounds. As an effective method, quantitative structure activity relationship (QSAR) was applied using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The proposed QSAR models showed reasonable predictivity of thiophene analogs (Rcv2=0.533, Rpred2=0.845) and included four molecular descriptors, namely IC3, RDF075m, Mor02m and R4e+. The optimal model for imidazopyridine derivatives (Rcv2=0.776, Rpred2=0.876) was shown to perform good in prediction accuracy, using GATS2m and BEHe1 descriptors. Analysis of the contour maps helped to identify structural requirements for the inhibitors and served as a basis for the design of the next generation of the inhibitor analogues. Docking studies were also employed to position the inhibitors into the polo-like kinase active site to determine the most probable binding mode. These studies may help to understand the factors influencing the binding affinity of chemicals and to develop alternative methods for prescreening and designing of polo-like kinase inhibitors.

  2. Path Planning Method for UUV Homing and Docking in Movement Disorders Environment

    Directory of Open Access Journals (Sweden)

    Zheping Yan

    2014-01-01

    Full Text Available Path planning method for unmanned underwater vehicles (UUV homing and docking in movement disorders environment is proposed in this paper. Firstly, cost function is proposed for path planning. Then, a novel particle swarm optimization (NPSO is proposed and applied to find the waypoint with minimum value of cost function. Then, a strategy for UUV enters into the mother vessel with a fixed angle being proposed. Finally, the test function is introduced to analyze the performance of NPSO and compare with basic particle swarm optimization (BPSO, inertia weight particle swarm optimization (LWPSO, EPSO, and time-varying acceleration coefficient (TVAC. It has turned out that, for unimodal functions, NPSO performed better searching accuracy and stability than other algorithms, and, for multimodal functions, the performance of NPSO is similar to TVAC. Then, the simulation of UUV path planning is presented, and it showed that, with the strategy proposed in this paper, UUV can dodge obstacles and threats, and search for the efficiency path.

  3. Engineering Evaluation of International Low Impact Docking System Latch Hooks

    Science.gov (United States)

    Martinez, J.; Patin, R.; Figert, J.

    2013-01-01

    The international Low Impact Docking System (iLIDS) provides a structural arrangement that allows for visiting vehicles to dock with the International Space Station (ISS) (Fig 1). The iLIDS docking units are mechanically joined together by a series of active and passive latch hooks. In order to preserve docking capability at the existing Russian docking interfaces, the iLIDS latch hooks are required to conform to the existing Russian design. The latch hooks are classified as being fail-safe. Since the latch hooks are fail-safe, the hooks are not fracture critical and a fatigue based service life assessment will satisfy the structural integrity requirements. Constant amplitude fatigue testing to failure on four sets of active/passive iLIDS latch hooks was performed at load magnitudes of 10, 11, and 12 kips. Failure analysis of the hook fatigue failures identified multi-site fatigue initiation that was effectively centered about the hook mid-plane (consistent with the 3D model results). The fatigue crack initiation distribution implies that the fatigue damage accumulation effectively results in a very low aspect ratio surface crack (which can be simulated as thru-thickness crack). Fatigue damage progression resulted in numerous close proximity fatigue crack initiation sites. It was not possible to determine if fatigue crack coalescence occurs during cyclic loading or as result of the fast fracture response. The presence of multiple fatigue crack initiation sites on different planes will result in the formation of ratchet marks as the cracks coalesce. Once the stable fatigue crack becomes unstable and the fast fracture advances across the remaining ligament and the plane stress condition at a free-surface will result in failure along a 45 deg. shear plane (slant fracture) and the resulting inclined edge is called a shear lip. The hook thickness on the plane of fatigue crack initiation is 0.787". The distance between the shear lips on this plane was on the order of 0

  4. Rendezvous and Docking Technology for Space Flight%空间交会对接技术

    Institute of Scientific and Technical Information of China (English)

    郑永煌

    2011-01-01

    空间交会对接是载人航天工程非常重要的基本技术.在介绍空间交会对接技术发展历史和中国首次交会对接取得圆满成功的基础上,阐述了空间交会对接技术的基本概念、技术难点、控制方式和交会对接过程,并着重介绍了四种交会对接机构的特点.最后介绍了中国首次交会对接任务规划、天宫一号目标飞行器和神舟八号飞船的特点以及两次空间交会对接过程.%Rendezvous and Docking is a very important basic technology of Manned Space Engineering. Firstly, rendezvous and docking technology development history is provided, and the significance of China first rendezvous and docking success is presented. Secondly, the basic conception, technology difficulty, control mode and docking process of rendezvous and docking technology are explained.Thirdly, four docking mechanism characteristics are special provided. Finally, China first rendezvous and docking mission planning,characteristic of Tiangong-1 target flight vehicle and Shenzhou-8 spacecraft and two rendezvous and docking successes are presented.

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

    Indian Academy of Sciences (India)

    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 ...

  6. 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

  7. HDOCK: a web server for protein–protein and protein–DNA/RNA docking based on a hybrid strategy

    Science.gov (United States)

    Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong

    2017-01-01

    Abstract Protein–protein and protein–DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein–protein and protein–DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10–20 min for a docking run. Tested on the cases with weakly homologous complexes of server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. PMID:28521030

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

    Science.gov (United States)

    Li, Haiou; Lu, Liyao; Chen, Rong; Quan, Lijun; Xia, Xiaoyan; Lü, Qiang

    2014-01-01

    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.

  9. 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.

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

    Science.gov (United States)

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

    2015-06-01

    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.

  11. Borda application of selection planning scheduling method in dock engineering consultants in Central Sulawesi province Indonesia

    Directory of Open Access Journals (Sweden)

    Siti Fatimah

    2015-04-01

    Full Text Available The aim of this paper to find out the planning scheduling method that used in dock engineering consultants as a project supervisor dock. This research use qualitative approach to find the most preferred method by engineering consultants, this research was explorative that test and find out the most preferred method. This research showed that dock engineering consultants in Palu City, Central Sulawesi most preferred curve-s method than method such as CPM, PERT, PDM, and Bar Chart. This research can help further research to determine differences and similarities the project planning scheduling method and being basic for The New Dock Engineering Consultans. This research looking for the most preferred method with limited respondents dock engineering consultans in Palu City, Central Sulawesi.

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

    DEFF Research Database (Denmark)

    Frank, Scott 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 similar......:10.1038/onc.2016.345....

  13. Does a Structured Data Collection Form Improve The Accuracy of ...

    African Journals Online (AJOL)

    and multiple etiologies for similar presentation. Standardized forms may harmonize the initial assessment, improve accuracy of diagnosis and enhance outcomes. Objectives: To determine the extent to which use of a structured data collection form (SDCF) affected the diagnostic accuracy of AAP. Methodology: A before and ...

  14. Space vehicle with customizable payload and docking station

    Science.gov (United States)

    Judd, Stephen; Dallmann, Nicholas; McCabe, Kevin; Seitz, Daniel

    2018-01-30

    A "black box" space vehicle solution may allow a payload developer to define the mission space and provide mission hardware within a predetermined volume and with predetermined connectivity. Components such as the power module, radios and boards, attitude determination and control system (ADCS), command and data handling (C&DH), etc. may all be provided as part of a "stock" (i.e., core) space vehicle. The payload provided by the payload developer may be plugged into the space vehicle payload section, tested, and launched without custom development of core space vehicle components by the payload developer. A docking station may facilitate convenient development and testing of the space vehicle while reducing handling thereof.

  15. Solving a molecular docking problem by the modified PSO method

    Directory of Open Access Journals (Sweden)

    A. P. Karpenko

    2014-01-01

    Full Text Available The paper presents an canonical method of the swarm particles in two modifications to raise this method efficiency in solving multi-extreme problems of high dimension optimization. The essence of PSO-M1 modification is to form two new points to attract swarm particles (along with the points which are responsible for inertial, cognitive, and social components of canonical method. These new points represent the best points of sets of particles-neighbours of a given point. The modification aims to diversify search. All free parameters of the PSO-M1 method (as well as an canonical method are static. In contrast, one of such parameters of PSO-M2 modification is dynamic. So this modification represents an example of a self-adaptive method of optimization. The modification aims to intensify search. A computing experiment to study the method efficiency and its abovementioned modifications at solving the test problems of optimization showed advantages of offered modifications in comparison with canonical method, revealed a superiority of PSO-M2 modification both over canonical method, and over PSO-M1 modification. Using the PSO-M2 method allows us to solve the 28-dimensional molecular docking problem of HIV1 protease and darunaviry 3U7S as the molecules of receptor and a ligand, respectively. Results of computing experiment have shown that the PSO-M2 method successfully finds the position of ligand close to native and can be recommended for solving the molecular docking problems as an alternative to genetic algorithm.

  16. Homology modeling, molecular docking and DNA binding studies of nucleotide excision repair UvrC protein from M. tuberculosis.

    Science.gov (United States)

    Parulekar, Rishikesh S; Barage, Sagar H; Jalkute, Chidambar B; Dhanavade, Maruti J; Fandilolu, Prayagraj M; Sonawane, Kailas D

    2013-08-01

    Mycobacterium tuberculosis is a Gram positive, acid-fast bacteria belonging to genus Mycobacterium, is the leading causative agent of most cases of tuberculosis. The pathogenicity of the bacteria is enhanced by its developed DNA repair mechanism which consists of machineries such as nucleotide excision repair. Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. UvrC protein is a part of this complex and thus helps to repair the damaged DNA of M. tuberculosis. Hence, structural bioinformatics study of UvrC protein from M. tuberculosis was carried out using homology modeling and molecular docking techniques. Assessment of the reliability of the homology model was carried out by predicting its secondary structure along with its model validation. The predicted structure was docked with the ATP and the interacting amino acid residues of UvrC protein with the ATP were found to be TRP539, PHE89, GLU536, ILE402 and ARG575. The binding of UvrC protein with the DNA showed two different domains. The residues from domain I of the protein VAL526, THR524 and LEU521 interact with the DNA whereas, amino acids interacting from the domain II of the UvrC protein included ARG597, GLU595, GLY594 and GLY592 residues. This predicted model could be useful to design new inhibitors of UvrC enzyme to prevent pathogenesis of Mycobacterium and so the tuberculosis.

  17. An Efficient ABC_DE_Based Hybrid Algorithm for Protein–Ligand Docking

    Directory of Open Access Journals (Sweden)

    Boxin Guan

    2018-04-01

    Full Text Available Protein–ligand docking is a process of searching for the optimal binding conformation between the receptor and the ligand. Automated docking plays an important role in drug design, and an efficient search algorithm is needed to tackle the docking problem. To tackle the protein–ligand docking problem more efficiently, An ABC_DE_based hybrid algorithm (ADHDOCK, integrating artificial bee colony (ABC algorithm and differential evolution (DE algorithm, is proposed in the article. ADHDOCK applies an adaptive population partition (APP mechanism to reasonably allocate the computational resources of the population in each iteration process, which helps the novel method make better use of the advantages of ABC and DE. The experiment tested fifty protein–ligand docking problems to compare the performance of ADHDOCK, ABC, DE, Lamarckian genetic algorithm (LGA, running history information guided genetic algorithm (HIGA, and swarm optimization for highly flexible protein–ligand docking (SODOCK. The results clearly exhibit the capability of ADHDOCK toward finding the lowest energy and the smallest root-mean-square deviation (RMSD on most of the protein–ligand docking problems with respect to the other five algorithms.

  18. 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.

  19. Mathematical Modeling and Kinematics Analysis of Double Spherical Shell Rotary Docking Skirt

    Directory of Open Access Journals (Sweden)

    Gong Haixia

    2017-01-01

    Full Text Available In order to solve the problem of large trim and heel angles of the wrecked submarine, the double spherical shell rotating docking skirt is studied. According to the working principle of the rotating docking skirt, and the fixed skirt, the directional skirt, the angle skirt are simplified as the connecting rod. Therefore, the posture equation and kinematics model of the docking skirt are deduced, and according to the kinematics model, the angle of rotation of the directional skirt and the angle skirt is obtained when the wrecked submarine is in different trim and heel angles. Through the directional skirt and angle skirt with the matching rotation can make docking skirt interface in the 0°~2γ range within the rotation, to complete the docking skirt and the wrecked submarine docking. The MATLAB software is used to visualize the rotation angle of fixed skirt and directional skirt, which lays a good foundation for the development of the control of the double spherical shell rotating docking skirt in future.

  20. Fast and accurate grid representations for atom-based docking with partner flexibility.

    Science.gov (United States)

    de Vries, Sjoerd J; Zacharias, Martin

    2017-06-30

    Macromolecular docking methods can broadly be divided into geometric and atom-based methods. Geometric methods use fast algorithms that operate on simplified, grid-like molecular representations, while atom-based methods are more realistic and flexible, but far less efficient. Here, a hybrid approach of grid-based and atom-based docking is presented, combining precalculated grid potentials with neighbor lists for fast and accurate calculation of atom-based intermolecular energies and forces. The grid representation is compatible with simultaneous multibody docking and can tolerate considerable protein flexibility. When implemented in our docking method ATTRACT, grid-based docking was found to be ∼35x faster. With the OPLSX forcefield instead of the ATTRACT coarse-grained forcefield, the average speed improvement was >100x. Grid-based representations may allow atom-based docking methods to explore large conformational spaces with many degrees of freedom, such as multiple macromolecules including flexibility. This increases the domain of biological problems to which docking methods can be applied. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  1. GPCR-Bench: A Benchmarking Set and Practitioners' Guide for G Protein-Coupled Receptor Docking.

    Science.gov (United States)

    Weiss, Dahlia R; Bortolato, Andrea; Tehan, Benjamin; Mason, Jonathan S

    2016-04-25

    Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a publically available docking benchmarking set in the spirit of the DUD and DUD-E reference data sets for validation studies, containing 25 nonredundant high-resolution GPCR costructures with an accompanying set of diverse ligands and computational decoy molecules for each target. Benchmarking sets are often used to compare docking protocols; however, it is important to evaluate docking methods not by "retrospective" hit rates but by the actual likelihood that they will produce novel prospective hits. Therefore, docking protocols must not only rank active molecules highly but also produce good poses that a chemist will select for purchase and screening. Currently, no simple objective machine-scriptable function exists that can do this; instead, docking hit lists must be subjectively examined in a consistent way to compare between docking methods. We present here a case study highlighting considerations we feel are of importance when evaluating a method, intended to be useful as a practitioners' guide.

  2. 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.

  3. 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

  4. 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.

  5. System and Method for Automated Rendezvous, Docking and Capture of Autonomous Underwater Vehicles

    Science.gov (United States)

    Stone, William C. (Inventor); Clark, Evan (Inventor); Richmond, Kristof (Inventor); Paulus, Jeremy (Inventor); Kapit, Jason (Inventor); Scully, Mark (Inventor); Kimball, Peter (Inventor)

    2018-01-01

    A system for automated rendezvous, docking, and capture of autonomous underwater vehicles at the conclusion of a mission comprising of comprised of a docking rod having lighted, pulsating (in both frequency and light intensity) series of LED light strips thereon, with the LEDs at a known spacing, and the autonomous underwater vehicle specially designed to detect and capture the docking rod and then be lifted structurally by a spherical end strop about which the vehicle can be pivoted and hoisted up (e.g., onto a ship). The method of recovery allows for very routine and reliable automated recovery of an unmanned underwater asset.

  6. 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

  7. Meditation experience predicts introspective accuracy.

    Directory of Open Access Journals (Sweden)

    Kieran C R Fox

    Full Text Available The accuracy of subjective reports, especially those involving introspection of one's own internal processes, remains unclear, and research has demonstrated large individual differences in introspective accuracy. It has been hypothesized that introspective accuracy may be heightened in persons who engage in meditation practices, due to the highly introspective nature of such practices. We undertook a preliminary exploration of this hypothesis, examining introspective accuracy in a cross-section of meditation practitioners (1-15,000 hrs experience. Introspective accuracy was assessed by comparing subjective reports of tactile sensitivity for each of 20 body regions during a 'body-scanning' meditation with averaged, objective measures of tactile sensitivity (mean size of body representation area in primary somatosensory cortex; two-point discrimination threshold as reported in prior research. Expert meditators showed significantly better introspective accuracy than novices; overall meditation experience also significantly predicted individual introspective accuracy. These results suggest that long-term meditators provide more accurate introspective reports than novices.

  8. Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer.

    Science.gov (United States)

    Metelli, Alessandra; Wu, Bill X; Fugle, Caroline W; Rachidi, Saleh; Sun, Shaoli; Zhang, Yongliang; Wu, Jennifer; Tomlinson, Stephen; Howe, Philip H; Yang, Yi; Garrett-Mayer, Elizabeth; Liu, Bei; Li, Zihai

    2016-12-15

    GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGFβ bioactivity and promoted malignant transformation in immunodeficient mice. In breast carcinoma-bearing mice that were immunocompetent, GARP overexpression promoted Foxp3 + Treg activity, which in turn contributed to enhancing cancer progression and metastasis. Notably, administration of a GARP-specific mAb limited metastasis in an orthotopic model of human breast cancer. Overall, these results define the oncogenic effects of the GARP-TGFβ axis in the tumor microenvironment and suggest mechanisms that might be exploited for diagnostic and therapeutic purposes. Cancer Res; 76(24); 7106-17. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. An effective docking strategy for virtual screening based on multi-objective optimization algorithm

    Directory of Open Access Journals (Sweden)

    Kang Ling

    2009-02-01

    Full Text Available Abstract Background Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. Results In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. Conclusion The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.

  10. In-vitro dissolution rate and molecular docking studies of cabergoline drug with β-cyclodextrin

    Science.gov (United States)

    Shanmuga priya, Arumugam; Balakrishnan, Suganya bharathi; Veerakanellore, Giri Babu; Stalin, Thambusamy

    2018-05-01

    The physicochemical properties and dissolution profile of cabergoline drug (CAB) with β-cyclodextrin (β-CD) inclusion complex were investigated by the UV spectroscopy. The inclusion complex has used to calculate the stability constant and gives the stoichiometry molar ratio is 1:1 between CAB and β-CD. The phase solubility diagram and the aqueous solubility of CAB (60%) was found to be enhanced by β-CD. In addition, the phase solubility profile of CAB with β-CD was classified as AL-type. Binary systems of CAB with β-CD were prepared by Physical mixture, Kneading and solvent evaporation methods. The solid-state properties of the inclusion complex were characterized by Fourier transformation-infrared spectroscopy, Differential scanning calorimetry, Powder X-ray diffractometric patterns and Scanning electron microscopic techniques. Theoretically, β-CD and CAB inclusion complex obtained by molecular docking studies, it is in good correlation with the results obtained through experimental methods using the Schrödinger software program. In-vitro dissolution profiles of the inclusion complexes were carried out and obvious increase in dissolution rate was observed when compared with pure CAB drug and the complexes.

  11. Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study.

    Directory of Open Access Journals (Sweden)

    Huai-Chun Chen

    Full Text Available The second messenger lipid PIP(3 (phosphatidylinositol-3,4,5-trisphosphate is generated by the lipid kinase PI3K (phosphoinositide-3-kinase in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP(3-specific pleckstrin homology (PH domains to the membrane surface. Despite the broad importance of PIP(3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP(3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP(3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i PIP(3 target lipid that provides specificity and affinity, and (ii PS facilitator lipid that enhances the PIP(3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP(3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP(3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP(3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral

  12. Tail Docking of Canine Puppies: Reassessment of the Tail's Role in Communication, the Acute Pain Caused by Docking and Interpretation of Behavioural Responses.

    Science.gov (United States)

    Mellor, David J

    2018-05-31

    Laws, regulations and professional standards increasingly aim to ban or restrict non-therapeutic tail docking in canine puppies. These constraints have usually been justified by reference to loss of tail participation in communication between dogs, the acute pain presumed to be caused during docking itself, subsequent experiences of chronic pain and heightened pain sensitivity, and the occurrence of other complications. These areas are reconsidered here. First, a scientifically robust examination of the dynamic functional foundations, sensory components and key features of body language that are integral to canine communication shows that the role of the tail has been greatly underestimated. More specifically, it shows that tail behaviour is so embedded in canine communication that docking can markedly impede unambiguous interactions between different dogs and between dogs and people. These interactions include the expression of wide ranges of both negative and positive emotions, moods and intentions that are of daily significance for dog welfare. Moreover, all docked dogs may experience these impediments throughout their lives, which challenges assertions by opponents to such bans or restrictions that the tail is a dispensable appendage. Second, and in contrast, a re-examination of the sensory capacities of canine puppies reveals that they cannot consciously experience acute or chronic pain during at least the first week after birth, which is when they are usually docked. The contrary view is based on questionable between-species extrapolation of information about pain from neurologically mature newborns such as calves, lambs, piglets and human infants, which certainly can consciously experience pain in response to injury, to neurologically immature puppies which remain unconscious and therefore unable to experience pain until about two weeks after birth. Third, underpinned by the incorrect conclusion that puppies are conscious at the usual docking age, it is

  13. Tail Docking of Canine Puppies: Reassessment of the Tail’s Role in Communication, the Acute Pain Caused by Docking and Interpretation of Behavioural Responses

    Directory of Open Access Journals (Sweden)

    David J. Mellor

    2018-05-01

    Full Text Available Laws, regulations and professional standards increasingly aim to ban or restrict non-therapeutic tail docking in canine puppies. These constraints have usually been justified by reference to loss of tail participation in communication between dogs, the acute pain presumed to be caused during docking itself, subsequent experiences of chronic pain and heightened pain sensitivity, and the occurrence of other complications. These areas are reconsidered here. First, a scientifically robust examination of the dynamic functional foundations, sensory components and key features of body language that are integral to canine communication shows that the role of the tail has been greatly underestimated. More specifically, it shows that tail behaviour is so embedded in canine communication that docking can markedly impede unambiguous interactions between different dogs and between dogs and people. These interactions include the expression of wide ranges of both negative and positive emotions, moods and intentions that are of daily significance for dog welfare. Moreover, all docked dogs may experience these impediments throughout their lives, which challenges assertions by opponents to such bans or restrictions that the tail is a dispensable appendage. Second, and in contrast, a re-examination of the sensory capacities of canine puppies reveals that they cannot consciously experience acute or chronic pain during at least the first week after birth, which is when they are usually docked. The contrary view is based on questionable between-species extrapolation of information about pain from neurologically mature newborns such as calves, lambs, piglets and human infants, which certainly can consciously experience pain in response to injury, to neurologically immature puppies which remain unconscious and therefore unable to experience pain until about two weeks after birth. Third, underpinned by the incorrect conclusion that puppies are conscious at the usual

  14. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    KAUST Repository

    Oliva, Romina M.; Vangone, Anna; Cavallo, Luigi

    2013-01-01

    ) 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

  16. 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.

  17. A collaborative filtering approach for protein-protein docking scoring functions.

    Science.gov (United States)

    Bourquard, Thomas; Bernauer, Julie; Azé, Jérôme; Poupon, Anne

    2011-04-22

    A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate conformations mimicking the complex existing in vivo between two proteins, and a scoring function is used to rank them in order to extract a native-like one. We have already shown that using Voronoi constructions and a well chosen set of parameters, an accurate scoring function could be designed and optimized. However to be able to perform large-scale in silico exploration of the interactome, a near-native solution has to be found in the ten best-ranked solutions. This cannot yet be guaranteed by any of the existing scoring functions. In this work, we introduce a new procedure for conformation ranking. We previously developed a set of scoring functions where learning was performed using a genetic algorithm. These functions were used to assign a rank to each possible conformation. We now have a refined rank using different classifiers (decision trees, rules and support vector machines) in a collaborative filtering scheme. The scoring function newly obtained is evaluated using 10 fold cross-validation, and compared to the functions obtained using either genetic algorithms or collaborative filtering taken separately. This new approach was successfully applied to the CAPRI scoring ensembles. We show that for 10 targets out of 12, we are able to find a near-native conformation in the 10 best ranked solutions. Moreover, for 6 of them, the near-native conformation selected is of high accuracy. Finally, we show that this function dramatically enriches the 100 best-ranking conformations in near-native structures.

  18. The development of an affinity evaluation and prediction system by using protein–protein docking simulations and parameter tuning

    Directory of Open Access Journals (Sweden)

    Koki Tsukamoto

    2009-01-01

    Full Text Available Koki Tsukamoto1, Tatsuya Yoshikawa1,2, Kiyonobu Yokota1, Yuichiro Hourai1, Kazuhiko Fukui11Computational Biology Research Center (CBRC, National Institute of Advanced Industrial Science and Technology (AIST, Koto-ku, Tokyo, Japan; 2Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Toyonaka, Osaka, JapanAbstract: A system was developed to evaluate and predict the interaction between protein pairs by using the widely used shape complementarity search method as the algorithm for docking simulations between the proteins. We used this system, which we call the affinity evaluation and prediction (AEP system, to evaluate the interaction between 20 protein pairs. The system first executes a “round robin” shape complementarity search of the target protein group, and evaluates the interaction between the complex structures obtained by the search. These complex structures are selected by using a statistical procedure that we developed called ‘grouping’. At a prevalence of 5.0%, our AEP system predicted protein–protein interactions with a 50.0% recall, 55.6% precision, 95.5% accuracy, and an F-measure of 0.526. By optimizing the grouping process, our AEP system successfully predicted 10 protein pairs (among 20 pairs that were biologically relevant combinations. Our ultimate goal is to construct an affinity database that will provide cell biologists and drug designers with crucial information obtained using our AEP system.Keywords: protein–protein interaction, affinity analysis, protein–protein docking, FFT, massive parallel computing

  19. A simple and reliable approach to docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints

    International Nuclear Information System (INIS)

    Tang, Chun; Clore, G. Marius

    2006-01-01

    A simple and reliable approach for docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints (as few as three from a single point) in combination with a novel representation for an attractive potential between mapped interaction surfaces is described. Unambiguous assignments of very sparse intermolecular NOEs are obtained using a reverse labeling strategy in which one the components is fully deuterated with the exception of selective protonation of the δ-methyl groups of isoleucine, while the other component is uniformly 13 C-labeled. This labeling strategy can be readily extended to selective protonation of Ala, Leu, Val or Met. The attractive potential is described by a 'reduced' radius of gyration potential applied specifically to a subset of interfacial residues (those with an accessible surface area ≥ 50% in the free proteins) that have been delineated by chemical shift perturbation. Docking is achieved by rigid body minimization on the basis of a target function comprising the sparse NOE distance restraints, a van der Waals repulsion potential and the 'reduced' radius of gyration potential. The method is demonstrated for two protein-protein complexes (EIN-HPr and IIA Glc -HPr) from the bacterial phosphotransferase system. In both cases, starting from 100 different random orientations of the X-ray structures of the free proteins, 100% convergence is achieved to a single cluster (with near identical atomic positions) with an overall backbone accuracy of ∼2 A. The approach described is not limited to NMR, since interfaces can also be mapped by alanine scanning mutagenesis, and sparse intermolecular distance restraints can be derived from double cycle mutagenesis, cross-linking combined with mass spectrometry, or fluorescence energy transfer

  20. A simple and reliable approach to docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chun; Clore, G. Marius [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail: mariusc@intra.niddk.nih.gov

    2006-09-15

    A simple and reliable approach for docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints (as few as three from a single point) in combination with a novel representation for an attractive potential between mapped interaction surfaces is described. Unambiguous assignments of very sparse intermolecular NOEs are obtained using a reverse labeling strategy in which one the components is fully deuterated with the exception of selective protonation of the {delta}-methyl groups of isoleucine, while the other component is uniformly {sup 13}C-labeled. This labeling strategy can be readily extended to selective protonation of Ala, Leu, Val or Met. The attractive potential is described by a 'reduced' radius of gyration potential applied specifically to a subset of interfacial residues (those with an accessible surface area {>=} 50% in the free proteins) that have been delineated by chemical shift perturbation. Docking is achieved by rigid body minimization on the basis of a target function comprising the sparse NOE distance restraints, a van der Waals repulsion potential and the 'reduced' radius of gyration potential. The method is demonstrated for two protein-protein complexes (EIN-HPr and IIA{sup Glc}-HPr) from the bacterial phosphotransferase system. In both cases, starting from 100 different random orientations of the X-ray structures of the free proteins, 100% convergence is achieved to a single cluster (with near identical atomic positions) with an overall backbone accuracy of {approx}2 A. The approach described is not limited to NMR, since interfaces can also be mapped by alanine scanning mutagenesis, and sparse intermolecular distance restraints can be derived from double cycle mutagenesis, cross-linking combined with mass spectrometry, or fluorescence energy transfer.

  1. Cooperative Rendezvous and Docking for Underwater Robots Using Model Predictive Control and Dual Decomposition

    DEFF Research Database (Denmark)

    Nielsen, Mikkel Cornelius; Johansen, Tor Arne; Blanke, Mogens

    2018-01-01

    This paper considers the problem of rendezvous and docking with visual constraints in the context of underwater robots with camera-based navigation. The objective is the convergence of the vehicles to a common point while maintaining visual contact. The proposed solution includes the design of a ...... of a distributed model predictive controller based on dual decomposition, which allows for optimization in a decentralized fashion. The proposed distributed controller enables rendezvous and docking between vehicles while maintaining visual contact....

  2. A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements.

    Science.gov (United States)

    Powers, Chelsea N; Setzer, William N

    2015-01-01

    The purpose of this study is to use a molecular docking approach to identify potential estrogen mimics or anti-estrogens in phytochemicals found in popular dietary herbal supplements. In this study, 568 phytochemicals found in 17 of the most popular herbal supplements sold in the United States were built and docked with two isoforms of the estrogen receptor, ERα and ERβ (a total of 27 different protein crystal structures). The docking results revealed six strongly docking compounds in Echinacea, three from milk thistle (Silybum marianum), three from Gingko biloba, one from Sambucus nigra, none from maca (Lepidium meyenii), five from chaste tree (Vitex agnus-castus), two from fenugreek (Trigonella foenum-graecum), and two from Rhodiola rosea. Notably, of the most popular herbal supplements for women, there were numerous compounds that docked strongly with the estrogen receptor: Licorice (Glycyrrhiza glabra) had a total of 26 compounds strongly docking to the estrogen receptor, 15 with wild yam (Dioscorea villosa), 11 from black cohosh (Actaea racemosa), eight from muira puama (Ptychopetalum olacoides or P. uncinatum), eight from red clover (Trifolium pratense), three from damiana (Turnera aphrodisiaca or T. diffusa), and three from dong quai (Angelica sinensis). Of possible concern were the compounds from men's herbal supplements that exhibited strong docking to the estrogen receptor: Gingko biloba had three compounds, gotu kola (Centella asiatica) had two, muira puama (Ptychopetalum olacoides or P. uncinatum) had eight, and Tribulus terrestris had six compounds. This molecular docking study has revealed that almost all popular herbal supplements contain phytochemical components that may bind to the human estrogen receptor and exhibit selective estrogen receptor modulation. As such, these herbal supplements may cause unwanted side effects related to estrogenic activity.

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

    Science.gov (United States)

    Venkatraman, Vishwesh; Yang, Yifeng D; Sael, Lee; Kihara, Daisuke

    2009-12-09

    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. 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-alphaRMSD 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.

  4. 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 Thomas P. Stafford, commander of the American ASTP prime crew, is on the right. The other crewman is Cosmonaut Aleksey A. Leonov, commander of the Soviet ASTP prime crew. The training session simulated activities on the second day in Earth orbit. The Docking Module is designed to link the Apollo and Soyuz spacecraft.

  5. Automated waste canister docking and emplacement using a sensor-based intelligent controller

    International Nuclear Information System (INIS)

    Drotning, W.D.

    1992-08-01

    A sensor-based intelligent control system is described that utilizes a multiple degree-of-freedom robotic system for the automated remote manipulation and precision docking of large payloads such as waste canisters. Computer vision and ultrasonic proximity sensing are used to control the automated precision docking of a large object with a passive target cavity. Real-time sensor processing and model-based analysis are used to control payload position to a precision of ± 0.5 millimeter

  6. 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.

  7. Enhanced reliability and accuracy for field deployable bioforensic detection and discrimination of Xylella fastidiosa subsp. pauca, causal agent of citrus variegated chlorosis using razor ex technology and TaqMan quantitative PCR.

    Science.gov (United States)

    Ouyang, Ping; Arif, Mohammad; Fletcher, Jacqueline; Melcher, Ulrich; Ochoa Corona, Francisco Manuel

    2013-01-01

    A reliable, accurate and rapid multigene-based assay combining real time quantitative PCR (qPCR) and a Razor Ex BioDetection System (Razor Ex) was validated for detection of Xylella fastidiosa subsp. pauca (Xfp, a xylem-limited bacterium that causes citrus variegated chlorosis [CVC]). CVC, which is exotic to the United States, has spread through South and Central America and could significantly impact U.S. citrus if it arrives. A method for early, accurate and sensitive detection of Xfp in plant tissues is needed by plant health officials for inspection of products from quarantined locations, and by extension specialists for detection, identification and management of disease outbreaks and reservoir hosts. Two sets of specific PCR primers and probes, targeting Xfp genes for fimbrillin and the periplasmic iron-binding protein were designed. A third pair of primers targeting the conserved cobalamin synthesis protein gene was designed to detect all possible X. fastidiosa (Xf) strains. All three primer sets detected as little as 1 fg of plasmid DNA carrying X. fastidiosa target sequences and genomic DNA of Xfp at as little as 1 - 10 fg. The use of Razor Ex facilitates a rapid (about 30 min) in-field assay capability for detection of all Xf strains, and for specific detection of Xfp. Combined use of three primer sets targeting different genes increased the assay accuracy and broadened the range of detection. To our knowledge, this is the first report of a field-deployable rapid and reliable bioforensic detection and discrimination method for a bacterial phytopathogen based on multigene targets.

  8. Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments

    Directory of Open Access Journals (Sweden)

    Renata De Paris

    2015-01-01

    Full Text Available 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.

  9. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Spectroscopic, structural and drug docking studies of carbocysteine

    Science.gov (United States)

    Manivannan, M.; Rajeshwaran, K.; Govindhan, R.; Karthikeyan, B.

    2017-09-01

    Carbocysteine or carbocisteine having the empirical formula C5H9NO4S,is one of the most therapeutically prescribed expectorant, sold under the brand name viz., Mucodyne (UK and India), Rhinathiol and Mucolite. In pediatric respiratory pathology, it can relieve the symptoms of obstructive pulmonary disease (COPD) and bronchiectasis. On the consideration of its extensive pharmaceutical usage and medicinal value, we have investigated its chemical structure and composition by employing various spectral techniques like 1H, 13C NMR, FT-IR,Raman, UV-Visible spectroscopy and powder X-ray diffraction method. Density Functional Theoretical (DFT) studies on its electronic structure is also carried out. Drug docking studies were carried out to ascertain the nature of molecular interaction with the biological protein system. Furthermore theoretical Raman spectrum of this molecule has been computed and compared with the experimental Raman spectrum. The forbidden energy gap between its frontier molecular orbitals, viz., HOMO-LUMO is calculated and correlated with its observed λmax value. Atomic orbitals which are mainly contributes to the frontier molecular orbitals were identified. Molecular electrostatic potential diagram has been mapped to explain its chemical activity. Based on the results, a suitable mechanism of its protein binding mode and drug action has been discussed.

  11. Biological and Docking Studies of Sulfonamide Derivatives of 4-Aminophenazone

    International Nuclear Information System (INIS)

    Akhtar, M.S.; Ismail, A.; Murtaza, S.; Shamim, S.; Tahir, M.N.; Usman Ali Rana, U.A.

    2016-01-01

    Sulfonamide derivatives of 4-aminophenazone (4APZ) were synthesized and accordingly characterized by spectroscopic techniques. These newly synthesized compounds were examined for their biological activities such as enzyme inhibition, analgesic, antibacterial, antioxidant and DNA interaction. A direct correlation between enzyme inhibition activity and concentration of the compounds was observed both by experimental and molecular docking studies. Analgesic activity of the compounds was investigated by formalin-induced paw licking (FIPL), acetic acid-induced writhing (AIW) and heat conduction methods in mice. Membrane stabilization effect was determined by hypotonicity-induced hemolysis. Bacterial strains, S. aureus, S. epidermidis, B. subtilis, E. coli, P. aeruginosa, S. mutans and A. odontolyticus were used for investigating the antibacterial potential of the compounds. Antioxidant potential was investigated by Ferric Reducing Antioxidant Power assay (FRAP) and DPPH free radical scavenging method. DNA interaction studies of the synthesized compounds showed weak interaction. Hyperchromic effect was observed along the series and large positive K values were obtained for most of the compounds. (author)

  12. HERMES docking/berthing system pilot study. Quantitative assessment

    International Nuclear Information System (INIS)

    Munoz Blasco, J.; Goicoechea Sanchez, F.J.

    1993-01-01

    This study falls within the framework of the incorporation of quantitative risk assessment to the activities planned for the ESA-HERMES project (ESA/ CNES). The main objective behind the study was the analysis and evaluation of the potential contribution of so-called probabilistic or quantitative safety analysis to the optimization of the safety development process for the systems carrying out the safety functions required by the new and complex HERMES Space Vehicle. For this purpose, a pilot study was considered a good start in quantitative safety assessments (QSA), as this approach has been frequently used in the past to establish a solid base in large-scale QSA application programs while avoiding considerable economic risks. It was finally decided to select the HERMES docking/berthing system with Man Tender Free Flyer as the case-study. This report describes the different steps followed in the study, along with the main insights obtained and the general conclusions drawn from the study results. (author)

  13. Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

    Directory of Open Access Journals (Sweden)

    Hatem A. Abuelizz

    2017-06-01

    Full Text Available A new series of quinazoline-4(3H-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H-ones (1–24 were examined in the maximal electroshock (MES induced seizures and subcutaneous pentylenetetrazole (scPTZ induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100% against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II. The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

  14. Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls

    Directory of Open Access Journals (Sweden)

    Hezekiel Mathambo Kumalo

    2015-01-01

    Full Text Available he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds to completion rather than to equilibrium. Covalent inhibitors possessed some significant advantages over non-covalent inhibitors such as covalent warheads can target rare, non-conserved residue of a particular target protein and thus led to development of highly selective inhibitors, covalent inhibitors can be effective in targeting proteins with shallow binding cleavage which will led to development of novel inhibitors with increased potency than non-covalent inhibitors. Several computational approaches have been developed to simulate covalent interactions; however, this is still a challenging area to explore. Covalent molecular docking has been recently implemented in the computer-aided drug design workflows to describe covalent interactions between inhibitors and biological targets. In this review we highlight: (i covalent interactions in biomolecular systems; (ii the mathematical framework of covalent molecular docking; (iii implementation of covalent docking protocol in drug design workflows; (iv applications covalent docking: case studies and (v shortcomings and future perspectives of covalent docking. To the best of our knowledge; this review is the first account that highlights different aspects of covalent docking with its merits and pitfalls. We believe that the method and applications highlighted in this study will help future efforts towards the design of irreversible inhibitors.

  15. Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina.

    Directory of Open Access Journals (Sweden)

    Max W Chang

    Full Text Available BACKGROUND: The AutoDock family of software has been widely used in protein-ligand docking research. This study compares AutoDock 4 and AutoDock Vina in the context of virtual screening by using these programs to select compounds active against HIV protease. METHODOLOGY/PRINCIPAL FINDINGS: Both programs were used to rank the members of two chemical libraries, each containing experimentally verified binders to HIV protease. In the case of the NCI Diversity Set II, both AutoDock 4 and Vina were able to select active compounds significantly better than random (AUC = 0.69 and 0.68, respectively; p<0.001. The binding energy predictions were highly correlated in this case, with r = 0.63 and iota = 0.82. For a set of larger, more flexible compounds from the Directory of Universal Decoys, the binding energy predictions were not correlated, and only Vina was able to rank compounds significantly better than random. CONCLUSIONS/SIGNIFICANCE: In ranking smaller molecules with few rotatable bonds, AutoDock 4 and Vina were equally capable, though both exhibited a size-related bias in scoring. However, as Vina executes more quickly and is able to more accurately rank larger molecules, researchers should look to it first when undertaking a virtual screen.

  16. HPEPDOCK: a web server for blind peptide-protein docking based on a hierarchical algorithm.

    Science.gov (United States)

    Zhou, Pei; Jin, Bowen; Li, Hao; Huang, Sheng-You

    2018-05-09

    Protein-peptide interactions are crucial in many cellular functions. Therefore, determining the structure of protein-peptide complexes is important for understanding the molecular mechanism of related biological processes and developing peptide drugs. HPEPDOCK is a novel web server for blind protein-peptide docking through a hierarchical algorithm. Instead of running lengthy simulations to refine peptide conformations, HPEPDOCK considers the peptide flexibility through an ensemble of peptide conformations generated by our MODPEP program. For blind global peptide docking, HPEPDOCK obtained a success rate of 33.3% in binding mode prediction on a benchmark of 57 unbound cases when the top 10 models were considered, compared to 21.1% for pepATTRACT server. HPEPDOCK also performed well in docking against homology models and obtained a success rate of 29.8% within top 10 predictions. For local peptide docking, HPEPDOCK achieved a high success rate of 72.6% on a benchmark of 62 unbound cases within top 10 predictions, compared to 45.2% for HADDOCK peptide protocol. Our HPEPDOCK server is computationally efficient and consumed an average of 29.8 mins for a global peptide docking job and 14.2 mins for a local peptide docking job. The HPEPDOCK web server is available at http://huanglab.phys.hust.edu.cn/hpepdock/.

  17. A cross docking pipeline for improving pose prediction and virtual screening performance

    Science.gov (United States)

    Kumar, Ashutosh; Zhang, Kam Y. J.

    2018-01-01

    Pose prediction and virtual screening performance of a molecular docking method depend on the choice of protein structures used for docking. Multiple structures for a target protein are often used to take into account the receptor flexibility and problems associated with a single receptor structure. However, the use of multiple receptor structures is computationally expensive when docking a large library of small molecules. Here, we propose a new cross-docking pipeline suitable to dock a large library of molecules while taking advantage of multiple target protein structures. Our method involves the selection of a suitable receptor for each ligand in a screening library utilizing ligand 3D shape similarity with crystallographic ligands. We have prospectively evaluated our method in D3R Grand Challenge 2 and demonstrated that our cross-docking pipeline can achieve similar or better performance than using either single or multiple-receptor structures. Moreover, our method displayed not only decent pose prediction performance but also better virtual screening performance over several other methods.

  18. Test Expectancy Affects Metacomprehension Accuracy

    Science.gov (United States)

    Thiede, Keith W.; Wiley, Jennifer; Griffin, Thomas D.

    2011-01-01

    Background: Theory suggests that the accuracy of metacognitive monitoring is affected by the cues used to judge learning. Researchers have improved monitoring accuracy by directing attention to more appropriate cues; however, this is the first study to more directly point students to more appropriate cues using instructions regarding tests and…

  19. Does filler database size influence identification accuracy?

    Science.gov (United States)

    Bergold, Amanda N; Heaton, Paul

    2018-06-01

    Police departments increasingly use large photo databases to select lineup fillers using facial recognition software, but this technological shift's implications have been largely unexplored in eyewitness research. Database use, particularly if coupled with facial matching software, could enable lineup constructors to increase filler-suspect similarity and thus enhance eyewitness accuracy (Fitzgerald, Oriet, Price, & Charman, 2013). However, with a large pool of potential fillers, such technologies might theoretically produce lineup fillers too similar to the suspect (Fitzgerald, Oriet, & Price, 2015; Luus & Wells, 1991; Wells, Rydell, & Seelau, 1993). This research proposes a new factor-filler database size-as a lineup feature affecting eyewitness accuracy. In a facial recognition experiment, we select lineup fillers in a legally realistic manner using facial matching software applied to filler databases of 5,000, 25,000, and 125,000 photos, and find that larger databases are associated with a higher objective similarity rating between suspects and fillers and lower overall identification accuracy. In target present lineups, witnesses viewing lineups created from the larger databases were less likely to make correct identifications and more likely to select known innocent fillers. When the target was absent, database size was associated with a lower rate of correct rejections and a higher rate of filler identifications. Higher algorithmic similarity ratings were also associated with decreases in eyewitness identification accuracy. The results suggest that using facial matching software to select fillers from large photograph databases may reduce identification accuracy, and provides support for filler database size as a meaningful system variable. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  20. 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.

  1. Methodology for Developing a Probabilistic Risk Assessment Model of Spacecraft Rendezvous and Dockings

    Science.gov (United States)

    Farnham, Steven J., II; Garza, Joel, Jr.; Castillo, Theresa M.; Lutomski, Michael

    2011-01-01

    In 2007 NASA was preparing to send two new visiting vehicles carrying logistics and propellant to the International Space Station (ISS). These new vehicles were the European Space Agency s (ESA) Automated Transfer Vehicle (ATV), the Jules Verne, and the Japanese Aerospace and Explorations Agency s (JAXA) H-II Transfer Vehicle (HTV). The ISS Program wanted to quantify the increased risk to the ISS from these visiting vehicles. At the time, only the Shuttle, the Soyuz, and the Progress vehicles rendezvoused and docked to the ISS. The increased risk to the ISS was from an increase in vehicle traffic, thereby, increasing the potential catastrophic collision during the rendezvous and the docking or berthing of the spacecraft to the ISS. A universal method of evaluating the risk of rendezvous and docking or berthing was created by the ISS s Risk Team to accommodate the increasing number of rendezvous and docking or berthing operations due to the increasing number of different spacecraft, as well as the future arrival of commercial spacecraft. Before the first docking attempt of ESA's ATV and JAXA's HTV to the ISS, a probabilistic risk model was developed to quantitatively calculate the risk of collision of each spacecraft with the ISS. The 5 rendezvous and docking risk models (Soyuz, Progress, Shuttle, ATV, and HTV) have been used to build and refine the modeling methodology for rendezvous and docking of spacecrafts. This risk modeling methodology will be NASA s basis for evaluating the addition of future ISS visiting spacecrafts hazards, including SpaceX s Dragon, Orbital Science s Cygnus, and NASA s own Orion spacecraft. This paper will describe the methodology used for developing a visiting vehicle risk model.

  2. A unified conformational selection and induced fit approach to protein-peptide docking.

    Directory of Open Access Journals (Sweden)

    Mikael Trellet

    Full Text Available Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II, flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.

  3. Sensitivity of molecular docking to induced fit effects in influenza virus neuraminidase

    Science.gov (United States)

    Birch, Louise; Murray, Christopher W.; Hartshorn, Michael J.; Tickle, Ian J.; Verdonk, Marcel L.

    2002-12-01

    Many proteins undergo small side chain or even backbone movements on binding of different ligands into the same protein structure. This is known as induced fit and is potentially problematic for virtual screening of databases against protein targets. In this report we investigate the limits of the rigid protein approximation used by the docking program, GOLD, through cross-docking using protein structures of influenza neuraminidase. Neuraminidase is known to exhibit small but significant induced fit effects on ligand binding. Some neuraminidase crystal structures caused concern due to the bound ligand conformation and GOLD performed poorly on these complexes. A `clean' set, which contained unique, unambiguous complexes, was defined. For this set, the lowest energy structure was correctly docked (i.e. RMSD < 1.5 Å away from the crystal reference structure) in 84% of proteins, and the most promiscuous protein (1mwe) was able to dock all 15 ligands accurately including those that normally required an induced fit movement. This is considerably better than the 70% success rate seen with GOLD against general validation sets. Inclusion of specific water molecules involved in water-mediated hydrogen bonds did not significantly improve the docking performance for ligands that formed water-mediated contacts but it did prevent docking of ligands that displaced these waters. Our data supports the use of a single protein structure for virtual screening with GOLD in some applications involving induced fit effects, although care must be taken to identify the protein structure that performs best against a wide variety of ligands. The performance of GOLD was significantly better than the GOLD implementation of ChemScore and the reasons for this are discussed. Overall, GOLD has shown itself to be an extremely good, robust docking program for this system.

  4. Test expectancy affects metacomprehension accuracy.

    Science.gov (United States)

    Thiede, Keith W; Wiley, Jennifer; Griffin, Thomas D

    2011-06-01

    Theory suggests that the accuracy of metacognitive monitoring is affected by the cues used to judge learning. Researchers have improved monitoring accuracy by directing attention to more appropriate cues; however, this is the first study to more directly point students to more appropriate cues using instructions regarding tests and practice tests. The purpose of the present study was to examine whether the accuracy metacognitive monitoring was affected by the nature of the test expected. Students (N= 59) were randomly assigned to one of two test expectancy groups (memory vs. inference). Then after reading texts, judging learning, completed both memory and inference tests. Test performance and monitoring accuracy were superior when students received the kind of test they had been led to expect rather than the unexpected test. Tests influence students' perceptions of what constitutes learning. Our findings suggest that this could affect how students prepare for tests and how they monitoring their own learning. ©2010 The British Psychological Society.

  5. CPdock: the complementarity plot for docking of proteins: implementing multi-dielectric continuum electrostatics.

    Science.gov (United States)

    Basu, Sankar

    2017-12-07

    The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (S m , E m ) for amino acid side-chains buried within the protein interior or interface and plots them in a two-dimensional plot having knowledge-based probabilistic quality estimates for the residues as well as for the whole structure. The current report essentially presents an upgraded version of the plot with the implementation of the advanced multi-dielectric functionality (as in Delphi version 6.2 or higher) in the computation of electrostatic complementarity to make the validation tool physico-chemically more realistic. The two methods (single- and multi-dielectric) agree decently in their resultant E m values, and hence, provisions for both methods have been kept in the software suite. So to speak, the global electrostatic balance within a well-folded protein and/or a well-packed interface seems only marginally perturbed by the choice of different internal dielectric values. However, both from theoretical as well as practical grounds, the more advanced multi-dielectric version of the plot is certainly recommended for potentially producing more reliable results. The report also presents a new methodology and a variant plot, namely CP dock , based on the same principles of complementarity specifically designed to be used in the docking of proteins. The efficacy of the method to discriminate between good and bad docked protein complexes has been tested on a recent state-of-the-art docking benchmark. The results unambiguously indicate that CP dock can indeed be effective in the initial screening phase of a docking scoring pipeline before going into more sophisticated and computationally expensive scoring functions. CP dock has been made available at https://github.com/nemo8130/CPdock . Graphical Abstract An example showing

  6. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs.

    Science.gov (United States)

    Shiri, Fereshteh; Pirhadi, Somayeh; Ghasemi, Jahan B

    2016-03-01

    Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD) and the enhanced replacement method (ERM) were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND) approach. After variable selection, GRIND were correlated with activity values (pIC50) by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q (2) value of 0.77, an [Formula: see text] of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap) implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

  7. Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs

    Directory of Open Access Journals (Sweden)

    Fereshteh Shiri

    2016-03-01

    Full Text Available Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD and the enhanced replacement method (ERM were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND approach. After variable selection, GRIND were correlated with activity values (pIC50 by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q2 value of 0.77, an rpred2 of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

  8. Structure Prediction, Molecular Dynamics Simulation and Docking Studies of D-Specific Dehalogenase from Rhizobium sp. RC1

    Directory of Open Access Journals (Sweden)

    Ismaila Yada Sudi

    2012-11-01

    Full Text Available Currently, there is no three-dimensional structure of D-specific dehalogenase (DehD in the protein database. We modeled DehD using ab initio technique, performed molecular dynamics (MD simulation and docking of D-2-chloropropionate (D-2CP, D-2-bromopropionate (D-2BP, monochloroacetate (MCA, monobromoacetate (MBA, 2,2-dichloropropionate (2,2-DCP, d,l-2,3-dichloropropionate (d,l-2,3-DCP, and 3-chloropropionate (3-CP into the DehD active site. The sequences of DehD and D-2-haloacid dehalogenase (HadD from Pseudomonas putida AJ1 have 15% sequence similarity. The model had 80% of the amino acid residues in the most favored region when compared to the crystal structure of DehI from Pseudomonas putida PP3. Docking analysis revealed that Arg107, Arg134 and Tyr135 interacted with D-2CP, and Glu20 activated the water molecule for hydrolytic dehalogenation. Single residue substitutions at 25–30 °C showed that polar residues of DehD were stable when substituted with nonpolar residues and showed a decrease in activity within the same temperature range. The molecular dynamics simulation of DehD and its variants showed that in R134A variant, Arg107 interacted with D-2CP, while in Y135A, Gln221 and Arg231 interacted with D-2CP. It is our emphatic belief that the new model will be useful for the rational design of DehDs with enhanced potentials.

  9. Binding of naringin and naringenin with hen egg white lysozyme: A spectroscopic investigation and molecular docking study

    Science.gov (United States)

    Das, Sourav; Ghosh, Pooja; Koley, Sudipta; Singha Roy, Atanu

    2018-03-01

    The interactions of naringenin (NG) and naringin (NR) with Hen Egg White Lysozyme (HEWL) in aqueous medium have been investigated using UV-vis spectroscopy, steady-state fluorescence, circular dichroism (CD), Fourier Transform infrared spectroscopy (FT-IR) and molecular docking analyses. Both NG and NR can quench the intrinsic fluorescence of HEWL via static quenching mechanism. At 300 K, the value of binding constant (Kb) of HEWL-NG complex (5.596 ± 0.063 × 104 M- 1) was found to be greater than that of HEWL-NR complex (3.404 ± 0.407 × 104 M- 1). The negative ΔG° values in cases of both the complexes specify the spontaneous binding. The binding distance between the donor (HEWL) and acceptor (NG/NR) was estimated using the Försters theory and the possibility of non-radiative energy transfer from HEWL to NG/NR was observed. The presence of metal ions (Ca2 +, Cu2 + and Fe2 +) decreased the binding affinity of NG/NR towards HEWL. Synchronous fluorescence studies indicate the change in Trp micro-environment due to the incorporation of NG/NR into HEWL. CD and FT-IR studies indicated that the α-helicity of the HEWL was slightly enhanced due to ligand binding. NG and NR inhibited the enzymatic activity of HEWL and exhibited their affinity for the active site of HEWL. Molecular docking studies revealed that both NG and NR bind in the close vicinity of Trp 62 and Trp 63 residues which is vital for the catalytic activity.

  10. Forecast Accuracy Uncertainty and Momentum

    OpenAIRE

    Bing Han; Dong Hong; Mitch Warachka

    2009-01-01

    We demonstrate that stock price momentum and earnings momentum can result from uncertainty surrounding the accuracy of cash flow forecasts. Our model has multiple information sources issuing cash flow forecasts for a stock. The investor combines these forecasts into an aggregate cash flow estimate that has minimal mean-squared forecast error. This aggregate estimate weights each cash flow forecast by the estimated accuracy of its issuer, which is obtained from their past forecast errors. Mome...

  11. 对接机构分系统研制%Development of Docking Subsystem

    Institute of Scientific and Technical Information of China (English)

    陈宝东; 郑云青; 邵济明; 陈萌

    2011-01-01

    The composition, control scheduling, design, and reliability and safety of the docking subsystem of China's Shenzhou-8 spaceship and Tiangong-1 target spacecraft were introduced in this paper. The key technologies of the general design, dynamic simulation, test and important part design in the design of the docking subsystem were given out. The tests, such as the general characteristic test, docking and separating test, docking test system in thermal vacuum, and life test, and test results were presented briefly. The whole research phase of the docking subsystem was reviewed.%介绍了我国神舟八号飞船和天宫一号目标飞行器对接试验的对接机构分系统的组成、控制时序、设计方案,以及可靠性与安全性。给出了对接机构分系统研制中总体设计、动力学仿真、试验和关键部件研制等关键技术,以及整机特性测试、连接分离试验、热真空对接与分离试验、寿命试验等验证情况。回顾了对接机构分系统的研制过程。

  12. Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling.

    Science.gov (United States)

    Wu, Chia-Lun; Buszard, Bree; Teng, Chun-Hung; Chen, Wei-Lin; Warr, Coral G; Tiganis, Tony; Meng, Tzu-Ching

    2011-10-01

    PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

  13. NPPD: A Protein-Protein Docking Scoring Function Based on Dyadic Differences in Networks of Hydrophobic and Hydrophilic Amino Acid Residues

    Directory of Open Access Journals (Sweden)

    Edward S. C. Shih

    2015-03-01

    Full Text Available Protein-protein docking (PPD predictions usually rely on the use of a scoring function to rank docking models generated by exhaustive sampling. To rank good models higher than bad ones, a large number of scoring functions have been developed and evaluated, but the methods used for the computation of PPD predictions remain largely unsatisfactory. Here, we report a network-based PPD scoring function, the NPPD, in which the network consists of two types of network nodes, one for hydrophobic and the other for hydrophilic amino acid residues, and the nodes are connected when the residues they represent are within a certain contact distance. We showed that network parameters that compute dyadic interactions and those that compute heterophilic interactions of the amino acid networks thus constructed allowed NPPD to perform well in a benchmark evaluation of 115 PPD scoring functions, most of which, unlike NPPD, are based on some sort of protein-protein interaction energy. We also showed that NPPD was highly complementary to these energy-based scoring functions, suggesting that the combined use of conventional scoring functions and NPPD might significantly improve the accuracy of current PPD predictions.

  14. Trait Perception Accuracy and Acquaintance Within Groups: Tracking Accuracy Development.

    Science.gov (United States)

    Brown, Jill A; Bernieri, Frank

    2017-05-01

    Previous work on trait perception has evaluated accuracy at discrete stages of relationships (e.g., strangers, best friends). A relatively limited body of literature has investigated changes in accuracy as acquaintance within a dyad or group increases. Small groups of initially unacquainted individuals spent more than 30 hr participating in a wide range of activities designed to represent common interpersonal contexts (e.g., eating, traveling). We calculated how accurately each participant judged others in their group on the big five traits across three distinct points within the acquaintance process: zero acquaintance, after a getting-to-know-you conversation, and after 10 weeks of interaction and activity. Judgments of all five traits exhibited accuracy above chance levels after 10 weeks. An examination of the trait rating stability revealed that much of the revision in judgments occurred not over the course of the 10-week relationship as suspected, but between zero acquaintance and the getting-to-know-you conversation.

  15. Human and server docking prediction for CAPRI round 30-35 using LZerD with combined scoring functions.

    Science.gov (United States)

    Peterson, Lenna X; Kim, Hyungrae; Esquivel-Rodriguez, Juan; Roy, Amitava; Han, Xusi; Shin, Woong-Hee; Zhang, Jian; Terashi, Genki; Lee, Matt; Kihara, Daisuke

    2017-03-01

    We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues' spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, that is whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. Proteins 2017; 85:513-527. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Autonomous docking control of visual-servo type underwater vehicle system aiming at underwater automatic charging

    International Nuclear Information System (INIS)

    Yanou, Akira; Ohnishi, Shota; Ishiyama, Shintaro; Minami, Mamoru

    2015-01-01

    A visual-servo type remotely operated vehicle (ROV) system with binocular wide-angle lens was developed to survey submarine resources, decontaminate radiation from mud in dam lake and so on. This paper explores the experiments on regulator performance and underwater docking of the robot system utilizing Genetic Algorithm (GA) for real-time recognition of the robot's relative position and posture through 3D marker. The visual servoing performances have been verified as follows; (1) The stability performances of the proposed regulator system have been evaluated by exerting abrupt distrubane force while the ROV is controlled by visual servoing. (2) The proposed system can track time-variant desired target position in x-axis (front-back direction of the robot). (3) The underwater docking can be completed by switching visual servoing and docking modes based on the error threshold, and by giving time-varying desired target position and orientation to the controller as a desired pose. (author)

  17. Blinded evaluation of farnesoid X receptor (FXR) ligands binding using molecular docking and free energy calculations

    Science.gov (United States)

    Selwa, Edithe; Elisée, Eddy; Zavala, Agustin; Iorga, Bogdan I.

    2018-01-01

    Our participation to the D3R Grand Challenge 2 involved a protocol in two steps, with an initial analysis of the available structural data from the PDB allowing the selection of the most appropriate combination of docking software and scoring function. Subsequent docking calculations showed that the pose prediction can be carried out with a certain precision, but this is dependent on the specific nature of the ligands. The correct ranking of docking poses is still a problem and cannot be successful in the absence of good pose predictions. Our free energy calculations on two different subsets provided contrasted results, which might have the origin in non-optimal force field parameters associated with the sulfonamide chemical moiety.

  18. 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.

  19. Domain requirements for the Dock adapter protein in growth- cone signaling.

    Science.gov (United States)

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  20. The Drosophila DOCK family protein Sponge is required for development of the air sac primordium

    Energy Technology Data Exchange (ETDEWEB)

    Morishita, Kazushge; Anh Suong, Dang Ngoc; Yoshida, Hideki; Yamaguchi, Masamitsu, E-mail: myamaguc@kit.ac.jp

    2017-05-15

    Dedicator of cytokinesis (DOCK) family genes are known as DOCK1-DOCK11 in mammals. DOCK family proteins mainly regulate actin filament polymerization and/or depolymerization and are GEF proteins, which contribute to cellular signaling events by activating small G proteins. Sponge (Spg) is a Drosophila counterpart to mammalian DOCK3/DOCK4, and plays a role in embryonic central nervous system development, R7 photoreceptor cell differentiation, and adult thorax development. In order to conduct further functional analyses on Spg in vivo, we examined its localization in third instar larval wing imaginal discs. Immunostaining with purified anti-Spg IgG revealed that Spg mainly localized in the air sac primordium (ASP) in wing imaginal discs. Spg is therefore predicted to play an important role in the ASP. The specific knockdown of Spg by the breathless-GAL4 driver in tracheal cells induced lethality accompanied with a defect in ASP development and the induction of apoptosis. The monitoring of ERK signaling activity in wing imaginal discs by immunostaining with anti-diphospho-ERK IgG revealed reductions in the ERK signal cascade in Spg knockdown clones. Furthermore, the overexpression of D-raf suppressed defects in survival and the proliferation of cells in the ASP induced by the knockdown of Spg. Collectively, these results indicate that Spg plays a critical role in ASP development and tracheal cell viability that is mediated by the ERK signaling pathway. - Highlights: • Spg mainly localizes in the air sac primordium in wing imaginal discs. • Spg plays a critical role in air sac primordium development. • Spg positively regulates the ERK signal cascade.

  1. The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production

    Directory of Open Access Journals (Sweden)

    Miho Ushijima

    2018-02-01

    Full Text Available A hallmark of humoral immune responses is the production of antibodies. This process involves a complex cascade of molecular and cellular interactions, including recognition of specific antigen by the B cell receptor (BCR, which triggers activation of B cells and differentiation into plasma cells (PCs. Although activation of the small GTPase Rac has been implicated in BCR-mediated antigen recognition, its precise role in humoral immunity and the upstream regulator remain elusive. DOCK2 is a Rac-specific guanine nucleotide exchange factor predominantly expressed in hematopoietic cells. We found that BCR-mediated Rac activation was almost completely lost in DOCK2-deficient B cells, resulting in defects in B cell spreading over the target cell-membrane and sustained growth of BCR microclusters at the interface. When wild-type B cells were stimulated in vitro with anti-IgM F(ab′2 antibody in the presence of IL-4 and IL-5, they differentiated efficiently into PCs. However, BCR-mediated PC differentiation was severely impaired in the case of DOCK2-deficient B cells. Similar results were obtained in vivo when DOCK2-deficient B cells expressing a defined BCR specificity were adoptively transferred into mice and challenged with the cognate antigen. In addition, by generating the conditional knockout mice, we found that DOCK2 expression in B-cell lineage is required to mount antigen-specific IgG antibody. These results highlight important role of the DOCK2–Rac axis in PC differentiation and IgG antibody responses.

  2. The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production.

    Science.gov (United States)

    Ushijima, Miho; Uruno, Takehito; Nishikimi, Akihiko; Sanematsu, Fumiyuki; Kamikaseda, Yasuhisa; Kunimura, Kazufumi; Sakata, Daiji; Okada, Takaharu; Fukui, Yoshinori

    2018-01-01

    A hallmark of humoral immune responses is the production of antibodies. This process involves a complex cascade of molecular and cellular interactions, including recognition of specific antigen by the B cell receptor (BCR), which triggers activation of B cells and differentiation into plasma cells (PCs). Although activation of the small GTPase Rac has been implicated in BCR-mediated antigen recognition, its precise role in humoral immunity and the upstream regulator remain elusive. DOCK2 is a Rac-specific guanine nucleotide exchange factor predominantly expressed in hematopoietic cells. We found that BCR-mediated Rac activation was almost completely lost in DOCK2-deficient B cells, resulting in defects in B cell spreading over the target cell-membrane and sustained growth of BCR microclusters at the interface. When wild-type B cells were stimulated in vitro with anti-IgM F(ab') 2 antibody in the presence of IL-4 and IL-5, they differentiated efficiently into PCs. However, BCR-mediated PC differentiation was severely impaired in the case of DOCK2-deficient B cells. Similar results were obtained in vivo when DOCK2-deficient B cells expressing a defined BCR specificity were adoptively transferred into mice and challenged with the cognate antigen. In addition, by generating the conditional knockout mice, we found that DOCK2 expression in B-cell lineage is required to mount antigen-specific IgG antibody. These results highlight important role of the DOCK2-Rac axis in PC differentiation and IgG antibody responses.

  3. In silico predictive studies of mAHR congener binding using homology modelling and molecular docking.

    Science.gov (United States)

    Panda, Roshni; Cleave, A Suneetha Susan; Suresh, P K

    2014-09-01

    The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies. © The Author(s) 2012.

  4. Molecular dynamics modeling the synthetic and biological polymers interactions pre-studied via docking

    Science.gov (United States)

    Tsvetkov, Vladimir B.; Serbin, Alexander V.

    2014-06-01

    In previous works we reported the design, synthesis and in vitro evaluations of synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic anchors), as a novel class of inhibitors of the human immunodeficiency virus type 1 ( HIV-1) entry into human cells. Recently, these synthetic polymers interactions with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad repeat regions [ HR1]3 of viral envelope protein gp41, were pre-studied via docking in terms of newly formulated algorithm for stepwise approximation from fragments of polymeric backbone and side-group models toward real polymeric chains. In the present article the docking results were verified under molecular dynamics ( MD) modeling. In contrast with limited capabilities of the docking, the MD allowed of using much more large models of the polymeric ligands, considering flexibility of both ligand and target simultaneously. Among the synthesized polymers the dinorbornen anchors containing alternating copolymers of maleic acid were selected as the most representative ligands (possessing the top anti-HIV activity in vitro in correlation with the highest binding energy in the docking). To verify the probability of binding of the polymers with the [HR1]3 in the sites defined via docking, various starting positions of polymer chains were tried. The MD simulations confirmed the main docking-predicted priority for binding sites, and possibilities for axial and belting modes of the ligands-target interactions. Some newly MD-discovered aspects of the ligand's backbone and anchor units dynamic cooperation in binding the viral target clarify mechanisms of the synthetic polymers anti-HIV activity and drug resistance prevention.

  5. Biological evaluation and molecular docking of Rhein as a multi-targeted radiotherapy sensitization agent of nasopharyngeal carcinoma

    Science.gov (United States)

    Su, Zhengying; Tian, Wei; Li, Jing; Wang, Chunmiao; Pan, Zhiyu; Li, Danrong; Hou, Huaxin

    2017-11-01

    Radiation resistance of nasopharyngeal carcinoma (NPC) is a joint effect caused by complex molecular mechanisms. The development of multi-target radiotherapy sensitization agents offered a promising method for the treatment of NPC. In this work, the probability of Rhein to be a multi-target radiotherapy sensitization agent was explored through computer aid virtual screening by inverse docking study. In order to validate the accuracy of the computational results, radiotherapy sensitization of Rhein to NPC cells and its effects on the expression of target proteins were evaluated separately by CCK8 assay and Western blotting analysis. Our result demonstrated that Rhein possessed strong binding affinity with RAC1 and HSP90. No cytotoxic concentration of Rhein had radiosensitization effect on nasopharyngeal carcinoma CNE1 cells. After treatment with Rhein and 2Gy radiation, the expression of RAC1 upregulated and the expression of HSP90 down-regulated in cells. Based on the above data, Rhein is likely to become an attractive lead compound for the future design of multi-target radiotherapy sensitization agents.

  6. Omnidirectional angle constraint based dynamic six-degree-of-freedom measurement for spacecraft rendezvous and docking simulation

    Science.gov (United States)

    Shi, Shendong; Yang, Linghui; Lin, Jiarui; Ren, Yongjie; Guo, Siyang; Zhu, Jigui

    2018-04-01

    In this paper we present a novel omnidirectional angle constraint based method for dynamic 6-DOF (six-degree-of-freedom) measurement. A photoelectric scanning measurement network is employed whose photoelectric receivers are fixed on the measured target. They are in a loop distribution and receive signals from rotating transmitters. Each receiver indicates an angle constraint direction. Therefore, omnidirectional angle constraints can be constructed in each rotation cycle. By solving the constrained optimization problem, 6-DOF information can be obtained, which is independent of traditional rigid coordinate system transformation. For the dynamic error caused by the measurement principle, we present an interpolation method for error reduction. Accuracy testing is performed in an 8  ×  8 m measurement area with four transmitters. The experimental results show that the dynamic orientation RMSEs (root-mean-square errors) are reduced from 0.077° to 0.044°, 0.040° to 0.030° and 0.032° to 0.015° in the X, Y, and Z axes, respectively. The dynamic position RMSE is reduced from 0.65 mm to 0.24 mm. This method is applied during the final approach phase in the rendezvous and docking simulation. Experiments under different conditions are performed in a 40  ×  30 m area, and the method is verified to be effective.

  7. Technical Note: Mobile accelerator guidance using an optical tracker during docking in IOERT procedures.

    Science.gov (United States)

    Marinetto, Eugenio; Victores, Juan González; García-Sevilla, Mónica; Muñoz, Mercedes; Calvo, Felipe Ángel; Balaguer, Carlos; Desco, Manuel; Pascau, Javier

    2017-10-01

    Intraoperative electron radiation therapy (IOERT) involves the delivery of a high radiation dose during tumor resection in a shorter time than other radiation techniques, thus improving local control of tumors. However, a linear accelerator device is needed to produce the beam safely. Mobile linear accelerators have been designed as dedicated units that can be moved into the operating room and deliver radiation in situ. Correct and safe dose delivery is a key concern when using mobile accelerators. The applicator is commonly fixed to the patient's bed to ensure that the dose is delivered to the prescribed location, and the mobile accelerator is moved to dock the applicator to the radiation beam output (gantry). In a typical clinical set-up, this task is time-consuming because of safety requirements and the limited degree of freedom of the gantry. The objective of this study was to present a navigation solution based on optical tracking for guidance of docking to improve safety and reduce procedure time. We used an optical tracker attached to the mobile linear accelerator to track the prescribed localization of the radiation collimator inside the operating room. Using this information, the integrated navigation system developed computes the movements that the mobile linear accelerator needs to perform to align the applicator and the radiation gantry and warns the physician if docking is unrealizable according to the available degrees of freedom of the mobile linear accelerator. Furthermore, we coded a software application that connects all the necessary functioning elements and provides a user interface for the system calibration and the docking guidance. The system could safeguard against the spatial limitations of the operating room, calculate the optimal arrangement of the accelerator and reduce the docking time in computer simulations and experimental setups. The system could be used to guide docking with any commercial linear accelerator. We believe that the

  8. Synthesis and characterization of curcumin-sulfonamide hybrids: Biological evaluation and molecular docking studies

    Science.gov (United States)

    Banuppriya, Govindharasu; Sribalan, Rajendran; Padmini, Vediappen

    2018-03-01

    Curcumin-sulfonamide hybrids (4a-e) were synthesized and their in vitro antioxidant, anti-inflammatory and anticancer activities were studied. The synthesized compounds showed a very good potent activity towards antioxidant and anti-inflammatory studies rather than its parent as well as standard. These compounds have exhibited an excellent toxicity effect to the cancer cell lines such as A549 and AGS. The compounds 4a and 4c have showed good anticancer activity than curcumin. The molecular docking studies were also performed against various Epidermal Growth Factor Receptor (EGFR) enzymes. The DFT calculations were also done in order to support the docking results.

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

    OpenAIRE

    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 organic Dutch pig farmers. “Biting” (of tails, ears, or limbs) was identified by the farmers as a main welfare problem in pig farming. About half of the farmers reported to have no tail biting prob...

  10. Acute peg in hole docking in the management of infected non-union of long bones

    OpenAIRE

    Dhar, Shabir Ahmed; Mir, Mohammed Ramzan; Ahmed, Molvi Sajjad; Afzal, Suhail; Butt, Mohammed Farooq; Badoo, A. R.; Dar, Irshad Tabasum; Hussain, Anwar

    2007-01-01

    The Ilizarov method has been studied extensively in the management of non-union of long bones. In most cases this involves filling of defects present primarily or after débridement by bone transport. Acute docking over gaps longer than 2 cm has not been adequately studied, however. The purpose of this paper is to report the efficacy of acute peg in hole docking as a bone graft-sparing modality in the management of infected non-union of long bones.

  11. Acute peg in hole docking in the management of infected non-union of long bones.

    Science.gov (United States)

    Dhar, Shabir Ahmed; Mir, Mohammed Ramzan; Ahmed, Molvi Sajjad; Afzal, Suhail; Butt, Mohammed Farooq; Badoo, A R; Dar, Irshad Tabasum; Hussain, Anwar

    2008-08-01

    The Ilizarov method has been studied extensively in the management of non-union of long bones. In most cases this involves filling of defects present primarily or after débridement by bone transport. Acute docking over gaps longer than 2 cm has not been adequately studied, however. The purpose of this paper is to report the efficacy of acute peg in hole docking as a bone graft-sparing modality in the management of infected non-union of long bones.

  12. Diagnostic accuracy in virtual dermatopathology

    DEFF Research Database (Denmark)

    Mooney, E.; Kempf, W.; Jemec, G.B.E.

    2012-01-01

    Background Virtual microscopy is used for teaching medical students and residents and for in-training and certification examinations in the United States. However, no existing studies compare diagnostic accuracy using virtual slides and photomicrographs. The objective of this study was to compare...... diagnostic accuracy of dermatopathologists and pathologists using photomicrographs vs. digitized images, through a self-assessment examination, and to elucidate assessment of virtual dermatopathology. Methods Forty-five dermatopathologists and pathologists received a randomized combination of 15 virtual...... slides and photomicrographs with corresponding clinical photographs and information in a self-assessment examination format. Descriptive data analysis and comparison of groups were performed using a chi-square test. Results Diagnostic accuracy in dermatopathology using virtual dermatopathology...

  13. HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy.

    Science.gov (United States)

    Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong; Huang, Sheng-You

    2017-07-03

    Protein-protein and protein-DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein-protein and protein-DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10-20 min for a docking run. Tested on the cases with weakly homologous complexes of server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

    Science.gov (United States)

    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  15. Which is the most preventive measure against tail damage in finisher pigs: tail docking, straw provision or lowered stocking density?

    DEFF Research Database (Denmark)

    Larsen, Mona Lilian Vestbjerg; Andersen, Heidi Mai-Lis; Pedersen, Lene Juul

    2018-01-01

    One challenge of intensive pig production is tail damage caused by tail biting, and farmers often decrease the prevalence of tail damage through tail docking. However, tail docking is not an optimal preventive measure against tail damage and thus, it would be preferable to replace it. The aim of ...

  16. Collective animal decisions: preference conflict and decision accuracy.

    Science.gov (United States)

    Conradt, Larissa

    2013-12-06

    Social animals frequently share decisions that involve uncertainty and conflict. It has been suggested that conflict can enhance decision accuracy. In order to judge the practical relevance of such a suggestion, it is necessary to explore how general such findings are. Using a model, I examine whether conflicts between animals in a group with respect to preferences for avoiding false positives versus avoiding false negatives could, in principle, enhance the accuracy of collective decisions. I found that decision accuracy nearly always peaked when there was maximum conflict in groups in which individuals had different preferences. However, groups with no preferences were usually even more accurate. Furthermore, a relatively slight skew towards more animals with a preference for avoiding false negatives decreased the rate of expected false negatives versus false positives considerably (and vice versa), while resulting in only a small loss of decision accuracy. I conclude that in ecological situations in which decision accuracy is crucial for fitness and survival, animals cannot 'afford' preferences with respect to avoiding false positives versus false negatives. When decision accuracy is less crucial, animals might have such preferences. A slight skew in the number of animals with different preferences will result in the group avoiding that type of error more that the majority of group members prefers to avoid. The model also indicated that knowing the average success rate ('base rate') of a decision option can be very misleading, and that animals should ignore such base rates unless further information is available.

  17. Directional preference may enhance hunting accuracy in foraging foxes

    Czech Academy of Sciences Publication Activity Database

    Červený, J.; Begall, S.; Koubek, Petr; Nováková, P.; Burda, H.

    2011-01-01

    Roč. 7, č. 3 (2011), s. 355-357 ISSN 1744-9561 R&D Projects: GA ČR GA524/06/0687; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : fox * hunting behaviour * magnetoreception * magnetic alignment Subject RIV: GK - Forestry Impact factor: 3.762, year: 2011

  18. Evidence for Enhanced Interoceptive Accuracy in Professional Musicians

    OpenAIRE

    Schirmer-Mokwa, Katharina L.; Fard, Pouyan R.; Zamorano, Anna M.; Finkel, Sebastian; Birbaumer, Niels; Kleber, Boris A.

    2015-01-01

    Interoception is defined as the perceptual activity involved in the processing of internal bodily signals. While the ability of internal perception is considered a relatively stable trait, recent data suggest that learning to integrate multisensory information can modulate it. Making music is a uniquely rich multisensory experience that has shown to alter motor, sensory, and multimodal representations in the brain of musicians. We hypothesize that musical training also heightens interoceptive...

  19. Evidence for enhanced interoceptive accuracy in professional musicians

    OpenAIRE

    Katharina eSchirmer-Mokwa; Pouyan Rafiei Fard; Anna Maria Zamorano; Sebastian eFinkel; Niels eBirbaumer; Niels eBirbaumer; Boris Alexander Kleber

    2015-01-01

    Interoception is defined as the perceptual activity involved in the processing of internal bodily signals. While the ability of internal perception is considered a relatively stable trait, recent data suggest that learning to integrate multisensory information can modulate it. Making music is a uniquely rich multisensory experience that has shown to alter motor, sensory, and multimodal representations in the brain of musicians. We hypothesize that musical training also heightens interoceptive...

  20. Accuracy Enhancement of CT Measurements using Data Filtering

    DEFF Research Database (Denmark)

    Stolfi, Alessandro; Kallasse, Maarja-Helena; Carli, Lorenzo

    2016-01-01

    This paper describes the impact of data filtering on CT capability to inspect assemblies. The investigation was carried out using an industrial multi-material assembly provided by Novo Nordisk A/S. The assembly comprises two parts made of polyoxymethylene (POM) and of an alloy comprising polycarb...

  1. Dual Inhibition of AChE and BChE with the C-5 Substituted Derivative of Meldrum’s Acid: Synthesis, Structure Elucidation, and Molecular Docking Studies

    Directory of Open Access Journals (Sweden)

    Haroon Mehfooz

    2017-07-01

    Full Text Available Alzheimer’s disease (AD lies in the category of those diseases which are still posing challenges to medicinal chemists, and the search for super-effective drugs for the treatment of AD is a work in progress. The inhibition of cholinesterase is considered a viable strategy to enhance the level of acetylcholine in the brain. The C-5 substituted derivative of Meldrum’s acid was synthesized and screened against acetylcholinesterase (AChE and butyrylcholinesterase (BChE enzyme inhibition activity. The simple and unique structure of synthesized derivative 3 was found to be good for the dual inhibition of both enzymes (AChE and BChE. 2,2-Dimethyl-5-(([2-(trifluoromethyl phenyl]aminomethylidene-1,3-dioxane-4,6-dione (3 showed significant inhibition against AChE, with an IC50 value of 1.13 ± 0.03 µ M (Standard Neostigmine 22.2 ± 3.2 µM, and moderate inhibition against BChE, with an IC50 value of 2.12 ± 1.22 µM (Standard Neostigmine 49.6 ± 6.11 µM. The structural insights reveal that compound 3 possesses intriguing reactive groups, which can potentially evoke the non-covalent interactions and possibly assist by binding in the active site of the target protein. Docking simulations revealed that the compound 3 showed binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained, as the best docked poses showed important binding features mostly based on interactions due to oxygen atoms and the aromatic moieties of the compound. The docking computations coupled with the experimental findings ascertained that the compound 3 can serve as a scaffold for the dual inhibitors of the human acetylcholine esterases.

  2. Applications of the NRGsuite and the Molecular Docking Software FlexAID in Computational Drug Discovery and Design.

    Science.gov (United States)

    Morency, Louis-Philippe; Gaudreault, Francis; Najmanovich, Rafael

    2018-01-01

    Docking simulations help us understand molecular interactions. Here we present a hands-on tutorial to utilize FlexAID (Flexible Artificial Intelligence Docking), an open source molecular docking software between ligands such as small molecules or peptides and macromolecules such as proteins and nucleic acids. The tutorial uses the NRGsuite PyMOL plugin graphical user interface to set up and visualize docking simulations in real time as well as detect and refine target cavities. The ease of use of FlexAID and the NRGsuite combined with its superior performance relative to widely used docking software provides nonexperts with an important tool to understand molecular interactions with direct applications in structure-based drug design and virtual high-throughput screening.

  3. Cadastral Database Positional Accuracy Improvement

    Science.gov (United States)

    Hashim, N. M.; Omar, A. H.; Ramli, S. N. M.; Omar, K. M.; Din, N.

    2017-10-01

    Positional Accuracy Improvement (PAI) is the refining process of the geometry feature in a geospatial dataset to improve its actual position. This actual position relates to the absolute position in specific coordinate system and the relation to the neighborhood features. With the growth of spatial based technology especially Geographical Information System (GIS) and Global Navigation Satellite System (GNSS), the PAI campaign is inevitable especially to the legacy cadastral database. Integration of legacy dataset and higher accuracy dataset like GNSS observation is a potential solution for improving the legacy dataset. However, by merely integrating both datasets will lead to a distortion of the relative geometry. The improved dataset should be further treated to minimize inherent errors and fitting to the new accurate dataset. The main focus of this study is to describe a method of angular based Least Square Adjustment (LSA) for PAI process of legacy dataset. The existing high accuracy dataset known as National Digital Cadastral Database (NDCDB) is then used as bench mark to validate the results. It was found that the propose technique is highly possible for positional accuracy improvement of legacy spatial datasets.

  4. Classification Accuracy Is Not Enough

    DEFF Research Database (Denmark)

    Sturm, Bob L.

    2013-01-01

    A recent review of the research literature evaluating music genre recognition (MGR) systems over the past two decades shows that most works (81\\%) measure the capacity of a system to recognize genre by its classification accuracy. We show here, by implementing and testing three categorically...

  5. The hidden KPI registration accuracy.

    Science.gov (United States)

    Shorrosh, Paul

    2011-09-01

    Determining the registration accuracy rate is fundamental to improving revenue cycle key performance indicators. A registration quality assurance (QA) process allows errors to be corrected before bills are sent and helps registrars learn from their mistakes. Tools are available to help patient access staff who perform registration QA manually.

  6. [Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology].

    Science.gov (United States)

    Du, Ran-Feng; Zhang, Xiao-Hua; Ye, Xiao-Tong; Yu, Wen-Kang; Wang, Yun

    2016-07-01

    Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness. Copyright© by the Chinese Pharmaceutical Association.

  7. Occurrence of Potato virus X on hybrid dock in Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Petrzik, Karel

    2009-01-01

    Roč. 53, č. 1 (2009), s. 49-52 ISSN 0001-723X R&D Projects: GA AV ČR(CZ) 1QS500510558 Institutional research plan: CEZ:AV0Z50510513 Keywords : hybrid dock * potato virus X * Radish mosaic virus * Turnip yellow mosaic virus Subject RIV: EE - Microbiology, Virology Impact factor: 0.746, year: 2009

  8. Rendezvous and Docking Strategy for Crewed Segment of the Asteroid Redirect Mission

    Science.gov (United States)

    Hinkel, Heather D.; Cryan, Scott P.; D'Souza, Christopher; Dannemiller, David P.; Brazzel, Jack P.; Condon, Gerald L.; Othon, William L.; Williams, Jacob

    2014-01-01

    This paper will describe the overall rendezvous, proximity operations and docking (RPOD) strategy in support of the Asteroid Redirect Crewed Mission (ARCM), as part of the Asteroid Redirect Mission (ARM). The focus of the paper is on the crewed mission phase of ARM, starting with the establishment of Orion in the Distant Retrograde Orbit (DRO) and ending with docking to the Asteroid Redirect Vechicle (ARV). The paper will detail the sequence of maneuvers required to execute the rendezvous and proximity operations mission phases along with the on-board navigation strategies, including the final approach phase. The trajectories to be considered will include target vehicles in a DRO. The paper will also discuss the sensor requirements for rendezvous and docking and the various trade studies associated with the final sensor selection. Building on the sensor requirements and trade studies, the paper will include a candidate sensor concept of operations, which will drive the selection of the sensor suite; concurrently, it will be driven by higher level requirements on the system, such as crew timeline constraints and vehicle consummables. This paper will address how many of the seemingly competing requirements will have to be addressed to create a complete system and system design. The objective is to determine a sensor suite and trajectories that enable Orion to successfully rendezvous and dock with a target vehicle in trans lunar space. Finally, the paper will report on the status of a NASA action to look for synergy within RPOD, across the crewed and robotic asteroid missions.

  9. Just-in-Time Retail Distribution : A Systems Perspective on Cross-Docking

    NARCIS (Netherlands)

    Buijs, Paul; Danhof, Hans W.; Wortmann, J.(Hans) C.

    2016-01-01

    Cross-docking is a just-in-time strategy for distribution logistics. It is aimed at reducing inventory levels and distribution lead times by creating a seamless flow of products from suppliers to customers. Prior supply chain literature has argued that creating such a seamless product flows requires

  10. Storing Fresh Produce for Fast Retrieval in an Automated Compact Cross-dock System

    NARCIS (Netherlands)

    Zaerpour, N.; Yu, Y.; de Koster, R.B.M.

    2015-01-01

    We study temporary storage of fresh produce in a cross-dock center. In order to minimize cooling cost, compact storage systems are used. A major disadvantage of these systems is that additional retrieval time is needed, caused by necessary reshuffles due to the improper storage sequence of unit

  11. Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.

    Directory of Open Access Journals (Sweden)

    Priya Antony

    Full Text Available 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.

  12. 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

  13. The pepATTRACT web server for blind, large-scale peptide-protein docking.

    Science.gov (United States)

    de Vries, Sjoerd J; Rey, Julien; Schindler, Christina E M; Zacharias, Martin; Tuffery, Pierre

    2017-07-03

    Peptide-protein interactions are ubiquitous in the cell and form an important part of the interactome. Computational docking methods can complement experimental characterization of these complexes, but current protocols are not applicable on the proteome scale. pepATTRACT is a novel docking protocol that is fully blind, i.e. it does not require any information about the binding site. In various stages of its development, pepATTRACT has participated in CAPRI, making successful predictions for five out of seven protein-peptide targets. Its performance is similar or better than state-of-the-art local docking protocols that do require binding site information. Here we present a novel web server that carries out the rigid-body stage of pepATTRACT. On the peptiDB benchmark, the web server generates a correct model in the top 50 in 34% of the cases. Compared to the full pepATTRACT protocol, this leads to some loss of performance, but the computation time is reduced from ∼18 h to ∼10 min. Combined with the fact that it is fully blind, this makes the web server well-suited for large-scale in silico protein-peptide docking experiments. The rigid-body pepATTRACT server is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/pepATTRACT. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. 19 CFR 4.1 - Boarding of vessels; cutter and dock passes.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Boarding of vessels; cutter and dock passes. 4.1... OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.1 Boarding of... regulations. (4) The master of any vessel shall not authorize the boarding or leaving of his vessel by any...

  15. What in silico molecular docking can do for the 'bench-working ...

    Indian Academy of Sciences (India)

    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 ...

  16. Conceptual design of the hot cell facility universal docking station at ITER

    International Nuclear Information System (INIS)

    Dammann, A.; Benchikhoune, M.; Friconneau, J.P.; Ivanov, V.; Lemee, A.; Martins, J.P.; Tamassy, G.

    2011-01-01

    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.

  17. 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.

  18. 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.

  19. Data of the molecular dynamics simulations of mutations in the human connexin46 docking interface

    Directory of Open Access Journals (Sweden)

    Patrik Schadzek

    2016-06-01

    The data described here are related to the research article entitled “The cataract related mutation N188T in human connexin46 (hCx46 revealed a critical role for residue N188 in the docking process of gap junction channels” (Schadzek et al., 2015 [1].

  20. Systematic and efficient side chain optimization for molecular docking using a cheapest-path procedure.

    Science.gov (United States)

    Schumann, Marcel; Armen, Roger S

    2013-05-30

    Molecular docking of small-molecules is an important procedure for computer-aided drug design. Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding. However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem. Here we describe a new docking approach with a very fast, graph-based optimization algorithm for assignment of the near-optimal set of residue rotamers. We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking (average ROC AUC of 0.693 vs. 0.623). Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures. Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement. Copyright © 2013 Wiley Periodicals, Inc.

  1. Implementation of Statistical Process Control: Evaluating the Mechanical Performance of a Candidate Silicone Elastomer Docking Seal

    Science.gov (United States)

    Oravec, Heather Ann; Daniels, Christopher C.

    2014-01-01

    The National Aeronautics and Space Administration has been developing a novel docking system to meet the requirements of future exploration missions to low-Earth orbit and beyond. A dynamic gas pressure seal is located at the main interface between the active and passive mating components of the new docking system. This seal is designed to operate in the harsh space environment, but is also to perform within strict loading requirements while maintaining an acceptable level of leak rate. In this study, a candidate silicone elastomer seal was designed, and multiple subscale test articles were manufactured for evaluation purposes. The force required to fully compress each test article at room temperature was quantified and found to be below the maximum allowable load for the docking system. However, a significant amount of scatter was observed in the test results. Due to the stochastic nature of the mechanical performance of this candidate docking seal, a statistical process control technique was implemented to isolate unusual compression behavior from typical mechanical performance. The results of this statistical analysis indicated a lack of process control, suggesting a variation in the manufacturing phase of the process. Further investigation revealed that changes in the manufacturing molding process had occurred which may have influenced the mechanical performance of the seal. This knowledge improves the chance of this and future space seals to satisfy or exceed design specifications.

  2. Docking of flexible ligands to flexible receptors in solution by molecular dynamics simulation

    NARCIS (Netherlands)

    Mangoni, R; Roccatano, D; Di Nola, A

    1999-01-01

    In this paper, a method of simulating the docking of small flexible ligands to flexible receptors in water is reported. The method is based on molecular dynamics simulations and is an extension of an algorithm previously reported by Di Nola et al, (Di Nola et al,, Proteins 1994;19:174-182), The

  3. 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.

  4. In silico docking studies of aldose reductase inhibitory activity of commercially available flavonoids

    Directory of Open Access Journals (Sweden)

    Arumugam Madeswaran

    2012-12-01

    Full Text Available The primary objective of this study was to investigate the aldose reductase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like biochanin, butein, esculatin, fisetin and herbacetin were selected. Epalrestat, a known aldose reductase inhibitor was used as the standard. 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 -9.33 kcal/mol to -7.23 kcal/mol when compared with that of the standard (-8.73 kcal/mol. Inhibition constant (144.13 µM to 4.98 µM and intermolecular energy (-11.42 kcal/mol to -7.83 kcal/mol of the flavonoids also coincide with the binding energy. All the selected flavonoids contributed aldose reductase inhibitory activity because of its structural properties. These molecular docking analyses could lead to the further development of potent aldose reductase inhibitors for the treatment of diabetes.

  5. Lactone size dependent reactivity in Candida antarctica lipase B: A molecular dynamics and docking study

    NARCIS (Netherlands)

    Veld, M.A.J.; Fransson, L.; Palmans, A.R.A.; Meijer, E.W.; Hult, K.

    2009-01-01

    Size matters: Lactones have extensively been studied as monomers in enzymatic polymerization reactions. Large lactones showed an unexpectedly high reactivity in these reactions. A combination of docking and molecular dynamics studies have been used to explain this high reactivity in terms of

  6. An Insight into the Anticancer Activities of Ru(II-Based Metallocompounds Using Docking Methods

    Directory of Open Access Journals (Sweden)

    Peter A. Ajibade

    2013-09-01

    Full Text Available Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

  7. Demonstration of Self-Training Autonomous Neural Networks in Space Vehicle Docking Simulations

    Science.gov (United States)

    Patrick, M. Clinton; Thaler, Stephen L.; Stevenson-Chavis, Katherine

    2006-01-01

    Neural Networks have been under examination for decades in many areas of research, with varying degrees of success and acceptance. Key goals of computer learning, rapid problem solution, and automatic adaptation have been elusive at best. This paper summarizes efforts at NASA's Marshall Space Flight Center harnessing such technology to autonomous space vehicle docking for the purpose of evaluating applicability to future missions.

  8. What in silico molecular docking can do for the 'bench-working ...

    Indian Academy of Sciences (India)

    RB, FL http://www.biosolveit.de/FlexX/. Commercial program available for Linux and Windows, part of the LeadIT software solution. Good user interface. Takes account of the metal coordination. It allows the user to select which atoms of the ligand and the protein are able to be joined by a covalent bound. Dock 6 (Kuntz et al.

  9. 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...

  10. Defining the limits of homology modeling in information-driven protein docking

    NARCIS (Netherlands)

    Garcia Lopes Maia Rodrigues, João; Melquiond, A S J; Karaca, E; Trellet, M; van Dijk, M; van Zundert, G C P; Schmitz, C; de Vries, S J; Bordogna, A; Bonati, L; Kastritis, P L; Bonvin, Alexandre M J J; Garcia Lopes Maia Rodrigues, João

    2013-01-01

    Information-driven docking is currently one of the most successful approaches to obtain structural models of protein interactions as demonstrated in the latest round of CAPRI. While various experimental and computational techniques can be used to retrieve information about the binding mode, the

  11. An Experimental Investigation of Leak Rate Performance of a Subscale Candidate Elastomer Docking Space Seal

    Science.gov (United States)

    Garafolo, Nicholas G.; Daniels, Christopher C.

    2011-01-01

    A novel docking seal was developed for the main interface seal of NASA s Low Impact Docking System (LIDS). This interface seal was designed to maintain acceptable leak rates while being exposed to the harsh environmental conditions of outer space. In this experimental evaluation, a candidate docking seal assembly called Engineering Development Unit (EDU58) was characterized and evaluated against the Constellation Project leak rate requirement. The EDU58 candidate seal assembly was manufactured from silicone elastomer S0383-70 vacuum molded in a metal retainer ring. Four seal designs were considered with unique characteristic heights. The leak rate performance was characterized through a mass point leak rate method by monitoring gas properties within an internal control volume. The leakage performance of the seals were described herein at representative docking temperatures of -50, +23, and +50 C for all four seal designs. Leak performance was also characterized at 100, 74, and 48 percent of full closure. For all conditions considered, the candidate seal assemblies met the Constellation Project leak rate requirement.

  12. Activated Cdc42 kinase regulates Dock localization in male germ cells during Drosophila spermatogenesis.

    Science.gov (United States)

    Abdallah, Abbas M; Zhou, Xin; Kim, Christine; Shah, Kushani K; Hogden, Christopher; Schoenherr, Jessica A; Clemens, James C; Chang, Henry C

    2013-06-15

    Deregulation of the non-receptor tyrosine kinase ACK1 (Activated Cdc42-associated kinase) correlates with poor prognosis in cancers and has been implicated in promoting metastasis. To further understand its in vivo function, we have characterized the developmental defects of a null mutation in Drosophila Ack, which bears a high degree of sequence similarity to mammalian ACK1 but lacks a CRIB domain. We show that Ack, while not essential for viability, is critical for sperm formation. This function depends on Ack tyrosine kinase activity and is required cell autonomously in differentiating male germ cells at or after the spermatocyte stage. Ack associates predominantly with endocytic clathrin sites in spermatocytes, but disruption of Ack function has no apparent effect on clathrin localization and receptor-mediated internalization of Boss (Bride of sevenless) protein in eye discs. Instead, Ack is required for the subcellular distribution of Dock (dreadlocks), the Drosophila homolog of the SH2- and SH3-containing adaptor protein Nck. Moreover, Dock forms a complex with Ack, and the localization of Dock in male germ cells depends on its SH2 domain. Together, our results suggest that Ack-dependent tyrosine phosphorylation recruits Dock to promote sperm differentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Xiaodong Gao

    2016-05-01

    Full Text Available Checkpoint kinase 1 (Chk1 is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure–activity relationship (3D-QSAR modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q2 values (0.531, 0.726, fitted correlation r2 coefficients (higher than 0.90, and standard error of prediction (less than 0.250. These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

  14. Density functional theory analysis and molecular docking evaluation of 1-(2, 5-dichloro-4-sulfophenyl)-3-methyl-5-pyrazolone as COX2 inhibitor against inflammatory diseases

    Science.gov (United States)

    Kavitha, T.; Velraj, G.

    2017-08-01

    The molecular structure of 1-(2, 5-Dichloro-4-Sulfophenyl)-3-Methyl-5-Pyrazolone (DSMP) was optimized using DFT/B3LYP/6-31++G(d,p) level and its corresponding experimental as well as theoretical FT-IR, FT-Raman vibrational frequencies and UV-Vis spectral analysis were carried out. The vibrational assignments and total energy distributions of each vibration were presented with the aid of Veda 4xx software. The molecular electrostatic potential, HOMO-LUMO energies, global and local reactivity descriptors and natural bond orbitals were analyzed in order to find the most possible reactive sites of the molecule and it was found that DSMP molecule possess enhanced nucleophilic activity. One of the common known COX2 inhibitor, celecoxib (CXB) was also found to exhibit similar reactivity properties and hence DSMP was also expected to inhibit COX enzymes. In order to detect the COX inhibition nature of DSMP, molecular docking analysis was carried out with the help of Autodock software. For that, the optimized structure was in turn used for docking DSMP with COX enzymes. The binding energy scores and inhibitory constant values reveal that the DSMP molecule possess good binding affinity and low inhibition constant towards COX2 enzyme and hence it can be used as an anti-inflammatory drug after carrying out necessary biological tests.

  15. Fragment-based docking: development of the CHARMMing Web user interface as a platform for computer-aided drug design.

    Science.gov (United States)

    Pevzner, Yuri; Frugier, Emilie; Schalk, Vinushka; Caflisch, Amedeo; Woodcock, H Lee

    2014-09-22

    Web-based user interfaces to scientific applications are important tools that allow researchers to utilize a broad range of software packages with just an Internet connection and a browser. One such interface, CHARMMing (CHARMM interface and graphics), facilitates access to the powerful and widely used molecular software package CHARMM. CHARMMing incorporates tasks such as molecular structure analysis, dynamics, multiscale modeling, and other techniques commonly used by computational life scientists. We have extended CHARMMing's capabilities to include a fragment-based docking protocol that allows users to perform molecular docking and virtual screening calculations either directly via the CHARMMing Web server or on computing resources using the self-contained job scripts generated via the Web interface. The docking protocol was evaluated by performing a series of "re-dockings" with direct comparison to top commercial docking software. Results of this evaluation showed that CHARMMing's docking implementation is comparable to many widely used software packages and validates the use of the new CHARMM generalized force field for docking and virtual screening.

  16. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors

    Directory of Open Access Journals (Sweden)

    Rushikesh Sable

    2015-06-01

    Full Text Available Blocking protein-protein interactions (PPI using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  17. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors.

    Science.gov (United States)

    Sable, Rushikesh; Jois, Seetharama

    2015-06-23

    Blocking protein-protein interactions (PPI) using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  18. Inertial Measures of Motion for Clinical Biomechanics: Comparative Assessment of Accuracy under Controlled Conditions – Changes in Accuracy over Time

    Science.gov (United States)

    Lebel, Karina; Boissy, Patrick; Hamel, Mathieu; Duval, Christian

    2015-01-01

    Background Interest in 3D inertial motion tracking devices (AHRS) has been growing rapidly among the biomechanical community. Although the convenience of such tracking devices seems to open a whole new world of possibilities for evaluation in clinical biomechanics, its limitations haven’t been extensively documented. The objectives of this study are: 1) to assess the change in absolute and relative accuracy of multiple units of 3 commercially available AHRS over time; and 2) to identify different sources of errors affecting AHRS accuracy and to document how they may affect the measurements over time. Methods This study used an instrumented Gimbal table on which AHRS modules were carefully attached and put through a series of velocity-controlled sustained motions including 2 minutes motion trials (2MT) and 12 minutes multiple dynamic phases motion trials (12MDP). Absolute accuracy was assessed by comparison of the AHRS orientation measurements to those of an optical gold standard. Relative accuracy was evaluated using the variation in relative orientation between modules during the trials. Findings Both absolute and relative accuracy decreased over time during 2MT. 12MDP trials showed a significant decrease in accuracy over multiple phases, but accuracy could be enhanced significantly by resetting the reference point and/or compensating for initial Inertial frame estimation reference for each phase. Interpretation The variation in AHRS accuracy observed between the different systems and with time can be attributed in part to the dynamic estimation error, but also and foremost, to the ability of AHRS units to locate the same Inertial frame. Conclusions Mean accuracies obtained under the Gimbal table sustained conditions of motion suggest that AHRS are promising tools for clinical mobility assessment under constrained conditions of use. However, improvement in magnetic compensation and alignment between AHRS modules are desirable in order for AHRS to reach their

  19. Silencing of dedicator of cytokinesis (DOCK180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (AIRE).

    Science.gov (United States)

    Mohan, Jasna Jagan; Narayan, Prashanth; Padmanabhan, Renjini Ambika; Joseph, Selin; Kumar, Pradeep G; Laloraya, Malini

    2018-03-08

    Dedicator of cytokinesis (DOCK 180) involved in cytoskeletal reorganization is primarily a cytosolic molecule. It is recently shown to be nuclear in HeLa cells but its nuclear function is not known. The spatiotemporal distribution of DOCK180 in uterus was studied in uterine cytoplasmic and nuclear compartments during the "window of implantation." The functional significance of nuclear DOCK180 was explored by homology modeling, co-immunoprecipitation assays, and mass spectrometric analysis. Dock180's role in early pregnancy was ascertained by Dock 180 silencing and subsequent quantitative real-time PCR and Western blotting analysis. Our study shows a nuclear DOCK180 in the uterus during "window of implantation." Estrogen and progesterone mediate expression and nuclear translocation of DOCK180. The nuclear function of DOCK180 is attributed to its ability to import autoimmune regulator (AIRE) into the nucleus. Silencing of Dock180 inhibited AIRE nuclear shuttling which influenced its downstream targets, thereby affecting decidualization with AIRE and HOXA-10 as the major players as well as lack of implantation site formation due to impact on angiogenesis-associated genes. DOCK180 has an indispensable role in pregnancy establishment as knocking down Dock180 abrogates pregnancy by a consolidated impact on decidualization and angiogenesis by regulating AIRE nuclear entry. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Enhanced PM10 bounded PAHs from shipping emissions

    Science.gov (United States)

    Pongpiachan, S.; Hattayanone, M.; Choochuay, C.; Mekmok, R.; Wuttijak, N.; Ketratanakul, A.

    2015-05-01

    Earlier studies have highlighted the importance of maritime transport as a main contributor of air pollutants in port area. The authors intended to investigate the effects of shipping emissions on the enhancement of PM10 bounded polycyclic aromatic hydrocarbons (PAHs) and mutagenic substances in an industrial area of Rayong province, Thailand. Daily PM10 speciation data across two air quality observatory sites in Thailand during 2010-2013 were collected. Diagnostic binary ratios of PAH congeners, analysis of variances (ANOVA), and principal component analysis (PCA) were employed to evaluate the enhanced genotoxicity of PM10 during the docking period. Significant increase of PAHs and mutagenic index (MI) of PM10 were observed during the docking period in both sampling sites. Although stationary sources like coal combustions from power plants and vehicular exhausts from motorway can play a great role in enhancing PAH concentrations, regulating shipping emissions from diesel engine in the port area like Rayong is predominantly crucial.

  1. Surface Expression of TGF-β Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer

    Science.gov (United States)

    Metelli, Alessandra; Wu, Bill X; Fugle, Caroline W; Rachidi, Saleh; Sun, Shaoli; Zhang, Yongliang; Wu, Jennifer; Tomlinson, Stephen; Howe, Philip; Yang, Yi; Garrett-Mayer, Elizabeth; Liu, Bei; Li, Zihai

    2016-01-01

    GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGF-β which is expressed naturally by platelets and regulatory T cells. Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGF-β in the tumor microenvironment. We found that human breast, lung and colon cancers expressed GARP aberrantly. In genetic studies in normal mammary gland epithelial and carcinoma cells, GARP expression increased TGF-β bioactivity and promoted malignant transformation in immune deficient mice. In breast carcinoma-bearing mice that were immune competent, GARP overexpression promoted Foxp3+ regulatory T cell activity, which in turn contributed to enhancing cancer progression and metastasis. Notably, administration of a panel of GARP-specific monoclonal antibodies limited metastasis in an orthotopic model of human breast cancer. Overall, these results define the oncogenic effects of the GARP-TGF-β axis in the tumor microenvironment and suggest mechanisms that might be exploited for diagnostic and therapeutic purposes. PMID:27913437

  2. Selectivity analyses of γ-benzylidene digoxin derivatives to different Na,K-ATPase α isoforms: a molecular docking approach.

    Science.gov (United States)

    Pessôa, Marco T C; Alves, Silmara L G; Taranto, Alex G; Villar, José A F P; Blanco, Gustavo; Barbosa, Leandro A

    2018-12-01

    Digoxin and other cardiotonic steroids (CTS) exert their effect by inhibiting Na,K-ATPase (NKA) activity. CTS bind to the various NKA isoforms that are expressed in different cell types, which gives CTS their narrow therapeutic index. We have synthesised a series of digoxin derivatives (γ-Benzylidene digoxin derivatives) with substitutions in the lactone ring (including non-oxygen and ether groups), to obtain CTS with better NKA isoform specificity. Some of these derivatives show some NKA isoform selective effects, with BD-3, BD-8, and BD-13 increasing NKA α2 activity, BD-5 inhibiting NKA α1 and NKA α3, BD-10 reducing NKA α1, but stimulating NKA α2 and α3; and BD-14, BD-15, and BD-16 enhancing NKA α3 activity. A molecular-docking approach favoured NKA isoform specific interactions for the compounds that supported their observed activity. These results show that BD compounds are a new type of CTS with the capacity to target NKA activity in an isoform-specific manner.

  3. Technique for Increasing Accuracy of Positioning System of Machine Tools

    Directory of Open Access Journals (Sweden)

    Sh. Ji

    2014-01-01

    Full Text Available The aim of research is to improve the accuracy of positioning and processing system using a technique for optimization of pressure diagrams of guides in machine tools. The machining quality is directly related to its accuracy, which characterizes an impact degree of various errors of machines. The accuracy of the positioning system is one of the most significant machining characteristics, which allow accuracy evaluation of processed parts.The literature describes that the working area of the machine layout is rather informative to characterize the effect of the positioning system on the macro-geometry of the part surfaces to be processed. To enhance the static accuracy of the studied machine, in principle, two groups of measures are possible. One of them points toward a decrease of the cutting force component, which overturns the slider moments. Another group of measures is related to the changing sizes of the guide facets, which may lead to their profile change.The study was based on mathematical modeling and optimization of the cutting zone coordinates. And we find the formula to determine the surface pressure of the guides. The selected parameters of optimization are v