Tethering sockets and wrenches

Science.gov (United States)

Johnson, E. P.

1990-07-01

The tethering of sockets and wrenches was accomplished to improve the safety of working over motor segments. To accomplish the tethering of the sockets to the ratchets, a special design was implemented in which a groove was machined into each socket. Each socket was then fitted with a snap ring that can spin around the machined groove. The snap ring is tethered to the handle of the ratchet. All open end wrenches are also tethered to the ratchet or to the operator, depending upon the type. Tests were run to ensure that the modified tools meet torque requirements. The design was subsequently approved by Space Safety.

Experiments and Numerical Simulations of Electrodynamic Tether

Science.gov (United States)

Iki, Kentaro; Kawamoto, Satomi; Takahashi, Ayaka; Ishimoto, Tomori; Yanagida, Atsushi; Toda, Susumu

As an effective means of suppressing space debris growth, the Aerospace Research and Development Directorate of the Japan Aerospace Exploration Agency (JAXA) has been investigating an active space debris removal system that employs highly efficient electrodynamic tether (EDT) technology for orbital transfer. This study investigates tether deployment dynamics by means of on-ground experiments and numerical simulations of an electrodynamic tether system. Some key parameters used in the numerical simulations, such as the elastic modulus and damping ratio of the tether, the spring constant of the coiling of the tether, and deployment friction, must be estimated, and various experiments are conducted to determine these values. As a result, the following values were obtained: The elastic modulus of the tether was 40 GPa, and the damping ratio of the tether was 0.02. The spring constant and the damping ratio of the tether coiling were 10-4 N/m and 0.025 respectively. The deployment friction was 0.038ν + 0.005 N. In numerical simulations using a multiple mass tether model, tethers with lengths of several kilometers are deployed and the attitude dynamics of satellites attached to the end of the tether and tether libration are calculated. As a result, the simulations confirmed successful deployment of the tether with a length of 500 m using the electrodynamic tether system.

Tethered Satellite System Contingency Investigation Board

Science.gov (United States)

1992-11-01

The Tethered Satellite System (TSS-1) was launched aboard the Space Shuttle Atlantis (STS-46) on July 31, 1992. During the attempted on-orbit operations, the Tethered Satellite System failed to deploy successfully beyond 256 meters. The satellite was retrieved successfully and was returned on August 6, 1992. The National Aeronautics and Space Administration (NASA) Associate Administrator for Space Flight formed the Tethered Satellite System (TSS-1) Contingency Investigation Board on August 12, 1992. The TSS-1 Contingency Investigation Board was asked to review the anomalies which occurred, to determine the probable cause, and to recommend corrective measures to prevent recurrence. The board was supported by the TSS Systems Working group as identified in MSFC-TSS-11-90, 'Tethered Satellite System (TSS) Contingency Plan'. The board identified five anomalies for investigation: initial failure to retract the U2 umbilical; initial failure to flyaway; unplanned tether deployment stop at 179 meters; unplanned tether deployment stop at 256 meters; and failure to move tether in either direction at 224 meters. Initial observations of the returned flight hardware revealed evidence of mechanical interference by a bolt with the level wind mechanism travel as well as a helical shaped wrap of tether which indicated that the tether had been unwound from the reel beyond the travel by the level wind mechanism. Examination of the detailed mission events from flight data and mission logs related to the initial failure to flyaway and the failure to move in either direction at 224 meters, together with known preflight concerns regarding slack tether, focused the assessment of these anomalies on the upper tether control mechanism. After the second meeting, the board requested the working group to complete and validate a detailed integrated mission sequence to focus the fault tree analysis on a stuck U2 umbilical, level wind mechanical interference, and slack tether in upper tether

Space Station tethered elevator system

Science.gov (United States)

Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

1989-01-01

The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

Coat/Tether Interactions—Exception or Rule?

Science.gov (United States)

Schröter, Saskia; Beckmann, Sabrina; Schmitt, Hans Dieter

2016-01-01

Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers. PMID:27243008

Coat/Tether Interactions-Exception or Rule?

Science.gov (United States)

Schroeter, Saskia; Beckmann, Sabrina; Schmitt, Hans Dieter

2016-01-01

Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers.

Two Tethered Balloon Systems

Science.gov (United States)

Youngbluth, Otto; Owens, Thomas L.; Storey, Richard W.

1990-01-01

Systems take meteorological measurements for variety of research projects. Report describes work done by NASA Langley Research Center in atmospheric research using tethered balloon systems composed of commercially available equipment. Two separate tethered balloon systems described in report have payloads and configurations tailored to requirements of specific projects. Each system capable of measuring atmospheric parameter or species in situ and then telemetering this data in real time to ground station. Meteorological data and concentration of ozone typically measured. Indicates instrumented tethered balloon systems have distinct advantages over other systems for gathering data on troposphere.

Autonomous Rendezvous and Docking with Nonfull Field of View for Tethered Space Robot

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Panfeng Huang

2017-01-01

Full Text Available In the ultra-close approaching phase of tethered space robot, a highly stable self-attitude control is essential. However, due to the field of view limitation of cameras, typical point features are difficult to extract, where commonly adopted position-based visual servoing cannot be valid anymore. To provide robot’s relative position and attitude with the target, we propose a monocular visual servoing control method using only the edge lines of satellite brackets. Firstly, real time detection of edge lines is achieved based on image gradient and region growing. Then, we build an edge line based model to estimate the relative position and attitude between the robot and the target. Finally, we design a visual servoing controller combined with PD controller. Experimental results demonstrate that our algorithm can extract edge lines stably and adjust the robot’s attitude to satisfy the grasping requirements.

Space tether dynamics: an introduction

Science.gov (United States)

Denny, Mark

2018-05-01

The dynamics of orbiting tethers (space elevators and skyhooks) is developed from an unusual direction: Lagrangian rather than Newtonian mechanics. These basic results are derived among others: space elevator required length with and without counterweight, location and magnitude of maximum tether tension, skyhook orbital parameters and tether tension. These conceptual devices are being increasingly discussed as technologically feasible; here they make an interesting pedagogical application of Lagrangian mechanics suitable for undergraduate physics students.

The space station tethered elevator system

Science.gov (United States)

Anderson, Loren A.

1989-01-01

The optimized conceptual engineering design of a space station tethered elevator is presented. The elevator is an unmanned mobile structure which operates on a ten kilometer tether spanning the distance between the Space Station and a tethered platform. Elevator capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The potential uses, parameters, and evolution of the spacecraft design are discussed. Engineering development of the tethered elevator is the result of work conducted in the following areas: structural configurations; robotics, drive mechanisms; and power generation and transmission systems. The structural configuration of the elevator is presented. The structure supports, houses, and protects all systems on board the elevator. The implementation of robotics on board the elevator is discussed. Elevator robotics allow for the deployment, retrieval, and manipulation of tethered objects. Robotic manipulators also aid in hooking the elevator on a tether. Critical to the operation of the tethered elevator is the design of its drive mechanisms, which are discussed. Two drivers, located internal to the elevator, propel the vehicle along a tether. These modular components consist of endless toothed belts, shunt-wound motors, regenerative power braking, and computer controlled linear actuators. The designs of self-sufficient power generation and transmission systems are reviewed. Thorough research indicates all components of the elevator will operate under power provided by fuel cells. The fuel cell systems will power the vehicle at seven kilowatts continuously and twelve kilowatts maximally. A set of secondary fuel cells provides redundancy in the unlikely event of a primary system failure. Power storage exists in the form of Nickel-Hydrogen batteries capable of powering the elevator under maximum loads.

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.

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.

Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane.

Science.gov (United States)

Johnson, Jennifer L; He, Jing; Ramadass, Mahalakshmi; Pestonjamasp, Kersi; Kiosses, William B; Zhang, Jinzhong; Catz, Sergio D

2016-02-12

The small GTPase Rab11 and its effectors control trafficking of recycling endosomes, receptor replenishment and the up-regulation of adhesion and adaptor molecules at the plasma membrane. Despite recent advances in the understanding of Rab11-regulated mechanisms, the final steps mediating docking and fusion of Rab11-positive vesicles at the plasma membrane are not fully understood. Munc13-4 is a docking factor proposed to regulate fusion through interactions with SNAREs. In hematopoietic cells, including neutrophils, Munc13-4 regulates exocytosis in a Rab27a-dependent manner, but its possible regulation of other GTPases has not been explored in detail. Here, we show that Munc13-4 binds to Rab11 and regulates the trafficking of Rab11-containing vesicles. Using a novel Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) assay, we demonstrate that Munc13-4 binds to Rab11a but not to dominant negative Rab11a. Immunoprecipitation analysis confirmed the specificity of the interaction between Munc13-4 and Rab11, and super-resolution microscopy studies support the interaction of endogenous Munc13-4 with Rab11 at the single molecule level in neutrophils. Vesicular dynamic analysis shows the common spatio-temporal distribution of Munc13-4 and Rab11, while expression of a calcium binding-deficient mutant of Munc13-4 significantly affected Rab11 trafficking. Munc13-4-deficient neutrophils showed normal endocytosis, but the trafficking, up-regulation, and retention of Rab11-positive vesicles at the plasma membrane was significantly impaired. This correlated with deficient NADPH oxidase activation at the plasma membrane in response to Rab11 interference. Our data demonstrate that Munc13-4 is a Rab11-binding partner that regulates the final steps of Rab11-positive vesicle docking at the plasma membrane. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators

Directory of Open Access Journals (Sweden)

Mandë Holford

2009-10-01

Full Text Available Neuronal circuits depend on the precise regulation of cell-surface receptors and ion channels. An ongoing challenge in neuroscience research is deciphering the functional contribution of specific receptors and ion channels using engineered modulators. A novel strategy, termed “tethered toxins”, was recently developed to characterize neuronal circuits using the evolutionary derived selectivity of venom peptide toxins and endogenous peptide ligands, such as lynx1 prototoxins. Herein, the discovery and engineering of cell-surface tethered peptides is reviewed, with particular attention given to their cell-autonomy, modular composition, and genetic targeting in different model organisms. The relative ease with which tethered peptides can be engineered, coupled with the increasing number of neuroactive venom toxins and ligand peptides being discovered, imply a multitude of potentially innovative applications for manipulating neuronal circuits and tissue-specific cell networks, including treatment of disorders caused by malfunction of receptors and ion channels.

Coat/tether interactions – exceptions or rule?

Directory of Open Access Journals (Sweden)

Saskia eSchroeter

2016-05-01

Full Text Available Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers.

Tether Elevator Crawler Systems (TECS)

Science.gov (United States)

Swenson, Frank R.

1987-01-01

One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation.

Science.gov (United States)

Koubek, Emily J; Santy, Lorraine C

2018-05-04

Hepatocyte growth factor (HGF) is a potent signaling factor that acts on epithelial cells, causing them to dissociate and scatter. This migration is coordinated by a number of small GTPases, such as ARF6 and Rac1. Active ARF6 is required for HGF-stimulated migration and intracellular levels of ARF6-GTP and Rac1-GTP increase following HGF treatment. During migration, cross talk between ARF6 and Rac1 occurs through formation of a multi-protein complex containing the ARF-GEF cytohesin-2, the scaffolding protein GRASP/Tamalin, and the Rac1-GEF Dock180. Previously, the role of ARF6 in this process was unclear. We have now found that ARF6 and ARF1 regulate trafficking of GRASP and Dock180 to the plasma membrane following HGF treatment. Trafficking of GRASP and Dock180 is impaired by blocking ARF6-mediated recycling pathways and is required for HGF-stimulated Rac1 activation. Finally, HGF treatment stimulates association of GRASP and Dock180. Inhibition of ARF6 trafficking pathways traps GRASP and Dock180 as a complex in the cell.

Molecular Structure of Membrane Tethers

NARCIS (Netherlands)

Baoukina, Svetlana; Marrink, Siewert J.; Tieleman, D. Peter

2012-01-01

Membrane tethers are nanotubes formed by a lipid bilayer. They play important functional roles in cell biology and provide an experimental window on lipid properties. Tethers have been studied extensively in experiments and described by theoretical models, but their molecular structure remains

Space Environmental Effects on Coated Tether Materials

Science.gov (United States)

Gittemeier, Keith A.; Hawk, Clark W.; Finckenor, Miria M.; Watts, Ed

2005-01-01

The University of Alabama in Huntsville s Propulsion Research Center has teamed with NASA's Marshall Space Flight Center (MSFC) to research the effects of atomic oxygen (AO) bombardment on coated tether materials. Tethers Unlimited Inc. has provided several candidate tether materials with various coatings for AO exposure in MSFC s Atomic Oxygen Beam Facility. Additional samples were exposed to ultraviolet (UV) radiation at MSFC. AO erodes most organic materials, and ultraviolet radiation embrittles polymers. This test series was performed to determine the effect of AO and UV on the mechanical integrity of tether materials that were treated with AO-protective coatings, such as polyhedral oligomeric silsesquioxane (POSS) or metallization. Both TUI's Multi-Application Survivable Tether (MAST) Experiment and Marshall Space Flight Center s Momentum Exchange Electrodynamic Reboost (MXER) programs will benefit from this research by helping to determine tether materials and coatings that give the longest life with the lowest mass penalty.

Membrane tethering complexes in the endosomal system

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Anne eSpang

2016-05-01

Full Text Available Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the CORVET complex, while fusion of late endosomes with lysosomes depends on the HOPS complex. Recycling through the TGN and to the plasma membrane is facilitated by the GARP and EARP complexes, respectively. However, there are other tethering functions in the endosomal system as there are multiple pathways through which proteins can be delivered from endosomes to either the TGN or the plasma membrane. Furthermore, complexes that may be part of novel tethering complexes have been recently identified. Thus it is likely that more tethering factors exist. In this review, I will provide an overview of different tethering complexes of the endosomal system and discuss how they may provide specificity in membrane traffic.

Attitude control analysis of tethered de-orbiting

Science.gov (United States)

Peters, T. V.; Briz Valero, José Francisco; Escorial Olmos, Diego; Lappas, V.; Jakowski, P.; Gray, I.; Tsourdos, A.; Schaub, H.; Biesbroek, R.

2018-05-01

The increase of satellites and rocket upper stages in low earth orbit (LEO) has also increased substantially the danger of collisions in space. Studies have shown that the problem will continue to grow unless a number of debris are removed every year. A typical active debris removal (ADR) mission scenario includes launching an active spacecraft (chaser) which will rendezvous with the inactive target (debris), capture the debris and eventually deorbit both satellites. Many concepts for the capture of the debris while keeping a connection via a tether, between the target and chaser have been investigated, including harpoons, nets, grapples and robotic arms. The paper provides an analysis on the attitude control behaviour for a tethered de-orbiting mission based on the ESA e.Deorbit reference mission, where Envisat is the debris target to be captured by a chaser using a net which is connected to the chaser with a tether. The paper provides novel insight on the feasibility of tethered de-orbiting for the various mission phases such as stabilization after capture, de-orbit burn (plus stabilization), stabilization during atmospheric pass, highlighting the importance of various critical mission parameters such as the tether material. It is shown that the selection of the appropriate tether material while using simple controllers can reduce the effort needed for tethered deorbiting and can safely control the attitude of the debris/chaser connected with a tether, without the danger of a collision.

Tethering factors as organizers of intracellular vesicular traffic.

Science.gov (United States)

Yu, I-Mei; Hughson, Frederick M

2010-01-01

Intracellular trafficking entails the budding, transport, tethering, and fusion of transport vesicles and other membrane carriers. Here we review recent progress toward a mechanistic understanding of vesicle tethering. The known tethering factors are large complexes important for one or more intracellular trafficking pathways and are capable of interacting directly with many of the other principal components of the cellular trafficking machinery. Our review emphasizes recent developments in the in vitro reconstitution of vesicle tethering and the structural characterization of multisubunit tethering factors. The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work.

Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation.

Science.gov (United States)

Asghar, Adeel; Lajeunesse, Audrey; Dulla, Kalyan; Combes, Guillaume; Thebault, Philippe; Nigg, Erich A; Elowe, Sabine

2015-09-24

During mitosis, Bub1 kinase phosphorylates histone H2A-T120 to promote centromere sister chromatid cohesion through recruitment of shugoshin (Sgo) proteins. The regulation and dynamics of H2A-T120 phosphorylation are poorly understood. Using quantitative phosphoproteomics we show that Bub1 is autophosphorylated at numerous sites. We confirm mitosis-specific autophosphorylation of a several residues and show that Bub1 activation is primed in interphase but fully achieved only in mitosis. Mutation of a single autophosphorylation site T589 alters kinetochore turnover of Bub1 and results in uniform H2A-T120 phosphorylation and Sgo recruitment along chromosome arms. Consequently, improper sister chromatid resolution and chromosome segregation errors are observed. Kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Recruitment of the Bub1-Bub3-BubR1 axis to kinetochores has recently been extensively studied. Our data provide novel insight into the regulation and kinetochore residency of Bub1 and indicate that its localization is dynamic and tightly controlled through feedback autophosphorylation.

Atmospheric Electricity and Tethered Aerostats, Volume 1

Science.gov (United States)

1976-05-11

CATALOG NUMBER AFETR -TR-76-07 __ 4. TITLE (and Subtitle) -. TYPE OF REPORT & PERIOD COVERED ATMOSPHERIC ELECTRICITY AND TETHERED AEROSTATS, FINAL. 1...Electricity Faraday Capes Balloons Lightning Effects , Protection, Warning Systems Conducting and Non-Conducting ’Tethers Potential Geadient Anomalies...and identifying feasible protective systems. After a brief introductory section math models of effects of tethered balloons on surrounding

Tether Deployer And Brake

Science.gov (United States)

Carroll, Joseph A.; Alexander, Charles M.

1993-01-01

Design concept promises speed, control, and reliability. Scheme for deploying tether provides for fast, free, and snagless payout and fast, dependable braking. Developed for small, expendable tethers in outer space, scheme also useful in laying transoceanic cables, deploying guidance wires to torpedoes and missiles, paying out rescue lines from ship to ship via rockets, deploying antenna wires, releasing communication and power cables to sonobuoys and expendable bathythermographs, and in reeling out lines from fishing rods.

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.

Review of deployment technology for tethered satellite systems

Science.gov (United States)

Yu, B. S.; Wen, H.; Jin, D. P.

2018-03-01

Tethered satellite systems (TSSs) have attracted significant attention due to their potential and valuable applications for scientific research. With the development of various launched on-orbit missions, the deployment of tethers is considered a crucial technology for operation of a TSS. Both past orbiting experiments and numerical results have shown that oscillations of the deployed tether due to the Coriolis force and environmental perturbations are inevitable and that the impact between the space tether and end-body at the end of the deployment process leads to complicated nonlinear phenomena. Hence, a set of suitable control methods plays a fundamental role in tether deployment. This review article summarizes previous work on aspects of the dynamics, control, and ground-based experiments of tether deployment. The relevant basic principles, analytical expressions, simulation cases, and experimental results are presented as well.

Dynamic multibody modeling for tethered space elevators

Science.gov (United States)

Williams, Paul

2009-08-01

This paper presents a fundamental modeling strategy for dealing with powered and propelled bodies moving along space tethers. The tether is divided into a large number of discrete masses, which are connected by viscoelastic springs. The tether is subject to the full range of forces expected in Earth orbit in a relatively simple manner. Two different models of the elevator dynamics are presented. In order to capture the effect of the elevator moving along the tether, the elevator dynamics are included as a separate body in both models. One model treats the elevator's motion dynamically, where propulsive and friction forces are applied to the elevator body. The second model treats the elevator's motion kinematically, where the distance along the tether is determined by adjusting the lengths of tether on either side of the elevator. The tether model is used to determine optimal configurations for the space elevator. A modal analysis of two different configurations is presented which show that the fundamental mode of oscillation is a pendular one around the anchor point with a period on the order of 160 h for the in-plane motion, and 24 h for the out-of-plane motion. Numerical simulation results of the effects of the elevator moving along the cable are presented for different travel velocities and different elevator masses.

Atmospheric Electricity and Tethered Aerostats, Volume 2

Science.gov (United States)

1976-05-11

EASTERN TEST RANGE PATRICK AIR FORCE BASE, FLORIDA 11 MAY 1976 028 099 AFETR -TR-76-07 ATMOSPHERIC ELECTRICITY AND ~TETHERED AEROSTATS, VOLUME 11 Range...number) Atmospheric Electricity Lightning- Effects , Protection, Warning Balloons Systems Conducting & Nonconducting Tethers Potential Gradient Anomalies...if necessary and Identify by block number) Part A, "Atmospheric Electrical Effects of and on Tethered Balloon Systems," by Latham includes airborne

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.

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.

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

GRASP: A multitasking tether

Directory of Open Access Journals (Sweden)

Catherine eRabouille

2016-01-01

Full Text Available Originally identified as Golgi stacking factors in vitro, the Golgi reassembly stacking protein (GRASP family has been shown to act as membrane tethers with multiple cellular roles. As an update to previous comprehensive reviews of the GRASP family (Vinke et al., 2011 (Giuliani et al., 2011;Jarvela and Linstedt, 2012, we outline here the latest findings concerning their diverse roles. New insights into the mechanics of GRASP-mediated tethering come from recent crystal structures. The models of how GRASP65 and GRASP55 tether membranes relate directly to their role in Golgi ribbon formation in mammalian cells and the unlinking of the ribbon at the onset of mitosis. However, it is also clear that GRASPs act outside the Golgi with roles at the ER and ER exit sites (ERES. Furthermore, the proteins of this family display other roles upon cellular stress, especially in mediating unconventional secretion of both transmembrane proteins (Golgi bypass and cytoplasmic proteins (through secretory autophagosomes.

Passivity-Based Control of a Rigid Electrodynamic Tether

DEFF Research Database (Denmark)

Larsen, Martin Birkelund; Blanke, Mogens

2011-01-01

Electrodynamic tethers provide actuation for performing orbit correction of spacecrafts. When an electrodynamic tether system is orbiting the Earth in an inclined orbit, periodic changes in the magnetic field result in a family of unstable periodic solutions in the attitude motion. This paper shows...... how these periodic solutions can be stabilized by controlling only the current through the tether. A port-controlled Hamiltonian formulation is employed to describe the tethered satellite system and a passive input-output connection is utilized in the control design. The control law consists of two...

Assessing tether anchor labeling and usability in pickup trucks.

Science.gov (United States)

Klinich, Kathleen D; Manary, Miriam A; Malik, Laura A; Flannagan, Carol A; Jermakian, Jessica S

2018-04-03

The objective of this study was to investigate vehicle factors associated with child restraint tether use and misuse in pickup trucks and evaluate 4 labeling interventions designed to educate consumers on proper tether use. Volunteer testing was performed with 24 subjects and 4 different pickup trucks. Each subject performed 8 child restraint installations among the 4 pickups using 2 forward-facing restraints: a Britax Marathon G4.1 and an Evenflo Triumph. Vehicles were selected to represent 4 different implementations of tether anchors among pickups: plastic loop routers (Chevrolet Silverado), webbing routers (Ram), back wall anchors (Nissan Frontier), and webbing routers plus metal anchors (Toyota Tundra). Interventions included a diagram label, Quick Response (QR) Code linked to video instruction, coordinating text label, and contrasting text tag. Subjects used the child restraint tether in 93% of trials. However, tether use was completely correct in only 9% of trials. An installation was considered functional if the subject attached the tether to a tether anchor and had a tight installation (ignoring routing and head restraint position); 28% of subjects achieved a functional installation. The most common installation error was attaching the tether hook to the anchor/router directly behind the child restraint (near the top of the seatback) rather than placing the tether through the router and attaching it to the anchor in the adjacent seating position. The Nissan Frontier, with the anchor located on the back wall of the cab, had the highest rate of correct installations but also had the highest rate of attaching the tether to components other than the tether anchor (seat adjustor, child restraint storage hook, around head restraint). None of the labeling interventions had a significant effect on correct installation; not a single subject scanned the QR Code to access the video instruction. Subjects with the most successful installations spent extensive time

Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

International Nuclear Information System (INIS)

Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

2003-01-01

Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

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

Mobile tethering: Overview, perspectives and challengess

NARCIS (Netherlands)

Constantinescu, M.; Onur, E.; Durmus, Y.; Nikou, S.; Reuver, M. de; Bouwman, H.; Djurica, M.; Glatz, P.M.

2014-01-01

Purpose: The purpose of this paper is to analyze mobile tethering from technological and social perspectives. Mobile tethering allows us to share cellular data connection with others over WiFi, Bluetooth or USB. Although the technology is ready and has promising outcomes, service providers and the

Membrane Tethering Complexes in the Endosomal System

OpenAIRE

Spang, Anne

2016-01-01

Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the class C core vacuole/endosome tethering (CORVET) complex, while fusion of late endosomes with lysosomes depends on the homotypic fusion and vacuole protein sorting (HOPS) complex. Recycling through the trans-Golgi network (TGN) and to the plasma membrane is...

Enabling Tethered Exploration on Mars, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Strong science motivations exist for exploring hard to reach terrain on Mars and the leading systems proposed to do so require tethers. While tethers are used...

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.

Parsing the roles of neck-linker docking and tethered head diffusion in the stepping dynamics of kinesin.

Science.gov (United States)

Zhang, Zhechun; Goldtzvik, Yonathan; Thirumalai, D

2017-11-14

Kinesin walks processively on microtubules (MTs) in an asymmetric hand-over-hand manner consuming one ATP molecule per 16-nm step. The individual contributions due to docking of the approximately 13-residue neck linker to the leading head (deemed to be the power stroke) and diffusion of the trailing head (TH) that contributes in propelling the motor by 16 nm have not been quantified. We use molecular simulations by creating a coarse-grained model of the MT-kinesin complex, which reproduces the measured stall force as well as the force required to dislodge the motor head from the MT, to show that nearly three-quarters of the step occurs by bidirectional stochastic motion of the TH. However, docking of the neck linker to the leading head constrains the extent of diffusion and minimizes the probability that kinesin takes side steps, implying that both the events are necessary in the motility of kinesin and for the maintenance of processivity. Surprisingly, we find that during a single step, the TH stochastically hops multiple times between the geometrically accessible neighboring sites on the MT before forming a stable interaction with the target binding site with correct orientation between the motor head and the [Formula: see text] tubulin dimer.

Tether applications for space station

Science.gov (United States)

Nobles, W.

1986-01-01

A wide variety of space station applications for tethers were reviewed. Many will affect the operation of the station itself while others are in the category of research or scientific platforms. One of the most expensive aspects of operating the space station will be the continuing shuttle traffic to transport logistic supplies and payloads to the space station. If a means can be found to use tethers to improve the efficiency of that transportation operation, it will increase the operating efficiency of the system and reduce the overall cost of the space station. The concept studied consists of using a tether to lower the shuttle from the space station. This results in a transfer of angular momentum and energy from the orbiter to the space station. The consequences of this transfer is studied and how beneficial use can be made of it.

Investigation of electrodynamic stabilization and control of long orbiting tethers

Science.gov (United States)

Colombo, G.; Arnold, D.

1984-01-01

The state-of-the-art in tether modelling among participants in the Tethered Satellite System (TSS) Program, the slack tether and its behavior, and certain advanced applications of the tether to problems in orbital mechanics are identified. The features and applications of the TSS software set are reviewed. Modelling the slack tether analytically with as many as 50 mass points and the application of this new model to a study of the behavior of a broken tether near the Shuttle are described. A reel control algorithm developed by SAO and examples of its use are described, including an example which also demonstrates the use of the tether in transferring a heavy payload from a low-orbiting Shuttle to a high circular orbit. Capture of a low-orbiting payload by a Space Station in high circular orbit is described. Energy transfer within a dumbbell-type spacecraft by cyclical reeling operations or gravitational effects on the natural elasticity of the connecting tether, it is shown, can circularize the orbit of the spacecraft.

Flowing Plasma Interaction with an Electric Sail Tether Element

Science.gov (United States)

Schneider, Todd; Vaughn, Jason; Wright, Kenneth; Anderson, Allen; Stone, Nobie

2017-01-01

Harnessing the power of the solar wind, an Electric Sail, or E-sail, is a relatively new concept that promises to deliver high speed propellant-less propulsion. The electric sail is an invention made in 2006 at the Kumpula Space Centre in Finland by Pekka Janhunen [Janhunen and Sandroos, 2007]. At its core, an electric sail utilizes multiple positively biased tethers which exchange momentum with solar wind protons via the repelling electric field established around each tether, in other words, by reflecting the solar wind protons. Recognizing the solar wind is a plasma, the effective repelling area of each tether is increased significantly by the formation a plasma sheath around each tether. Fig. 1 shows schematically a spacecraft employing an electric sail. The positive voltage bias (greater than10kV) applied to each tether naturally results in electron collection. Therefore, the electric sail concept necessarily includes an electron source (electron gun) to return collected electrons to space and maintain the positive bias of the tether system.

Modeling and Simulation of a Tethered Harpoon for Comet Sampling

Science.gov (United States)

Quadrelli, Marco B.

2014-01-01

This paper describes the development of a dynamic model and simulation results of a tethered harpoon for comet sampling. This model and simulation was done in order to carry out an initial sensitivity analysis for key design parameters of the tethered system. The harpoon would contain a canister which would collect a sample of soil from a cometary surface. Both a spring ejected canister and a tethered canister are considered. To arrive in close proximity of the spacecraft at the end of its trajectory so it could be captured, the free-flying canister would need to be ejected at the right time and with the proper impulse, while the tethered canister must be recovered by properly retrieving the tether at a rate that would avoid an excessive amplitude of oscillatory behavior during the retrieval. The paper describes the model of the tether dynamics and harpoon penetration physics. The simulations indicate that, without the tether, the canister would still reach the spacecraft for collection, that the tether retrieval of the canister would be achievable with reasonable fuel consumption, and that the canister amplitude upon retrieval would be insensitive to variations in vertical velocity dispersion.

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

Tension waves in tethered satellite cables

Science.gov (United States)

Lallman, F. J.

1984-01-01

A one-degree-of-freedom simulation of the Tethered Satellite System (TSS) was programmed using a distributed system model of the tether based on the one-dimensional wave equation. This model represents the time varying tension profile along the tether as the sum of two traveling waves of tension moving in opposite directions. A control loop was devised which combines a deployment rate command with the measured tension at the deployer to produce a smooth, stable rate of deployment of the subsatellite. Simulation results show a buildup of periodic bursts of high frequency oscillation in tension. This report covers the mathematical modelling and simulation results and explains the reason for the observed oscillations. The design of a possible vibration damping device is discussed.

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

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

The stochastic dynamics of tethered microcantilevers in a viscous fluid

Energy Technology Data Exchange (ETDEWEB)

Robbins, Brian A.; Paul, Mark R. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Radiom, Milad; Ducker, William A. [Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Walz, John Y. [Department of Chemical Engineering, University of Kentucky, Lexington, Kentucky 40506 (United States)

2014-10-28

We explore and quantify the coupled dynamics of a pair of micron scale cantilevers immersed in a viscous fluid that are also directly tethered to one another at their tips by a spring force. The spring force, for example, could represent the molecular stiffness or elasticity of a biomolecule or material tethered between the cantilevers. We use deterministic numerical simulations with the fluctuation-dissipation theorem to compute the stochastic dynamics of the cantilever pair for the conditions of experiment when driven only by Brownian motion. We validate our approach by comparing directly with experimental measurements in the absence of the tether which shows excellent agreement. Using numerical simulations, we quantify the correlated dynamics of the cantilever pair over a range of tether stiffness. Our results quantify the sensitivity of the auto- and cross-correlations of equilibrium fluctuations in cantilever displacement to the stiffness of the tether. We show that the tether affects the magnitude of the correlations which can be used in a measurement to probe the properties of an attached tethering substance. For the configurations of current interest using micron scale cantilevers in water, we show that the magnitude of the fluid coupling between the cantilevers is sufficiently small such that the influence of the tether can be significant. Our results show that the cross-correlation is more sensitive to tether stiffness than the auto-correlation indicating that a two-cantilever measurement has improved sensitivity when compared with a measurement using a single cantilever.

Models of dynamic extraction of lipid tethers from cell membranes

International Nuclear Information System (INIS)

Nowak, Sarah A; Chou, Tom

2010-01-01

When a ligand that is bound to an integral membrane receptor is pulled, the membrane and the underlying cytoskeleton can deform before either the membrane delaminates from the cytoskeleton or the ligand detaches from the receptor. If the membrane delaminates from the cytoskeleton, it may be further extruded and form a membrane tether. We develop a phenomenological model for this process by assuming that deformations obey Hooke's law up to a critical force at which the cell membrane locally detaches from the cytoskeleton and a membrane tether forms. We compute the probability of tether formation and show that tethers can be extruded only within an intermediate range of force loading rates and pulling velocities. The mean tether length that arises at the moment of ligand detachment is computed as are the force loading rates and pulling velocities that yield the longest tethers

Lyapunov Orbits in the Jupiter System Using Electrodynamic Tethers

Science.gov (United States)

Bokelmann, Kevin; Russell, Ryan P.; Lantoine, Gregory

2013-01-01

Various researchers have proposed the use of electrodynamic tethers for power generation and capture from interplanetary transfers. The effect of tether forces on periodic orbits in Jupiter-satellite systems are investigated. A perturbation force is added to the restricted three-body problem model and a series of simplifications allows development of a conservative system that retains the Jacobi integral. Expressions are developed to find modified locations of equilibrium positions. Modified families of Lyapunov orbits are generated as functions of tether size and Jacobi integral. Zero velocity curves and stability analyses are used to evaluate the dynamical properties of tether-modified orbits.

The PROPEL Electrodynamic Tether Demonstration Mission

Science.gov (United States)

Bilen, Sven G.; Johnson, C. Les; Wiegmann, Bruce M.; Alexander, Leslie; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael

2012-01-01

The PROPEL ("Propulsion using Electrodynamics") mission will demonstrate the operation of an electrodynamic tether propulsion system in low Earth orbit and advance its technology readiness level for multiple applications. The PROPEL mission has two primary objectives: first, to demonstrate the capability of electrodynamic tether technology to provide robust and safe, near-propellantless propulsion for orbit-raising, de-orbit, plane change, and station keeping, as well as to perform orbital power harvesting and formation flight; and, second, to fully characterize and validate the performance of an integrated electrodynamic tether propulsion system, qualifying it for infusion into future multiple satellite platforms and missions with minimal modification. This paper provides an overview of the PROPEL system and design reference missions; mission goals and required measurements; and ongoing PROPEL mission design efforts.

Use of top tethers with forward-facing child restraints: observations and driver interviews.

Science.gov (United States)

Eichelberger, Angela H; Decina, Lawrence E; Jermakian, Jessica S; McCartt, Anne T

2014-02-01

Despite the safety benefits, many parents do not use top tethers with forward-facing child restraints. Detailed information was collected about why parents are not using tethers. The sample included 479 drivers who had forward-facing child restraints installed in passenger vehicles equipped with tether anchors. The survey was conducted primarily at shopping centers, recreation facilities, child care facilities, car seat check events, and health care facilities in mostly suburban areas surrounding Philadelphia, Washington, DC, Fredericksburg (VA), and Seattle. Drivers were surveyed about their knowledge and use of tethers and experience with child restraints. Tether use was observed to verify whether tethers were being used correctly. Fifty-six percent of forward-facing child restraints were installed with the tether; 39% were installed with the tether used correctly. The tether was used with 71% of LATCH lower anchor installations and 33% of seat belt installations. Drivers who installed child restraints without tethers most often said they did not know about the tether or how to use it. Although the tether use rate was slightly higher in the current research than in previous studies, many parents and caregivers still use forward-facing child restraints without attaching the tether. Because the main problem is lack of awareness of the tether or how to use it, public education should focus specifically on the safety benefits of tethers and how to use them. Information about why caregivers fail to use top tethers is potentially useful to child restraint manufacturers, child passenger safety technicians, and others who work with parents to improve motor vehicle safety. Copyright © 2013 Elsevier Ltd and National Safety Council. All rights reserved.

Numerical modelling of elastic space tethers

DEFF Research Database (Denmark)

Kristiansen, Kristian Uldall; Palmer, P. L.; Roberts, R. M.

2012-01-01

In this paper the importance of the ill-posedness of the classical, non-dissipative massive tether model on an orbiting tether system is studied numerically. The computations document that via the regularisation of bending resistance a more reliable numerical integrator can be produced. Furthermo....... It is also shown that on the slow manifold the dynamics of the satellites are well-approximated by the finite dimensional slack-spring model....

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.

Modeling and Control of Electrodynamic Tethers - an Energy and Topology Approach

DEFF Research Database (Denmark)

Larsen, Martin Birkelund

A space tether is a cable used to connect spacecrafts in an orbiting structure. If an electrical current is lead through the tether, it can be utilized to provide propulsion for the spacecraft. In this case the cable is referred to as an electrodynamic tether. The system utilizes the magnetic field...... of the Earth for creating a Lorentz force along the tether which occur when a current carrying wire operates in a magnetic field. The use of electrodynamic tethers are interesting since they operate solely on electrical energy, which can be provided by solar panels of the spacecrafts. In this way the amount...... when using electrodynamic tethers is that the force created along the tether is based on an external uncontrollable condition, namely the magnetic field. Even whit a known model of the magnetic field, limitations to the creation of the Lorentz force still exists, since the force can only be generated...

One kilometer (1 km) electric solar wind sail tether produced automatically.

Science.gov (United States)

Seppänen, Henri; Rauhala, Timo; Kiprich, Sergiy; Ukkonen, Jukka; Simonsson, Martin; Kurppa, Risto; Janhunen, Pekka; Hæggström, Edward

2013-09-01

We produced a 1 km continuous piece of multifilament electric solar wind sail tether of μm-diameter aluminum wires using a custom made automatic tether factory. The tether comprising 90,704 bonds between 25 and 50 μm diameter wires is reeled onto a metal reel. The total mass of 1 km tether is 10 g. We reached a production rate of 70 m/24 h and a quality level of 1‰ loose bonds and 2‰ rebonded ones. We thus demonstrated that production of long electric solar wind sail tethers is possible and practical.

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.

Selected Tether Applications Cost Model

Science.gov (United States)

Keeley, Michael G.

1988-01-01

Diverse cost-estimating techniques and data combined into single program. Selected Tether Applications Cost Model (STACOM 1.0) is interactive accounting software tool providing means for combining several independent cost-estimating programs into fully-integrated mathematical model capable of assessing costs, analyzing benefits, providing file-handling utilities, and putting out information in text and graphical forms to screen, printer, or plotter. Program based on Lotus 1-2-3, version 2.0. Developed to provide clear, concise traceability and visibility into methodology and rationale for estimating costs and benefits of operations of Space Station tether deployer system.

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.

Single-Molecule Tethered Particle Motion: Stepwise Analyses of Site-Specific DNA Recombination

Directory of Open Access Journals (Sweden)

Hsiu-Fang Fan

2018-05-01

Full Text Available Tethered particle motion/microscopy (TPM is a biophysical tool used to analyze changes in the effective length of a polymer, tethered at one end, under changing conditions. The tether length is measured indirectly by recording the Brownian motion amplitude of a bead attached to the other end. In the biological realm, DNA, whose interactions with proteins are often accompanied by apparent or real changes in length, has almost exclusively been the subject of TPM studies. TPM has been employed to study DNA bending, looping and wrapping, DNA compaction, high-order DNA–protein assembly, and protein translocation along DNA. Our TPM analyses have focused on tyrosine and serine site-specific recombinases. Their pre-chemical interactions with DNA cause reversible changes in DNA length, detectable by TPM. The chemical steps of recombination, depending on the substrate and the type of recombinase, may result in a permanent length change. Single molecule TPM time traces provide thermodynamic and kinetic information on each step of the recombination pathway. They reveal how mechanistically related recombinases may differ in their early commitment to recombination, reversibility of individual steps, and in the rate-limiting step of the reaction. They shed light on the pre-chemical roles of catalytic residues, and on the mechanisms by which accessory proteins regulate recombination directionality.

TMBM: Tethered Micro-Balloons on Mars

Science.gov (United States)

Sims, M. H.; Greeley, R.; Cutts, J. A.; Yavrouian, A. H.; Murbach, M.

2000-01-01

The use of balloons/aerobots on Mars has been under consideration for many years. Concepts include deployment during entry into the atmosphere from a carrier spacecraft, deployment from a lander, use of super-pressurized systems for long duration flights, 'hot-air' systems, etc. Principal advantages include the ability to obtain high-resolution data of the surface because balloons provide a low-altitude platform which moves relatively slowly. Work conducted within the last few years has removed many of the technical difficulties encountered in deployment and operation of balloons/aerobots on Mars. The concept proposed here (a tethered balloon released from a lander) uses a relatively simple approach which would enable aspects of Martian balloons to be tested while providing useful and potentially unique science results. Tethered Micro-Balloons on Mars (TMBM) would be carried to Mars on board a future lander as a stand-alone experiment having a total mass of one to two kilograms. It would consist of a helium balloon of up to 50 cubic meters that is inflated after landing and initially tethered to the lander. Its primary instrumentation would be a camera that would be carried to an altitude of up to tens of meters above the surface. Imaging data would be transmitted to the lander for inclusion in the mission data stream. The tether would be released in stages allowing different resolutions and coverage. In addition during this staged release a lander camera system may observe the motion of the balloon at various heights above he lander. Under some scenarios upon completion of the primary phase of TMBM operations, the tether would be cut, allowing TMBM to drift away from the landing site, during which images would be taken along the ground.

Analytical investigation of the dynamics of tethered constellations in Earth orbit, phase 2

Science.gov (United States)

Lorenzini, Enrico C.; Gullahorn, Gordon E.; Cosmo, Mario L.; Estes, Robert D.; Grossi, Mario D.

1994-01-01

This final report covers nine years of research on future tether applications and on the actual flights of the Small Expendable Deployment System (SEDS). Topics covered include: (1) a description of numerical codes used to simulate the orbital and attitude dynamics of tethered systems during station keeping and deployment maneuvers; (2) a comparison of various tethered system simulators; (3) dynamics analysis, conceptual design, potential applications and propagation of disturbances and isolation from noise of a variable gravity/microgravity laboratory tethered to the Space Station; (4) stability of a tethered space centrifuge; (5) various proposed two-dimensional tethered structures for low Earth orbit for use as planar array antennas; (6) tethered high gain antennas; (7) numerical calculation of the electromagnetic wave field on the Earth's surface on an electrodynamically tethered satellite; (8) reentry of tethered capsules; (9) deployment dynamics of SEDS-1; (10) analysis of SEDS-1 flight data; and (11) dynamics and control of SEDS-2.

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.

Tethered Nanoparticle–Polymer Composites: Phase Stability and Curvature

KAUST Repository

Srivastava, Samanvaya

2012-04-17

Phase behavior of poly(ethylene glycol) (PEG) tethered silica nanoparticles dispersed in PEG hosts is investigated using small-angle X-ray scattering. Phase separation in dispersions of densely grafted nanoparticles is found to display strikingly different small-angle X-ray scattering signatures in comparison to phase-separated composites comprised of bare or sparsely grafted nanoparticles. A general diagram for the dispersion state and phase stability of polymer tethered nanoparticle-polymer composites incorporating results from this as well as various other contemporary studies is presented. We show that in the range of moderate to high grafting densities the dispersion state of nanoparticles in composites is largely insensitive to the grafting density of the tethered chains and chemistry of the polymer host. Instead, the ratio of the particle diameter to the size of the tethered chain and the ratio of the molecular weights of the host and tethered polymer chains (P/N) are shown to play a dominant role. Additionally, we find that well-functionalized nanoparticles form stable dispersions in their polymer host beyond the P/N limit that demarcates the wetting/dewetting transition in polymer brushes on flat substrates interacting with polymer melts. A general strategy for achieving uniform nanoparticle dispersion in polymers is proposed. © 2012 American Chemical Society.

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/.

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.

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.

The Science and Applications Tethered Platform (SATP) project

Science.gov (United States)

Merlina, P.

1986-01-01

The capabilities of tether systems in orbit are going to be demonstrated by the first planned flights of the Tethered Satellite System (TSS). These test flights will investigate the properties of tether systems as low altitude atmospheric research facilities and as electric power generators. Studies are being conducted with the purpose of testing a variety of concepts and approaches. A comparative analysis of results will allow the choosing of the most promising ideas for further development. The broad range of applications presently under study include applications in electrodynamics, transportation, microgravity in addition to basic research. The SATP project definition study is now about midway through its first phase. The analyses conducted have led to an appraisal of users interest in the project and to a deeper understanding of the problems associated with large, long-lived tether systems in space. In addition, two specialized platform designs, devoted to microgravity and precise pointing applications, are being studied because of their potential usefulness and the promise of technical feasibility.

Relaxation Dynamics of Nanoparticle-Tethered Polymer Chains

KAUST Repository

Kim, Sung A

2015-09-08

© 2015 American Chemical Society. Relaxation dynamics of nanoparticle-tethered cis-1,4-polyisoprene (PI) are investigated using dielectric spectroscopy and rheometry. A model system composed of polymer chains densely grafted to spherical SiO2 nanoparticles to form self-suspended suspensions facilitates detailed studies of slow global chain and fast segmental mode dynamics under surface and geometrical confinement-from experiments performed in bulk materials. We report that unentangled polymer molecules tethered to nanoparticles relax far more slowly than their tethered entangled counterparts. Specifically, at fixed grafting density we find, counterintuitively, that increasing the tethered polymer molecular weight up to values close to the entanglement molecular weight speeds up chain relaxation dynamics. Decreasing the polymer grafting density for a fixed molecular weight has the opposite effect: it dramatically slows down chain relaxation, increases interchain coupling, and leads to a transition in rheological response from simple fluid behavior to viscoelastic fluid behavior for tethered PI chains that are unentangled by conventional measures. Increasing the measurement temperature produces an even stronger elastic response and speeds up molecular relaxation at a rate that decreases with grafting density and molecular weight. These observations are discussed in terms of chain confinement driven by crowding between particles and by the existence of an entropic attractive force produced by the space-filling constraint on individual chains in a self-suspended material. Our results indicate that the entropic force between densely grafted polymer molecules couples motions of individual chains in an analogous manner to reversible cross-links in associating polymers.

Climber Motion Optimization for the Tethered Space Elevator

NARCIS (Netherlands)

Williams, P.; Ockels, W.J.

The tethered space elevator could provide a revolutionary means for enabling cheap transportation to geostationary altitude and beyond. Assuming that such a system can be built, one of the dynamic design problems is determining a means of moving the elevator along the tether so as to minimize the

The effects of tether placement on antibody stability on surfaces

Science.gov (United States)

Grawe, Rebecca W.; Knotts, Thomas A.

2017-06-01

Despite their potential benefits, antibody microarrays have fallen short of performing reliably and have not found widespread use outside of the research setting. Experimental techniques have been unable to determine what is occurring on the surface of an atomic level, so molecular simulation has emerged as the primary method of investigating protein/surface interactions. Simulations of small proteins have indicated that the stability of the protein is a function of the residue on the protein where a tether is placed. The purpose of this research is to see whether these findings also apply to antibodies, with their greater size and complexity. To determine this, 24 tethering locations were selected on the antibody Protein Data Bank (PDB) ID: 1IGT. Replica exchange simulations were run on two different surfaces, one hydrophobic and one hydrophilic, to determine the degree to which these tethering sites stabilize or destabilize the antibody. Results showed that antibodies tethered to hydrophobic surfaces were in general less stable than antibodies tethered to hydrophilic surfaces. Moreover, the stability of the antibody was a function of the tether location on hydrophobic surfaces but not hydrophilic surfaces.

Tethered Pyrotechnic Apparatus for Acquiring a Ground Sample

Science.gov (United States)

Jones, Jack; Zimmerman, Wayne; Wu, Jiunn Jenq; Badescu, Mircea; Sherrit, Stewart

2009-01-01

A proposed alternative design for the balloon-borne ground-sampling system described in the immediately preceding article would not rely on free fall to drive a harpoonlike sample-collecting device into the ground. Instead, the harpoon-like sample-collecting device would be a pyrotechnically driven, tethered projectile. The apparatus would include a tripod that would be tethered to the gondola. A gun for shooting the projectile into the ground would be mounted at the apex of the tripod. The gun would include an electronic trigger circuit, a chamber at the breech end containing a pyrotechnic charge, and a barrel. A sabot would be placed in the barrel just below the pyrotechnic charge, and the tethered projectile would be placed in the barrel just below the sabot. The tripod feet would be equipped with contact sensors connected to the trigger circuit. In operation, the tripod would be lowered to the ground on its tether. Once contact with the ground was detected by the sensors on all three tripod feet, the trigger circuit would fire the pyrotechnic charge to drive the projectile into the ground. (Requiring contact among all three tripod feet and the ground would ensure that the projectile would be fired into the ground, rather than up toward the gondola or the balloon.) The tethered projectile would then be reeled back up to the gondola for analysis of the sample.

Fluid-membrane tethers: minimal surfaces and elastic boundary layers.

Science.gov (United States)

Powers, Thomas R; Huber, Greg; Goldstein, Raymond E

2002-04-01

Thin cylindrical tethers are common lipid bilayer membrane structures, arising in situations ranging from micromanipulation experiments on artificial vesicles to the dynamic structure of the Golgi apparatus. We study the shape and formation of a tether in terms of the classical soap-film problem, which is applied to the case of a membrane disk under tension subject to a point force. A tether forms from the elastic boundary layer near the point of application of the force, for sufficiently large displacement. Analytic results for various aspects of the membrane shape are given.

Dynamics and stability of a tethered centrifuge in low earth orbit

Science.gov (United States)

Quadrelli, B. M.; Lorenzini, E. C.

1992-01-01

The three-dimensional attitude dynamics of a spaceborne tethered centrifuge for artificial gravity experiments in low earth orbit is analyzed using two different methods. First, the tethered centrifuge is modeled as a dumbbell with a straight viscoelastic tether, point tip-masses, and sophisticated environmental models such as nonspherical gravity, thermal perturbations, and a dynamic atmospheric model. The motion of the centrifuge during spin-up, de-spin, and steady-rotation is then simulated. Second, a continuum model of the tether is developed for analyzing the stability of lateral tether oscillations. Results indicate that the maximum fluctuation about the 1-g radial acceleration level is less than 0.001 g; the time required for spin-up and de-spin is less than one orbit; and lateral oscillations are stable for any practical values of the system parameters.

T-Rex: A Japanese Space Tether Experiment

Science.gov (United States)

Johnson, Les

2009-01-01

Electrodynamic tether (EDT) thrusters work by virtue of the force a magnetic field exerts on a wire carrying an electrical current. The force, which acts on any charged particle moving through a magnetic field (including the electrons moving in a current-carrying wire), were concisely expressed by Lorentz in 1895 in an equation that now bears his name. The force acts in a direction perpendicular to both the direction of current flow and the magnetic field vector. Electric motors make use of this force: a wire loop in a magnetic field is made to rotate by the torque the Lorentz Force exerts on it due to an alternating current in the loop times so as to keep the torque acting in the same sense. The motion of the loop is transmitted to a shaft, thus providing work. Although the working principle of EDT thrusters is not new, its application to space transportation may be significant. In essence, an EDT thruster is just a clever way of getting an electrical current to flow in a long orbiting wire (the tether) so that the Earth s magnetic field will accelerate the wire and, consequently the payload attached to the wire. The direction of current flow in the tether, either toward or away from the Earth along the local vertical, determines whether the magnetic force will raise or lower the orbit. The bias voltage of a vertically deployed metal tether, which results just from its orbital motion (assumed eastward) through Earth s magnetic field, is positive with respect to the ambient plasma at the top and negative at the bottom. This polarization is due to the action of the Lorentz force on the electrons in the tether. Thus, the natural current flow is the result of negative electrons being attracted to the upper end and then returned to the plasma at the lower end. The magnetic force in this case has a component opposite to the direction of motion, and thus leads to a lowering of the orbit and eventually to re-entry. In this generator mode of operation the Lorentz Force

Tethered Forth system for FPGA applications

Science.gov (United States)

Goździkowski, Paweł; Zabołotny, Wojciech M.

2013-10-01

This paper presents the tethered Forth system dedicated for testing and debugging of FPGA based electronic systems. Use of the Forth language allows to interactively develop and run complex testing or debugging routines. The solution is based on a small, 16-bit soft core CPU, used to implement the Forth Virtual Machine. Thanks to the use of the tethered Forth model it is possible to minimize usage of the internal RAM memory in the FPGA. The function of the intelligent terminal, which is an essential part of the tethered Forth system, may be fulfilled by the standard PC computer or by the smartphone. System is implemented in Python (the software for intelligent terminal), and in VHDL (the IP core for FPGA), so it can be easily ported to different hardware platforms. The connection between the terminal and FPGA may be established and disconnected many times without disturbing the state of the FPGA based system. The presented system has been verified in the hardware, and may be used as a tool for debugging, testing and even implementing of control algorithms for FPGA based systems.

Learning characteristics of a space-time neural network as a tether skiprope observer

Science.gov (United States)

Lea, Robert N.; Villarreal, James A.; Jani, Yashvant; Copeland, Charles

1993-01-01

The Software Technology Laboratory at the Johnson Space Center is testing a Space Time Neural Network (STNN) for observing tether oscillations present during retrieval of a tethered satellite. Proper identification of tether oscillations, known as 'skiprope' motion, is vital to safe retrieval of the tethered satellite. Our studies indicate that STNN has certain learning characteristics that must be understood properly to utilize this type of neural network for the tethered satellite problem. We present our findings on the learning characteristics including a learning rate versus momentum performance table.

Trace gas measurements from tethered balloon platforms

Science.gov (United States)

Bandy, Alan R.; Bandy, Terese L.; Youngbluth, Otto; Owens, Thomas L.

1987-01-01

Instrumentation and chemical sampling and analysis procedures are described for making measurements of atmospheric carbon disulfide in the concentration range 1-1000 pptv from tethered balloon platforms. Results of a study on the CS2 composition of air downward of a saltwater marsh are reported. A method for obtaining the necessary data for solving the budget equations for surface fluxes, chemical formation rates and chemical destruction rates using data acquired from tethered balloon platforms is presented.

Transitions of tethered chain molecules under tension.

Science.gov (United States)

Luettmer-Strathmann, Jutta; Binder, Kurt

2014-09-21

An applied tension force changes the equilibrium conformations of a polymer chain tethered to a planar substrate and thus affects the adsorption transition as well as the coil-globule and crystallization transitions. Conversely, solvent quality and surface attraction are reflected in equilibrium force-extension curves that can be measured in experiments. To investigate these effects theoretically, we study tethered chains under tension with Wang-Landau simulations of a bond-fluctuation lattice model. Applying our model to pulling experiments on biological molecules we obtain a good description of experimental data in the intermediate force range, where universal features dominate and finite size effects are small. For tethered chains in poor solvent, we observe the predicted two-phase coexistence at transitions from the globule to stretched conformations and also discover direct transitions from crystalline to stretched conformations. A phase portrait for finite chains constructed by evaluating the density of states for a broad range of solvent conditions and tensions shows how increasing tension leads to a disappearance of the globular phase. For chains in good solvents tethered to hard and attractive surfaces we find the predicted scaling with the chain length in the low-force regime and show that our results are well described by an analytical, independent-bond approximation for the bond-fluctuation model for the highest tensions. Finally, for a hard or slightly attractive surface the stretching of a tethered chain is a conformational change that does not correspond to a phase transition. However, when the surface attraction is sufficient to adsorb a chain it will undergo a desorption transition at a critical value of the applied force. Our results for force-induced desorption show the transition to be discontinuous with partially desorbed conformations in the coexistence region.

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

Dynamic analysis of the tether transportation system using absolute nodal coordinate formulation

Science.gov (United States)

Sun, Xin; Xu, Ming; Zhong, Rui

2017-10-01

Long space tethers are becoming a rising concern as an alternate way for transportation in space. It benefits from fuel economizing. This paper focuses on the dynamics of the tether transportation system, which consists of two end satellites connected by a flexible tether, and a movable vehicle driven by the actuator carried by itself. The Absolute Nodal Coordinate Formulation is applied to the establishment of the equation of motion, so that the influence caused by the distributed mass and elasticity of the tether is introduced. Moreover, an approximated method for accelerating the calculation of the generalized gravitational forces on the tether is proposed by substituting the volume integral every step into summation of finite terms. Afterwards, dynamic evolutions of such a system in different configurations are illustrated using numerical simulations. The deflection of the tether and the trajectory of the crawler during the transportation is investigated. Finally, the effect on the orbit of the system due to the crawler is revealed.

Thrust Control During Towing of Space Debris using an Elastic Tether

Directory of Open Access Journals (Sweden)

A. D. Ledkov

2014-01-01

Full Text Available The paper considers a maneuver for deorbiting the large space debris using an active spacecraft connected with the debris by an elastic tether. Tether slacking during the maneuver can lead to the tether rupture, kinking, and winding on the descending object. Therefore it is important to prevent slacking. The objective of this work is to find the law of thrust force control of the active spacecraft to ensure a continuously strained tether during the maneuver.Using Lagrange formalism a mathematical model to describe the system plane motion is developed. This model considers the active spacecraft as a mass point, the space debris as a rigid body, and the tether as a weightless elastic rod. A thrust force is directed along the local horizon of the spacecraft. Linearization of nonlinear differential equation describing longitudinal oscillations of the tether length is performed. Its phase portrait is analyzed. An approximate expression describing the position of the center on the phase portrait is obtained. A time-optimal control with full feedback to ensure that the tether is in the strained state is found by solving the Bellman equation. To use the obtained optimal law it is necessary to set the measuring equipment on the spacecraft, which is capable of accurate measuring a distance to the space debris and its relative velocity. An alternative control law, which is simpler in terms of the practical implementation, is proposed. As an example, the descent from an orbit of nonfunctioning Soviet satellite Meteor-2 is considered. It is shown that both proposed laws provide continuous strain of the tether during deorbiting of the satellite. Moreover, slack does not occur even at the first period of oscillation of the tether length. It is shown that the use of the proposed control laws leads to slight increase of deorbiting time as compared to the case of using the constant thrust.The results can be used to develop the control systems of small spacecrafts

Sonography compared with MR imaging in the evaluation of card tethering following myelomeningocele repair

International Nuclear Information System (INIS)

Newman, B.; Bowen, A.; Albright, L.

1989-01-01

This paper reports on MR imaging and videotaped US spine examinations to evaluate cord tethering were retrospectively compared in 12 children with prior myelomeningocele repair and correlated with clinical and surgical findings. Although US did not delineate normal or abnormal anatomy as well as MR imaging, both types of studies confirmed the presence of tethering in 10 patients. One child with a normal US examination and abnormal MR images had tethering confirmed surgically. A second child had a US study suggestive of tethering with equivocal MR images. Postoperative studies in eight patients correlated less well; US suggested persistent tethering in five patients and MR imaging indicated tethering in two

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

Protein tethering enables rapid and label-free SERS platform for screening drugs of abuse (Conference Presentation)

Science.gov (United States)

Siddhanta, Soumik; Wróbel, Maciej S.; Barman, Ishan

2017-02-01

A quick, cost-effective method for detection of drugs of abuse in biological fluids would be of great value in healthcare, law enforcement, and home testing applications. The alarming rise in narcotics abuse has led to considerable focus on developing potent and versatile analytical tools that can address this societal problem. While laboratory testing plays a key role in the current detection of drug misuse and the evaluation of patients with drug induced intoxication, these typically require expensive reagents and trained personnel, and may take hours to complete. Thus, a significant unmet need is to engineer a facile method that can rapidly detect drugs with little sample preparation, especially the bound fraction that is typically dominant in the blood stream. Here we report an approach that combines the exquisite sensitivity of surface enhanced Raman spectroscopy (SERS) and a facile protein tethering mechanism to reliably detect four different classes of drugs, barbiturate, benzodiazepine, amphetamine and benzoylecgonine. The proposed approach harnesses the reliable and specific attachment of proteins to both drugs and nanoparticle to facilitate the enhancement of spectral markers that are sensitive to the presence of the drugs. In conjunction with chemometric tools, we have shown the ability to quantify these drugs lower than levels achievable by existing clinical immunoassays. Through molecular docking simulations, we also probe the mechanistic underpinnings of the protein tethering approach, opening the door to detection of a broad class of narcotics in biological fluids within a few minutes as well as for groundwater analysis and toxin detection.

High-field MR imaging of tethered cord

International Nuclear Information System (INIS)

Sigal, R.; Bicetre, L.; Blass, C.; Doyon, D.; Pariente, D.

1986-01-01

MR imaging examinations of 12 patients with tethered cord syndrome have been performed on a 1.5-T MR imaging unit. Patients ranged in age from 3 to 60 years. MR findings were compared with those of myelography and metrizamide CT in all cases. Five patients underwent surgical control and postoperative MR imaging. Sagittal and axial sections were obtained using a spin-echo multisection, multiecho technique. T1-axial weighted images (SE 600/25) were sufficient to locate the position of the tip of the conus. They also allowed identification of extraspinal and intraspinal lipomas and clear-cut demarcation form associated tethered cord. Drawbacks of MR imaging were lack of precise depiction of the bone structures and the fact that clear identification of abnormal roots was problematic. The craniovertebral junction was always checked; two asymptomatic Chiari malformations were visualized. This study leads the authors to conclude that MR imaging should be used as the examination of first choice in the management of tethered cord syndrome

The investigation of tethered satellite system dynamics

Science.gov (United States)

Lorenzini, E. C.

1986-01-01

The analysis of the rotational dynamics of the satellite was focused on the rotational amplitude increase of the satellite, with respect to the tether, during retrieval. The dependence of the rotational amplitude upon the tether tension variation to the power 1/4 was thoroughly investigated. The damping of rotational oscillations achievable by reel control was also quantified while an alternative solution that makes use of a lever arm attached with a universal joint to the satellite was proposed. Comparison simulations between the Smithsonian Astrophysical Observatory and the Martin Marietta (MMA) computer code of reteival maneuvers were also carried out. The agreement between the two, completely independent, codes was extremely close, demonstrating the reliability of the models. The slack tether dynamics during reel jams was analytically investigated in order to identify the limits of applicability of the SLACK3 computer code to this particular case. Test runs with SLACK3 were also carried out.

Robust Design of Docking Hoop for Recovery of Autonomous Underwater Vehicle with Experimental Results

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Wei Peng Lin

2015-12-01

Full Text Available Control systems prototyping is usually constrained by model complexity, embedded system configurations, and interface testing. The proposed control system prototyping of a remotely-operated vehicle (ROV with a docking hoop (DH to recover an autonomous underwater vehicle (AUV named AUVDH using a combination of software tools allows the prototyping process to be unified. This process provides systematic design from mechanical, hydrodynamics, dynamics modelling, control system design, and simulation to testing in water. As shown in a three-dimensional simulation of an AUVDH model using MATLAB™/Simulink™ during the launch and recovery process, the control simulation of a sliding mode controller is able to control the positions and velocities under the external wave, current, and tether forces. In the water test using the proposed Python-based GUI platform, it shows that the AUVDH is capable to perform station-keeping under the external disturbances.

Vesicle fusion observed by content transfer across a tethered lipid bilayer.

Science.gov (United States)

Rawle, Robert J; van Lengerich, Bettina; Chung, Minsub; Bendix, Poul Martin; Boxer, Steven G

2011-10-19

Synaptic transmission is achieved by exocytosis of small, synaptic vesicles containing neurotransmitters across the plasma membrane. Here, we use a DNA-tethered freestanding bilayer as a target architecture that allows observation of content transfer of individual vesicles across the tethered planar bilayer. Tethering and fusion are mediated by hybridization of complementary DNA-lipid conjugates inserted into the two membranes, and content transfer is monitored by the dequenching of an aqueous content dye. By analyzing the diffusion profile of the aqueous dye after vesicle fusion, we are able to distinguish content transfer across the tethered bilayer patch from vesicle leakage above the patch. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Hierarchical Structure in Semicrystalline Polymers Tethered to Nanospheres

KAUST Repository

Kim, Sung A

2014-01-28

We report on structural and dynamic transitions of polymers tethered to nanoparticles. In particular, we use X-ray diffraction, vibrational spectroscopy, and thermal measurements to investigate multiscale structure and dynamic transitions of poly(ethylene glycol) (PEG) chains densely grafted to SiO2 nanoparticles. The approach used for synthesizing these hybrid particles leads to homogeneous SiO2-PEG composites with polymer grafting densities as high as 1.5 chains/nm2, which allows the hybrid materials to exist as self-suspended suspensions with distinct hierarchical structure and thermal properties. On angstrom and nanometer length scales, the tethered PEG chains exhibit more dominant TTG conformations and helix unit cell structure, in comparison to the untethered polymer. The nanoparticle tethered PEG chains are also reported to form extended crystallites on tens of nanometers length scales and to exhibit more stable crystalline structure on small dimensions. On length scales comparable to the size of each hybrid SiO 2-PEG unit, the materials are amorphous presumably as a result of the difficulty fitting the nanoparticle anchors into the PEG crystal lattice. This structural change produces large effects on the thermal transitions of PEG molecules tethered to nanoparticles. © 2014 American Chemical Society.

NASA Langley Research Center tethered balloon systems

Science.gov (United States)

Owens, Thomas L.; Storey, Richard W.; Youngbluth, Otto

1987-01-01

The NASA Langley Research Center tethered balloon system operations are covered in this report for the period of 1979 through 1983. Meteorological data, ozone concentrations, and other data were obtained from in situ measurements. The large tethered balloon had a lifting capability of 30 kilograms to 2500 meters. The report includes descriptions of the various components of the balloon systems such as the balloons, the sensors, the electronics, and the hardware. Several photographs of the system are included as well as a list of projects including the types of data gathered.

Tethered catalysts for the hydration of carbon dioxide

Science.gov (United States)

Valdez, Carlos A; Satcher, Jr., Joe H; Aines, Roger D; Wong, Sergio E; Baker, Sarah E; Lightstone, Felice C; Stolaroff, Joshuah K

2014-11-04

A system is provided that substantially increases the efficiency of CO.sub.2 capture and removal by positioning a catalyst within an optimal distance from the air-liquid interface. The catalyst is positioned within the layer determined to be the highest concentration of carbon dioxide. A hydrophobic tether is attached to the catalyst and the hydrophobic tether modulates the position of the catalyst within the liquid layer containing the highest concentration of carbon dioxide.

Numerical Simulation of Tethered Underwater Kites for Power Generation

Science.gov (United States)

Ghasemi, Amirmahdi; Olinger, David; Tryggvason, Gretar

2015-11-01

An emerging renewable energy technology, tethered undersea kites (TUSK), which is used to extract hydrokinetic energy from ocean and tidal currents, is studied. TUSK systems consist of a rigid-winged ``kite,'' or glider, moving in an ocean current which is connected by tethers to a floating buoy on the ocean surface. The TUSK kite is a current speed enhancement device since the kite can move in high-speed, cross-current motion at 4-6 times the current velocity, thus producing more power than conventional marine turbines. A computational simulation is developed to simulate the dynamic motion of an underwater kite and extendable tether. A two-step projection method within a finite volume formulation, along with an Open MP acceleration method, is employed to solve the Navier-Stokes equations. An immersed boundary method is incorporated to model the fluid-structure interaction of the rigid kite (with NACA 0012 airfoil shape in 2D and NACA 0021 airfoil shape in 3D simulations) and the fluid flow. PID control methods are used to adjust the kite angle of attack during power (tether reel-out) and retraction (reel-in) phases. Two baseline simulations (for kite motions in two and three dimensions) are studied, and system power output, flow field vorticity, tether tension, and hydrodynamic coefficients (lift and drag) for the kite are determined. The simulated power output shows good agreement with established theoretical results for a kite moving in two-dimensions.

Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

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Chinatsu Mukai

Full Text Available Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase. We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

Science.gov (United States)

Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L; Hinchman, Meleana M; Travis, Alexander J

2013-01-01

Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

Tethered Ozonesonde Measurements During FRAPPE July-August 2014

Science.gov (United States)

Oltmans, S. J.; Johnson, B.; Sterling, C. W.; Cullis, P.; Hall, E. G.; Jordan, A. F.; Wendell, J.; Schnell, R. C.; McClure-Begley, A.; Thompson, A. M.

2015-12-01

O3 and temperature profiles were measured from tethered ozonesondes from surface to 400 m above ground level on 9 days during the summer of 2014 Colorado Front Range Air Pollution and Photochemistry Experiment (FRAPPE). The portable tethered ozonesonde system was set up at one of 3 sites located next to a Colorado Department of Public Health and Environment surface monitoring station. The day and site chosen were based on the previous day O3 and weather forecast. Measurements typically began at 8:30 AM and ended at 4:30 PM, averaging 40 profiles in one day. The ozonesonde when sampling at the surface consistently read within 0-3 ppbv of the surface monitor at each of the sites with a typical daytime range of 20-90 ppbv. The hourly values were averaged at 50 meter intervals showing O3 production rates were consistently around 8 ppbv per hour from 50 to 300 meters above ground level. On sunny, light wind days the O3 mixing ratio reached a maximum of 80-90 ppbv between 14:00 and 15:00 local time. The generally constant mixing ratio with height and highest mixing ratios above the surface indicate that photochemical O3 production was taking place throughout the profile. Continuous O3 profiles from a tall tower (5 and 300 m) and daily ozonesondes tracked O3 variability through the experiment. High O3 at each site was associated with different local wind directions. At Ft. Collins winds were generally out of the southeast, at Chatfield from the northeast, and at City Park Golf Course more variable. The tether system was developed at NOAA/ESRL to provide a cost effective method to measure O3 profiles on a continuous basis. The tether system consisted of a deep sea fishing pole, electric motor driving the reel with light-weight fishing line attached to the balloon ozonesonde, a tether control box, and laptop. The in house software package monitored data and controlled the tether speed and turn-around point based on real time GPS altitude from the transmitting radiosonde.

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

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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.

An Effective Approach Control Scheme for the Tethered Space Robot System

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Zhongjie Meng

2014-09-01

Full Text Available The tethered space robot system (TSR, which is composed of a platform, a gripper and a space tether, has great potential in future space missions. Given the relative motion among the platform, tether, gripper and the target, an integrated approach model is derived. Then, a novel coordinated approach control scheme is presented, in which the tether tension, thrusters and the reaction wheel are all utilized. It contains the open-loop trajectory optimization, the feedback trajectory control and attitude control. The numerical simulation results show that the rendezvous between TSR and the target can be realized by the proposed coordinated control scheme, and the propellant consumption is efficiently reduced. Moreover, the control scheme performs well in the presence of the initial state's perturbations, actuator characteristics and sensor errors.

Modelling a tethered mammalian sperm cell undergoing hyperactivation

KAUST Repository

Curtis, M.P.

2012-09-01

The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

Modelling a tethered mammalian sperm cell undergoing hyperactivation

KAUST Repository

Curtis, M.P.; Kirkman-Brown, J.C.; Connolly, T.J.; Gaffney, E.A.

2012-01-01

The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

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

Tethered elevator and platforms as space station facilities: Systems studies and demonstrative experiments

Science.gov (United States)

1986-01-01

Several key concepts of the science and applications tethered platforms were studied. Some conclusions reached are herein listed. Tether elevator and platform could improve the space station scientific and applicative capabilities. The space elevator presents unique characteristics as microgravity facility and as a tethered platform servicing vehicle. Pointing platforms could represent a new kind of observation facility for large class of payloads. The dynamical, control and technological complexity of these concepts advised demonstrative experiments. The on-going tethered satellite system offers the opportunity to perform such experiments. And feasibility studies are in progress.

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.

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)

Protein docking prediction using predicted protein-protein interface

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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.

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.

Forces, energetics, and dynamics of conjugated-carbon ring tethers adhered to CNTs: a computational investigation.

Science.gov (United States)

Filla, Nicholas; Ramasamy, Ramaraja; Wang, Xianqiao

2018-04-25

The strength and nature of the interactions between carbon nanotubes (CNTs) and molecular tethers plays a vital role in technology such as CNT-enzyme sensors. Tethers that attach noncovalently to CNTs are ideal for retaining the electrical properties of the CNTs since they do not degrade the CNT surface and effect its electrical conductivity. However, leaching due to weak CNT-tether attachment is very common when using noncovalent tethers, and this has limited their use in commercial products including biosensors. Thus, understanding the fundamental mechanics governing the strength of CNT-tether adhesion is crucial for the design of highly sensitive, viable sensors. Here, we computationally investigate the adhesion strength of CNT-tether complexes with 8 different tethering molecules designed to adhere noncovalently to the CNT surface. We study the effects of CNT diameter, CNT chirality, and the size/geometry of the tethering molecule on the adhesion energy and force. Our results show an asymptotic relationship between adhesion strength and CNT diameter. Calculations show that noncovalent tethers tested here can reach adhesion forces and energies that are up to 21% and 54% of the strength of the carbon-carbon single bond force and bond energy respectively. We anticipate our results will help guide CNT-enzyme sensor design to produce sensors with high sensitivity and minimal leaching.

Novel roaming and stationary tethered aerial robots for continuous mobile missions in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Gu, Beom W.; Choi, Su Y.; Rim, Chun T. [Dept. of Nuclear and Quantum Engineering, KAIST, Daejeon (Korea, Republic of); Choi, Young Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cai, Guowei; Seneviratne, Lakmal [Dept. of Aerospace Engineering, Khalifa University, Abu Dhabi (United Arab Emirates)

2016-08-15

In this paper, new tethered aerial robots including roaming tethered aerial robots (RTARs) for radioactive material sampling and stationary tethered aerial robots (STARs) for environment monitoring are proposed to meet extremely-long-endurance missions of nuclear power plants. The flight of the proposed tethered aerial robots may last for a few days or even a few months as long as the tethered cable provides continuous power. A high voltage AC or DC power system was newly adopted to reduce the mass of the tethered cable. The RTAR uses a tethered cable spooled from the aerial robot and an aerial tension control system. The aerial tension control system provides the appropriate tension to the tethered cable, which is accordingly laid down on the ground as the RTAR roams. The STAR includes a tethered cable spooled from the ground and a ground tension control system, which enables the STAR to reach high altitudes. Prototypes of the RTAR and STAR were designed and successfully demonstrated in outdoor environments, where the load power, power type, operating frequency, and flight attitude of the RTAR and STAR were: 180 W, AC 100 kHz, and 20 m; and 300 W, AC or DC 100 kHz, and 80 m, respectively.

Novel Roaming and Stationary Tethered Aerial Robots for Continuous Mobile Missions in Nuclear Power Plants

Directory of Open Access Journals (Sweden)

Beom W. Gu

2016-08-01

Full Text Available In this paper, new tethered aerial robots including roaming tethered aerial robots (RTARs for radioactive material sampling and stationary tethered aerial robots (STARs for environment monitoring are proposed to meet extremely-long-endurance missions of nuclear power plants. The flight of the proposed tethered aerial robots may last for a few days or even a few months as long as the tethered cable provides continuous power. A high voltage AC or DC power system was newly adopted to reduce the mass of the tethered cable. The RTAR uses a tethered cable spooled from the aerial robot and an aerial tension control system. The aerial tension control system provides the appropriate tension to the tethered cable, which is accordingly laid down on the ground as the RTAR roams. The STAR includes a tethered cable spooled from the ground and a ground tension control system, which enables the STAR to reach high altitudes. Prototypes of the RTAR and STAR were designed and successfully demonstrated in outdoor environments, where the load power, power type, operating frequency, and flight attitude of the RTAR and STAR were: 180 W, AC 100 kHz, and 20 m; and 300 W, AC or DC 100 kHz, and 80 m, respectively.

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

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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

Kv7 channels can function without constitutive calmodulin tethering.

Directory of Open Access Journals (Sweden)

Juan Camilo Gómez-Posada

Full Text Available M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC, a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.

Electron Emitter for small-size Electrodynamic Space Tether using MEMS Technology

DEFF Research Database (Denmark)

Fleron, René A. W.; Blanke, Mogens

2004-01-01

Adjustment of the orbit of a spacecraft using the forces created by an electro-dynamic space-tether has been shown as a theoretic possibility in recent literature. Practical implementation is being pursued for larger scale missions where a hot filament device controls electron emission...... and the current flowing in the electrodynamic space tether. Applications to small spacecraft, or space debris in the 1–10 kg range, possess difficulties with electron emission technology, as low power emitting devices are needed. This paper addresses the system concepts of a small spacecraft electrodynamic tether...... system with focus on electron emitter design and manufacture using micro-electro-mechanical- system (MEMS) technology. The paper addresses the system concepts of a small size electrodynamic tether mission and shows a novel electron emitter for the 1-2 mA range where altitude can be effectively affected...

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...

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.

Multilevel Parallelization of AutoDock 4.2.

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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.

Results from a tethered rocket experiment (Charge-2)

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Kawashima, N.; Sasaki, S.; Oyama, K. I.; Hirao, K.; Obayashi, T.; Raitt, W. J.; White, A. B.; Williamson, P. R.; Banks, P. M.; Sharp, W. F.

A tethered payload experiment (Charge-2) was carried out as an international program between Japan and the USA using a NASA sounding rocket at White Sands Missile Range. The objective of the experiment was to perform a new type of active experiment in space by injecting an electron beam from a mother-daughter rocket system connected with a long tether wire. The electron beam with voltage and current up to 1 kV and 80 mA (nominal) was injected from the mother payload. An insulated conductive wire of 426 m length connected the two payloads, the longest tether system flown so far. The electron gun system and diagnostic instruments (plasma, optical, particle and wave) functioned correctly throughout the flight. The potential rise of the mother payload during the electron beam emission was measured with respect to the daughter payload. The beam trajectory was detected by a camera onboard the mother rocket. Wave generation and current induction in the wire during the beam emission were also studied.

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.

Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism.

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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.

Long-term evaluation of intraoperative neurophysiological monitoring-assisted tethered cord surgery

NARCIS (Netherlands)

Dulfer, S E; Drost, G; Lange, F; Journee, H L; Wapstra, F H; Hoving, E W

2017-01-01

PURPOSE: Patients with tethered spinal cord have been investigated for short-term effects after tethered spinal cord surgery in the past. However, little is known about the long-term effects in this patient group. In this retrospective, longitudinal, observational study, a patient sample of a

Self-assembled tethered bimolecular lipid membranes.

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Sinner, Eva-Kathrin; Ritz, Sandra; Naumann, Renate; Schiller, Stefan; Knoll, Wolfgang

2009-01-01

This chapter describes some of the strategies developed in our group for designing, constructing and structurally and functionally characterizing tethered bimolecular lipid membranes (tBLM). We introduce this platform as a novel model membrane system that complements the existing ones, for example, Langmuir monolayers, vesicular liposomal dispersions and bimolecular ("black") lipid membranes. Moreover, it offers the additional advantage of allowing for studies of the influence of membrane structure and order on the function of integral proteins, for example, on how the composition and organization of lipids in a mixed membrane influence the ion translocation activity of integral channel proteins. The first strategy that we introduce concerns the preparation of tethered monolayers by the self-assembly of telechelics. Their molecular architecture with a headgroup, a spacer unit (the "tether") and the amphiphile that mimics the lipid molecule allows them to bind specifically to the solid support thus forming the proximal layer of the final architecture. After fusion of vesicles that could contain reconstituted proteins from a liposomal dispersion in contact to this monolayer the tethered bimolecular lipid membrane is obtained. This can then be characterized by a broad range of surface analytical techniques, including surface plasmon spectroscopies, the quartz crystal microbalance, fluorescence and IR spectroscopies, and electrochemical techniques, to mention a few. It is shown that this concept allows for the construction of tethered lipid bilayers with outstanding electrical properties including resistivities in excess of 10 MOmega cm2. A modified strategy uses the assembly of peptides as spacers that couple covalently via their engineered sulfhydryl or lipoic acid groups at the N-terminus to the employed gold substrate, while their C-terminus is being activated afterward for the coupling of, for example, dimyristoylphosphatidylethanol amine (DMPE) lipid molecules

Two-Way Tether Gun

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Sanger, George F.

1994-01-01

Safety-tether device enables crewmembers on spacecraft to retrieve crewmember drifting away from spacecraft. Alternatively, drifting crewmember who carries device uses it to grasp and return to spacecraft. Also used on Earth. For example, rescuer on vessel or pier uses it to retrieve and haul drowning or unconscious person to safety; drifting person or rescuer in water uses it to grasp and hold onto support.

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.

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.

Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

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Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

2017-12-04

Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

Investigation of electrodynamic stabilization and control of long orbiting tethers. [space shuttle payloads

Science.gov (United States)

Arnold, D. A.; Dobrowolny, M.

1981-01-01

An algorithm for using electric currents to control pendular oscillations induced by various perturbing forces on the Skyhook wire is considered. Transverse and vertical forces on the tether; tether instability modes and causes during retrieval by space shuttle; simple and spherical pendulum motion and vector damping; and current generation and control are discussed. A computer program for numerical integration of the in-plane and out-of-plane displacements of the tether vs time was developed for heuristic study. Some techniques for controlling instabilities during payload retrieval and methods for employing the tether for launching satellites from the space shuttle are considered. Derivations and analyses of a general nature used in all of the areas studied are included.

Position Control of an X4-Flyer Using a Tether

Directory of Open Access Journals (Sweden)

, Keigo Watanabe

2014-10-01

Full Text Available In Japan, aging of infrastructures, such as roads, bridges, and water and sewer services, etc. poses a problem, and it is required to extend the life-span of such infrastructures by maintenance. Among infrastructures, especially bridges are periodically inspected by short range visual observations, which check the damage and deterioration of the surface. However, since there are some cases where the short range visual observation is difficult, an alternative method is required so as to replace the short range visual observation with it. So, "X4-Flyer" is very attractive because of realizing a movement at high altitude easily. The objective of this study is to develop a tethered X4- Flyer, so that the conventional short range visual observation of bridges is replaced by it. In this paper, a method for the measurement and control of the position is described by using a tether for controlling the position of the X4-Flyer. In addition, it is checked whether the tethered X4-Flyer can control the position using the proposed method or not, letting it fly in a state in which a tether is being attached.

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.

Synthesis and insertion chemistry of mixed tether uranium metallocene complexes

Energy Technology Data Exchange (ETDEWEB)

Siladke, Nathan A.; LeDuc, Jennifer; Ziller, Joseph W.; Evans, William J. [Department of Chemistry, University of California, Irvine, CA (United States)

2012-11-12

The synthesis of mixed tethered alkyl uranium metallocenes has been investigated by examining the reactivity of the bis(tethered alkyl) metallocene [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC){sub 2}U] (1) with substrates that react with only one of the U-C linkages. The effect of these mixed tether coordination environments on the reactivity of the remaining U-C bond has been studied by using CO insertion chemistry. One equivalent of azidoadamantane (AdN{sub 3}) reacts with 1 to yield the mixed tethered alkyl triazenido complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}-CH{sub 2}NNN-Ad-κ{sup 2}N{sup 1,3})]. Similarly, a single equivalent of CS{sub 2} reacts with 1 to form the mixed tethered alkyl dithiocarboxylate complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}- CH{sub 2}C(S){sub 2}-κ{sup 2}S,S{sup '})], a reaction that constitutes the first example of CS{sub 2} insertion into a U{sup 4+}-C bond. Complex 1 reacts with one equivalent of pyridine N-oxide by C-H bond activation of the pyridine ring to form a mixed tethered alkyl cyclometalated pyridine N-oxide complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 3})U(C{sub 6}H{sub 4}NO-κ{sup 2} C,O)]. The remaining (η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC){sup 2-} ligand in each of these mixed tethered species show reactivity towards CO and tethered enolate ligands form by insertion. Subsequent rearrangement have been identified in [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 3})U(C{sub 5}H{sub 4}NO-κ{sup 2}C,O)(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}C(=CH{sub 2})O- κO)] and [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}NNN-Ad-κ{sup 2}N{sup 1,3})U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}C(=CH{sub 2})O-κO)]. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Simulations of momentum transfer process between solar wind plasma and bias voltage tethers of electric sail thruster

Science.gov (United States)

Xia, Guangqing; Han, Yajie; Chen, Liuwei; Wei, Yanming; Yu, Yang; Chen, Maolin

2018-06-01

The interaction between the solar wind plasma and the bias voltage of long tethers is the basic mechanism of the electric sail thruster. The momentum transfer process between the solar wind plasma and electric tethers was investigated using a 2D full particle PIC method. The coupled electric field distribution and deflected ion trajectory under different bias voltages were compared, and the influence of bias voltage on momentum transfer process was analyzed. The results show that the high potential of the bias voltage of long tethers will slow down, stagnate, reflect and deflect a large number of ions, so that ion cavities are formed in the vicinity of the tether, and the ions will transmit the axial momentum to the sail tethers to produce the thrust. Compared to the singe tether, double tethers show a better thrust performance.

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 .

Low Earth Orbit Environmental Effects on Space Tether Materials

Science.gov (United States)

Finckernor, Miria M.; Gitlemeier, Keith A.; Hawk, Clark W.; Watts, Ed

2005-01-01

Atomic oxygen (AO) and ultraviolet (UV) radiation erode and embrittle most polymeric materials. This research was designed to test several different materials and coatings under consideration for their application to space tethers, for resistance to these effects. The samples were vacuum dehydrated, weighed and then exposed to various levels of AO or UV radiation at the NASA Marshall Space Flight Center. They were then re-weighed to determine mass loss due to atomic oxygen erosion, inspected for damage and tensile tested to determine strength loss. The experiments determined that the Photosil coating process, while affording some protection, damaged the tether materials worse than the AO exposure. TOR-LM also failed to fully protect the materials, especially from UV radiation. The POSS and nickel coatings did provide some protection to the tethers, which survived the entire test regime. M5 was tested, uncoated, and survived AO exposure, though its brittleness prevented any tensile testing.

The motion and control of a complex three-body space tethered system

Science.gov (United States)

Shi, Gefei; Zhu, Zhanxia; Chen, Shiyu; Yuan, Jianping; Tang, Biwei

2017-11-01

This paper is mainly devoted to investigating the dynamics and stability control of a three body-tethered satellite system which contains a main satellite and two subsatellites connected by two straight, massless and inextensible tethers. Firstly, a detailed mathematical model is established in the central gravitational field. Then, the dynamic characteristics of the established system are investigated and analyzed. Based on the dynamic analysis, a novel sliding mode prediction model (SMPM) control strategy is proposed to suppress the motion of the built tethered system. The numerical results show that the proposed underactuated control law is highly effective in suppressing the attitude/libration motion of the underactuated three-body tethered system. Furthermore, cases of different target angles are also examined and analyzed. The simulation results reveal that even if the final equilibrium states differ from different selections of the target angles, the whole system can still be maintained in acceptable areas.

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.

NASA Docking System (NDS) Technical Integration Meeting

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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.

Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin.

Directory of Open Access Journals (Sweden)

Ying Wu

2008-11-01

Full Text Available Drosophila clock neurons are self-sustaining cellular oscillators that rely on negative transcriptional feedback to keep circadian time. Proper regulation of organismal rhythms of physiology and behavior requires coordination of the oscillations of individual clock neurons within the circadian control network. Over the last decade, it has become clear that a key mechanism for intercellular communication in the circadian network is signaling between a subset of clock neurons that secrete the neuropeptide pigment dispersing factor (PDF and clock neurons that possess its G protein-coupled receptor (PDFR. Furthermore, the specific hypothesis has been proposed that PDF-secreting clock neurons entrain the phase of organismal rhythms, and the cellular oscillations of other clock neurons, via the temporal patterning of secreted PDF signals. In order to test this hypothesis, we have devised a novel technique for altering the phase relationship between circadian transcriptional feedback oscillation and PDF secretion by using an ion channel-directed spider toxin to modify voltage-gated Na(+ channel inactivation in vivo. This technique relies on the previously reported "tethered-toxin" technology for cell-autonomous modulation of ionic conductances via heterologous expression of subtype-specific peptide ion channel toxins as chimeric fusion proteins tethered to the plasma membrane with a glycosylphosphatidylinositol (GPI anchor. We demonstrate for the first time, to our knowledge, the utility of the tethered-toxin technology in a transgenic animal, validating four different tethered spider toxin ion channel modifiers for use in Drosophila. Focusing on one of these toxins, we show that GPI-tethered Australian funnel-web spider toxin delta-ACTX-Hv1a inhibits Drosophila para voltage-gated Na(+ channel inactivation when coexpressed in Xenopus oocytes. Transgenic expression of membrane-tethered delta-ACTX-Hv1a in vivo in the PDF-secreting subset of clock neurons

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

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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.

Experiments and simulation of a net closing mechanism for tether-net capture of space debris

Science.gov (United States)

Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

2017-10-01

This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

Cooperative networks : The mobile tethering game

NARCIS (Netherlands)

Constantinescu, M.; Bouwman, H.; Djurica, M.; Durmus, Y.; Onur, E.; Reuver, M. de

2012-01-01

We propose an analysis of cooperation for data sharing and the behavioral aspects involved in the process of decision making. Starting with the tethering capabilities of recent devices we apply game theoretical principles and models, inquire what makes the cooperation work, and what are the

Tethered balloon-based measurements of meteorological variables and aerosols

Science.gov (United States)

Sentell, R. J.; Storey, R. W.; Chang, J. J. C.; Jacobsen, S. J.

1976-01-01

Tethered balloon based measurements of the vertical distributions of temperature, humidity, wind speed, and aerosol concentrations were taken over a 4-hour period beginning at sunrise on June 29, 1976, at Wallops Island, Virginia. Twelve consecutive profiles of each variable were obtained from ground to about 500 meters. These measurements were in conjuction with a noise propagation study on remotely arrayed acoustic range (ROMAAR) at Wallops Flight Center. An organized listing of these vertical soundings is presented. The tethered balloon system configuration utilized for these measurements is described.

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...

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.

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.

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.

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.

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.

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....

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

Science.gov (United States)

D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

2017-11-01

Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

Observing Formation of Flux Rope by Tether-cutting Reconnection in the Sun

Energy Technology Data Exchange (ETDEWEB)

Xue, Zhike; Yan, Xiaoli; Yang, Liheng; Wang, Jincheng; Zhao, Li, E-mail: zkxue@ynao.ac.cn [Yunnan Observatories, Chinese Academy of Sciences, Kunming Yunnan 650216 (China)

2017-05-10

Tether-cutting reconnection is considered as one mechanism for the formation of a flux rope. It has been proposed for more than 30 years; however, so far, direct observations of it are very rare. In this Letter, we present observations of the formation of a flux rope via tether-cutting reconnection in NOAA AR 11967 on 2014 February 2 by combining observations with the New Vacuum Solar Telescope and the Solar Dynamic Observatory . The tether-cutting reconnection occurs between two sets of highly sheared magnetic arcades. Comprehensive observational evidence of the reconnection is as follows: changes of the connections between the arcades, brightenings at the reconnection site, hot outflows, formation of a flux rope, slow-rise motion of the flux rope, and flux cancelation. The outflows are along three directions from the reconnection site to the footpoints with the velocities from 24 ± 1 km s{sup −1} to 69 ± 5 km s{sup −1}. Additionally, it is found that the newly formed flux rope connects far footpoints and has a left-handed twisted structure with many fine threads and a concave-up-shape structure in the middle. All the observations are in agreement with the tether-cutting model and provide evidence that tether-cutting reconnection leads to the formation of the flux rope associated with flux shear flow and cancelation.

Relaxation Dynamics of Nanoparticle-Tethered Polymer Chains

KAUST Repository

Kim, Sung A; Mangal, Rahul; Archer, Lynden A.

2015-01-01

© 2015 American Chemical Society. Relaxation dynamics of nanoparticle-tethered cis-1,4-polyisoprene (PI) are investigated using dielectric spectroscopy and rheometry. A model system composed of polymer chains densely grafted to spherical SiO2

Phobos L1 Operational Tether Experiment (PHLOTE)

Data.gov (United States)

National Aeronautics and Space Administration — A sensor package that “floats” just above the surface of Phobos, suspended by a tether from a small spacecraft operating at the Mars/Phobos Lagrange 1 (L1) Point...

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.

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

Lumbosacral arachnoid cyst with tethered cord: A rare case report

Directory of Open Access Journals (Sweden)

S K Jain

2012-01-01

Full Text Available Arachnoid cysts are cerebrospinal fluid collections in the spine that can present with neurological symptoms or be discovered accidentally. Intradural location of such cysts especially in the lumbosacral region is relatively rare. The association of such cysts with other congenital anomalies such as tethered cord lends evidence to the developmental origin of arachnoid cysts. We report a case of lumbosacral arachnoid cyst with tethered cord in a 6-year-old male child and discuss the etiopathogenesis and management options.

Unilateral pedicle screws asymmetric tethering: an innovative method to create idiopathic deformity

Directory of Open Access Journals (Sweden)

Zhang Xuesong

2007-10-01

Full Text Available Abstract Objective To evaluate the feasibility of the method that unilateral pedicle screws asymmetric tethering in concave side in combination with convex rib resection for creating idiopathic deformity. Summary of background data Various methods are performed to create idiopathic deformity. Among these methods, posterior asmmetric tethering of the spine shows satisfying result, but some drawbacks related to the current posterior asymmetric tether were still evident. Materials and methods Unilateral pedicle screws asymmetric tethering was performed to 14 female goats (age: 5–8 week-old, weight: 6–8 kg in concave side in combination with convex rib resection. Dorsoventral and lateral plain radiographs were taken of each thoracic spine in the frontal and sagittal planes right after the surgery and later every 4 weeks. Results All animals ambulated freely after surgery. For technical reasons, 2 goats were excluded (one animal died for anesthetic during the surgery, and one animal was lost for instrumental fail due to postoperative infection. Radiography showed that 11 goats exhibited scoliosis with convex toward to the right side, and as the curve increased with time, only 1 goat showed nonprogressive. The initial scoliosis generated in the progressors after the procedures measured 29.0° on average (range 23.0°–38.5° and increased to 43.0° on average (range 36.0°–58.0° over 8 to 10 weeks. The average progression of 14.0° was measured. The curvature immediately after tethering surgery (the initial Cobb angle did have a highly significant correlation with the final curvature (p Conclusion Unilateral pedicle screws asymmetric tethering is a practical method to create experimental scoliosis, especially for those who would like to study the correction of this deformity.

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.

Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.

Directory of Open Access Journals (Sweden)

Martin Rottman

Full Text Available Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone. Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.

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

Two-Stage Winch for Kites and Tethered Balloons or Blimps

Science.gov (United States)

Miles, Ted; Bland, Geoff

2011-01-01

A winch system provides a method for launch and recovery capabilities for kites and tethered blimps or balloons. Low power consumption is a key objective, as well as low weight for portability. This is accomplished by decoupling the tether-line storage and wind ing/ unwinding functions, and providing tailored and efficient mechanisms for each. The components of this system include rotational power input devices such as electric motors or other apparatus, line winding/unwinding reel(s), line storage reel(s), and independent drive trains. Power is applied to the wind/unwind reels to transport the tether line. Power is also applied to a line storage reel, from either the wind/unwind power source, the wind/unwind reel itself, or separate power source. The speeds of the two reels are synchronized, but not dependent on each other. This is accomplished via clutch mechanisms, variable transmissions, or independent motor controls. The speed of the storage reel is modulated as the effective diameter of the reel changes with line accumulation.

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.

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.

FCAPD Protective Coating for Space Tethers, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Alameda Applied Sciences Corporation (AASC) proposes to demonstrate extended service lifetime of space tethers in the Low Earth Orbit (LEO) environment by using...

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

The mechanics of motorised momentum exchange tethers when applied to active debris removal from LEO

Energy Technology Data Exchange (ETDEWEB)

Caldecott, Ralph; Kamarulzaman, Dayangku N. S.; Kirrane, James P.; Cartmell, Matthew P.; Ganilova, Olga A. [Department of Mechanical Engineering, University of Sheffield, Mappin St., Sheffield, S1 3JD, England (United Kingdom)

2014-12-10

The concept of momentum exchange when applied to space tethers for propulsion is well established, and a considerable body of literature now exists on the on-orbit modelling, the dynamics, and also the control of a large range of tether system applications. The authors consider here a new application for the Motorised Momentum Exchange Tether by highlighting three key stages of development leading to a conceptualisation that can subsequently be developed into a technology for Active Debris Removal. The paper starts with a study of the on-orbit mechanics of a full sized motorised tether in which it is shown that a laden and therefore highly massasymmetrical tether can still be forced to spin, and certainly to librate, thereby confirming its possible usefulness for active debris removal (ADR). The second part of the paper concentrates on the modelling of the centripetal deployment of a symmetrical MMET in order to get it initialized for debris removal operations, and the third and final part of the paper provides an entry into scale modelling for low cost mission design and testing. It is shown that the motorised momentum exchange tether offers a potential solution to the removal of large pieces of orbital debris, and that dynamic methodologies can be implemented to in order to optimise the emergent design.

The mechanics of motorised momentum exchange tethers when applied to active debris removal from LEO

International Nuclear Information System (INIS)

Caldecott, Ralph; Kamarulzaman, Dayangku N. S.; Kirrane, James P.; Cartmell, Matthew P.; Ganilova, Olga A.

2014-01-01

The concept of momentum exchange when applied to space tethers for propulsion is well established, and a considerable body of literature now exists on the on-orbit modelling, the dynamics, and also the control of a large range of tether system applications. The authors consider here a new application for the Motorised Momentum Exchange Tether by highlighting three key stages of development leading to a conceptualisation that can subsequently be developed into a technology for Active Debris Removal. The paper starts with a study of the on-orbit mechanics of a full sized motorised tether in which it is shown that a laden and therefore highly massasymmetrical tether can still be forced to spin, and certainly to librate, thereby confirming its possible usefulness for active debris removal (ADR). The second part of the paper concentrates on the modelling of the centripetal deployment of a symmetrical MMET in order to get it initialized for debris removal operations, and the third and final part of the paper provides an entry into scale modelling for low cost mission design and testing. It is shown that the motorised momentum exchange tether offers a potential solution to the removal of large pieces of orbital debris, and that dynamic methodologies can be implemented to in order to optimise the emergent design

Electrodynamic Tethers and E-Sails as Active Experiment Testbeds and Technologies in Space

Science.gov (United States)

Gilchrist, B. E.; Wiegmann, B.; Johnson, L.; Bilen, S. G.; Habash Krause, L.; Miars, G.; Leon, O.

2017-12-01

The use of small-to-large flexible structures in space such as tethers continues to be studied for scientific and technology applications. Here we will consider tether electrodynamic and electrostatic interactions with magneto-plasmas in ionospheres, magnetospheres, and interplanetary space. These systems are enabling fundamental studies of basic plasma physics phenomena, allowing direct studies of the space environment, and generating technological applications beneficial for science missions. Electrodynamic tethers can drive current through the tether based on the Lorenz force adding or extracting energy from its orbit allowing for the study of charged bodies or plasma plumes moving through meso-sonic magnetoplasmas [1]. Technologically, this also generates propulsive forces requiring no propellant and little or no consumables in any planetary system with a magnetic field and ionosphere, e.g., Jupiter [2]. Further, so called electric sails (E-sails) are being studied to provide thrust through momentum exchange with the hypersonic solar wind. The E-sail uses multiple, very long (10s of km) charged, mostly bare rotating conducting tethers to deflect solar wind protons. It is estimated that a spacecraft could achieve a velocity over 100 km/s with time [3,4]. 1. Banks, P.M., "Review of electrodynamic tethers for space plasma science," J. Spacecraft and Rockets, vol. 26, no. 4, pp. 234-239, 1989. 2. Talley, C., J. Moore, D. Gallagher, and L. Johnson, "Propulsion and power from a rotating electrodynamic tether at Jupiter," 38th AIAA Aerospace Sciences Meeting and Exhibit, January 2000. 3. Janhunen, P., "The electric sail—A new propulsion method which may enable fast missions to the outer solar system," J. British Interpl. Soc., vol. 61, no. 8, pp. 322-325, 2008. 4. Wiegman, B., T. Scheider, A. Heaton, J. Vaughn, N. Stone, and K. Wright, "The Heliopause Electrostatic Rapid Transit System (HERTS)—Design, trades, and analyses performed in a two-year NASA investigation

Physisorbed Polymer-Tethered Lipid Bilayer with Lipopolymer Gradient

Directory of Open Access Journals (Sweden)

Christoph A. Naumann

2012-11-01

Full Text Available Physisorbed polymer-tethered lipid bilayers consisting of phospholipids and lipopolymers represent an attractive planar model membrane platform, in which bilayer fluidity and membrane elastic properties can be regulated through lipopolymer molar concentration. Herein we report a method for the fabrication of such a planar model membrane system with a lateral gradient of lipopolymer density. In addition, a procedure is described, which leads to a sharp boundary between regions of low and high lipopolymer molar concentrations. Resulting gradients and sharp boundaries are visualized on the basis of membrane buckling structures at elevated lipopolymer concentrations using epifluorescence microscopy and atomic force microscopy. Furthermore, results from spot photobleaching experiments are presented, which provide insight into the lipid lateral fluidity in these model membrane architectures. The presented experimental data highlight a planar, solid-supported membrane characterized by fascinating length scale-dependent dynamics and elastic properties with remarkable parallels to those observed in cellular membranes.

Tethered Aerostat Effects on Nearby Seismometers

Energy Technology Data Exchange (ETDEWEB)

Bowman, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-12-01

This report assesses seismic interference generated by a tethered aerostat. The study was motivated by a planned aerostat deployment within the footprint of the Dry Alluvium Geology seismic network. No evidence was found for seismic interference generated by the aerostat, and thus the e ects on the Dry Alluvium Geology sensors will be negligible.

Template-directed ligation of tethered mononucleotides by t4 DNA ligase for kinase ribozyme selection.

Directory of Open Access Journals (Sweden)

David G Nickens

Full Text Available BACKGROUND: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 5' or 2' OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 5' phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxyribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A(2>A(1>A(3>A(4>A(0>A(6>A(8>A(10 and T(2>T(3>T(4>T(6 approximately T(1>T(8>T(10. Bridging T's generally gave higher yield of ligated product than bridging A's. ATP concentrations above 33 microM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (>90% joined a correctly paired, or TratioG wobble-paired, substrate on the 3' side of the ligation junction while discriminating approximately 100-fold against most mispaired substrates. Tethered dC and dG gave the highest ligation rates and yields, followed by tethered deoxyinosine (dI and dT, with the slowest reactions for tethered dA. The same kinetic trends were observed in ligase-mediated capture in complex reaction mixtures with multiple substrates. The "universal" analog 5-nitroindole (dNI did not support ligation when

STICS: surface-tethered iterative carbohydrate synthesis.

Science.gov (United States)

Pornsuriyasak, Papapida; Ranade, Sneha C; Li, Aixiao; Parlato, M Cristina; Sims, Charles R; Shulga, Olga V; Stine, Keith J; Demchenko, Alexei V

2009-04-14

A new surface-tethered iterative carbohydrate synthesis (STICS) technology is presented in which a surface functionalized 'stick' made of chemically stable high surface area porous gold allows one to perform cost efficient and simple synthesis of oligosaccharide chains; at the end of the synthesis, the oligosaccharide can be cleaved off and the stick reused for subsequent syntheses.

Hierarchical Structure in Semicrystalline Polymers Tethered to Nanospheres

KAUST Repository

Kim, Sung A; Archer, Lynden A.

2014-01-01

We report on structural and dynamic transitions of polymers tethered to nanoparticles. In particular, we use X-ray diffraction, vibrational spectroscopy, and thermal measurements to investigate multiscale structure and dynamic transitions of poly

Biomechanical simulations of costo-vertebral and anterior vertebral body tethers for the fusionless treatment of pediatric scoliosis.

Science.gov (United States)

Aubin, Carl-Éric; Clin, Julien; Rawlinson, Jeremy

2018-01-01

Compression-based fusionless tethers are an alternative to conventional surgical treatments of pediatric scoliosis. Anterior approaches place an anterior (ANT) tether on the anterolateral convexity of the deformed spine to modify growth. Posterior, or costo-vertebral (CV), approaches have not been assessed for biomechanical and corrective effectiveness. The objective was to biomechanically assess CV and ANT tethers using six patient-specific, finite element models of adolescent scoliotic patients (11.9 ± 0.7 years, Cobb 34° ± 10°). A validated algorithm simulated the growth and Hueter-Volkmann growth modulation over a period of 2 years with the CV and ANT tethers at two initial tensions (100, 200 N). The models without tethering also simulated deformity progression with Cobb angle increasing from 34° to 56°, axial rotation 11° to 13°, and kyphosis 28° to 32° (mean values). With the CV tether, the Cobb angle was reduced to 27° and 20° for tensions of 100 and 200 N, respectively, kyphosis to 21° and 19°, and no change in axial rotation. With the ANT tether, Cobb was reduced to 32° and 9° for 100 and 200 N, respectively, kyphosis unchanged, and axial rotation to 3° and 0°. While the CV tether mildly corrected the coronal curve over a 2-year growth period, it had sagittal lordosing effect, particularly with increasing initial axial rotation (>15°). The ANT tether achieved coronal correction, maintained kyphosis, and reduced the axial rotation, but over-correction was simulated at higher initial tensions. This biomechanical study captured the differences between a CV and ANT tether and indicated the variability arising from the patient-specific characteristics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:254-264, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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.

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.

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

Position Control of an X4-Flyer Using a Tether

Directory of Open Access Journals (Sweden)

Yusuke Ouchi

2016-05-01

Full Text Available In Japan, aging of infrastructures, such as roads,bridges, and water and sewer services, etc. poses a problem, andit is required to extend the life-span of such infrastructures bymaintenance. Among infrastructures, especially bridges areperiodically inspected by short range visual observations, whichcheck the damage and deterioration of the surface. However,since there are some cases where the short range visualobservation is difficult, an alternative method is required so as toreplace the short range visual observation with it. So, "X4-Flyer"is very attractive because of realizing a movement at high altitudeeasily. The objective of this study is to develop a tethered X4-Flyer, so that the conventional short range visual observation ofbridges is replaced by it. In this paper, a method for themeasurement and control of the position is described by using atether for controlling the position of the X4-Flyer. In addition, itis checked whether the tethered X4-Flyer can control the positionusing the proposed method or not, letting it fly in a state in whicha tether is being attached

Tethered elevator: A unique opportunity for space processing

Science.gov (United States)

Monti, R.

1986-01-01

The latest fluid dynamic and material science experiments in the microgravity environment have emphasized the importance of the residual gravity level and of the g-jitter on fluid physics phenomena. The tethered elevator presents the possibility of providing variable g-levels (both steady and g-jitter) around a very low steady g-level (that can be realized when the elevator is near the center of mass of the space station-tether complex). When positioning a variable periodic oscillation to the payload a clean g-jitter disturbance can be obtained that would not be otherwise obtainable by other systems. These two possibilities make the elevator a facility to help resolve a number of still open questions that are preventing wider utilization of the space environment in the microgravity area.

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...

Tethered Nanoparticle–Polymer Composites: Phase Stability and Curvature

KAUST Repository

Srivastava, Samanvaya; Agarwal, Praveen; Archer, Lynden A.

2012-01-01

different small-angle X-ray scattering signatures in comparison to phase-separated composites comprised of bare or sparsely grafted nanoparticles. A general diagram for the dispersion state and phase stability of polymer tethered nanoparticle-polymer

Dynamics Model for a Multi-Tethered Space-Based Interferometer

National Research Council Canada - National Science Library

Gates, Stephen

2000-01-01

.... Tether constitutive behavior is discussed. Prescribed motion of any system degrees of freedom is treated, and expressions for the corresponding constraint force/torque components are established.

Microcirculation within Grooved Substrates regulates Cell Positioning and Cell Docking inside Microfluidic Channels

Science.gov (United States)

Manbachi, Amir; Shrivastava, Shamit; Cioffi, Margherita; Chung, Bong Geun; Moretti, Matteo; Demirci, Utkan; Yliperttula, Marjo; Khademhosseini, Ali

2009-01-01

Immobilization of cells inside microfluidic devices is a promising approach for enabling studies related to drug screening and cell biology. Despite extensive studies in using grooved substrates for immobilizing cells inside channels, a systematic study of the effects of various parameters that influence cell docking and retention within grooved substrates has not been performed. We demonstrate using computational simulations that the fluid dynamic environment within microgrooves significantly varies with groove width, generating micro-circulation areas in smaller microgrooves. Wall shear stress simulation predicted that shear stresses were in opposite direction in smaller grooves (25 and 50 μm wide) in comparison to those in wider grooves (75 and 100 μm wide). To validate the simulations, cells were seeded within microfluidic devices, where microgrooves of different widths were aligned perpendicularly to the direction of the flow. Experimental results showed that, as predicted, the inversion of the local direction of shear stress within the smaller grooves resulted in alignment of cells on two opposite sides of the grooves under the same flow conditions. Also, the amplitude of shear stress within microgrooved channels significantly influenced cell retainment in the channels. Therefore, our studies suggest that microscale shear stresses greatly influence cellular docking, immobilization, and retention in fluidic systems and should be considered for the design of cell-based microdevices. PMID:18432345

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.

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.

Ionic-Liquid-Tethered Nanoparticles: Hybrid Electrolytes

KAUST Repository

Moganty, Surya S.

2010-10-22

A new class of solventless electrolytes was created by tethering ionic liquids to hard inorganic ZrO2 nanostructures (see picture; NIM=nanoscale ionic material). These hybrid fluids exhibit exceptional redox stability windows, excellent thermal stability, good lithium transference numbers, long-term interfacial stability in the presence of a lithium anode and, when doped with lithium salt, reasonable ionic conductivities.

System Dynamics and Feedforward Control for Tether-Net Space Robot System

Directory of Open Access Journals (Sweden)

Guang Zhai

2009-06-01

Full Text Available A new concept using flexible tether-net system to capture space debris is presented in this paper. With a mass point assumption the tether-net system dynamic model is established in orbital frame by applying Lagrange Equations. In order to investigate the net in-plane trajectories during after cast, the non-control R-bar and V-bar captures are simulated with ignoring the out-of-plane libration, the effect of in-plane libration on the trajectories of the capture net is demonstrated by simulation results. With an effort to damp the in-plane libration, the control scheme based on tether tension is investigated firstly, after that an integrated control scheme is proposed by introduced the thrusters into the system, the nonlinear close-loop dynamics is linearised by feedforward strategy, the simulation results show that feedforward controllor is effective for in-plane libration damping and enable the capture net to track an expected trajectory.

Application of the NASCAP Spacecraft Simulation Tool to Investigate Electrodynamic Tether Current Collection in LEO

Science.gov (United States)

Adams, Mitzi; HabashKrause, Linda

2012-01-01

Recent interest in using electrodynamic tethers (EDTs) for orbital maneuvering in Low Earth Orbit (LEO) has prompted the development of the Marshall ElectroDynamic Tether Orbit Propagator (MEDTOP) model. The model is comprised of several modules which address various aspects of EDT propulsion, including calculation of state vectors using a standard orbit propagator (e.g., J2), an atmospheric drag model, realistic ionospheric and magnetic field models, space weather effects, and tether librations. The natural electromotive force (EMF) attained during a radially-aligned conductive tether results in electrons flowing down the tether and accumulating on the lower-altitude spacecraft. The energy that drives this EMF is sourced from the orbital energy of the system; thus, EDTs are often proposed as de-orbiting systems. However, when the current is reversed using satellite charged particle sources, then propulsion is possible. One of the most difficult challenges of the modeling effort is to ascertain the equivalent circuit between the spacecraft and the ionospheric plasma. The present study investigates the use of the NASA Charging Analyzer Program (NASCAP) to calculate currents to and from the tethered satellites and the ionospheric plasma. NASCAP is a sophisticated set of computational tools to model the surface charging of three-dimensional (3D) spacecraft surfaces in a time-varying space environment. The model's surface is tessellated into a collection of facets, and NASCAP calculates currents and potentials for each one. Additionally, NASCAP provides for the construction of one or more nested grids to calculate space potential and time-varying electric fields. This provides for the capability to track individual particles orbits, to model charged particle wakes, and to incorporate external charged particle sources. With this study, we have developed a model of calculating currents incident onto an electrodynamic tethered satellite system, and first results are shown

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.

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.

Long distance cell communication using spherical tether balloons

Science.gov (United States)

Manchanda, R. K.; Rajagopalan, Vasudevan; Vasudevan, Rajagopalan; Mehrotra, R. K.; Sreenivasan, S.; Pawaskar, M.; Subba Rao Jonnalagadda, Venkata; Buduru, Suneelkumar; Kulkarni, P. M.

A proof-of-concept experiment was conducted for long-range cell communication for rural tele-phony and internet. We designed and fabricated a spherical tether balloon to carry the con-ventional micro base transceiver station (BTS) along with three slotted antenna to cover 2-pi radius. AC power and optical fiber were anchored along with the tether line. A special fre-quency license was obtained from Wireless Planning Commission (WPC) wing of Department of Telecommunication (DoT), India for the period of experiment so as not to affect the opera-tional networks. The experiments were carried out for different BTS heights up to 500 meter. Signal measurement both in data mode and voice quality were done in different quadrant using mobile vans. This paper describes the methodology (under patenting) and utility of technique for operational application.

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.

Tethered "kiteplane" design for the Laddermill project

NARCIS (Netherlands)

Breukels, J.; Ockels, W.

2005-01-01

The Laddermill is an innovative concept for generating energy from wind using large kite-like wings on a tether. The wings are able to fly in both the regime of airplanes and kites. We therefore call these structures "kiteplanes". By providing a recurring motion with a large lift during ascending

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.

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

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

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

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.

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.

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.

Measurement of calcium influx in tethered rings of rabbit aorta under tension

International Nuclear Information System (INIS)

Gleason, M.M.; Ratz, P.H.; Flaim, S.F.

1985-01-01

Calcium (Ca) influx in vascular smooth muscle is routinely measured in untethered preparations not under passive stretch, and Ca influx data are correlated with data for steady-state isometric tension obtained under parallel conditions from tethered preparations under passive stretch. The validity of this method was tested by simultaneous measurement of Ca influx and tension in tethered rings of rabbit thoracic aorta. Ca influx ( 45 Ca 3-min pulse) and tension were measured at 3 and 30 min after norepinephrine (NE) or KCl and under control (no agonist) conditions. Active tension was significantly altered by variations in passive tension. Ca influx was unaffected by passive tension under control, NE, or KCl conditions, and results were similar at 3 and 30 min. The results confirm the validity of correlating Ca influx data from untethered rings with steady-state contractile response data obtained from tethered rings under similar experimental conditions

Domain requirements for the Dock adapter protein in growth- cone signaling

OpenAIRE

Rao, Yong; Zipursky, S. Lawrence

1998-01-01

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 speci...

MOLECULAR DOCKING OF COMPOUNDS FROM Chaetomium Sp. AGAINST HUMAN ESTROGEN RECEPTOR ALPHA IN SEARCHING ANTI BREAST CANCER

Directory of Open Access Journals (Sweden)

Maywan Hariono

2016-05-01

Full Text Available A study on molecular docking-based virtual screening has been conducted to select virtual hit of compounds, reported its existence in fungal endophytes of Chaetomium sp. as cytotoxic agent of breast cancer. The ligands were docked into Human Estrogen Receptor alpha (HERa as the protein which regulates the breast cancer growth via estradiol-estrogen receptor binding intervention. The results showed that two compounds bearing xanthone and two compounds bearing benzonaphtyridinedione scaffolds were selected as virtual hit ligands for HERa leading to the conclusion that these compounds were good to be developed as anti breast cancer.

Acquisition of Ice-Tethered Profilers with Velocity (ITP-V) Instruments for Future Arctic Studies

Science.gov (United States)

2016-11-15

San Diego, CA, IEEE Xplore . Toole, J. M., R. A. Krishfield, M.-L. Timmennans, and A. Proshutinsky, 2011: The Ice-Tethered Profiler: Argo ofthe Arctic, Oceanogr., 24, 126-135. 4 ...observations from Ice-Tethered Profilers, MTS/ IEEE Oceans’ 2015, Washington DC, 1-10. Krishfield, R., J. Toole, A. Proshutinsky, and M.-L. Timmennans, 2008

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...

Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

International Nuclear Information System (INIS)

Abu-Hamdah, Rania; Cho, Won Jin; Hoerber, J.K.H.; Jena, Bhanu P.

2006-01-01

It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 μm in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles

Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Abu-Hamdah, Rania [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Cho, Won Jin [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Hoerber, J.K.H. [Department of Physics, University of Bristol, Bristol BS8 1TD (United Kingdom); Jena, Bhanu P. [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States)]. E-mail: bjena@med.wayne.edu

2006-06-15

It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 {mu}m in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles.

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

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

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

Space webs based on rotating tethered formations

Science.gov (United States)

Palmerini, Giovanni B.; Sgubini, Silvano; Sabatini, Marco

2009-07-01

Several on-going studies indicate the interest for large, light orbiting structures, shaped as fish nets or webs: along the ropes of the web small spacecraft can move like spiders to position and re-locate, at will, pieces of hardware devoted to specific missions. The concept could be considered as an intermediate solution between the large monolithic structure, heavy and expensive to realize, but easy to control, and the formations of satellites, where all system members are completely free and should manoeuvre in order to acquire a desired configuration. Instead, the advantage of having a "hard-but-light" link among the different grids lays in the partition of the tasks among system components and in a possible overall reduction of the control system complexity and cost. Unfortunately, there is no stable configuration for an orbiting, two-dimensional web made by light, flexible tethers which cannot support compression forces. A possible solution is to make use of centrifugal forces to pull the net, with a reduced number of simple thrusters located at the tips of the tethers to initially acquire the required spin. In this paper a dynamic analysis of a simplified rotating web is performed, in order to evaluate the spinning velocity able to satisfy the requirement for the stability of the system. The model adopted overlaps simpler elements, each of them given by a tether (made up of a number of linear finite elements) connecting two extreme bodies accommodating the spinning thrusters. The combination of these "diameter-like" elements provides the web, shaped according to the specific requirements. The net is primarily considered as subjected to Keplerian attraction and J2 and drag perturbations only, but its behaviour under thermal inputs is also investigated.

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.

The shear flow processing of controlled DNA tethering and stretching for organic molecular electronics.

Science.gov (United States)

Yu, Guihua; Kushwaha, Amit; Lee, Jungkyu K; Shaqfeh, Eric S G; Bao, Zhenan

2011-01-25

DNA has been recently explored as a powerful tool for developing molecular scaffolds for making reproducible and reliable metal contacts to single organic semiconducting molecules. A critical step in the process of exploiting DNA-organic molecule-DNA (DOD) array structures is the controlled tethering and stretching of DNA molecules. Here we report the development of reproducible surface chemistry for tethering DNA molecules at tunable density and demonstrate shear flow processing as a rationally controlled approach for stretching/aligning DNA molecules of various lengths. Through enzymatic cleavage of λ-phage DNA to yield a series of DNA chains of various lengths from 17.3 μm down to 4.2 μm, we have investigated the flow/extension behavior of these tethered DNA molecules under different flow strengths in the flow-gradient plane. We compared Brownian dynamic simulations for the flow dynamics of tethered λ-DNA in shear, and found our flow-gradient plane experimental results matched well with our bead-spring simulations. The shear flow processing demonstrated in our studies represents a controllable approach for tethering and stretching DNA molecules of various lengths. Together with further metallization of DNA chains within DOD structures, this bottom-up approach can potentially enable efficient and reliable fabrication of large-scale nanoelectronic devices based on single organic molecules, therefore opening opportunities in both fundamental understanding of charge transport at the single molecular level and many exciting applications for ever-shrinking molecular circuits.

Calculating Payload for a Tethered Balloon System

Science.gov (United States)

Charles D. Tangren

1980-01-01

A graph method to calculate payload for a tethered balloon system, with the supporting helium lift and payload equations. is described. The balloon system is designed to collect emissions data during the convective-lift and no-convective-lift phases of a forest fire. A description of the balloon system and a list of factors affecting balloon selection are included....

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.

Towing Asteroids with Gravity Tractors Enhanced by Tethers and Solar Sails

Science.gov (United States)

Shen, Haijun; Roithmayr, Carlos M.

2015-01-01

Material collected from an asteroid's surface can be used to increase gravitational attraction between the asteroid and a Gravity Tractor (GT); the spacecraft therefore operates more effectively and is referred to as an Enhanced Gravity Tractor (EGT). The use of tethers and solar sails to further improve effectiveness and simplify operations is investigated. By employing a tether, the asteroidal material can be placed close to the asteroid while the spacecraft is stationed farther away, resulting in a better safety margin and improved thruster efficiency. A solar sail on a spacecraft can naturally provide radial offset and inter-spacecraft separation required for multiple EGTs.

Stability control of a flexible maneuverable tethered space net robot

Science.gov (United States)

Zhang, Fan; Huang, Panfeng

2018-04-01

As a promising solution for active space debris capture and removal, a maneuverable Tethered Space Net Robot (TSNR) is proposed as an improved Space Tethered Net (TSN). In addition to the advantages inherit to the TSN, the TSNR's maneuverability expands the capture's potential. However, oscillations caused by the TSNR's flexibility and elasticity of make higher requests of the control scheme. Based on the dynamics model, a modified adaptive super-twisting sliding mode control scheme is proposed in this paper for TSNR stability control. The proposed continuous control force can effectively suppress oscillations. Theoretical verification and numerical simulations demonstrate that the desired trajectory can be tracked steadily and efficiently by employing the proposed control scheme.

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

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.

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.

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...

Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

Science.gov (United States)

Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

2015-01-01

The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

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.

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.

Tethered spinal cord: the effect of neurosurgery on the lower urinary tract and male sexual function

NARCIS (Netherlands)

Boemers, T. M.; van Gool, J. D.; de Jong, T. P.

1995-01-01

To determine the effect of neurosurgical untethering on the lower urinary tract and male sexual function, in patients with tethered spinal cord. Thirty-six children with tethered spinal cord due to neurospinal dysraphism were assessed clinically and urodynamically before and after surgical

Operator's Manual for SHEBA Powered Tether Balloon System

Science.gov (United States)

Lappen, Cara-Lyn; Randall, David A.

1998-01-01

The Surface Heat and Energy Budget of the Arctic (SHEBA) was an intensive field project which took place in the Arctic Ocean from October 1997 through October 1998. Its purpose was to measure as many facets of the Arctic environment as possible so that we would be able to better understand the interaction between the ice, atmosphere, and ocean and their interactions with global climate. One aspect of the atmospheric field component was launching tethered balloons to monitor the profiles of temperature, wind, pressure, and humidity, as well as examine the vertical structure of cloud droplet sizes and distributions. The tethered balloon that we used was one specially designed for use in freezing climates by SPEC Corporation in Boulder, Colorado. A special winch that was able to withstand Arctic temperature and weather became necessary when the testing of simple winch systems used in warmer climates failed under these extreme conditions. The purpose of this manual is to acquaint any new user to the powered tethered balloon system deployed at the The Surface Heat and Energy Budget of the Arctic (SHEBA ice camp. It includes a description of the preparations necessary to get ready for a launch, the mechanics of the actual launch, and an account of the proper procedure for taking down the equipment when finished. It will also include tips on how to minimize potential equipment failures, some trouble shooting, and some safety ideas. This manual is designed so that new operators can use the system with minimal previous training. At the end of this manual, the reader will find a quick checklist.

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

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

Electromechanical engineering in SnO2 nanoparticle tethered hybrid ionic liquid

Science.gov (United States)

Deb, Debalina; Bhattacharya, Subhratanu

2017-05-01

Challenge of developing electrolytes comprising synergic properties of high mechanical strength with superior electrical and electrochemical properties has so far been unmet towards the application of secondary storage devices. In this research, we have engineered the electromechanical properties of 2-(trimethylamino) ethyl methacrylate bis(trifluoromethylsulfonyl) imide [TMEM]TFSI ionic liquid by tethering silane modified SnO2 nanoparticles within it. Different percentages of tethering are employed to achieve improved ionic conductivity, better discharge/ charging ratio (40%) along with gel like mechanical properties. Our findings appear to provide an optimal solution towards the future prospects in application in a number of areas, notably in energy-related technologies.

Dishevelled links basal body docking and orientation in ciliated epithelial cells

Science.gov (United States)

Vladar, Eszter K.; Axelrod, Jeffrey D.

2014-01-01

Some epithelia contain cells with multiple, motile cilia that beat in a concerted fashion. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and of the coordinated planar polarization of cilia that leads to their concerted motility. Recent, elegant work by Park and colleagues, using embryonic frog epidermis, demonstrates that Dishevelled (Dvl), a key regulator of both the Wnt/β-catenin and Planar Cell Polarity (PCP) pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID:18819800

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.

Stationary Tether Device for Buoy Apparatus and System for Using

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — A rigid, neutrally buoyant hydrodynamicaly-faired tether and associated fastening hardware that loosely holds a bathymetric float at a predetermined distance from a...

Fiber Optic Shape Sensing for Tethered Marsupial Rovers, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Building upon the successful proof of concept work in Phase I, Luna Innovations Incorporated is proposing to design, build, and test a sensing tether for marsupial...

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.

75 FR 47316 - Centennial Challenges 2010 Strong Tether Challenge

Science.gov (United States)

2010-08-05

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION Centennial Challenges 2010 Strong Tether Challenge... teams that wish to compete may register. Centennial Challenges is a program of prize competitions to..., please visit: http://www.spaceward.org/elevator2010-ts . For general information on the NASA Centennial...

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

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.

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.

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 .

Clustering of tethered satellite system simulation data by an adaptive neuro-fuzzy algorithm

Science.gov (United States)

Mitra, Sunanda; Pemmaraju, Surya

1992-01-01

Recent developments in neuro-fuzzy systems indicate that the concepts of adaptive pattern recognition, when used to identify appropriate control actions corresponding to clusters of patterns representing system states in dynamic nonlinear control systems, may result in innovative designs. A modular, unsupervised neural network architecture, in which fuzzy learning rules have been embedded is used for on-line identification of similar states. The architecture and control rules involved in Adaptive Fuzzy Leader Clustering (AFLC) allow this system to be incorporated in control systems for identification of system states corresponding to specific control actions. We have used this algorithm to cluster the simulation data of Tethered Satellite System (TSS) to estimate the range of delta voltages necessary to maintain the desired length rate of the tether. The AFLC algorithm is capable of on-line estimation of the appropriate control voltages from the corresponding length error and length rate error without a priori knowledge of their membership functions and familarity with the behavior of the Tethered Satellite System.

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.

Tethered balloon operation for wintering aerosol measurements in the lower troposphere at Syowa Station, Antarctica

OpenAIRE

Keiichiro Hara; Kazuo Osada; Takashi Yamanouchi

2007-01-01

The 46th Japanese Antarctic Research Expedition (JARE-46) carried out twenty seven tethered-balloon-borne aerosol measurements at Syowa Station for better understanding of aerosol chemical and physical properties in the lower troposphere from 6th January 2005 until 11 December 2005. This report summarizes the plan, preparation, field activities and some troubles/problems in the tethered-balloon observations.

Tethered balloon operation for wintering aerosol measurements in the lower troposphere at Syowa Station, Antarctica

Directory of Open Access Journals (Sweden)

Keiichiro Hara

2007-03-01

Full Text Available The 46th Japanese Antarctic Research Expedition (JARE-46 carried out twenty seven tethered-balloon-borne aerosol measurements at Syowa Station for better understanding of aerosol chemical and physical properties in the lower troposphere from 6th January 2005 until 11 December 2005. This report summarizes the plan, preparation, field activities and some troubles/problems in the tethered-balloon observations.

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.

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.)

Lifting options for stratospheric aerosol geoengineering: advantages of tethered balloon systems.

Science.gov (United States)

Davidson, Peter; Burgoyne, Chris; Hunt, Hugh; Causier, Matt

2012-09-13

The Royal Society report 'Geoengineering the Climate' identified solar radiation management using albedo-enhancing aerosols injected into the stratosphere as the most affordable and effective option for geoengineering, but did not consider in any detail the options for delivery. This paper provides outline engineering analyses of the options, both for batch-delivery processes, following up on previous work for artillery shells, missiles, aircraft and free-flying balloons, as well as a more lengthy analysis of continuous-delivery systems that require a pipe connected to the ground and supported at a height of 20 km, either by a tower or by a tethered balloon. Towers are shown not to be practical, but a tethered balloon delivery system, with high-pressure pumping, appears to have much lower operating and capital costs than all other delivery options. Instead of transporting sulphuric acid mist precursors, such a system could also be used to transport slurries of high refractive index particles such as coated titanium dioxide. The use of such particles would allow useful experiments on opacity, coagulation and atmospheric chemistry at modest rates so as not to perturb regional or global climatic conditions, thus reducing scale-up risks. Criteria for particle choice are discussed, including the need to minimize or prevent ozone destruction. The paper estimates the time scales and relatively modest costs required if a tethered balloon system were to be introduced in a measured way with testing and development work proceeding over three decades, rather than in an emergency. The manufacture of a tether capable of sustaining the high tensions and internal pressures needed, as well as strong winds, is a significant challenge, as is the development of the necessary pumping and dispersion technologies. The greatest challenge may be the manufacture and launch of very large balloons, but means have been identified to significantly reduce the size of such balloons or aerostats.

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.

Stabilization of periodic solutions in a tethered satellite system by damping injection

DEFF Research Database (Denmark)

Larsen, Martin Birkelund; Blanke, Mogens

2009-01-01

presents a control design for stabilizing these periodic solutions. The design consists of a control law for stabilizing the open-loop equilibrium and a bias term which forces the system trajectory away from the equilibrium. The tether needs to be positioned away from open-loop equilibrium for the tether...... to affect the orbit parameters. An approximation of the periodic solutions of the closed loop system is found as a series expansion in the parameter plane spanned by the controller gain and the bias term. The stability of the solutions is investigated using linear Floquet analysis of the variational...

Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

KAUST Repository

Agarwal, Praveen; Kim, Sung A.; Archer, Lynden A.

2012-01-01

Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered

Disaster Coverage Predication for the Emerging Tethered Balloon Technology: Capability for Preparedness, Detection, Mitigation, and Response.

Science.gov (United States)

Alsamhi, Saeed H; Samar Ansari, Mohd; Rajput, Navin S

2018-04-01

A disaster is a consequence of natural hazards and terrorist acts, which have significant potential to disrupt the entire wireless communication infrastructure. Therefore, the essential rescue squads and recovery operations during a catastrophic event will be severely debilitated. To provide efficient communication services, and to reduce casualty mortality and morbidity during the catastrophic events, we proposed the Tethered Balloon technology for disaster preparedness, detection, mitigation, and recovery assessment. The proposed Tethered Balloon is applicable to any type of disaster except for storms. The Tethered Balloon is being actively researched and developed as a simple solution to improve the performance of rescues, facilities, and services of emergency medical communication in the disaster area. The most important requirement for rescue and relief teams during or after the disaster is a high quality of service of delivery communication services to save people's lives. Using our proposed technology, we report that the Tethered Balloon has a large disaster coverage area. Therefore, the rescue and research teams are given higher priority, and their performance significantly improved in the particular coverage area. Tethered Balloon features made it suitable for disaster preparedness, mitigation, and recovery. The performance of rescue and relief teams was effective and efficient before and after the disaster as well as can be continued to coordinate the relief teams until disaster recovery. (Disaster Med Public Health Preparedness. 2018;12:222-231).

Refining the tethering of American oysters (Crassostrea virginica) to measure the effects of two environmental stressors.

Science.gov (United States)

Poirier, Luke A; Gilbert, Shane T C; St-Hilaire, Sophie; Davidson, Jeff; Cox, Ruth; Quijón, Pedro A

2018-02-01

Tethering assays, or the physical restraint of test organisms, has been used in the past to measure selected organisms' response to stressors while removing the observer from the experimental setting. Although informative for monitoring and hypothesis testing, these assays often used microfilaments that have been found to be too invasive or prone to biases given their effects on test organisms' behavior. Here, we describe a new variation of tethering using American oysters (Crassostrea virginica) and illustrate its use in the study of their mortality rates as a result of two stressors: siltation and predation by a non-indigenous species. Our protocol identified a resistant (non-toxic) glue that could be used to attach oysters to stone slabs, thus partially mimicking the natural cementation of the shell to natural substrates. This variation of tethering was harmless and maintained oysters' body position and natural ability to filter feed. Using tethered oysters in separate two-week field cage experiments, we also show how siltation and predation by a non-indigenous species (the European green crab, Carcinus maenas), caused a gradual, easily measurable increase in oyster mortality rates. We argue that this variation of tethering is a cost-effective and advantageous way to monitor or test the effects of these and other stressors on oysters and similar species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isothermal pumping analysis for high-altitude tethered balloons.

Science.gov (United States)

Kuo, Kirsty A; Hunt, Hugh E M

2015-06-01

High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe.

Associative visual learning by tethered bees in a controlled visual environment.

Science.gov (United States)

Buatois, Alexis; Pichot, Cécile; Schultheiss, Patrick; Sandoz, Jean-Christophe; Lazzari, Claudio R; Chittka, Lars; Avarguès-Weber, Aurore; Giurfa, Martin

2017-10-10

Free-flying honeybees exhibit remarkable cognitive capacities but the neural underpinnings of these capacities cannot be studied in flying insects. Conversely, immobilized bees are accessible to neurobiological investigation but display poor visual learning. To overcome this limitation, we aimed at establishing a controlled visual environment in which tethered bees walking on a spherical treadmill learn to discriminate visual stimuli video projected in front of them. Freely flying bees trained to walk into a miniature Y-maze displaying these stimuli in a dark environment learned the visual discrimination efficiently when one of them (CS+) was paired with sucrose and the other with quinine solution (CS-). Adapting this discrimination to the treadmill paradigm with a tethered, walking bee was successful as bees exhibited robust discrimination and preferred the CS+ to the CS- after training. As learning was better in the maze, movement freedom, active vision and behavioral context might be important for visual learning. The nature of the punishment associated with the CS- also affects learning as quinine and distilled water enhanced the proportion of learners. Thus, visual learning is amenable to a controlled environment in which tethered bees learn visual stimuli, a result that is important for future neurobiological studies in virtual reality.

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.

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

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.

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.

A Fiber-Optic Tether for the Hull Search UUV System Documentation

National Research Council Canada - National Science Library

Buescher, J. G

2006-01-01

...) conducting ship hull inspection missions, defines the required specifications that will allow the integration and installation of a FO tether system on UUVs with ship hull inspection capability...

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.

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.

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.

A simplified tether model for molecular motor transporting cargo

International Nuclear Information System (INIS)

Fang-Zhen, Li; Li-Chun, Jiang

2010-01-01

Molecular motors are proteins or protein complexes which function as transporting engines in biological cells. This paper models the tether between motor and its cargo as a symmetric linear potential. Different from Elston and Peskin's work for which performance of the system was discussed only in some limiting cases, this study produces analytic solutions of the problem for general cases by simplifying the transport system into two physical states, which makes it possible to discuss the dynamics of the motor–cargo system in detail. It turns out that the tether strength between motor and cargo should be greater than a threshold or the motor will fail to transport the cargo, which was not discussed by former researchers yet. Value of the threshold depends on the diffusion coefficients of cargo and motor and also on the strength of the Brownian ratchets dragging the system. The threshold approaches a finite constant when the strength of the ratchet tends to infinity. (general)

Phase 3 study of selected tether applications in space. Volume 2: Study results

Science.gov (United States)

1986-01-01

Engineering designs were developed relative to a tethered launch assist from the Shuttle for payloads up to 10,000 kg mass and the tethering of a 15,000 kg science platform from the space station. These designs are used for a cost benefit analysis which assesses the feasibility of using such systems as a practical alternative to what would otherwise be accomplished by conventional means. The term conventional as related to both these applications is intended to apply to the use of some form(s) of chemical propulsion system.

Tethered Contactless Mobile Nuclear Environment Monitoring Robot

International Nuclear Information System (INIS)

Choi, S. Y.; Lee, E. S.; Lee, Kun J.; Kim, Su H.; Rim, C. T.

2013-01-01

In fact, the nuclear environment monitoring is significantly crucial for early detection of NPP accident, radiological emergency, the estimation of radiation exposure to nearby residents as well as the long term radioactivity. In the UAE, the nuclear environment monitoring is, however, quite challenging because sampling locations are far from NPPs and the outdoor temperature and humidity are very high for NPP workers to collect soil, air, and water samples. Therefore, nuclear environment monitoring robots (Nubos) are strongly needed for the NPPs in the UAE. The Nubos can be remotely controlled to collect samples in extreme environment instead of NPP workers. Moreover, the Nubos can be unmanned ground vehicles (UGVs), unmanned aerial vehicles (UAVs) and unmanned marine vehicles (UMVs) to collect soil, air, and water samples, respectively. In this paper, the prototype development of UGV type Nubos using power cable for a long distance power delivery, called Tethered contactless mobile Nubo is introduced and validated by experiments. In this paper, the prototype development of Tethered Contactless Mobile (TeCoM) Nubo, which can be powered continuously within several km distance and avoid tangled cable, and the indoor test are finished. As further works, outdoor demonstration and a grand scale R and D proposal of practical Nubo will be proceeded

Tethered Contactless Mobile Nuclear Environment Monitoring Robot

Energy Technology Data Exchange (ETDEWEB)

Choi, S. Y.; Lee, E. S.; Lee, Kun J.; Kim, Su H.; Rim, C. T. [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2013-05-15

In fact, the nuclear environment monitoring is significantly crucial for early detection of NPP accident, radiological emergency, the estimation of radiation exposure to nearby residents as well as the long term radioactivity. In the UAE, the nuclear environment monitoring is, however, quite challenging because sampling locations are far from NPPs and the outdoor temperature and humidity are very high for NPP workers to collect soil, air, and water samples. Therefore, nuclear environment monitoring robots (Nubos) are strongly needed for the NPPs in the UAE. The Nubos can be remotely controlled to collect samples in extreme environment instead of NPP workers. Moreover, the Nubos can be unmanned ground vehicles (UGVs), unmanned aerial vehicles (UAVs) and unmanned marine vehicles (UMVs) to collect soil, air, and water samples, respectively. In this paper, the prototype development of UGV type Nubos using power cable for a long distance power delivery, called Tethered contactless mobile Nubo is introduced and validated by experiments. In this paper, the prototype development of Tethered Contactless Mobile (TeCoM) Nubo, which can be powered continuously within several km distance and avoid tangled cable, and the indoor test are finished. As further works, outdoor demonstration and a grand scale R and D proposal of practical Nubo will be proceeded.

Stability analysis and trend study of a balloon tethered in a wind, with experimental comparisons

Science.gov (United States)

Redd, L. T.; Bland, S. R.; Bennett, R. M.

1973-01-01

A stability analysis and trend study for a balloon tethered in a steady wind are presented. The linearized, stability-derivative type analysis includes balloon aerodynamics, buoyancy, mass (including apparent mass), and static forces resulting from the tether cable. The analysis has been applied to a balloon 7.64 m in length, and the results are compared with those from tow tests of this balloon. This comparison shows that the analysis gives reasonable predictions for the damping, frequencies, modes of motion, and stability boundaries exhibited by the balloon. A trend study for the 7.64-m balloon was made to illustrate how the stability boundaries are affected by changes in individual stability parameters. The trends indicated in this study may also be applicable to many other tethered-balloon systems.

Tethered by Self-Generated Flow: Mucus String Augmented Feeding Current Generation in Larval Oysters

Science.gov (United States)

Jiang, H.; Wheeler, J.; Anderson, E.

2016-02-01

Marine zooplankton live in a nutritionally dilute environment. To survive, they must process an enormous volume of water relative to their own body volume for food. To achieve this, many zooplankters including copepods, invertebrate larvae, and protists create a feeding current to concentrate and transport food items to their food gathering structures. To enhance the efficiency of the feeding current, these zooplankters often rely on certain "tethering" mechanisms to retard their translational motion for producing a strong feeding current. The tethering force may include excess weight due to gravity, force from attachment to solid surfaces, and drag experienced by strategically placed morphological structures. Larval oysters are known from previous studies to release mucus strings during feeding, presumably for supplying a tethering force to enhance their feeding-current efficiency. But the underlying mechanism is unclear. In this study, we used a high-speed microscale imaging system (HSMIS) to observe the behavior of freely swimming and feeding larval oysters. We also used HSMIS to measure larval imposed feeding currents via a micro-particle image velocimetry (µPIV) technique. HSMIS allows observations along a vertically oriented focal plane in a relatively large water vessel with unprecedented spatial and temporal resolutions. Our high-speed videos show that a feeding larval oyster continuously released a long mucus string into its feeding current that flows downward; the feeding current subsequently dragged the mucus string downward. Analysis of our µPIV data combined with a hydrodynamic model further suggests that the drag force experienced by the mucus string in the feeding current contributes significantly to the tethering force required to generate the feeding current. Thus, mucus strings in larval oysters act as "anchors" in larval self-generated flow to actively tether the feeding larvae.

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.

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.

"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.

Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve

NARCIS (Netherlands)

Dal-Bianco, Jacob P; Aikawa, Elena; Bischoff, Joyce; Guerrero, J Luis; Hjortnaes, Jesper; Beaudoin, Jonathan; Szymanski, Catherine; Bartko, Philipp E; Seybolt, Margo M; Handschumacher, Mark D; Sullivan, Suzanne; Garcia, Michael L; Mauskapf, Adam; Titus, James S; Wylie-Sears, Jill; Irvin, Whitney S; Chaput, Miguel; Messas, Emmanuel; Hagège, Albert A; Carpentier, Alain; Levine, Robert A

2016-01-01

BACKGROUND: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that

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.

SATB1 tethers multiple gene loci to reprogram expression profiledriving breast cancer metastasis

Energy Technology Data Exchange (ETDEWEB)

Han, Hye-Jung; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

2006-07-13

Global changes in gene expression occur during tumor progression, as indicated by expression profiling of metastatic tumors. How this occurs is poorly understood. SATB1 functions as a genome organizer by folding chromatin via tethering multiple genomic loci and recruiting chromatin remodeling enzymes to regulate chromatin structure and expression of a large number of genes. Here we show that SATB1 is expressed at high levels in aggressive breast cancer cells, and is undetectable in non-malignant breast epithelial cells. Importantly, RNAi-mediated removal of SATB1 from highly-aggressive MDA-MB-231 cells altered the expression levels of over 1200 genes, restored breast-like acinar polarity in three-dimensional cultures, and prevented the metastastic phenotype in vivo. Conversely, overexpression of SATB1 in the less-aggressive breast cancer cell line Hs578T altered the gene expression profile and increased metastasis dramatically in vivo. Thus, SATB1 is a global regulator of gene expression in breast cancer cells, directly regulating crucial metastasis-associated genes, including ERRB2 (HER2/NEU), TGF-{beta}1, matrix metalloproteinase 3, and metastasin. The identification of SATB1 as a protein that re-programs chromatin organization and transcription profiles to promote breast cancer metastasis suggests a new model for metastasis and may provide means of therapeutic intervention.

Development of a Tethered Formation Flight Testbed for ISS, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The development of a testbed for the development and demonstration of technologies needed by tethered formation flying satellites is proposed. Such a testbed would...

Extracellular Signal-Regulated Kinase 2 (ERK2) Phosphorylation Sites and Docking Domain on the Nuclear Pore Complex Protein Tpr Cooperatively Regulate ERK2-Tpr Interaction

Czech Academy of Sciences Publication Activity Database

Vomastek, Tomáš; Iwanicky, M. P.; Burack, W. R.; Tiwari, D.; Kumar, D.; Parsons, J. T.; Weber, M. J.; Nandicoori, V. K.

2008-01-01

Roč. 28, č. 22 (2008), s. 6954-6966 ISSN 0270-7306 R&D Projects: GA AV ČR IAA500200716 Institutional research plan: CEZ:AV0Z50200510 Keywords : erk * docking domain * cell growth Subject RIV: EE - Microbiology, Virology Impact factor: 5.942, year: 2008

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.

Materials for advancement of MXER tether design (1000-371), Phase I

Data.gov (United States)

National Aeronautics and Space Administration — There exist a need to develop, identify, and classify various materials that can be used in the fabrication of electrodynamic tethers for various applications. These...

Implementation Options for the PROPEL Electrodynamic Tether Demonstration Mission

Science.gov (United States)

Bilen, Sven G.; Johnson, C. Les; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael; Stone, Nobie

2014-01-01

The PROPEL ("Propulsion using Electrodynamics") flight demonstration mission concept will demonstrate the use of an electrodynamic tether (EDT) for generating thrust, which will allow the propulsion system to overcome the limitations of the rocket equation. The mission concept has been developed by a team of government, industry, and academia partners led by NASA Marshall Space Flight Center (MSFC). PROPEL is being designed for versatility of the EDT system with multiple end users in mind and to be flexible with respect to platform. Previously, we reported on a comprehensive mission design for PROPEL with a mission duration of six months or longer with multiple mission goals including demonstration of significant boost, deboost, inclination change, and drag make-up activities. To explore a range of possible configurations, primarily driven by cost considerations, other mission concept designs have been pursued. In partnership with the NASA's Office of Chief Technologist (OCT) Game Changing Program, NASA MSFC Leadership, and the MSFC Advanced Concepts Office, a mission concept design was developed for a near-term EDT propulsion flight validation mission. The Electrodynamic Tether Propulsion Study (ETPS) defined an EDT propulsion system capable of very large delta-V for use on future missions developed by NASA, DoD, and commercial customers. To demonstrate the feasibility of an ETPS, the study focused on a space demonstration mission concept design with configuration of a pair of tethered satellite busses, one of which is the Japanese H-II Transfer Vehicle (HTV). The HTV would fly its standard ISS resupply mission. When resupply mission is complete, the ISS reconfigures and releases the HTV to perform the EDT experiment at safe orbital altitudes below the ISS. Though the focus of this particular mission concept design addresses a scenario involving the HTV or a similar vehicle, the propulsion system's capability is relevant to a number of applications, as noted above

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.

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.

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.

Folding of multidomain proteins: biophysical consequences of tethering even in apparently independent folding.

Science.gov (United States)

Arviv, Oshrit; Levy, Yaakov

2012-12-01

Most eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering-induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse-grained and atomistic molecular dynamics simulations of two two-domain constructs from the immunoglobulin-like β-sandwich fold. Each of these was experimentally shown to behave as the "sum of its parts," that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two-domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Copyright © 2012 Wiley Periodicals, Inc.

Biomimetic chimeric peptide-tethered hydrogels for human mesenchymal stem cell delivery.

Science.gov (United States)

Shim, Gayong; Kim, Gunwoo; Choi, Junhyeok; Yi, TacGhee; Cho, Yun Kyoung; Song, Sun Uk; Byun, Youngro; Oh, Yu-Kyoung

2015-12-01

Here, we report a chimeric peptide-tethered fibrin hydrogel scaffold for delivery of human mesenchymal stem cells (hMSC). Osteopontin-derived peptide (OP) was used as an hMSC-tethering moiety. OP showed hMSC adhesion properties and enhanced hMSC proliferation. A natural fibrin-binding protein-derived peptide (FBP) was tested for its ability to tether hMSC to the fibrin gel matrix. FBP loading on fibrin gels was 8.2-fold higher than that of a scrambled peptide (scFBP). FBP-loaded fibrin gels were retained at injection sites longer than scFBP-loaded fibrin gels, showing a 15.9-fold higher photon intensity of fluorescent FBP-grafted fibrin gels than fluorescent scFBP-loaded fibrin gels 48 h after injection. On the basis of the fibrin gel-binding properties of FBP and the hMSC-binding and proliferation-supporting properties of OP, we constructed chimeric peptides containing FBP and OP linked with a spacer (FBPsOP). Four days after transplantation, the survival of hMSC in FBPsOP-grafted fibrin gels was 3.9-fold higher than hMSC in fibrin gels alone. Our results suggest the potential of FBPsOP-grafted fibrin gels as a bioactive delivery system for enhanced survival of stem cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Acquisition of Human Operation Characteristics for Kite-based Tethered Flying Robot using Human Operation Data

OpenAIRE

Todoroki, Chiaki; Takahashi, Yasutake; Nakamura, Takayuki

2015-01-01

This paper shows human skill acquisition systems to control the kite-based tethered flying robot. The kite-based tethered flying robot has been proposed as a flying observation system with long-term activity capability[1]. It is a relatively new system and aimed to complement other information gathering systems using a balloon or an air vehicle. This paper shows some approaches of human operation characteristics acquisition based on fuzzy learning controller, knearest neighbor algorithm, and ...

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.

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.

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 ...

Control by damping Injection of Electrodynamic Tether System in an Inclined Orbit

DEFF Research Database (Denmark)

Larsen, Martin Birkelund; Blanke, Mogens

2009-01-01

dynamical system. Based on this model, a nonlinear controller is designed that will make the system asymptotically stable around its open-loop equilibrium. The control scheme handles the time-varying nature of the system in a suitable manner resulting in a large operational region. The performance...... of the closed loop system is treated using Floquet theory, investigating the closed loop properties for their dependency of the controller gain and orbit inclination.......Control of a satellite system with an electrodynamic tether as actuator is a time-periodic and underactuated control problem. This paper considers the tethered satellite in a Hamiltonian framework and determines a port-controlled Hamiltonian formulation that adequately describes the nonlinear...

A Correlational Analysis of Tethered Swimming, Swim Sprint Performance and Dry-land Power Assessments.

Science.gov (United States)

Loturco, I; Barbosa, A C; Nocentini, R K; Pereira, L A; Kobal, R; Kitamura, K; Abad, C C C; Figueiredo, P; Nakamura, F Y

2016-03-01

Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=- 0.82 and -0.74, respectively). Average force was very-largely/largely correlated with the 50- and 100-m performances (r=- 0.85 and -0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=- 0.72 and -0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump-squat was largely correlated (r=- 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Quinine-Promoted, Enantioselective Boron-Tethered Diels-Alder Reaction by Anomeric Control of Transition State Conformation.

Science.gov (United States)

Scholl, Katie; Dillashaw, John; Timpy, Evan; Lam, Yu-Hong; DeRatt, Lindsey; Benton, Tyler R; Powell, Jacqueline P; Houk, Kendall N; Morgan, Jeremy B

2018-05-01

Diels-Alder reactions of tethered vinyl-metal species offer the opportunity to fashion highly functionalized diol intermediates for synthesis. We have developed the first enantioselective boron-tethered Diels-Alder reaction using quinine as a chiral promoter. Quinine recovery, enantioselectivity enhancement, and manipulation of the cyclohexene core are also investigated. DFT modeling calculations confirm the role of quinine as a bidentate ligand enhancing reaction rates. The enantioselectivity of the cycloaddition is proposed to originate from a boron-centered anomeric effect.

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.

UV-Curable Hybrid Nanocomposite Coating to Protect Tether Polymer Materials, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — To address the NASA need for coatings to protect and strengthen tether materials for Momentum-exchange Electrodynamic Reboost (MXER) technology, Luminit, LLC,...

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

Science.gov (United States)

Alexander, Matthew S.; Casar, Juan Carlos; Motohashi, Norio; Vieira, Natássia M.; Eisenberg, Iris; Marshall, Jamie L.; Gasperini, Molly J.; Lek, Angela; Myers, Jennifer A.; Estrella, Elicia A.; Kang, Peter B.; Shapiro, Frederic; Rahimov, Fedik; Kawahara, Genri; Widrick, Jeffrey J.; Kunkel, Louis M.

2014-01-01

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which results in dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that is markedly reduced in the muscles of dystrophin-deficient mice (Dmdmdx-5Cv mice) and in DMD patient muscles. Here, we determined that muscle-specific transgenic overexpression of miR-486 in muscle of Dmdmdx-5Cv mice results in reduced serum creatine kinase levels, improved sarcolemmal integrity, fewer centralized myonuclei, increased myofiber size, and improved muscle physiology and performance. Additionally, we identified dedicator of cytokinesis 3 (DOCK3) as a miR-486 target in skeletal muscle and determined that DOCK3 expression is induced in dystrophic muscles. DOCK3 overexpression in human myotubes modulated PTEN/AKT signaling, which regulates muscle hypertrophy and growth, and induced apoptosis. Furthermore, several components of the PTEN/AKT pathway were markedly modulated by miR-486 in dystrophin-deficient muscle. Skeletal muscle–specific miR-486 overexpression in Dmdmdx-5Cv animals decreased levels of DOCK3, reduced PTEN expression, and subsequently increased levels of phosphorylated AKT, which resulted in an overall beneficial effect. Together, these studies demonstrate that stable overexpression of miR-486 ameliorates the disease progression of dystrophin-deficient skeletal muscle. PMID:24789910

Mini-open spinal column shortening for the treatment of adult tethered cord syndrome.

Science.gov (United States)

Safaee, Michael M; Winkler, Ethan A; Chou, Dean

2017-10-01

Tethered cord syndrome (TCS) is a challenging entity characterized by adhesions at the caudal spinal cord that prevent upward movement during growth and result in stretching of the cord with a concomitant constellation of neurologic symptoms. Although growth in height stops in adulthood, some patients still develop progressive symptoms; many underwent detethering as a child or adolescent, resulting in significant scar tissue and re-tethering. Recent strategies have focused on spinal column shortening to reduce tension on the spinal cord without exposing the previous de-tethering site. Mini-open and minimally invasive approaches avoid the large dissection and exposure associated with traditional approaches and are associated with reduced blood loss, shorter hospital stay, and similar outcomes when compared to conventional open approaches. We describe a technique for mini-open spinal column shortening. Using intraoperative navigation pedicle screws were placed at T10, T11, L1, and L2. A mini-open 3-column "egg shell" decancellation osteotomy of T12 was performed through a transpedicular approach with preservation of the superior and inferior endplates. This procedure was performed on a 28year old male with recurrent TCS and neurogenic bladder. Postoperative imaging showed a reduction in spinal column length of 1.5cm and evidence of decreased tension on the spinal cord. At last follow-up he was recovering well with improved urinary function. Spinal column shortening for adult TCS can be safely achieved through a mini-open approach. Future studies should compare the efficacy of this technique to both traditional de-tethering and open spinal column shortening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence.

Directory of Open Access Journals (Sweden)

Subhash C Verma

Full Text Available Kaposi's sarcoma associated herpesvirus is tightly linked to multiple human malignancies including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL and Multicentric Castleman's Disease (MCD. KSHV like other herpesviruses establishes life-long latency in the infected host by persisting as chromatin and tethering to host chromatin through the virally encoded protein Latency Associated Nuclear Antigen (LANA. LANA, a multifunctional protein, is capable of binding to a large number of cellular proteins responsible for transcriptional regulation of various cellular and viral pathways involved in blocking cell death and promoting cell proliferation. This leads to enhanced cell division and replication of the viral genome, which segregates faithfully in the dividing tumor cells. The mechanism of genome segregation is well known and the binding of LANA to nucleosomal proteins, throughout the cell cycle, suggests that these interactions play an important role in efficient segregation. Various biochemical methods have identified a large number of LANA binding proteins, including histone H2A/H2B, histone H1, MeCP2, DEK, CENP-F, NuMA, Bub1, HP-1, and Brd4. These nucleosomal proteins may have various functions in tethering of the viral genome during specific phases of the viral life cycle. Therefore, we performed a comprehensive analysis of their interaction with LANA using a number of different assays. We show that LANA binds to core nucleosomal histones and also associates with other host chromatin proteins including histone H1 and high mobility group proteins (HMGs. We used various biochemical assays including co-immunoprecipitation and in-vivo localization by split GFP and fluorescence resonance energy transfer (FRET to demonstrate their association.

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

Tuning peptide self-assembly by an in-tether chiral center

Science.gov (United States)

Hu, Kuan; Xiong, Wei; Li, Hu; Zhang, Pei-Yu; Yin, Feng; Zhang, Qianling; Jiang, Fan; Li, Zigang

2018-01-01

The self-assembly of peptides into ordered nanostructures is important for understanding both peptide molecular interactions and nanotechnological applications. However, because of the complexity and various self-assembling pathways of peptide molecules, design of self-assembling helical peptides with high controllability and tunability is challenging. We report a new self-assembling mode that uses in-tether chiral center-induced helical peptides as a platform for tunable peptide self-assembly with good controllability. It was found that self-assembling behavior was governed by in-tether substitutional groups, where chirality determined the formation of helical structures and aromaticity provided the driving force for self-assembly. Both factors were essential for peptide self-assembly to occur. Experiments and theoretical calculations indicate long-range crystal-like packing in the self-assembly, which was stabilized by a synergy of interpeptide π-π and π-sulfur interactions and hydrogen bond networks. In addition, the self-assembled peptide nanomaterials were demonstrated to be promising candidate materials for applications in biocompatible electrochemical supercapacitors.

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

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.

Diamond surface functionalization with biomimicry – Amine surface tether and thiol moiety for electrochemical sensors

Energy Technology Data Exchange (ETDEWEB)

Sund, James B., E-mail: jim@jamessund.com [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Causey, Corey P. [Departments of Chemistry and Biochemistry, Duke University, Durham, NC (United States); Wolter, Scott D. [Department of Physics, Elon University, Elon, NC 27244 (United States); Parker, Charles B., E-mail: charles.parker@duke.edu [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Stoner, Brian R. [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Research Triangle Institute (RTI) International, Research Triangle Park, NC (United States); Toone, Eric J. [Departments of Chemistry and Biochemistry, Duke University, Durham, NC (United States); Glass, Jeffrey T. [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States)

2014-05-01

Highlights: • Diamond surfaces were functionalized with organic molecules using a novel approach. • Used biomimicry to select a molecule to bind NO, similar to the human body. • Molecular orbital theory predicted the molecule-analyte oxidation behavior. • A thiol moiety was attached to an amine surface tether on the diamond surface. • XPS analysis verified each surface functionalization step. - Abstract: The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen–oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

Diamond surface functionalization with biomimicry – Amine surface tether and thiol moiety for electrochemical sensors

International Nuclear Information System (INIS)

Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

2014-01-01

Highlights: • Diamond surfaces were functionalized with organic molecules using a novel approach. • Used biomimicry to select a molecule to bind NO, similar to the human body. • Molecular orbital theory predicted the molecule-analyte oxidation behavior. • A thiol moiety was attached to an amine surface tether on the diamond surface. • XPS analysis verified each surface functionalization step. - Abstract: The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen–oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis

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...

Technical and economical assessment on tethered wind-energy systems (TWES)

Energy Technology Data Exchange (ETDEWEB)

Furuya, O.; Maekawa, S.

1982-06-01

The objective of the work reported was to establish the potential of tethered wind energy systems for energy conversion in the upper atmosphere. Of the concepts investigated, the Vertical Takeoff and Landing (VTOL) lift generation concept had the highest potential as compared to balloon, wind and hybrid concepts.

Diamond surface functionalization with biomimicry - Amine surface tether and thiol moiety for electrochemical sensors

Science.gov (United States)

Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

2014-05-01

The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen-oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

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.

Computer Programs for Calculating and Plotting the Stability Characteristics of a Balloon Tethered in a Wind

Science.gov (United States)

Bennett, R. M.; Bland, S. R.; Redd, L. T.

1973-01-01

Computer programs for calculating the stability characteristics of a balloon tethered in a steady wind are presented. Equilibrium conditions, characteristic roots, and modal ratios are calculated for a range of discrete values of velocity for a fixed tether-line length. Separate programs are used: (1) to calculate longitudinal stability characteristics, (2) to calculate lateral stability characteristics, (3) to plot the characteristic roots versus velocity, (4) to plot the characteristic roots in root-locus form, (5) to plot the longitudinal modes of motion, and (6) to plot the lateral modes for motion. The basic equations, program listings, and the input and output data for sample cases are presented, with a brief discussion of the overall operation and limitations. The programs are based on a linearized, stability-derivative type of analysis, including balloon aerodynamics, apparent mass, buoyancy effects, and static forces which result from the tether line.

Use of Tethered Enzymes as a Platform Technology for Rapid Analyte Detection.

Directory of Open Access Journals (Sweden)

Roy Cohen

Full Text Available Rapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs. As proof of principle, we use oriented immobilization of pyruvate kinase (PK and luciferase (Luc on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE, a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices.We performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815 with the current gold standard for biomarker detection, ELISA-with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA.Oriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using oriented immobilization of active

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.

Spinal column shortening for tethered cord syndrome associated with myelomeningocele, lumbosacral lipoma, and lipomyelomeningocele in children and young adults.

Science.gov (United States)

Aldave, Guillermo; Hansen, Daniel; Hwang, Steven W; Moreno, Amee; Briceño, Valentina; Jea, Andrew

2017-06-01

OBJECTIVE Tethered cord syndrome is the clinical manifestation of an abnormal stretch on the spinal cord, presumably causing mechanical injury, a compromised blood supply, and altered spinal cord metabolism. Tethered cord release is the standard treatment for tethered cord syndrome. However, direct untethering of the spinal cord carries potential risks, such as new neurological deficits from spinal cord injury, a CSF leak from opening the dura, and retethering of the spinal cord from normal scar formation after surgery. To avoid these risks, the authors applied spinal column shortening to children and transitional adults with primary and secondary tethered cord syndrome and report treatment outcomes. The authors' aim with this study was to determine the safety and efficacy of spinal column shortening for tethered cord syndrome by analyzing their experience with this surgical technique. METHODS The authors retrospectively reviewed the demographic and procedural data of children and young adults who had undergone spinal column shortening for primary or secondary tethered cord syndrome. RESULTS Seven patients with tethered cord syndrome caused by myelomeningocele, lipomyelomeningocele, and transitional spinal lipoma were treated with spinal column shortening. One patient with less than 24 months of follow-up was excluded from further analysis. There were 3 males and 4 females; the average age at the time was surgery was 16 years (range 8-30 years). Clinical presentations for our patients included pain (in 5 patients), weakness (in 4 patients), and bowel/bladder dysfunction (in 4 patients). Spinal column osteotomy was most commonly performed at the L-1 level, with fusion between T-12 and L-2 using a pedicle screw-rod construct. Pedicle subtraction osteotomy was performed in 6 patients, and vertebral column resection was performed in 1 patient. The average follow-up period was 31 months (range 26-37 months). Computed tomography-based radiographic outcomes showed solid

Endogenous opioids are involved in abnormal stereotyped behaviour of tethered sows

NARCIS (Netherlands)

Cronin, G.M.; Wiepkema, P.R.; Ree, van J.M.

1985-01-01

Tethered sows continuously performed stereotypies during a substantial part of the day time. A single subcutaneous injection with naloxone significantly decreased the profound stereotypies, while explorative behaviours of pigs were not affected by naloxone. In addition a long-term effect of naloxone

Endogenous opioids are involved in abnormal stereotyped behaviours of tethered sows

NARCIS (Netherlands)

Cronin, G.M.; Wiepkema, P.R.; Ree, J.M. van

1985-01-01

Tethered sows continuously performed stereotypies during a substantial part of the day time. A single subcutaneous injection with naloxone significantly decreased the profound stereotypies, while explorative behaviours of pigs were not affected by naloxone. In addition a long-term effect of naloxone

TETHERED BALLOON MEASUREMENTS OF BIOGENIC VOCS IN THE ATMOSPHERIC BOUNDARY LAYER

Science.gov (United States)

Measurements of biogenic volatile organic compounds (BVOCs) have been made on a tethered balloon platform in eleven field deployments between 1985 and 1996. A series of balloon sampling packages have been developed for these campaigns and they have been used to describe boundary ...

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.

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...

Analytical investigation of the dynamics of tethered constellations in Earth orbit, phase 2

Science.gov (United States)

Lorenzini, E. C.; Arnold, D. A.; Cosmo, M.; Grossi, M. D.

1986-10-01

The following topics related to the dynamics of the 4-mass tethered system are addressed: (1) the development of damping algorithms for damping the out-of-plane libration of the system and the interaction of the out-of-plane control with the other degrees of freedom; and (2) the development of environmental models to be added to the dynamics simulation computer code. The environmental models are specifically a new drag routine based on the Jacchia's 1977 model, a J(2) model and an accurate thermal model of the wire. Regarding topic (1) a survey of various out-of-plane libration control laws was carried out. Consequently a yo-yo control law with amplitude of the tether length variation proportional to the amplitude of the out-of-game libration has been selected. This control law provides good damping when applied to a (theoretical) two-dimensional system. In the actual 3-dimensional 4-mass tethered system, however, energy is transferred to the least damped degrees of freedom (the out-of-plane lateral deflections are still undamped in the present simulations) in such a way as to decrease the effectiveness of the algorithm for out-of-plane libration control. The addition of damping algorithms for the out-of-plane lateral deflections is therefore necessary.

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.

Compact, planar, translational piezoelectric bimorph actuator with Archimedes’ spiral actuating tethers

International Nuclear Information System (INIS)

Yang, Chenye; Liu, Sanwei; Livermore, Carol; Xie, Xin

2016-01-01

The design, analytical modelling, finite element analysis (FEA), and experimental characterization of a microelectromechanical system (MEMS) out-of-plane (vertical) translational piezoelectric lead–zirconate–titanate (PZT) bimorph actuator supported on Archimedes’ spiral tethers are presented. Three types of bimorph actuators with different electrode patterns (with spiral tethers half actuated, fully actuated with uniform polarity, or fully actuated with reversed polarity) are designed and modelled. The two actuators with the highest predicted performance (half actuated and fully actuated with uniform polarity) are implemented and characterized. Both designs are fabricated by commercial processes and are compatible with integration into more complex MEMS systems. Analytical modelling and FEA are used to analyze and predict the actuators’ displacements and blocking forces. Experimental measurements of the deflections and blocking forces of actuators with full uniform actuation and half actuation validate the design. At an applied voltage of 110 V, the out-of-plane deflections of the actuators with half actuation and full uniform actuation are measured at about 17 µ m and 29 µ m respectively, in good agreement with analytical predictions of 17.3 µ m and 34.2 µ m and FEA predictions of 17.1 µ m and 25.8 µ m. The blocking force for devices with half-actuated tethers is predicted to be 12 mN (analytical) and 10 mN (FEA), close to the experimental value of 9 mN. The blocking force for devices with full uniform actuation is predicted to be 23 mN (analytical) and 17 mN (FEA), as compared with 15 mN in experiments. (paper)

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...

Tethered Lubricants for Small Systems

Energy Technology Data Exchange (ETDEWEB)

Lynden A. Archer

2006-01-09

The objective of this research project is two-fold. First, to fundamentally understand friction and relaxation dynamics of polymer chains near surfaces; and second, to develop novel self-lubricated substrates suitable for MEMS devices. During the three-year performance period of this study the PI and his students have shown using theory and experiments that systematic introduction of disorder into tethered lubricant coatings (e.g. by using self-assembled monolayer (SAM) mixtures or SAMs with nonlinear, branched architectures) can be used to significantly reduce the friction coefficient of a surface. They have also developed a simple procedure based on dielectric spectroscopy for quantifying the effect of surface disorder on molecular relaxation in lubricant coatings. Details of research accomplishments in each area of the project are described in the body of the report.

Theseus: tethered distributed robotics (TDR)

Science.gov (United States)

Digney, Bruce L.; Penzes, Steven G.

2003-09-01

The Defence Research and Development Canada's (DRDC) Autonomous Intelligent System's program conducts research to increase the independence and effectiveness of military vehicles and systems. DRDC-Suffield's Autonomous Land Systems (ALS) is creating new concept vehicles and autonomous control systems for use in outdoor areas, urban streets, urban interiors and urban subspaces. This paper will first give an overview of the ALS program and then give a specific description of the work being done for mobility in urban subspaces. Discussed will be the Theseus: Thethered Distributed Robotics (TDR) system, which will not only manage an unavoidable tether but exploit it for mobility and navigation. Also discussed will be the prototype robot called the Hedgehog, which uses conformal 3D mobility in ducts, sewer pipes, collapsed rubble voids and chimneys.

Multifunctional-layered materials for creating membrane-restricted nanodomains and nanoscale imaging

Energy Technology Data Exchange (ETDEWEB)

Srinivasan, P., E-mail: prasri@ece.ucsb.edu, E-mail: srinivasan@lifesci.ucsb.edu [Department of Electrical and Computer Engineering, University of California, Santa Barbara, California 93106, USA and Neuroscience Research Institute, University of California, Santa Barbara, California 93106 (United States)

2016-01-18

Experimental platform that allows precise spatial positioning of biomolecules with an exquisite control at nanometer length scales is a valuable tool to study the molecular mechanisms of membrane bound signaling. Using micromachined thin film gold (Au) in layered architecture, it is possible to add both optical and biochemical functionalities in in vitro. Towards this goal, here, I show that docking of complementary DNA tethered giant phospholiposomes on Au surface can create membrane-restricted nanodomains. These nanodomains are critical features to dissect molecular choreography of membrane signaling complexes. The excited surface plasmon resonance modes of Au allow label-free imaging at diffraction-limited resolution of stably docked DNA tethered phospholiposomes, and lipid-detergent bicelle structures. Such multifunctional building block enables realizing rigorously controlled in vitro set-up to model membrane anchored biological signaling, besides serving as an optical tool for nanoscale imaging.

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.

Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

Energy Technology Data Exchange (ETDEWEB)

Zhu Ying [Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310009 (China); Wang Youxiang, E-mail: yx_wang@zju.edu.cn [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China); Hu Qiaoling; Shen Jiacong [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China)

2009-04-30

The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

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.

Effect of mass variation on dynamics of tethered system in orbital maneuvering

Science.gov (United States)

Sun, Liang; Zhao, Guowei; Huang, Hai

2018-05-01

In orbital maneuvering, the mass variation due to fuel consumption has an obvious impact on the dynamics of tethered system, which cannot be neglected. The contributions of the work are mainly shown in two aspects: 1) the improvement of the model; 2) the analysis of dynamics characteristics. As the mass is variable, and the derivative of the mass is directly considered in the traditional Lagrange equation, the expression of generalized force is complicated. To solve this problem, the coagulated derivative is adopted in the paper; besides, the attitude dynamics equations derived in this paper take into account the effect of mass variation and the drift of orbital trajectory at the same time. The bifurcation phenomenon, the pendular motion angular frequency, and amplitudes of tether vibration revealed in this paper can provide a reference for the parameters and controller design in practical engineering. In the article, a dumbbell model is adopted to analyze the dynamics of tethered system, in which the mass variation of base satellite is fully considered. Considering the practical application, the case of orbital transfer under a transversal thrust is mainly studied. Besides, compared with the analytical solutions of librational angles, the effects of mass variation on stability and librational characteristic are studied. Finally, in order to make an analysis of the effect on vibrational characteristic, a lumped model is introduced, which reveals a strong coupling of librational and vibrational characteristics.

Calculating the electromagnetic field on the earth due to an electrodynamic tethered system in the ionosphere

Science.gov (United States)

Estes, Robert D.

1989-01-01

A method is presented for calculating the electromagnetic wave field on the earth's surface associated with the operation of an electrodynamic tethered satellite system of constant or slowly varying current in the upper ionosphere. The wave field at the ionospheric boundary and on the earth's surface is obtained by numerical integration. The results suggest that the ionospheric waves do not propagate into the atmosphere and that the image of the Alfven wings from a steady-current tether should be greatly broadened on the earth's surface.

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.

Elasticity of Hard-Spheres-And-Tether Systems

International Nuclear Information System (INIS)

Farago, O.; Kantor, Y.

1999-01-01

Physical properties of a large class of systems ranging from noble gases to polymers and rubber are primarily determined by entropy, while the internal energy plays a minor role. Such systems can be conveniently modeled and numerically studied using ''hard' (i.e., ''infinity-or-zero'') potentials, such as hard sphere repulsive interactions, or inextensible (''tether'') bonds which limit the distance between the bonded monomers, but have zero energy at all permitted distances. The knowledge of elastic constants is very important for understanding the behavior of entropy-dominated systems. Computational methods for determination of the elastic constants in such systems are broadly classified into ''strain'' methods and (fluctuation methods. In the former, the elastic constants are extracted from stress-strain relations, while in the latter they are determined from measurements of stress fluctuations. The fluctuation technique usually enables more accurate and well-controlled determination of the elastic constants since in this method the elastic constants are computed directly from simulations of the un strained system with no need to deform the simulation cell and perform numerical differentiations. For central forces systems, the original ''fluctuation'' formalism can be applied provided the pair potential is twice differentiable. We have extended this formalism to apply to hard-spheres-and-tether models in which this requirement is not fulfilled. We found that for such models the components of the tensor of elastic constants can be related to (two-, three- and four-point) probability densities of contacts between hard spheres and stretched bonds. We have tested our formalism on simple (phantom networks and three-dimensional hard spheres systems

Synthesis and characterization of macromolecular rhodamine tethers and their interactions with P-glycoprotein.

Science.gov (United States)

Crawford, Lindsey; Putnam, David

2014-08-20

Rhodamine dyes are well-known P-glycoprotein (P-gp) substrates that have played an important role in the detection of inhibitors and other substrates of P-gp, as well as in the understanding of P-gp function. Macromolecular conjugates of rhodamines could prove useful as tethers for further probing of P-gp structure and function. Two macromolecular derivatives of rhodamine, methoxypolyethylene glycol-rhodamine6G and methoxypolyethylene glycol-rhodamine123, were synthesized through the 2'-position of rhodamine6G and rhodamine123, thoroughly characterized, and then evaluated by inhibition with verapamil for their ability to interact with P-gp and to act as efflux substrates. To put the results into context, the P-gp interactions of the new conjugates were compared to the commercially available methoxypolyethylene glycol-rhodamineB. FACS analysis confirmed that macromolecular tethers of rhodamine6G, rhodamine123, and rhodamineB were accumulated in P-gp expressing cells 5.2 ± 0.3%, 26.2 ± 4%, and 64.2 ± 6%, respectively, compared to a sensitive cell line that does not overexpress P-gp. Along with confocal imaging, the efflux analysis confirmed that the macromolecular rhodamine tethers remain P-gp substrates. These results open potential avenues for new ways to probe the function of P-gp both in vitro and in vivo.

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.

Self-consistent field theory of tethered polymers: one dimensional, three dimensional, strong stretching theories and the effects of excluded-volume-only interactions.

Science.gov (United States)

Suo, Tongchuan; Whitmore, Mark D

2014-11-28

We examine end-tethered polymers in good solvents, using one- and three-dimensional self-consistent field theory, and strong stretching theories. We also discuss different tethering scenarios, namely, mobile tethers, fixed but random ones, and fixed but ordered ones, and the effects and important limitations of including only binary interactions (excluded volume terms). We find that there is a "mushroom" regime in which the layer thickness is independent of the tethering density, σ, for systems with ordered tethers, but we argue that there is no such plateau for mobile or disordered anchors, nor is there one in the 1D theory. In the other limit of brushes, all approaches predict that the layer thickness scales linearly with N. However, the σ(1/3) scaling is a result of keeping only excluded volume interactions: when the full potential is included, the dependence is faster and more complicated than σ(1/3). In fact, there does not appear to be any regime in which the layer thickness scales in the combination Nσ(1/3). We also compare the results for two different solvents with each other, and with earlier Θ solvent results.

Self-consistent field theory of tethered polymers: One dimensional, three dimensional, strong stretching theories and the effects of excluded-volume-only interactions

International Nuclear Information System (INIS)

Suo, Tongchuan; Whitmore, Mark D.

2014-01-01

We examine end-tethered polymers in good solvents, using one- and three-dimensional self-consistent field theory, and strong stretching theories. We also discuss different tethering scenarios, namely, mobile tethers, fixed but random ones, and fixed but ordered ones, and the effects and important limitations of including only binary interactions (excluded volume terms). We find that there is a “mushroom” regime in which the layer thickness is independent of the tethering density, σ, for systems with ordered tethers, but we argue that there is no such plateau for mobile or disordered anchors, nor is there one in the 1D theory. In the other limit of brushes, all approaches predict that the layer thickness scales linearly with N. However, the σ 1/3 scaling is a result of keeping only excluded volume interactions: when the full potential is included, the dependence is faster and more complicated than σ 1/3 . In fact, there does not appear to be any regime in which the layer thickness scales in the combination Nσ 1/3 . We also compare the results for two different solvents with each other, and with earlier Θ solvent results

Cholesterol-Induced Buckling in Physisorbed Polymer-Tethered Lipid Monolayers

Directory of Open Access Journals (Sweden)

Christoph A. Naumann

2013-04-01

Full Text Available The influence of cholesterol concentration on the formation of buckling structures is studied in a physisorbed polymer-tethered lipid monolayer system using epifluorescence microscopy (EPI and atomic force microscopy (AFM. The monolayer system, built using the Langmuir-Blodgett (LB technique, consists of 3 mol % poly(ethylene glycol (PEG lipopolymers and various concentrations of the phospholipid, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC, and cholesterol (CHOL. In the absence of CHOL, AFM micrographs show only occasional buckling structures, which is caused by the presence of the lipopolymers in the monolayer. In contrast, a gradual increase of CHOL concentration in the range of 0–40 mol % leads to fascinating film stress relaxation phenomena in the form of enhanced membrane buckling. Buckling structures are moderately deficient in CHOL, but do not cause any notable phospholipid-lipopolymer phase separation. Our experiments demonstrate that membrane buckling in physisorbed polymer-tethered membranes can be controlled through CHOL-mediated adjustment of membrane elastic properties. They further show that CHOL may have a notable impact on molecular confinement in the presence of crowding agents, such as lipopolymers. Our results are significant, because they offer an intriguing prospective on the role of CHOL on the material properties in complex membrane architecture.

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.

Use of Tethered Enzymes as a Platform Technology for Rapid Analyte Detection

Science.gov (United States)

Cohen, Roy; Lata, James P.; Lee, Yurim; Hernández, Jean C. Cruz; Nishimura, Nozomi; Schaffer, Chris B.; Mukai, Chinatsu; Nelson, Jacquelyn L.; Brangman, Sharon A.; Agrawal, Yash; Travis, Alexander J.

2015-01-01

Background Rapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT) for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs). As proof of principle, we use oriented immobilization of pyruvate kinase (PK) and luciferase (Luc) on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE), a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices. Methods and findings We performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815) with the current gold standard for biomarker detection, ELISA—with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA. Conclusions Oriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using

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.

On the effect of tether composition on cis/trans selectivity in intramolecular Diels-Alder reactions.

Science.gov (United States)

Paddon-Row, Michael N; Longshaw, Alistair I; Willis, Anthony C; Sherburn, Michael S

2009-01-05

Intramolecular Diels-Alder (IMDA) transition structures (TSs) and energies have been computed at the B3LYP/6-31+G(d) and CBS-QB3 levels of theory for a series of 1,3,8-nonatrienes, H(2)C=CH-CH=CH-CH(2)-X-Z-CH=CH(2) [-X-Z- = -CH(2)-CH(2)- (1); -O-C(=O)- (2); -CH(2)-C(=O)- (3); -O-CH(2)- (4); -NH-C(=O)- (5); -S-C(=O)- (6); -O-C(=S)- (7); -NH-C(=S)- (8); -S-C(=S)- (9)]. For each system studied (1-9), cis- and trans-TS isomers, corresponding, respectively, to endo- and exo-positioning of the -C-X-Z- tether with respect to the diene, have been located and their relative energies (E(rel) (TS)) employed to predict the cis/trans IMDA product ratio. Although the E(rel) (TS) values are modest (typically NH or S), the IMDA cis stereoselectivity diminishes. The predicted stereochemical reaction preferences are explained in terms of two opposing effects operating in the cis-TS, namely (1) unfavorable torsional (eclipsing) strain about the C4-C5 bond, that is caused by the -C-X-C(=Y)- group's strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the endo-(thio)carbonyl group, C=Y, and the diene. The former interaction predominates when X is weakly electronegative (X=N, S), while the latter is dominant when X is more strongly electronegative (X=O), or a methylene group (X=CH(2)) which increases tether flexibility. These predictions hold up to experimental scrutiny, with synthetic IMDA reactions of 1, 2, 3, and 4 (published work) and 5, 6, and 8 (this work) delivering ratios close to those calculated. The reactions of thiolacrylate 5 and thioamide 8 represent the first examples of IMDA reactions with tethers of these types. Our results point to strategies for designing tethers, which lead to improved cis/trans-selectivities in IMDAs that are normally only weakly selective. Experimental verification of the validity of this claim comes in the form of fumaramide 14, which undergoes a more trans-selective IMDA reaction

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.

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

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

The effect of particle size on the morphology and thermodynamics of diblock copolymer/tethered-particle membranes

International Nuclear Information System (INIS)

Zhang, Bo; Edwards, Brian J.

2015-01-01

A combination of self-consistent field theory and density functional theory was used to examine the effect of particle size on the stable, 3-dimensional equilibrium morphologies formed by diblock copolymers with a tethered nanoparticle attached either between the two blocks or at the end of one of the blocks. Particle size was varied between one and four tenths of the radius of gyration of the diblock polymer chain for neutral particles as well as those either favoring or disfavoring segments of the copolymer blocks. Phase diagrams were constructed and analyzed in terms of thermodynamic diagrams to understand the physics associated with the molecular-level self-assembly processes. Typical morphologies were observed, such as lamellar, spheroidal, cylindrical, gyroidal, and perforated lamellar, with the primary concentration region of the tethered particles being influenced heavily by particle size and tethering location, strength of the particle-segment energetic interactions, chain length, and copolymer radius of gyration. The effect of the simulation box size on the observed morphology and system thermodynamics was also investigated, indicating possible effects of confinement upon the system self-assembly processes

The effect of particle size on the morphology and thermodynamics of diblock copolymer/tethered-particle membranes.

Science.gov (United States)

Zhang, Bo; Edwards, Brian J

2015-06-07

A combination of self-consistent field theory and density functional theory was used to examine the effect of particle size on the stable, 3-dimensional equilibrium morphologies formed by diblock copolymers with a tethered nanoparticle attached either between the two blocks or at the end of one of the blocks. Particle size was varied between one and four tenths of the radius of gyration of the diblock polymer chain for neutral particles as well as those either favoring or disfavoring segments of the copolymer blocks. Phase diagrams were constructed and analyzed in terms of thermodynamic diagrams to understand the physics associated with the molecular-level self-assembly processes. Typical morphologies were observed, such as lamellar, spheroidal, cylindrical, gyroidal, and perforated lamellar, with the primary concentration region of the tethered particles being influenced heavily by particle size and tethering location, strength of the particle-segment energetic interactions, chain length, and copolymer radius of gyration. The effect of the simulation box size on the observed morphology and system thermodynamics was also investigated, indicating possible effects of confinement upon the system self-assembly processes.

Otolith tethering in the zebrafish otic vesicle requires Otogelin and α-Tectorin.

Science.gov (United States)

Stooke-Vaughan, Georgina A; Obholzer, Nikolaus D; Baxendale, Sarah; Megason, Sean G; Whitfield, Tanya T

2015-03-15

Otoliths are biomineralised structures important for balance and hearing in fish. Their counterparts in the mammalian inner ear, otoconia, have a primarily vestibular function. Otoliths and otoconia form over sensory maculae and are attached to the otolithic membrane, a gelatinous extracellular matrix that provides a physical coupling between the otolith and the underlying sensory epithelium. In this study, we have identified two proteins required for otolith tethering in the zebrafish ear, and propose that there are at least two stages to this process: seeding and maintenance. The initial seeding step, in which otolith precursor particles tether directly to the tips of hair cell kinocilia, fails to occur in the einstein (eis) mutant. The gene disrupted in eis is otogelin (otog); mutations in the human OTOG gene have recently been identified as causative for deafness and vestibular dysfunction (DFNB18B). At later larval stages, maintenance of otolith tethering to the saccular macula is dependent on tectorin alpha (tecta) function, which is disrupted in the rolling stones (rst) mutant. α-Tectorin (Tecta) is a major constituent of the tectorial membrane in the mammalian cochlea. Mutations in the human TECTA gene can cause either dominant (DFNA8/12) or recessive (DFNB21) forms of deafness. Our findings indicate that the composition of extracellular otic membranes is highly conserved between mammals and fish, reinforcing the view that the zebrafish is an excellent model system for the study of deafness and vestibular disease. © 2015. Published by The Company of Biologists Ltd.

Tethered Balloon Operations at ARM AMF3 Site at Oliktok Point, AK

Science.gov (United States)

Dexheimer, D.; Lucero, D. A.; Helsel, F.; Hardesty, J.; Ivey, M.

2015-12-01

Oliktok Point has been the home of the Atmospheric Radiation Measurement Program's (ARM) third ARM Mobile Facility, or AMF3, since October 2013. The AMF3 is operated through Sandia National Laboratories and hosts instrumentation collecting continuous measurements of clouds, aerosols, precipitation, energy, and other meteorological variables. The Arctic region is warming more quickly than any other region due to climate change and Arctic sea ice is declining to record lows. Sparsity of atmospheric data from the Arctic leads to uncertainty in process comprehension, and atmospheric general circulation models (AGCM) are understood to underestimate low cloud presence in the Arctic. Increased vertical resolution of meteorological properties and cloud measurements will improve process understanding and help AGCMs better characterize Arctic clouds. SNL is developing a tethered balloon system capable of regular operation at AMF3 in order to provide increased vertical resolution atmospheric data. The tethered balloon can be operated within clouds at altitudes up to 7,000' AGL within DOE's R-2204 restricted area. Pressure, relative humidity, temperature, wind speed, and wind direction are recorded at multiple altitudes along the tether. These data were validated against stationary met tower data in Albuquerque, NM. The altitudes of the sensors were determined by GPS and calculated using a line counter and clinometer and compared. Wireless wetness sensors and supercooled liquid water content sensors have also been deployed and their data has been compared with other sensors. This presentation will provide an overview of the balloons, sensors, and test flights flown, and will provide a preliminary look at data from sensor validation campaigns and test flights.

Role of rab proteins in epithelial membrane traffic

NARCIS (Netherlands)

van Ijzendoorn, SCD; Mostov, KE; Hoekstra, D

2003-01-01

Small GTPase rab proteins play an important role in various aspects of membrane traffic, including cargo selection, vesicle budding, vesicle motility, tethering, docking, and fusion. Recent data suggest also that rabs, and their divalent effector proteins, organize organelle subdomains and as such

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.

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

The Tethered Balloon Current Generator - A space shuttle-tethered subsatellite for plasma studies and power generation

Science.gov (United States)

Williamson, P. R.; Banks, P. M.

1976-01-01

The objectives of the Tethered Balloon Current Generator experiment are to: (1) generate relatively large regions of thermalized, field-aligned currents, (2) produce controlled-amplitude Alfven waves, (3) study current-driven electrostatic plasma instabilities, and (4) generate substantial amounts of power or propulsion through the MHD interaction. A large balloon (a diameter of about 30 m) will be deployed with a conducting surface above the space shuttle at a distance of about 10 km. For a generally eastward directed orbit at an altitude near 400 km, the balloon, connected to the shuttle by a conducting wire, will be positive with respect to the shuttle, enabling it to collect electrons. At the same time, the shuttle will collect positive ions and, upon command, emit an electron beam to vary current flow in the system.

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...

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 ...

Evaluation of Computational Docking to Identify Pregnane X Receptor Agonists in the ToxCast Database

OpenAIRE

Kortagere, Sandhya; Krasowski, Matthew D.; Reschly, Erica J.; Venkatesh, Madhukumar; Mani, Sridhar; Ekins, Sean

2010-01-01

Background The pregnane X receptor (PXR) is a key transcriptional regulator of many genes [e.g., cytochrome P450s (CYP2C9, CYP3A4, CYP2B6), MDR1] involved in xenobiotic metabolism and excretion. Objectives As part of an evaluation of different approaches to predict compound affinity for nuclear hormone receptors, we used the molecular docking program GOLD and a hybrid scoring scheme based on similarity weighted GoldScores to predict potential PXR agonists in the ToxCast database of pesticides...

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.

Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

Science.gov (United States)

Yadav, Saveg; Pandey, Shrish Kumar; Singh, Vinay Kumar; Goel, Yugal; Kumar, Ajay; Singh, Sukh Mahendra

2017-01-01

Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP), with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA) and propionic acid (PA), with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

Directory of Open Access Journals (Sweden)

Saveg Yadav

Full Text Available Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP, with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA and propionic acid (PA, with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

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.

Nuclear pore complex tethers to the cytoskeleton.

Science.gov (United States)

Goldberg, Martin W

2017-08-01

The nuclear envelope is tethered to the cytoskeleton. The best known attachments of all elements of the cytoskeleton are via the so-called LINC complex. However, the nuclear pore complexes, which mediate the transport of soluble and membrane bound molecules, are also linked to the microtubule network, primarily via motor proteins (dynein and kinesins) which are linked, most importantly, to the cytoplasmic filament protein of the nuclear pore complex, Nup358, by the adaptor BicD2. The evidence for such linkages and possible roles in nuclear migration, cell cycle control, nuclear transport and cell architecture are discussed. Copyright © 2017. Published by Elsevier Ltd.

Approaching control for tethered space robot based on disturbance observer using super twisting law

Science.gov (United States)

Hu, Yongxin; Huang, Panfeng; Meng, Zhongjie; Wang, Dongke; Lu, Yingbo

2018-05-01

Approaching control is a key mission for the tethered space robot to perform the task of removing space debris. But the uncertainties of the TSR such as the change of model parameter have an important effect on the approaching mission. Considering the space tether and the attitude of the gripper, the dynamic model of the TSR is derived using Lagrange method. Then a disturbance observer is designed to estimate the uncertainty based on STW control method. Using the disturbance observer, a controller is designed, and the performance is compared with the dynamic inverse controller which turns out that the proposed controller performs better. Numerical simulation validates the feasibility of the proposed controller on the position and attitude tracking of the TSR.

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.

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.

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

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.

Identification of new 2,5-diketopiperazine derivatives as simultaneous effective inhibitors of αβ-tubulin and BCRP proteins: Molecular docking, Structure-Activity Relationships and virtual consensus docking studies

Science.gov (United States)

Fani, Najmeh; Sattarinezhad, Elham; Bordbar, Abdol-Khalegh

2017-06-01

In the first part of this paper, docking method was employed in order to study the binding mechanism of breast cancer resistance protein (BCRP) with a group of previously synthesized TPS-A derivatives which known as potent inhibitors of this protein to get insight into drug binding site of BCRP and to explore structure-activity relationship of these compounds. Molecular docking results showed that most of these compounds bind in the binding site of BCRP at the interface between the membrane and outer environment. In the second part, a group of designed TPS-A derivatives which showed good binding energies in the binding site of αβ-tubulin in the previous study were chosen to study their binding energies in the binding site of BCRP to investigate their simultaneous inhibitory effect on both αβ-tubulin and BCRP. The results showed that all of these compounds bind to the binding site of BCRP with relatively suitable binding energies and therefore could be potential inhibitors of both αβ-tubulin and BCRP proteins. Finally, virtual consensus docking method was utilized with the aim of design of new 2,5-diketopiperazine derivatives with significant inhibitory effect on both αβ-tubulin and BCRP proteins. For this purpose binding energies of a library of 2,5-diketopiperazine derivatives in the binding sites of αβ-tubulin and BCRP was investigated by using AutoDock and AutoDock vina tools. Molecular docking results revealed that a group of 36 compounds among them exhibit strong anti-tubulin and anti-BCRP activity.

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.

RIM, Munc13, and Rab3A interplay in acrosomal exocytosis

International Nuclear Information System (INIS)

Bello, Oscar D.; Zanetti, M. Natalia; Mayorga, Luis S.; Michaut, Marcela A.

2012-01-01

Exocytosis is a highly regulated, multistage process consisting of multiple functionally definable stages, including recruitment, targeting, tethering, priming, and docking of secretory vesicles with the plasma membrane, followed by calcium-triggered membrane fusion. The acrosome reaction of spermatozoa is a complex, calcium-dependent regulated exocytosis. Fusion at multiple sites between the outer acrosomal membrane and the cell membrane causes the release of the acrosomal contents and the loss of the membranes surrounding the acrosome. Not much is known about the molecules that mediate membrane docking in this particular fusion model. In neurons, the formation of the ternary RIM/Munc13/Rab3A complex has been suggested as a critical component of synaptic vesicles docking. Previously, we demonstrated that Rab3A localizes to the acrosomal region in human sperm, stimulates acrosomal exocytosis, and participates in an early stage during membrane fusion. Here, we report that RIM and Munc13 are also present in human sperm and localize to the acrosomal region. Like Rab3A, RIM and Munc13 participate in a prefusion step before the efflux of intra-acrosomal calcium. By means of a functional assay using antibodies and recombinant proteins, we show that RIM, Munc13 and Rab3A interplay during acrosomal exocytosis. Finally, we report by electron transmission microscopy that sequestering RIM and Rab3A alters the docking of the acrosomal membrane to the plasma membrane during calcium-activated acrosomal exocytosis. Our results suggest that the RIM/Munc13/Rab3 A complex participates in acrosomal exocytosis and that RIM and Rab3A have central roles in membrane docking. -- Highlights: ► RIM and Munc13 are present in human sperm and localize to the acrosomal region. ► RIM and Munc13 are necessary for acrosomal exocytosis. ► RIM and Munc13 participate before the acrosomal calcium efflux. ► RIM, Munc13 and Rab3A interplay in human sperm acrosomal exocytosis. ► RIM and Rab3A

A Quantitative Study of Tethered Chains in Various Solution Conditions Using Langmuir Diblock Copolymer Monolayers

Energy Technology Data Exchange (ETDEWEB)

Kent, Michael S.

1999-08-13

This article summarizes our investigations of tethered chain systems using Langmuir monolayer of polydimethysiloxane-poly styrene (PDMS-PS) diblock copolymers on organic liquids. In this system, the PDMS block adsorbs to the air surface while the PS block dangles into the subphase liquid. The air surface can be made either repulsive or attractive for the tethered PS chain segments by choosing a subphase liquid which has a surface tension lower or greater than that of PS, respectively. The segment profile of the PS block is determined by neutron reflection as a function of the surface density, the molecular weights of the PS and PDMS blocks, and the solution conditions. We cover the range of reduced surface density (SIGMA) characteristic of the large body of data in the literature for systems of chains tethered onto solid surfaces from dilute solution in good or theta solvent conditions (SIGMA < 12). We emphasize quantitative comparisons with analytical profile forms and scaling predictions. We find that the strong-stretching limit invoked in analytical SCF and scaling theories is not valid over this Z range. On the other hand, over a large portion of this range (SIGMA < 5) tethered layers are well described by a renormalization group theory addressing weakly interacting or noninteracting chains. Simultaneous with the study of the profile form, the free energy of the chains is examined through the surface tension. A strong increase in the surface pressure is observed with increasing surface density which determines the maximum surface density which can be achieved. This apparently nonequilibrium effect is attributed to steric interactions and limited lateral interpenetration. This effect may explain several outstanding discrepancies regarding the adsorption of end-functionalized chains and diblock copolymers onto solid surfaces.

Piperidinium tethered nanoparticle-hybrid electrolyte for lithium metal batteries

KAUST Repository

Korf, Kevin S.

2014-06-23

We report on the synthesis of novel piperidinium-based ionic liquid tethered nanoparticle hybrid electrolytes and investigate their physical and electrochemical properties. Hybrid electrolytes based on the ionic liquid 1-methyl-1-propylpiperidinium bis(trifluoromethanesulfone) imide covalently tethered to silica nanoparticles (SiO2-PP-TFSI) were blended with propylene carbonate-1 M lithium bis(trifluoromethanesulfone) imide (LiTFSI). We employed NMR analysis to confirm the successful creation of the hybrid material. Dielectric and rheological measurements show that these electrolytes exhibit exceptional room-temperature DC ionic conductivity (10-2 to 10 -3 S cm-1) as well as high shear mechanical moduli (105 to 106 Pa). Lithium transference numbers were found to increase with particle loading and to reach values as high as 0.22 at high particle loadings where the particle jam to form a soft glassy elastic medium. Analysis of lithium electrodeposits obtained in the hybrid electrolytes using SEM and EDX spectra show that the SiO2-PP-TFSI nanoparticles are able to smooth lithium deposition and inhibit lithium dendrite proliferation in Li metal batteries. LTOSiO2-PP-TFSI/PC in 1 M LiTFSILi half-cells based on the SiO2-PP-TFSI hybrid electrolytes exhibit attractive voltage profiles and trouble-free extended cycling behavior over more than 1000 cycles of charge and discharge. This journal is © the Partner Organisations 2014.

The radiation budget of stratocumulus clouds measured by tethered balloon instrumentation: Variability of flux measurements

Science.gov (United States)

Duda, David P.; Stephens, Graeme L.; Cox, Stephen K.

1990-01-01

Measurements of longwave and shortwave radiation were made using an instrument package on the NASA tethered balloon during the FIRE Marine Stratocumulus experiment. Radiation data from two pairs of pyranometers were used to obtain vertical profiles of the near-infrared and total solar fluxes through the boundary layer, while a pair of pyrgeometers supplied measurements of the longwave fluxes in the cloud layer. The radiation observations were analyzed to determine heating rates and to measure the radiative energy budget inside the stratocumulus clouds during several tethered balloon flights. The radiation fields in the cloud layer were also simulated by a two-stream radiative transfer model, which used cloud optical properties derived from microphysical measurements and Mie scattering theory.

Energy dissipation/transfer and stable attitude of spatial on-orbit tethered system

Science.gov (United States)

Hu, Weipeng; Song, Mingzhe; Deng, Zichen

2018-01-01

For the Tethered Satellite System, the coupling between the platform system and the solar panel is a challenge in the dynamic analysis. In this paper, the coupling dynamic behaviors of the Tethered Satellite System that is idealized as a planar flexible damping beam-spring-mass composite system are investigated via a structure-preserving method. Considering the coupling between the plane motion of the system, the oscillation of the spring and the transverse vibration of the beam, the dynamic model of the composite system is established based on the Hamiltonian variational principle. A symplectic dimensionality reduction method is proposed to decouple the dynamic system into two subsystems approximately. Employing the complex structure-preserving approach presented in our previous work, numerical iterations are performed between the two subsystems with weak damping to study the energy dissipation/transfer in the composite system, the effect of the spring stiffness on the energy distribution and the effect of the particle mass on the stability of the composite system. The numerical results show that: the energy transfer approach is uniquely determined by the initial attitude angle, while the energy dissipation speed is mainly depending on the initial attitude angle and the spring stiffness besides the weak damping. In addition, the mass ratio between the platform system and the solar panel determines the stable state as well as the time needed to reach the stable state of the composite system. The numerical approach presented in this paper provides a new way to deal with the coupling dynamic system and the conclusions obtained give some useful advices on the overall design of the Tethered Satellite System.

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.

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.

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.

Reverse cope elimination of hydroxylamines and alkenes or alkynes: theoretical investigation of tether length and substituent effects.

Science.gov (United States)

Krenske, Elizabeth H; Davison, Edwin C; Forbes, Ian T; Warner, Jacqueline A; Smith, Adrian L; Holmes, Andrew B; Houk, K N

2012-02-01

Quantum mechanical calculations have been used to study the intramolecular additions of hydroxylamines to alkenes and alkynes ("reverse Cope eliminations"). In intermolecular reverse Cope eliminations, alkynes are more reactive than alkenes. However, competition experiments have shown that tethering the hydroxylamine to the alkene or alkyne can reverse the reactivity order from that normally observed. The exact outcome depends on the length of the tether. In agreement with experiment, a range of density functional theory methods and CBS-QB3 calculations predict that the activation energies for intramolecular reverse Cope eliminations follow the order 6-exo-dig hydroxylamine and alkyne. Cyclization onto an alkene in the 5-exo-trig fashion incurs slightly less tether strain than a 6-exo-dig alkyne cyclization, but its activation energy is higher because the hydroxylamine fragment must distort more before the TS is reached. If the alkene terminus is substituted with two methyl groups, the barrier becomes so much higher that it is also disfavored compared to the 5- and 7-exo-dig cyclizations. © 2012 American Chemical Society

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.

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

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.

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.

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.

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...

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/.

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.

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.

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.

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

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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.

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...

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.

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.

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.

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.

Relationship between anaerobic capacity estimated using a single effort and 30-s tethered running outcomes.

Directory of Open Access Journals (Sweden)

Alessandro Moura Zagatto

Full Text Available The purpose of the current study was to investigate the relationship between alternative anaerobic capacity method (MAODALT and a 30-s all-out tethered running test. Fourteen male recreational endurance runners underwent a graded exercise test, a supramaximal exhaustive effort and a 30-s all-out test on different days, interspaced by 48h. After verification of data normality (Shapiro-Wilk test, the Pearson's correlation test was used to verify the association between the anaerobic estimates from the MAODALT and the 30-s all-out tethered running outputs. Absolute MAODALT was correlated with mean power (r = 0.58; P = 0.03, total work (r = 0.57; P = 0.03, and mean force (r = 0.79; P = 0.001. In addition, energy from the glycolytic pathway (E[La-] was correlated with mean power (r = 0.58; P = 0.03. Significant correlations were also found at each 5s interval between absolute MAODALT and force values (r between 0.75 and 0.84, and between force values and E[La-] (r between 0.73 to 0.80. In conclusion, the associations between absolute MAODALT and the mechanical outputs from the 30-s all-out tethered running test evidenced the importance of the anaerobic capacity for maintaining force during the course of time in short efforts.

Overload control of artificial gravity facility using spinning tether system for high eccentricity transfer orbits

Science.gov (United States)

Gou, Xing-wang; Li, Ai-jun; Tian, Hao-chang; Wang, Chang-qing; Lu, Hong-shi

2018-06-01

As the major part of space life supporting systems, artificial gravity requires further study before it becomes mature. Spinning tether system is a good alternative solution to provide artificial gravity for the whole spacecraft other than additional devices, and its longer tether length could significantly reduce spinning velocity and thus enhance comfortability. An approximated overload-based feedback method is proposed to provide estimated spinning velocity signals for controller, so that gravity level could be accurately controlled without complicated GPS modules. System behavior in high eccentricity transfer orbits is also studied to give a complete knowledge of the spinning stabilities. The application range of the proposed method is studied in various orbit cases and spinning velocities, indicating that it is accurate and reliable for most of the mission phases especially for the final constant gravity level phase. In order to provide stable gravity level for transfer orbit missions, a sliding mode controller based on estimated angular signals is designed for closed-loop control. Numerical results indicate that the combination of overload-based feedback and sliding mode controller could satisfy most of the long-term artificial gravity missions. It is capable of forming flexible gravity environment in relatively good accuracy even in the lowest possible orbital radiuses and high eccentricity orbits of crewed space missions. The proposed scheme provides an effective tether solution for the artificial gravity construction in interstellar travel.

Fullerenic structures and such structures tethered to carbon materials

Science.gov (United States)

Goel, Anish; Howard, Jack B.; Vander Sande, John B.

2010-01-05

The fullerenic structures include fullerenes having molecular weights less than that of C.sub.60 with the exception of C.sub.36 and fullerenes having molecular weights greater than C.sub.60. Examples include fullerenes C.sub.50, C.sub.58, C.sub.130, and C.sub.176. Fullerenic structure chemically bonded to a carbon surface is also disclosed along with a method for tethering fullerenes to a carbon material. The method includes adding functionalized fullerene to a liquid suspension containing carbon material, drying the suspension to produce a powder, and heat treating the powder.

Advanced Electrodynamic Tether Systems: Modeling of Scattering and Unsteady Effects

Science.gov (United States)

2008-06-06

spacecraft and satellites. A high altitude nuclear detonation would likely create a new high energy electron belt and increase the radiation risk to...our tether has no reason to roll, making O=0, and thus cosO =1. The y-component of the torque is thus expressed: < = < =< = FF cossin3 222 ’ (S...ions from the integral limits to manageable levels. Our goal is to isolate the permutations of initial velocities and impact parameters such that

The Reverse Cope Elimination of Hydroxylamines and Alkenes or Alkynes: Theoretical Investigation of Tether Length and Substituent Effects

Science.gov (United States)

Krenske, Elizabeth H.; Davison, Edwin C.; Forbes, Ian T.; Warner, Jacqueline A.; Smith, Adrian L.; Holmes, Andrew B.; Houk, K. N.

2012-01-01

Quantum mechanical calculations have been used to study the intramolecular additions of hydroxylamines to alkenes and alkynes (“reverse Cope eliminations”). In intermolecular reverse Cope eliminations, alkynes are more reactive than alkenes. However, competition experiments have shown that tethering the hydroxylamine to the alkene or alkyne can reverse the reactivity order from that normally observed. The exact outcome depends on the length of the tether. In agreement with experiment, a range of density functional theory methods and CBS-QB3 calculations predict that the activation energies for intramolecular reverse Cope eliminations follow the order 6-exo-dig hydroxylamine and alkyne. Cyclization onto an alkene in the 5-exo-trig fashion incurs slightly less tether strain than a 6-exo-dig alkyne cyclization, but its activation energy is higher because the hydroxylamine fragment must distort more before the TS is reached. If the alkene terminus is substituted with two methyl groups, the barrier becomes so much higher that it is also disfavored compared to the 5- and 7-exo-dig cyclizations. PMID:22280245

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.

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.

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

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.

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.

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.

Reversibly tethering growth factors to surfaces : guiding cell function at the cell-material interface

NARCIS (Netherlands)

Cabanas Danés, Jordi

2013-01-01

Development of novel methodologies for tethering growth factors (GFs) to materials is highly desired for the generation of biomaterials with improved tissue repair properties. Progress in the development of biomaterials that incorporate GFs and the in vivo performance of such biomaterials in tissue

Elongated membrane tethers, individually anchored by high affinity α4β1/VCAM-1 complexes, are the quantal units of monocyte arrests.

Directory of Open Access Journals (Sweden)

Calvin Chu

Full Text Available The α4β1 integrin facilitates both monocyte rolling and adhesion to the vascular endothelium and is physiologically activated by monocyte chemoattractant protein (MCP-1. The current study investigated the initial events in the adhesion of THP-1 cells to immobilized Vascular Cell Adhesion Molecule 1 (VCAM-1. Using AFM force measurements, cell adhesion was shown to be mediated by two populations of α4β1/VCAM-1 complexes. A low affinity form of α4β1 was anchored to the elastic elements of the cytoskeleton, while a higher affinity conformer was coupled to the viscous elements of the cell membrane. Within 100 ms of contact, THP-1 cells, stimulated by co-immobilized MCP-1, exhibited a tremendous increase in adhesion to VCAM-1. Enhanced cell adhesion was accompanied by a local decoupling of the cell membrane from the cytoskeleton and the formation of long membrane tethers. The tethers were individually anchored by multiple α4β1/VCAM-1 complexes that prolonged the extension of the viscous tethers. In vivo, the formation of these membrane tethers may provide the quantal structural units for the arrest of rolling monocytes within the blood vessels.

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.

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

Brownian motion of tethered nanowires.

Science.gov (United States)

Ota, Sadao; Li, Tongcang; Li, Yimin; Ye, Ziliang; Labno, Anna; Yin, Xiaobo; Alam, Mohammad-Reza; Zhang, Xiang

2014-05-01

Brownian motion of slender particles near a boundary is ubiquitous in biological systems and in nanomaterial assembly, but the complex hydrodynamic interaction in those systems is still poorly understood. Here, we report experimental and computational studies of the Brownian motion of silicon nanowires tethered on a substrate. An optical interference method enabled direct observation of microscopic rotations of the slender bodies in three dimensions with high angular and temporal resolutions. This quantitative observation revealed anisotropic and angle-dependent hydrodynamic wall effects: rotational diffusivity in inclined and azimuth directions follows different power laws as a function of the length, ∼ L(-2.5) and ∼ L(-3), respectively, and is more hindered for smaller inclined angles. In parallel, we developed an implicit simulation technique that takes the complex wire-wall hydrodynamic interactions into account efficiently, the result of which agreed well with the experimentally observed angle-dependent diffusion. The demonstrated techniques provide a platform for studying the microrheology of soft condensed matters, such as colloidal and biological systems near interfaces, and exploring the optimal self-assembly conditions of nanostructures.

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.

Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

KAUST Repository

Agarwal, Praveen

2012-12-01

Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered to nanoparticles and find that even conventionally unentangled chains manifest dynamical features similar to entangled, long-chain molecules. Our findings are shown to imply that crowding and confinement of polymers on particles produce topological constraints analogous to those in entangled systems. © 2012 American Physical Society.

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

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.

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.

DECK: Distance and environment-dependent, coarse-grained, knowledge-based potentials for protein-protein docking

Directory of Open Access Journals (Sweden)

Vakser Ilya A

2011-07-01

Full Text Available Abstract Background Computational approaches to protein-protein docking typically include scoring aimed at improving the rank of the near-native structure relative to the false-positive matches. Knowledge-based potentials improve modeling of protein complexes by taking advantage of the rapidly increasing amount of experimentally derived information on protein-protein association. An essential element of knowledge-based potentials is defining the reference state for an optimal description of the residue-residue (or atom-atom pairs in the non-interaction state. Results The study presents a new Distance- and Environment-dependent, Coarse-grained, Knowledge-based (DECK potential for scoring of protein-protein docking predictions. Training sets of protein-protein matches were generated based on bound and unbound forms of proteins taken from the DOCKGROUND resource. Each residue was represented by a pseudo-atom in the geometric center of the side chain. To capture the long-range and the multi-body interactions, residues in different secondary structure elements at protein-protein interfaces were considered as different residue types. Five reference states for the potentials were defined and tested. The optimal reference state was selected and the cutoff effect on the distance-dependent potentials investigated. The potentials were validated on the docking decoys sets, showing better performance than the existing potentials used in scoring of protein-protein docking results. Conclusions A novel residue-based statistical potential for protein-protein docking was developed and validated on docking decoy sets. The results show that the scoring function DECK can successfully identify near-native protein-protein matches and thus is useful in protein docking. In addition to the practical application of the potentials, the study provides insights into the relative utility of the reference states, the scope of the distance dependence, and the coarse-graining of

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.

Spontaneous mutation of Dock7 results in lower trabecular bone mass and impaired periosteal expansion in aged female Misty mice.

Science.gov (United States)

Le, Phuong T; Bishop, Kathleen A; Maridas, David E; Motyl, Katherine J; Brooks, Daniel J; Nagano, Kenichi; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

2017-12-01

adipocytes were elevated 3.5 fold over +/+ (p=0.014). Consistent with reduced bone formation, osteoblast gene expression of Alp, Col1a1, Runx-2, Sp7, and Bglap was significantly decreased in m/m whole bone. Furthermore, markers of osteoclasts were either unchanged or suppressed. Bone marrow stromal cell migration and motility were inhibited in culture and changes in senescence markers suggest that osteoblast function may also be inhibited with loss of Dock7 expression in m/m. Finally, increased Oil Red O staining in m/m ear mesenchymal stem cells during adipogenesis highlights a potential shift of cells from the osteogenic to adipogenic lineages. In summary, loss of Dock7 in the aging m/m resulted in an impairment of periosteal and endocortical envelope expansion, but did not alter age-related trabecular bone loss. These studies establish Dock7 as a critical regulator of both cortical and trabecular bone mass, and demonstrate for the first time a novel role of Dock7 in modulating compensatory changes in the periosteum with aging. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

DEFF Research Database (Denmark)

Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas

2009-01-01

of numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites......, the activation loop and the Z/TM in the C-terminal extension. We provide evidence that phosphorylation of the Z/TM site of PRK2 inhibits its interaction with PDK1. Our studies further provide a mechanistic model to explain different steps in the docking interaction and regulation. Interestingly, we found...... that the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2 and do...

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.

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.

Role of Double-Strand Break End-Tethering during Gene Conversion in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Suvi Jain

2016-04-01

Full Text Available Correct repair of DNA double-strand breaks (DSBs is critical for maintaining genome stability. Whereas gene conversion (GC-mediated repair is mostly error-free, repair by break-induced replication (BIR is associated with non-reciprocal translocations and loss of heterozygosity. We have previously shown that a Recombination Execution Checkpoint (REC mediates this competition by preventing the BIR pathway from acting on DSBs that can be repaired by GC. Here, we asked if the REC can also determine whether the ends that are engaged in a GC-compatible configuration belong to the same break, since repair involving ends from different breaks will produce potentially deleterious translocations. We report that the kinetics of repair are markedly delayed when the two DSB ends that participate in GC belong to different DSBs (termed Trans compared to the case when both DSB ends come from the same break (Cis. However, repair in Trans still occurs by GC rather than BIR, and the overall efficiency of repair is comparable. Hence, the REC is not sensitive to the "origin" of the DSB ends. When the homologous ends for GC are in Trans, the delay in repair appears to reflect their tethering to sequences on the other side of the DSB that themselves recombine with other genomic locations with which they share sequence homology. These data support previous observations that the two ends of a DSB are usually tethered to each other and that this tethering facilitates both ends encountering the same donor sequence. We also found that the presence of homeologous/repetitive sequences in the vicinity of a DSB can distract the DSB end from finding its bona fide homologous donor, and that inhibition of GC by such homeologous sequences is markedly increased upon deleting Sgs1 but not Msh6.

Tether-directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

Directory of Open Access Journals (Sweden)

Cox Liam R

2007-02-01

Full Text Available Abstract Background Using a silyl tether to unite an aldehyde electrophile and allylsilane nucleophile into a single molecule allows a subsequent Lewis-acid-mediated allylation to proceed in an intramolecular sense and therefore receive all the benefits associated with such processes. However, with the ability to cleave the tether post allylation, a product that is the result of a net intermolecular reaction can be obtained. In the present study, four diastereoisomeric β-silyloxy-α-methyl aldehydes, which contain an allylsilane tethered through the β-carbinol centre, have been prepared, in order to probe how the relative configuration of the two stereogenic centres affects the efficiency and selectivity of the intramolecular allylation. Results Syn-aldehydes, syn-4a and syn-4b, both react poorly, affording all four possible diastereoisomeric oxasilacycle products. In contrast, the anti aldehydes anti-4a and anti-4b react analogously to substrates that lack substitution at the α-site, affording only two of the four possible allylation products. Conclusion The outcome of the reaction with anti-aldehydes is in accord with reaction proceeding through a chair-like transition state (T.S.. In these systems, the sense of 1,3-stereoinduction can be rationalised by the aldehyde electrophile adopting a pseudoaxial orientation, which will minimise dipole-dipole interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent α to the reacting carbonyl group to adopt an unfavourable pseudoaxial position. It is therefore proposed that these substrates react through poorly-defined T.S.s and consequently exhibit essentially no stereoselectivity.

Stabilized platform for tethered balloon soundings of broadband long- and short-wave radiation

International Nuclear Information System (INIS)

Alzheimer, J.M.; Anderson, G.A.; Whiteman, C.D.

1993-01-01

Changes in the composition of trace gases in the earth's atmosphere have been reported by many observers, and a general concern has been expressed regarding possible changes to the earth's climate that may be caused by radiatively active gases introduced into the earth's atmosphere by man's activities. Radiatively active trace gases produce temperature changes in the earth's atmosphere through changes in radiative flux divergence. Our knowledge of and means of measuring radiative flux divergence is very limited. A few observations of vertical radiative flux divergences have been reported from aircraft from radiometersondes from towers and from large tethered balloons. These measurement techniques suffers from one or more drawbacks, including shallow sounding depths (towers), high cost (aircraft), complicated logistics (large tethered balloons), and limitation to nighttime hours (radiometersondes). Changes in radiative flux divergence caused by anthropogenic trace gases are expected to be quite small, and will be difficult to measure with existing broadband radiative flux instruments. The emphasis of present research in global climate change is thus being focused on improving radiative transfer algorithms in global climate models. The radiative parameterizations in these models are at an early stage of development and information is needed regarding their performance, especially in cloudy conditions. The impetus for the research reported in this paper is the need for a device that can supplement existing means of measuring vertical profiles of long- and short-wave irradiance and radiative flux divergence. We have designed a small tethered-balloon-based system that can make radiometric soundings through the atmospheric boundary layer. This paper discusses the concept, the design considerations, and the design and construction of this sounding system. The performance of the system will be tested in a series of balloon flights scheduled for the fall and winter of 1992

Significance of relative velocity in drag force or drag power estimation for a tethered float

Digital Repository Service at National Institute of Oceanography (India)

Vethamony, P.; Sastry, J.S.

There is difference in opinion regarding the use of relative velocity instead of particle velocity alone in the estimation of drag force or power. In the present study, a tethered spherical float which undergoes oscillatory motion in regular waves...

A magnetic tether system to investigate visual and olfactory mediated flight control in Drosophila.

Science.gov (United States)

Duistermars, Brian J; Frye, Mark

2008-11-21

It has been clear for many years that insects use visual cues to stabilize their heading in a wind stream. Many animals track odors carried in the wind. As such, visual stabilization of upwind tracking directly aids in odor tracking. But do olfactory signals directly influence visual tracking behavior independently from wind cues? Also, the recent deluge of research on the neurophysiology and neurobehavioral genetics of olfaction in Drosophila has motivated ever more technically sophisticated and quantitative behavioral assays. Here, we modified a magnetic tether system originally devised for vision experiments by equipping the arena with narrow laminar flow odor plumes. A fly is glued to a small steel pin and suspended in a magnetic field that enables it to yaw freely. Small diameter food odor plumes are directed downward over the fly's head, eliciting stable tracking by a hungry fly. Here we focus on the critical mechanics of tethering, aligning the magnets, devising the odor plume, and confirming stable odor tracking.

Tethered Balloon Technology in Design Solutions for Rescue and Relief Team Emergency Communication Services.

Science.gov (United States)

Alsamhi, Saeed Hamood; Ansari, Mohd Samar; Ma, Ou; Almalki, Faris; Gupta, Sachin Kumar

2018-05-23

The actions taken at the initial times of a disaster are critical. Catastrophe occurs because of terrorist acts or natural hazards which have the potential to disrupt the infrastructure of wireless communication networks. Therefore, essential emergency functions such as search, rescue, and recovery operations during a catastrophic event will be disabled. We propose tethered balloon technology to provide efficient emergency communication services and reduce casualty mortality and morbidity for disaster recovery. The tethered balloon is an actively developed research area and a simple solution to support the performance, facilities, and services of emergency medical communication. The most critical requirement for rescue and relief teams is having a higher quality of communication services which enables them to save people's lives. Using our proposed technology, it has been reported that the performance of rescue and relief teams significantly improved. OPNET Modeler 14.5 is used for a network simulated with the help of ad hoc tools (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

Analysis of tethered balloon data from San Nicolas Island on 8 July 1987

Science.gov (United States)

Cox, Stephen K.; Duda, David P.; Guinn, Thomas A.; Johnson-Pasqua, Christopher M.; Schubert, Wayne H.; Snider, Jack B.

1990-01-01

Analysis of the 8 July 1987 (Julian Day 189) tethered balloon flight from San Nicolas Island is summarized. The flight commenced at about 14:30 UTC (7:30 Pacific Daylight Time) and lasted six and one-half hours. The position of the Colorado State University (CSU) instrument package as a function of time is shown. For the purpose of presentation of results, researchers divided the flight into 13 legs. These legs consist of 20 minute constant level runs, with the exception of leg 1, which is a sounding from the surface to just above 930 mb. The laser ceilometer record of cloud base is also shown. The cloud base averaged around 970 mb during much of the flight but was more variable near the end. Before the tethered balloon flight commenced, a Communications Link Analysis and Simulation System (CLASS) sounding was released at 12:11 UTC (5:11 PDT). Temperature and moisture data below 927 mb for this sounding is shown. The sounding indicates a cloud top around 955 mb at this time.

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

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.

Flexural Stiffness of Myosin Va Subdomains as Measured from Tethered Particle Motion

Science.gov (United States)

Michalek, Arthur J.; Kennedy, Guy G.; Warshaw, David M.; Ali, M. Yusuf

2015-01-01

Myosin Va (MyoVa) is a processive molecular motor involved in intracellular cargo transport on the actin cytoskeleton. The motor's processivity and ability to navigate actin intersections are believed to be governed by the stiffness of various parts of the motor's structure. Specifically, changes in calcium may regulate motor processivity by altering the motor's lever arm stiffness and thus its interhead communication. In order to measure the flexural stiffness of MyoVa subdomains, we use tethered particle microscopy, which relates the Brownian motion of fluorescent quantum dots, which are attached to various single- and double-headed MyoVa constructs bound to actin in rigor, to the motor's flexural stiffness. Based on these measurements, the MyoVa lever arm and coiled-coil rod domain have comparable flexural stiffness (0.034 pN/nm). Upon addition of calcium, the lever arm stiffness is reduced 40% as a result of calmodulins potentially dissociating from the lever arm. In addition, the flexural stiffness of the full-length MyoVa construct is an order of magnitude less stiff than both a single lever arm and the coiled-coil rod. This suggests that the MyoVa lever arm-rod junction provides a flexible hinge that would allow the motor to maneuver cargo through the complex intracellular actin network. PMID:26770194

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) ...

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...

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

Estimation of added-mass and damping coefficients of a tethered spherical float using potential flow theory

Digital Repository Service at National Institute of Oceanography (India)

Vethamony, P.; Chandramohan, P.; Sastry, J.S.; Narasimhan, S.

Added-mass (alpha) and damping coefficients (beta) of a tethered spherical float, undergoing oscillatory motion in sinusoidal waves, have been derived from the motion generated velocity potential for one degree-of-freedom (surge) using potential...

Palladium-Catalyzed Tandem Oxidative Arylation/Olefination of Aromatic Tethered Alkenes/Alkynes.

Science.gov (United States)

Gao, Yang; Gao, Yinglan; Wu, Wanqing; Jiang, Huanfeng; Yang, Xiaobo; Liu, Wenbo; Li, Chao-Jun

2017-01-18

We describe herein a palladium-catalyzed tandem oxidative arylation/olefination reaction of aromatic tethered alkenes/alkynes for the synthesis of dihydrobenzofurans and 2 H-chromene derivatives. This reaction features a 1,2-difunctionalization of C-C π-bond with two C-H bonds using O 2 as terminal oxidant at room temperature. The products obtained are valuable synthons and important scaffolds in biological agents and natural products. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

GREEN: A program package for docking studies in rational drug design

Science.gov (United States)

Tomioka, Nobuo; Itai, Akiko

1994-08-01

A program package, GREEN, has been developed that enables docking studies between ligand molecules and a protein molecule. Based on the structure of the protein molecule, the physical and chemical environment of the ligand-binding site is expressed as three-dimensional grid-point data. The grid-point data are used for the real-time evaluation of the protein-ligand interaction energy, as well as for the graphical representation of the binding-site environment. The interactive docking operation is facilitated by various built-in functions, such as energy minimization, energy contribution analysis and logging of the manipulation trajectory. Interactive modeling functions are incorporated for designing new ligand molecules while considering the binding-site environment and the protein-ligand interaction. As an example of the application of GREEN, a docking study is presented on the complex between trypsin and a synthetic trypsin inhibitor. The program package will be useful for rational drug design, based on the 3D structure of the target protein.

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.

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。

RIM, Munc13, and Rab3A interplay in acrosomal exocytosis

Energy Technology Data Exchange (ETDEWEB)

Bello, Oscar D.; Zanetti, M. Natalia [Laboratorio de Biologia Celular y Molecular, Instituto de Histologia y Embriologia, IHEM (CONICET-UNCuyo), Facultad de Ciencias Medicas (Argentina); Laboratorio de Biologia Reproductiva, Instituto de Histologia y Embriologia, IHEM (CONICET-UNCuyo), Facultad de Ciencias Medicas (Argentina); Mayorga, Luis S. [Laboratorio de Biologia Celular y Molecular, Instituto de Histologia y Embriologia, IHEM (CONICET-UNCuyo), Facultad de Ciencias Medicas (Argentina); Michaut, Marcela A., E-mail: mmichaut@fcm.uncu.edu.ar [Laboratorio de Biologia Reproductiva, Instituto de Histologia y Embriologia, IHEM (CONICET-UNCuyo), Facultad de Ciencias Medicas (Argentina); Instituto de Ciencias Basicas, Universidad Nacional de Cuyo, Mendoza (5500) (Argentina)

2012-03-10

Exocytosis is a highly regulated, multistage process consisting of multiple functionally definable stages, including recruitment, targeting, tethering, priming, and docking of secretory vesicles with the plasma membrane, followed by calcium-triggered membrane fusion. The acrosome reaction of spermatozoa is a complex, calcium-dependent regulated exocytosis. Fusion at multiple sites between the outer acrosomal membrane and the cell membrane causes the release of the acrosomal contents and the loss of the membranes surrounding the acrosome. Not much is known about the molecules that mediate membrane docking in this particular fusion model. In neurons, the formation of the ternary RIM/Munc13/Rab3A complex has been suggested as a critical component of synaptic vesicles docking. Previously, we demonstrated that Rab3A localizes to the acrosomal region in human sperm, stimulates acrosomal exocytosis, and participates in an early stage during membrane fusion. Here, we report that RIM and Munc13 are also present in human sperm and localize to the acrosomal region. Like Rab3A, RIM and Munc13 participate in a prefusion step before the efflux of intra-acrosomal calcium. By means of a functional assay using antibodies and recombinant proteins, we show that RIM, Munc13 and Rab3A interplay during acrosomal exocytosis. Finally, we report by electron transmission microscopy that sequestering RIM and Rab3A alters the docking of the acrosomal membrane to the plasma membrane during calcium-activated acrosomal exocytosis. Our results suggest that the RIM/Munc13/Rab3 A complex participates in acrosomal exocytosis and that RIM and Rab3A have central roles in membrane docking. -- Highlights: Black-Right-Pointing-Pointer RIM and Munc13 are present in human sperm and localize to the acrosomal region. Black-Right-Pointing-Pointer RIM and Munc13 are necessary for acrosomal exocytosis. Black-Right-Pointing-Pointer RIM and Munc13 participate before the acrosomal calcium efflux. Black

Tethered capsule OCT endomicroscopy: from bench to bedside at the primary care office (Conference Presentation)

Science.gov (United States)

Gora, Michalina J.; Simmons, Leigh H.; Tiernan, Aubrey R.; Grant, Catriona N.; Soomro, Amna R.; Walker Corkery, Elizabeth S.; Rosenberg, Mireille; Metlay, Joshua P.; Tearney, Guillermo J.

2016-03-01

We have developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires microscopic images of the entire esophagus in unsedated subjects in a quick and comfortable procedure. To test its capabilities of TCE to become a population-based screening device, we conducted a clinical feasibility study in the primary care office. The swept-source OCT imaging system (1310nm central wavelength, 40kHz A-line rate, 10um axial resolution) together with the tethered capsule catheter (11x25mm capsule attached to a flexible tether) were transferred to the PCP office where unsedated patients scheduled for non-urgent PCP visits swallowed the capsule and microscopic OCT images of the entire esophagus were collected. After the whole length of the esophagus was imaged, the catheter was disinfected for reuse. Twenty subjects were enrolled in the study, including nine female and eleven male. All TCE procedures were performed by a nurse and lasted in average 5:42 ± 1:54 min. High-resolution images of the esophagus were obtained in all seventeen subjects that swallowed the capsule. Our clinical experience in this cohort, subject feedback, image quality, and technological adaptations for efficient utilization in this setting will be presented. The ease and simplicity of the procedure combined with high quality of the images demonstrate the potential for this technology to become a population-based screening device. Technology limitations and future development guided by findings from this initial experience will be discussed with the goal of effectively translating TCE to the outpatient primary care setting.

Targeting IL-17 AND IL-17D receptors of rheumatoid arthritis using phytocompounds: A Molecular Docking study

Science.gov (United States)

Thabitha, A.; Thoufic Ali, A. M. Mohamed; Shweta Kumari, Singh; Rakhi; Swami, Varsha; Mohana Priya, A.; Sajitha Lulu, S.

2017-11-01

Rheumatoid arthritis (RA) is a chronic autoimmune condition of the connective tissue in synovial joints, characterized by inflammation which can lead to bone and cartilage destruction. IL-17 and IL-17D cytokines produced by a number of cell types, primarily promote pro-inflammatory immune responses and negative regulator in fibroblast growth factor signalling. Thus, the promising therapeutic strategies focus on targeting these cytokines, which has led to the identification of effective inhibitors. However, several studies focused on identifying the anti-arthritic potential of natural compounds. Therefore, in the present study we undertook in silico investigations to decipher the anti-inflammatory prospective of phytocompounds by targeting IL-17 and IL-17D cytokines using Patch Dock algorithm. Additionally, IL-17 and IL-17D proteins structure were modelled and validated for molecular docking study. Further, phytocompounds based on anti-inflammatory property were subjected to Lipinski filter and ADMET properties indicated that all of these compounds showed desirable drug-like criteria. The outcome of this investigation sheds light on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA.

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.

ReFlexIn: a flexible receptor protein-ligand docking scheme evaluated on HIV-1 protease.

Directory of Open Access Journals (Sweden)

Simon Leis

Full Text Available For many targets of pharmaceutical importance conformational changes of the receptor protein are relevant during the ligand binding process. A new docking approach, ReFlexIn (Receptor Flexibility by Interpolation, that combines receptor flexibility with the computationally efficient potential grid representation of receptor molecules has been evaluated on the retroviral HIV-1 (Human Immunodeficiency Virus 1 protease system. An approximate inclusion of receptor flexibility is achieved by using interpolation between grid representations of individual receptor conformations. For the retroviral protease the method was tested on an ensemble of protease structures crystallized in the presence of different ligands and on a set of structures obtained from morphing between the unbound and a ligand-bound protease structure. Docking was performed on ligands known to bind to the protease and several non-binders. For the binders the ReFlexIn method yielded in almost all cases ligand placements in similar or closer agreement with experiment than docking to any of the ensemble members without degrading the discrimination with respect to non-binders. The improved docking performance compared to docking to rigid receptors allows for systematic virtual screening applications at very small additional computational cost.

On the escape transition of a tethered Gaussian chain; exact results in two conjugate ensembles

NARCIS (Netherlands)

Skvortsov, A.M.; Klushin, L.I.; Leermakers, F.A.M.

2006-01-01

Upon compression between two pistons an end-tethered polymer chain undergoes an abrupt transition from a confined coil state to an inhomogeneous flower-like conformation that is partially escaped from the gap. In the thermodynamic limit the system demonstrates a first-order phase transition. A

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.

Design and Operation of Automated Ice-Tethered Profilers for Real-Time Seawater Observations in the Polar Oceans

National Research Council Canada - National Science Library

Toole, J; Proshutinsky, A; Krishfield, R; Doherty, K; Frye, Daniel E; Hammar, T; Kemp, J; Peters, D; Heydt, K. von der

2006-01-01

An automated, easily-deployed Ice-Tethered Profiler (ITP) has been developed for deployment on perennial sea ice in polar oceans to measure changes in upper ocean temperature and salinity in all seasons...

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

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...

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

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....

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.

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.

Tethered cord in patients affected by anorectal malformations: a survey from the ARM-Net Consortium

NARCIS (Netherlands)

Fanjul, M.; Samuk, I.; Bagolan, P.; Leva, E.; Sloots, C.; Gine, C.; Aminoff, D.; Midrio, P.; Blaauw, I. de; Marcelis, C.L.M.; Rooij, I.A.L.M. van; Wester, T.; Zwink, N.

2017-01-01

PURPOSE: The goal of this study was to determine the degree of consensus in the management of spinal cord tethering (TC) in patients with anorectal malformation (ARM) in a large cohort of European pediatric centers. METHODS: A survey was sent to pediatric surgeons (one per center) members of the

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.

A tethered balloon system for observation of atmospheric temperature inversion

International Nuclear Information System (INIS)

Hayashi, Takashi; Kakuta, Michio

1979-05-01

In environmental assessment of near-shore nuclear plants, information is often required on the development of internal boundary layer (IBL) and associated fumigation condition. Single tower data is not sufficient to clarify the site-dependent IBL structure that affects the atmospheric diffusion in shoreline-stack-site boundary complex. A tethered balloon system has been developed, which comprises a fixed point kitoon and a car-borne small balloon. The system enables us to measure the detailed time-space distribution of temperature without much man-power. The system and example of field observations with it are described. (author)

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.

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.

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.

An autonomous rendezvous and docking system using cruise missile technologies