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Sample records for regulating tethering docking

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

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

    2010-01-01

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

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

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    Elena O Gracheva

    2010-10-01

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

  3. Autonomous Vision-Based Tethered-Assisted Rover Docking

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

    2013-01-01

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

  4. The secret life of tethers: the role of tethering factors in SNARE complex regulation

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    Michelle L Dubuke

    2016-05-01

    Full Text Available Trafficking in eukaryotic cells is a tightly regulated process to ensure correct cargo delivery to the proper destination organelle or plasma membrane. In this review, we focus on how the vesicle fusion machinery, the SNARE complex, is regulated by the interplay of the multisubunit tethering complexes (MTC with the SNAREs and Sec1/Munc18 (SM proteins. Although these factors are used in different stages of membrane trafficking, e.g. Golgi to plasma membrane transport vs vacuolar fusion, and in a variety of diverse eukaryotic cell types, many commonalities between their functions are being revealed. We explore the various protein-protein interactions and findings from functional reconstitution studies in order to highlight both their common features and the differences in their modes of regulation. These studies serve as a starting point for mechanistic explorations in other systems.

  5. 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.

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

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    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.

  7. The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering

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    Çamdere, Gamze; Guacci, Vincent; Stricklin, Jeremiah; Koshland, Douglas

    2015-01-01

    Cohesin tethers together regions of DNA, thereby mediating higher order chromatin organization that is critical for sister chromatid cohesion, DNA repair and transcriptional regulation. Cohesin contains a heterodimeric ATP-binding Cassette (ABC) ATPase comprised of Smc1 and Smc3 ATPase active sites. These ATPases are required for cohesin to bind DNA. Cohesin’s DNA binding activity is also promoted by the Eco1 acetyltransferase and inhibited by Wpl1. Recently we showed that after cohesin stably binds DNA, a second step is required for DNA tethering. This second step is also controlled by Eco1 acetylation. Here, we use genetic and biochemical analyses to show that this second DNA tethering step is regulated by cohesin ATPase. Furthermore, our results also suggest that Eco1 promotes cohesion by modulating the ATPase cycle of DNA-bound cohesin in a state that is permissive for DNA tethering and refractory to Wpl1 inhibition. DOI: http://dx.doi.org/10.7554/eLife.11315.001 PMID:26583750

  8. Emerging insights into the roles of membrane tethers from analysis of whole organisms: The tip of an iceberg?

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    Wei Hong eToh

    2016-02-01

    Full Text Available Membrane tethers have been identified throughout different compartments of the endomembrane system. It is now well established that a number of membrane tethers mediate docking of membrane carriers in anterograde and retrograde transport and in regulating the organization of membrane compartments. Much of our information on membrane tethers have been obtained from the analysis of individual membrane tethers in cultured cells. In the future it will be important to better appreciate the network of interactions mediated by tethers and the potential co-ordination of their collective functions in vivo. There are now a number of studies which have analyzed membrane tethers in tissues and organisms which are providing new insights into the role of this class of membrane protein at the physiological level. Here we review recent advances in the understanding of the function of membrane tethers from knock outs (or knock downs in whole organisms and from mutations in tethers associated with disease.

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

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    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.

  10. Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling.

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    Wu, Chia-Lun; Buszard, Bree; Teng, Chun-Hung; Chen, Wei-Lin; Warr, Coral G; Tiganis, Tony; Meng, Tzu-Ching

    2011-10-01

    PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

  11. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

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    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  12. ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology.

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    Manford, Andrew G; Stefan, Christopher J; Yuan, Helen L; Macgurn, Jason A; Emr, Scott D

    2012-12-11

    Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic approach, we identified three families of ER-PM tethering proteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, orthologs of the extended synaptotagmins), and Scs2 and Scs22 (vesicle-associated membrane protein-associated proteins). Loss of all six tethering proteins results in the separation of the ER from the PM and the accumulation of cytoplasmic ER. Importantly, we find that phosphoinositide signaling is misregulated at the PM, and the unfolded protein response is constitutively activated in the ER in cells lacking ER-PM tether proteins. These results reveal critical roles for ER-PM contacts in cell signaling, organelle morphology, and ER function. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Discovery of C-3 Tethered 2-oxo-benzo[1,4]oxazines as Potent Antioxidants: Bio-Inspired Based Design, Synthesis, Biological Evaluation, Cytotoxic, and in Silico Molecular Docking Studies

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    Vashundhra Sharma

    2018-03-01

    Full Text Available The discovery of C-3 tethered 2-oxo-benzo[1,4]oxazines as potent antioxidants is disclosed. All the analogs 20a-20ab have been synthesized via “on water” ultrasound-assisted irradiation conditions in excellent yields (upto 98%. All the compounds have been evaluated for their in vitro antioxidant activities using DPPH free radical scavenging assay as well as FRAP assay. The result showed promising antioxidant activities having IC50 values in the range of 4.74 ± 0.08 to 92.20 ± 1.54 μg/mL taking ascorbic acid (IC50 = 4.57 μg/mL as standard reference. In this study, compounds 20b and 20t, the most active compound of the series, showed IC50 values of 6.89 ± 0.07 μg/mL and 4.74 ± 0.08 μg/mL, respectively in comparison with ascorbic acid. In addition, the detailed SAR study shows that electron-withdrawing group increases antioxidant activity and vice versa. Furthermore, in the FRAP assay, eight compounds (20c, 20j, 20m, 20n, 20r, 20u, 20z, and 20aa were found more potent than standard reference BHT (C0.5FRAP = 546.0 ± 13.6 μM. The preliminary cytotoxic study reveals the non-toxic nature of active compounds 20b and 20t in non-cancerous 3T3 fibroblast cell lines in MTT assay up to 250 μg/mL concentration. The results were validated via carrying out in silico molecular docking studies of promising compounds 20a, 20b, and 20t in comparison with standard reference. To the best of our knowledge, this is the first detailed study of C-3 tethered 2-oxo-benzo[1,4]oxazines as potential antioxidant agents.

  14. Silencing of dedicator of cytokinesis (DOCK180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (AIRE).

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    Mohan, Jasna Jagan; Narayan, Prashanth; Padmanabhan, Renjini Ambika; Joseph, Selin; Kumar, Pradeep G; Laloraya, Malini

    2018-03-08

    Dedicator of cytokinesis (DOCK 180) involved in cytoskeletal reorganization is primarily a cytosolic molecule. It is recently shown to be nuclear in HeLa cells but its nuclear function is not known. The spatiotemporal distribution of DOCK180 in uterus was studied in uterine cytoplasmic and nuclear compartments during the "window of implantation." The functional significance of nuclear DOCK180 was explored by homology modeling, co-immunoprecipitation assays, and mass spectrometric analysis. Dock180's role in early pregnancy was ascertained by Dock 180 silencing and subsequent quantitative real-time PCR and Western blotting analysis. Our study shows a nuclear DOCK180 in the uterus during "window of implantation." Estrogen and progesterone mediate expression and nuclear translocation of DOCK180. The nuclear function of DOCK180 is attributed to its ability to import autoimmune regulator (AIRE) into the nucleus. Silencing of Dock180 inhibited AIRE nuclear shuttling which influenced its downstream targets, thereby affecting decidualization with AIRE and HOXA-10 as the major players as well as lack of implantation site formation due to impact on angiogenesis-associated genes. DOCK180 has an indispensable role in pregnancy establishment as knocking down Dock180 abrogates pregnancy by a consolidated impact on decidualization and angiogenesis by regulating AIRE nuclear entry. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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    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.

  16. Activated Cdc42 kinase regulates Dock localization in male germ cells during Drosophila spermatogenesis.

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    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.

  17. Molecular docking.

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    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.

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

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    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

  19. Tethering sockets and wrenches

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    Johnson, E. P.

    1990-01-01

    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.

  20. Tethering sockets and wrenches

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    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.

  1. CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling.

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    Cui, Hong-Yong; Wang, Shi-Jie; Miao, Ji-Yu; Fu, Zhi-Guang; Feng, Fei; Wu, Jiao; Yang, Xiang-Min; Chen, Zhi-Nan; Jiang, Jian-Li

    2016-02-02

    The acquisition of inappropriate migratory feature is crucial for tumor metastasis. It has been suggested that CD147 and Annexin A2 are involved in regulating tumor cell movement, while the regulatory mechanisms are far from clear. In this study, we demonstrated that CD147 physically interacted with the N-terminal domain of Annexin A2 and decreased Annexin A2 phosphorylation on tyrosine 23. In vitro kinase assay showed that the I domain of CD147 was indispensable for CD147-mediated downregulation of Annexin A2 phosphorylation by Src. Furthermore, we determined that p-Annexin A2 promoted the expression of dedicator of cytokinesis 3 (DOCK3) and DOCK3 blocked β-catenin nuclear translocation, resulting in inhibition of β-catenin signaling. In addition, DOCK3 inhibited lamellipodium dynamics and tumor cell movement. Also, we found that β-catenin signaling increased WAVE2 expression. Therefore, DOCK3 was characterized as a negative regulator of WAVE2 expression via inhibiting β-catenin signaling. Our study provides the first evidence that CD147 promotes tumor cell movement and metastasis via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling axis.

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

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    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.

  3. Why Not Space Tethers?

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    Stone, Noble H.

    2007-01-01

    The Tethered Satellite System Space Shuttle missions, TSS-1 in 1993 and TSS-1R in 1996, were the height of space tether technology development. Since NASA's investment of some $200M and two Shuttle missions in those two pioneering missions, there have been several smaller tether flight experiments, but interest in this promising technology has waned within NASA as well as the DOD agencies. This is curious in view of the unique capabilities of space tether systems and the fact that they have been flight validated and shown to perform as, or better than, expected in earth orbit. While it is true that the TSS-1, TSS-1R and SEDS-2 missions experienced technical difficulties, the causes of these early developmental problems are now known to be design or materials flaws that are (1) unrelated to the basic viability of space tether technology, and (2) they are readily corrected. The purpose of this paper is to review the dynamic and electrodynamic fundamentals of space tethers and the unique capabilities they afford (that are enabling to certain types of space missions); to elucidate the nature, cause, and solution of the early developmental problems; and to provide an update on progress made in development of the technology. Finally, it is shown that (1) all problems experienced during early development of the technology now have solutions; and (2) the technology has been matured by advances made in strength and robustness of tether materials, high voltage engineering in the space environment, tether health and status monitoring, and the elimination of the broken tether hazard. In view of this, it is inexplicable why this flight-validated technology has not been utilized in the past decade, considering the powerful and unique capabilities that space tethers can afford that are, not only required to carryout, otherwise, unobtainable missions, but can also greatly reduce the cost of certain on-going space operations.

  4. Two Tethered Balloon Systems

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    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.

  5. Tether Deployer And Brake

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    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.

  6. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

    OpenAIRE

    Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

    2012-01-01

    CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

  7. 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.

  8. Tethers in Space

    Science.gov (United States)

    Johnson, Les; Bilén, Sven G.; Gilchrist, Brian E.; Krause, Linda Habash

    2017-09-01

    This Special Section of Acta Astronautica contains several peer-reviewed papers selected from among those presented at the Fifth International Conference on Tethers in Space (TiS2016). After a hiatus of 21 years since the last Conference on Tethers in Space, TiS2016 brought together experts, practitioners, and other interested in space tethers and related fields. TiS2016 was held May 24-26, 2016 at The University of Michigan in Ann Arbor, Michigan, U.S.A. Leveraging the hard work of a great many volunteers, the conference co-chairs Prof. Brian Gilchrist and Prof. Sven Bilén welcomed an international contingent with authors from the U.S., Canada, Japan, Spain, China, Finland, Estonia, and Italy. The community provided updates on what has transpired since their last gathering by providing lessons learned; describing new technologies and subsystems; and proposing new tether missions and applications. Papers overviewed de-orbit systems, power generation, orbital maneuvering, momentum capture, debris removal, space tugs, space elevators, collision avoidance, and tether dynamics, among others.

  9. Orbital Propagation of Momentum Exchange Tether Systems

    Science.gov (United States)

    Westerhoff, John

    2002-01-01

    An advanced concept in in-space transportation currently being studied is the Momentum-Exchange/Electrodynamic Reboost Tether System (MXER). The system acts as a large momentum wheel, imparting a Av to a payload in low earth orbit (LEO) at the expense of its own orbital energy. After throwing a payload, the system reboosts itself using an electrodynamic tether to push against Earth's magnetic field and brings itself back up to an operational orbit to prepare for the next payload. The ability to reboost itself allows for continued reuse of the system without the expenditure of propellants. Considering the cost of lifting propellant from the ,ground to LEO to do the same Av boost at $10000 per pound, the system cuts the launch cost of the payload dramatically, and subsequently, the MXER system pays for itself after a small number of missions.1 One of the technical hurdles to be overcome with the MXER concept is the rendezvous maneuver. The rendezvous window for the capture of the payload is on the order of a few seconds, as opposed to traditional docking maneuvers, which can take as long ets necessary to complete a precise docking. The payload, therefore, must be able to match its orbit to meet up with the capture device on the end of the tether at a specific time and location in the future. In order to be able to determine that location, the MXER system must be numerically propagated forward in time to predict where the capture device will be at that instant. It should be kept in mind that the propagation computation must be done faster than real-time. This study focuses on the efforts to find and/or build the tools necessary to numerically propagate the motion of the MXER system as accurately as possible.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2003-09-25

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

  17. 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.

  18. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Somanath, Sangeeta [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Partridge, Christopher J. [Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Churchill Hospital, University of Oxford, Oxford, OX3 7LJ (United Kingdom); Marshall, Catriona [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Rowe, Tony [CSL Limited, 45 Poplar Road, Parkville, Victoria 3052 (Australia); Turner, Mark D., E-mail: mark.turner@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS (United Kingdom)

    2016-04-29

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  19. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    International Nuclear Information System (INIS)

    Somanath, Sangeeta; Partridge, Christopher J.; Marshall, Catriona; Rowe, Tony; Turner, Mark D.

    2016-01-01

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  20. 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.

  1. The Tethered Moon

    Science.gov (United States)

    Zahnle, Kevin; Lupu, Roxana Elena; Dubrovolskis, A. R.

    2014-01-01

    that the Moon's orbit evolves is limited by the modest radiative cooling rate of Earth's atmosphere, which in effect tethers the Moon to the Earth. Consequently the Moon's orbit evolves orders of magnitude more slowly than in conventional models. Slow orbital evolution promotes capture by orbital resonances that may have been important in the Earth-Moon system

  2. 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...

  3. 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.

  4. 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

  5. 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

  6. Two-Way Tether Gun

    Science.gov (United States)

    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.

  7. 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.

  8. Membrane tethering complexes in the endosomal system

    Directory of Open Access Journals (Sweden)

    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.

  9. 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...

  10. 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

  11. Tether dynamics and control results for tethered satellite system's initial flight

    Science.gov (United States)

    Chapel, Jim D.; Flanders, Howard

    The recent Tethered Satellite System-1 (TSS-1) mission has provided a wealth of data concerning the dynamics of tethered systems in space and has demonstrated the effectiveness of operational techniques designed to control these dynamics. In this paper, we review control techniques developed for managing tether dynamics, and discuss the results of using these techniques for the Tethered Satellite System's maiden flight on STS-46. In particular, the flight results of controlling libration dynamics, string dynamics, and slack tether are presented. These results show that tether dynamics can be safely managed. The overall stability of the system was found to be surprisingly good even at relatively short tether lengths. In fact, the system operated in passive mode at a tether length of 256 meters for over 9 hours. Only monitoring of the system was required during this time. Although flight anomalies prevented the planned deployment to 20 km, the extended operations at shorter tether lengths have proven the viability of using tethers in space. These results should prove invaluable in preparing for future missions with tethered objects in space.

  12. 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

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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

  20. 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....

  1. 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.

  2. 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.

  3. Rendezvous and docking tracker

    Science.gov (United States)

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

    1986-01-01

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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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....

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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

  13. 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.

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

    Science.gov (United States)

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

    2011-09-01

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

  15. Self-assembled tethered bimolecular lipid membranes.

    Science.gov (United States)

    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

  16. 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.

  17. 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

  18. 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.

  19. NASA Docking System (NDS) Technical Integration Meeting

    Science.gov (United States)

    Lewis, James L.

    2010-01-01

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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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

  14. 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

  15. 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...

  16. 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

  17. 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

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. DNA Electrochemistry with Tethered Methylene Blue

    Science.gov (United States)

    Pheeney, Catrina G.

    2012-01-01

    Methylene blue (MB′), covalently attached to DNA through a flexible C12 alkyl linker, provides a sensitive redox reporter in DNA electrochemistry measurements. Tethered, intercalated MB′ is reduced through DNA-mediated charge transport; the incorporation of a single base mismatch at position 3, 10, or 14 of a 17-mer causes an attenuation of the signal to 62 ± 3% of the well-matched DNA, irrespective of position in the duplex. The redox signal intensity for MB′–DNA is found to be least 3-fold larger than that of Nile blue (NB)–DNA, indicating that MB′ is even more strongly coupled to the π-stack. The signal attenuation due to an intervening mismatch does, however, depend on DNA film density and the backfilling agent used to passivate the surface. These results highlight two mechanisms for reduction of MB′ on the DNA-modified electrode: reduction mediated by the DNA base pair stack and direct surface reduction of MB′ at the electrode. These two mechanisms are distinguished by their rates of electron transfer that differ by 20-fold. The extent of direct reduction at the surface can be controlled by assembly and buffer conditions. PMID:22512327

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Computational methods for molecular docking

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-31

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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

  15. 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.

  16. 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.

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

    Science.gov (United States)

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

    2018-04-10

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

  18. The t-SNAREs syntaxin4 and SNAP23 but not v-SNARE VAMP2 are indispensable to tether GLUT4 vesicles at the plasma membrane in adipocyte

    International Nuclear Information System (INIS)

    Kawaguchi, Takayuki; Tamori, Yoshikazu; Kanda, Hajime; Yoshikawa, Mari; Tateya, Sanshiro; Nishino, Naonobu; Kasuga, Masato

    2010-01-01

    SNARE proteins (VAMP2, syntaxin4, and SNAP23) have been thought to play a key role in GLUT4 trafficking by mediating the tethering, docking and subsequent fusion of GLUT4-containing vesicles with the plasma membrane. The precise functions of these proteins have remained elusive, however. We have now shown that depletion of the vesicle SNARE (v-SNARE) VAMP2 by RNA interference in 3T3-L1 adipocytes inhibited the fusion of GLUT4 vesicles with the plasma membrane but did not affect tethering of the vesicles to the membrane. In contrast, depletion of the target SNAREs (t-SNAREs) syntaxin4 or SNAP23 resulted in impairment of GLUT4 vesicle tethering to the plasma membrane. Our results indicate that the t-SNAREs syntaxin4 and SNAP23 are indispensable for the tethering of GLUT4 vesicles to the plasma membrane, whereas the v-SNARE VAMP2 is not required for this step but is essential for the subsequent fusion event.

  19. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

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

  20. Vehicle routing with cross-docking

    DEFF Research Database (Denmark)

    Wen, Min; Larsen, Jesper; Clausen, Jens

    2009-01-01

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

  1. 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.

  2. 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.

  3. 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...

  4. 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)

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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 .

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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...

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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)

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Protein docking prediction using predicted protein-protein interface

    Directory of Open Access Journals (Sweden)

    Li Bin

    2012-01-01

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

  1. 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.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    David J. Mellor

    2018-05-01

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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Results from a tethered rocket experiment (Charge-2)

    Science.gov (United States)

    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.

  9. 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.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Paul A. Bates

    2010-09-01

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

  12. A 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.

  13. 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.

  14. 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

  15. 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/.

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Towards ligand docking including explicit interface water molecules.

    Directory of Open Access Journals (Sweden)

    Gordon Lemmon

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

  13. Tethered Transition Metals Promoted Photocatalytic System for Efficient Hydrogen Evolutions

    KAUST Repository

    Takanabe, Kazuhiro; Isimjan, Tayirjan; Yu, Weili; Del Gobbo, Silvano; Xu, Wei

    2015-01-01

    The present invention is directed, at least in part, to a process for improving the efficiency of a photocatalyst (a semiconductor photocatalyst) by tethering (depositing) a metal (e.g., metal ions of a late transition metal, such as nickel) to the semiconductor (photocatalyst) surface through the use of an organic ligand. More specifically, 1,2-ethanedithiol (EDT) functions as an excellent molecular linker (organic ligand) to attach a transition metal complex (e.g., nickel (Ni.sup.2+ ions)) to the semiconductor surface, which can be in the form of a cadmium sulfide surface. The photocatalyst has particular utility in generating hydrogen from H.sub.2S.

  14. Tethered Transition Metals Promoted Photocatalytic System for Efficient Hydrogen Evolutions

    KAUST Repository

    Takanabe, Kazuhiro

    2015-03-05

    The present invention is directed, at least in part, to a process for improving the efficiency of a photocatalyst (a semiconductor photocatalyst) by tethering (depositing) a metal (e.g., metal ions of a late transition metal, such as nickel) to the semiconductor (photocatalyst) surface through the use of an organic ligand. More specifically, 1,2-ethanedithiol (EDT) functions as an excellent molecular linker (organic ligand) to attach a transition metal complex (e.g., nickel (Ni.sup.2+ ions)) to the semiconductor surface, which can be in the form of a cadmium sulfide surface. The photocatalyst has particular utility in generating hydrogen from H.sub.2S.

  15. 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

  16. 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.

  17. 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)

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

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

    OpenAIRE

    Marco Zucca; Pietro Giuseppe Crespi; Nicola Longarini

    2017-01-01

    The paper presents the seismic vulnerability analysis of the military dry dock built in 1861 inside the Messina’s harbor. The study appears very important not only for the relevance of the dry dock itself, but also for its social, military and symbolic role. As a first step, the historical documentation about the dry dock delivered by the Military Technical Office, in charge of its maintenance, was thoroughly examined. This activity was fundamental to understand the construction methods, the ...

  10. Linear Actuator System for the NASA Docking System

    Science.gov (United States)

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

    2017-01-01

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

  11. Circular Orbit Target Capture Using Space Tether-Net System

    Directory of Open Access Journals (Sweden)

    Guang Zhai

    2013-01-01

    Full Text Available The space tether-net system for on-orbit capture is proposed in this paper. In order to research the dynamic behaviors during system deployment, both free and nonfree deployment dynamics in circular orbit are developed; the system motion with respect to Local Vertical and Local Horizontal frame is also researched with analysis and simulation. The results show that in the case of free deployment, the capture net follows curve trajectories due to the relative orbit dynamic perturbation, and the initial deployment velocities are planned by state transformation equations for static and floating target captures; in the case of non-free deployment, the system undergoes an altitude libration along the Local Vertical, and the analytical solutions that describe the attitude libration are obtained by using variable separation and integration. Finally, the dynamics of postdeployment system is also proved marginally stable if the critical initial conditions are satisfied.

  12. DOE Geothermal Data Repository - Tethering Data to Information: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Weers, J.; Anderson, A.

    2014-02-01

    Data are not inherently information. Without context, data are just numbers, figures, names, or points on a line. By assigning context to data, we can validate ideas, form opinions, and generate knowledge. This is an important distinction to information scientists, as we recognize that the context in which we keep our data plays a big part in generating its value. The mechanisms used to assign this context often include their own data, supplemental to the data being described and defining semantic relationships, commonly referred to as metadata. This paper provides the status of the DOE Geothermal Data Repository (DOE GDR), including recent efforts to tether data submissions to information, discusses the important distinction between data and information, outlines a path to generate useful knowledge from raw data, and details the steps taken in order to become a node on the National Geothermal Data System (NGDS).

  13. Tethered and Polymer Supported Bilayer Lipid Membranes: Structure and Function

    Directory of Open Access Journals (Sweden)

    Jakob Andersson

    2016-05-01

    Full Text Available Solid supported bilayer lipid membranes are model systems to mimic natural cell membranes in order to understand structural and functional properties of such systems. The use of a model system allows for the use of a wide variety of analytical tools including atomic force microscopy, impedance spectroscopy, neutron reflectometry, and surface plasmon resonance spectroscopy. Among the large number of different types of model membranes polymer-supported and tethered lipid bilayers have been shown to be versatile and useful systems. Both systems consist of a lipid bilayer, which is de-coupled from an underlying support by a spacer cushion. Both systems will be reviewed, with an emphasis on the effect that the spacer moiety has on the bilayer properties.

  14. 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

  15. Minimally invasive tethered cord release in children: A technical note

    Directory of Open Access Journals (Sweden)

    S. Kağan Başarslan

    2014-03-01

    Full Text Available Tethered cord release is commonly performed in pediatric neurosurgery. Nowadays, minimally invasive procedures are created growing interest due to its highly tolerable nature for surgery. It has been main purpose a minimal damaging on access route and maximum protection of normal structures in surgery. We present a surgical treatment of tethered cord syndrome, by which is provided the cord releasing unlike the many methods being applied with tissue removal. The main advantage of performing this surgery through 2 cm hole is to avoid removing ligamentum flavum and bony structure like lamina in addition to reduce the length of the incision and the related scar tissue. J Clin Exp Invest 2014; 5 (1: 115-117 Technical note: the patient was taken on the operating table in the sitting-prone position, and L5-S1 distance was determined by fluoroscopy. The skin and subcutaneous tissues was passed via a 2 cm vertical incision settled in 0.5 cm laterally from midline. L5-S1 distance and its covering ligamentum flavum are displayed by the guidance of L5 lamina. Williams’s retractor was placed in the distance after fetching microscope. The foregoing procedures are the same with microdiscectomic surgery. By a vertical incision made on the flavum, its both layer was lifted up and hanged with simple suture on the back tissue for a comfortable exposure of the Dura. Thecal sac was opened by 0.5 cm long vertical incision on the Dura after obtaining secure CSF drainage with the help of yellow-tipped syringe needle. With finding by a nerve hook, the phylum was burned and released securely. Then the Dura was sutured primarily for the closure by means of microsurgery instruments, and flavum was laid on it again.

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. Multilevel Parallelization of AutoDock 4.2.

    Science.gov (United States)

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

    2011-04-28

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

  2. 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.

  3. 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...

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

    Science.gov (United States)

    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.

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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,...

  10. 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...

  11. 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...

  12. 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.

  13. 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.

  14. An Effective Approach Control Scheme for the Tethered Space Robot System

    Directory of Open Access Journals (Sweden)

    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.

  15. 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

  16. 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...

  17. 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.

  18. 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

  19. 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 ...

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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

  5. Flow structures around a beetle in a tethered flight

    Science.gov (United States)

    Lee, Boogeon; Oh, Sehyeong; Park, Hyungmin; Choi, Haecheon

    2017-11-01

    In the present study, through a wind-tunnel experiment, we visualize the flow in a tethered flight of a rhinoceros beetle using a smoke-wire visualization technique. Measurements are done at five side planes along the wind span while varying the body angle (angle between the horizontal and the body axis) to investigate the influence of the stroke plane angle that was observed to change depending on the flight mode such as hovering, forward and takeoff flights so on. Observing that a large attached leading-edge vortex is only found on the hindwing, it is inferred that most of the aerodynamic forces would be generated by hindwings (flexible inner wings) compared to the elytra (hard outer wings). In addition, it is observed to use unsteady lift-generating mechanisms such as clap-and-fling, wing-wing interaction and wake capture. Finally, we discuss the relation between the advance ratio and Strouhal number by adjusting free-stream velocity and the body angle (i.e., angle of wake-induced flow). Supported by a Grant to Bio-Mimetic Robot Research Center Funded by Defense Acquisition Program Administration, and by ADD, Korea (UD130070ID).

  6. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N. K.

    2013-10-01

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  7. Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar, E-mail: neelesh81mph@gmail.com; Jain, N. K., E-mail: dr.jnarendr@gmail.com [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-10-15

    In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

  8. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Revisiting the tethered ureteral stents in children: a novel modification.

    Science.gov (United States)

    Kajbafzadeh, Abdol-Mohammad; Nabavizadeh, Behnam; Keihani, Sorena; Hosseini Sharifi, Seyed Hossein

    2015-06-01

    To propose a simple noninvasive method for ureteral stent retrieval using an extraction string sutured to the skin in children. A retrospective chart review was performed to gather relevant data from December 2005 to February 2013. After the surgeries, if indicated, a tethered double-J stent was placed in the ureter. A 5-0 non-absorbable Prolene stitch was used as an extraction string passing through the urethra and was sutured to subcoronal skin in boys or inner surface of labia majora in girls. For stent removal, a small amount of 2 % lidocaine jelly was pushed into the urethra 5 min before the procedure. The string was then pulled by continuous and gentle force until the entire stent was out. The suture was then cut to release the stent. No sedation or anesthesia was needed. A total of 378 double-J stents with extraction strings were inserted for a total of 325 patients (61.2 % male). Of the 53 patients with bilateral ureteral stents, one male patient (1.88 %) experienced early stent protrusion from urethral meatus. Two of 272 patients (0.73 %) with unilateral ureteral stent (one male and one female) encountered the same problem. All other stents were extracted successfully using the extraction string without any complications. No upward stent migration or suture site reaction was encountered. This method is a safe, easy-to-use, feasible and noninvasive alternative for cystoscopic stent removal with high success rate and minimal complications. This can lead to considerable saving in time and costs for patients, families and healthcare system.

  14. Turbulence measurements using tethered balloon instrumentation during FIRE 1987

    Science.gov (United States)

    Hignett, Phillip

    1990-01-01

    As part of the surface-based observations conducted on San Nicolas Island, the U.K. Meteorological Office operated a set of turbulence probes attached to a balloon tether cable. Typically six probes were used, each capable of measuring momentum, heat, and humidity fluxes. Two probes were fitted with net radiometers, one positioned above cloud and the other below; a third probe carried a Lyman-alpha hygrometer fitted with a pre-heater for the measurement of total water content. Some preliminary results are presented from the 14th July describing the variation in structure of the cloudy boundary layer during the daytime. This day was characterized by a complete cloud cover, an inversion height of approximately 600 m. and north-westerly winds of approximately 6 m.s(-1). As an illustration the equivalent potential temperature derived from a profile ascent made between approximately 0830 and 0930 (PDT) is shown. The data has been smoothed to a height resolution of about 4 metres. At this time the cloud base was approximately 200 m. and very light drizzle was reaching the surface. The vertical velocity variance and potential temperature flux for two periods are shown; the first (shown by full lines) immediately follows the profile and the second (shown by dashed lines) is central around 1400 (PDT). The data have been normalized by their maximum values in the first period. Cloud base has now risen to approximately 300 m. There is a marked variation during the morning, particularly in sigma w. The net radiative flux above cloud top has by now reached its maximum value.

  15. Low-Cost Propellant Launch From a Tethered Balloon

    Science.gov (United States)

    Wilcox, Brian

    2006-01-01

    A document presents a concept for relatively inexpensive delivery of propellant to a large fuel depot in low orbit around the Earth, for use in rockets destined for higher orbits, the Moon, and for remote planets. The propellant is expected to be at least 85 percent of the mass needed in low Earth orbit to support the NASA Exploration Vision. The concept calls for the use of many small ( 10 ton) spin-stabilized, multistage, solid-fuel rockets to each deliver 250 kg of propellant. Each rocket would be winched up to a balloon tethered above most of the atmospheric mass (optimal altitude 26 2 km). There, the rocket would be aimed slightly above the horizon, spun, dropped, and fired at a time chosen so that the rocket would arrive in orbit near the depot. Small thrusters on the payload (powered, for example, by boil-off gases from cryogenic propellants that make up the payload) would precess the spinning rocket, using data from a low-cost inertial sensor to correct for small aerodynamic and solid rocket nozzle misalignment torques on the spinning rocket; would manage the angle of attack and the final orbit insertion burn; and would be fired on command from the depot in response to observations of the trajectory of the payload so as to make small corrections to bring the payload into a rendezvous orbit and despin it for capture by the depot. The system is low-cost because the small rockets can be mass-produced using the same techniques as those to produce automobiles and low-cost munitions, and one or more can be launched from a U.S. territory on the equator (Baker or Jarvis Islands in the mid-Pacific) to the fuel depot on each orbit (every 90 minutes, e.g., any multiple of 6,000 per year).

  16. Biogenic nonmethane hydrocarbon emissions estimated from tethered balloon observations

    Science.gov (United States)

    Davis, K. J.; Lenschow, D. H.; Zimmerman, P. R.

    1994-01-01

    A new technique for estimating surface fluxes of trace gases, the mixed-layer gradient technique, is used to calculate isoprene and terpene emissions from forests. The technique is applied to tethered balloon measurements made over the Amazon forest and a pine-oak forest in Alabama at altitudes up to 300 m. The observations were made during the dry season Amazon Boundary Layer Experiment (ABLE 2A) and the Rural Oxidants in the Southern Environment 1990 experiment (ROSE I). Results from large eddy simulations of scalar transport in the clear convective boundary layer are used to infer fluxes from the balloon profiles. Profiles from the Amazon give a mean daytime emission of 3630 +/- 1400 micrograms isoprene sq m/h, where the uncertainty represents the standard deviation of the mean of eight flux estimates. Twenty profiles from Alabama give emissions of 4470 +/- 3300 micrograms isoprene sq m/h, 1740 +/- 1060 micrograms alpha-pinene sq m/h, and 790 +/- 560 micrograms beta-pinene sq m/h, respectively. These results are in agreement with emissions derived from chemical budgets. The emissions may be overestimated because of uncertainty about how to incorporate the effects of the canopy on the mixed-layer gradients. The large variability in these emission estimates is probably due to the relatively short sampling times of the balloon profiles, though spatially heterogeneous emissions may also play a role. Fluxes derived using this technique are representative of an upwind footprint of several kilometers and are independent of hydrocarbon oxidation rate and mean advection.

  17. 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) ...

  18. 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.

  19. 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.

  20. 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...

  1. 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.

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

    Data.gov (United States)

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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. Companies hone in on radar-docking technology

    Science.gov (United States)

    Howell, Elizabeth

    2009-11-01

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

  8. 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...

  9. 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.

  10. 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.

  11. 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).

  12. 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.

  13. 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.

  14. Demonstration of automated proximity and docking technologies

    Science.gov (United States)

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

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

  15. Combination of scoring schemes for protein docking

    Directory of Open Access Journals (Sweden)

    Schomburg Dietmar

    2007-08-01

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

  16. 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.

  17. 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...

  18. 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

  19. Airborne imaging for heritage documentation using the Fotokite tethered flying camera

    Science.gov (United States)

    Verhoeven, Geert; Lupashin, Sergei; Briese, Christian; Doneus, Michael

    2014-05-01

    safe operation of these devices is still an issue, certainly when flying on locations which can be crowded (such as students on excavations or tourists walking around historic places). As the future of UAS regulation remains unclear, this talk presents an alternative approach to aerial imaging: the Fotokite. Developed at the ETH Zürich, the Fotokite is a tethered flying camera that is essentially a multi-copter connected to the ground with a taut tether to achieve controlled flight. Crucially, it relies solely on onboard IMU (Inertial Measurement Unit) measurements to fly, launches in seconds, and is classified as not a UAS (Unmanned Aerial System), e.g. in the latest FAA (Federal Aviation Administration) UAS proposal. As a result it may be used for imaging cultural heritage in a variety of environments and settings with minimal training by non-experienced pilots. Furthermore, it is subject to less extensive certification, regulation and import/export restrictions, making it a viable solution for use at a greater range of sites than traditional methods. Unlike a balloon or a kite it is not subject to particular weather conditions and, thanks to active stabilization, is capable of a variety of intelligent flight modes. Finally, it is compact and lightweight, making it easy to transport and deploy, and its lack of reliance on GNSS (Global Navigation Satellite System) makes it possible to use in urban, overbuilt areas. After outlining its operating principles, the talk will present some archaeological case studies in which the Fotokite was used, hereby assessing its capabilities compared to the conventional UAS's on the market.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

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

    Science.gov (United States)

    Boesso, A.; Francesconi, A.

    2013-05-01

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

  15. 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.

  16. 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.

  17. Synthesis and characterization of tethered lipid assemblies for membrane protein reconstitution (Review).

    Science.gov (United States)

    Veneziano, Rémi; Rossi, Claire; Chenal, Alexandre; Brenner, Catherine; Ladant, Daniel; Chopineau, Joël

    2017-09-28

    Biological membranes and their related molecular mechanisms are essential for all living organisms. Membranes host numerous proteins and are responsible for the exchange of molecules and ions, cell signaling, and cell compartmentation. Indeed, the plasma membrane delimits the intracellular compartment from the extracellular environment and intracellular membranes. Biological membranes also play a major role in metabolism regulation and cellular physiology (e.g., mitochondrial membranes). The elaboration of membrane based biomimetic systems allows us to reconstitute and investigate, in controlled conditions, biological events occurring at the membrane interface. A whole variety of model membrane systems have been developed in the last few decades. Among these models, supported membranes were developed on various hydrophilic supports. The use of solid supports enables the direct use of surface sensitive techniques (e.g., surface plasmon resonance, quartz crystal microbalance, and atomic force microscopy) to monitor and quantify events occurring at the membrane surface. Tethered bilayer membranes (tBLMs) could be considered as an achievement of the first solid supported membranes described by the McConnell group. Tethered bilayers on solid supports were designed to delimit an inside compartment from an outside one. They were used for measuring interactions with ligands or incorporating large membrane proteins or complexes without interference with the support. In this context, the authors developed an easy concept of versatile tBLMs assembled on amino coated substrates that are formed upon the vesicle fusion rupture process applicable to protein-free vesicles as well as proteoliposomes. The phospholipid bilayer (natural or synthetic lipids) incorporated 5% of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-N-hydroxy succinimide to ensure the anchorage of the bilayer to the amino coated surface. The conditions for the formation of tBLMs on amino

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.)

  4. 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.

  5. 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...

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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 ...

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. Complete cDNA sequence coding for human docking protein

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-11

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

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

    African Journals Online (AJOL)

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

  10. 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.

  11. Optimization of Spacecraft Rendezvous and Docking using Interval Analysis

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    African Journals Online (AJOL)

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

  13. 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.

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

    DEFF Research Database (Denmark)

    Petersen, Hanne Løhmann; Røpke, Stefan

    2011-01-01

    delivery by one truck, or by being picked up and transported to the cross-dock by one vehicle, and subsequently delivered at its final destination by another vehicle. Handling times at customers sites and terminal are given. A typical daily instance includes 500-1,000 requests. We solve the problem using...

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

    Indian Academy of Sciences (India)

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

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

    African Journals Online (AJOL)

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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. Design of Tail-Clamp Peptide Nucleic Acid Tethered with Azobenzene Linker for Sequence-Specific Detection of Homopurine DNA

    Directory of Open Access Journals (Sweden)

    Shinjiro Sawada

    2017-10-01

    Full Text Available DNA carries genetic information in its sequence of bases. Synthetic oligonucleotides that can sequence-specifically recognize a target gene sequence are a useful tool for regulating gene expression or detecting target genes. Among the many synthetic oligonucleotides, tail-clamp peptide nucleic acid (TC-PNA offers advantages since it has two homopyrimidine PNA strands connected via a flexible ethylene glycol-type linker that can recognize complementary homopurine sequences via Watson-Crick and Hoogsteen base pairings and form thermally-stable PNA/PNA/DNA triplex structures. Here, we synthesized a series of TC-PNAs that can possess different lengths of azobenzene-containing linkers and studied their binding behaviours to homopurine single-stranded DNA. Introduction of azobenzene at the N-terminus amine of PNA increased the thermal stability of PNA-DNA duplexes. Further extension of the homopyrimidine PNA strand at the N-terminus of PNA-AZO further increased the binding stability of the PNA/DNA/PNA triplex to the target homopurine sequence; however, it induced TC-PNA/DNA/TC-PNA complex formation. Among these TC-PNAs, 9W5H-C4-AZO consisting of nine Watson-Crick bases and five Hoogsteen bases tethered with a beta-alanine conjugated azobenzene linker gave a stable 1:1 TC-PNA/ssDNA complex and exhibited good mismatch recognition. Our design for TC-PNA-AZO can be utilized for detecting homopurine sequences in various genes.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Turbulence fluxes and variances measured with a sonic anemometer mounted on a tethered balloon

    OpenAIRE

    Canut, Guylaine; Couvreux, Fleur; Lothon, Marie; Legain, Dominique; Piguet, Bruno; Lampert, Astrid; Maurel, William; Moulin, Eric

    2016-01-01

    This study presents the first deployment in field campaigns of a balloon-borne turbulence probe, developed with a sonic anemometer and an inertial motion sensor suspended below a tethered balloon. This system measures temperature and horizontal and vertical wind at high frequency and allows the estimation of heat and momentum fluxes as well as turbulent kinetic energy in the lower part of the boundary layer. The system was validated during three field experiments with differ...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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...

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2012-11-13

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

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

    Science.gov (United States)

    Jones, Ruel Edwin

    1991-01-01

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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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)

  3. 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.

  4. 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

  5. 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

  6. Evaluation of calix[4]arene tethered Schiff bases for anion recognition

    International Nuclear Information System (INIS)

    Chawla, H.M.; Munjal, Priyanka

    2016-01-01

    Two calix[4]arene tethered Schiff base derivatives (L1 and L2) have been synthesized and their ion recognition capability has been evaluated through NMR, UV–vis and fluorescence spectroscopy. L1 interacts with cyanide ions very selectively to usher a significant change in color and fluorescence intensity. On the other hand L2 does not show selectivity for anion sensing despite having the same functional groups as those present in L1. The differential observations may be attributed to plausible stereo control of anion recognition and tautomerization in the synthesized Schiff base derivatives.

  7. Evaluation of calix[4]arene tethered Schiff bases for anion recognition

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, H.M., E-mail: hmchawla@chemistry.iitd.ac.in; Munjal, Priyanka

    2016-11-15

    Two calix[4]arene tethered Schiff base derivatives (L1 and L2) have been synthesized and their ion recognition capability has been evaluated through NMR, UV–vis and fluorescence spectroscopy. L1 interacts with cyanide ions very selectively to usher a significant change in color and fluorescence intensity. On the other hand L2 does not show selectivity for anion sensing despite having the same functional groups as those present in L1. The differential observations may be attributed to plausible stereo control of anion recognition and tautomerization in the synthesized Schiff base derivatives.

  8. Experimental and analytical determination of stability parameters for a balloon tethered in a wind

    Science.gov (United States)

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

    1973-01-01

    Experimental and analytical techniques for determining stability parameters for a balloon tethered in a steady wind are described. These techniques are applied to a particular 7.64-meter-long balloon, and the results are presented. The stability parameters of interest appear as coefficients in linearized stability equations and are derived from the various forces and moments acting on the balloon. In several cases the results from the experimental and analytical techniques are compared and suggestions are given as to which techniques are the most practical means of determining values for the stability parameters.

  9. Turbulence fluxes and variances measured with a sonic anemometer mounted on a tethered balloon

    Science.gov (United States)

    Canut, Guylaine; Couvreux, Fleur; Lothon, Marie; Legain, Dominique; Piguet, Bruno; Lampert, Astrid; Maurel, William; Moulin, Eric

    2016-09-01

    This study presents the first deployment in field campaigns of a balloon-borne turbulence probe, developed with a sonic anemometer and an inertial motion sensor suspended below a tethered balloon. This system measures temperature and horizontal and vertical wind at high frequency and allows the estimation of heat and momentum fluxes as well as turbulent kinetic energy in the lower part of the boundary layer. The system was validated during three field experiments with different convective boundary-layer conditions, based on turbulent measurements from instrumented towers and aircraft.

  10. Ozone profiles from tethered balloon measurements in an urban plume experiment

    Science.gov (United States)

    Youngbluth, O., Jr.; Storey, R. W.; Clendenin, C. G.; Jones, S.; Leighty, B.

    1981-01-01

    NASA Langley Research Center used two tethered balloon systems to measure ozone in the general area of Norfolk, Va. The large balloon system which has an altitude range of 1,500 meters was located at Wallops Island, Va., and the smaller balloon which has an altitude range of 900 meters was located at Chesapeake, Va. Each balloon system measured ozone, temperature, humidity, wind speed, and wind direction from ground to its maximum altitude. From these measurements and from the location of the balloon sites, areas of ozone generation and ozone transport may be inferred. The measurements which were taken during August 1979 are discussed as well as the measurement techniques.

  11. 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.

  12. Observer enhanced control for spin-stabilized tethered formation in earth orbit

    Science.gov (United States)

    Guang, Zhai; Yuyang, Li; Liang, Bin

    2018-04-01

    This paper addresses the issues relevant to control of spin-stabilized tethered formation in circular orbit. Due to the dynamic complexities and nonlinear perturbations, it is challenging to promote the control precision for the formation deployment and maintenance. In this work, the formation dynamics are derived with considering the spinning rate of the central body, then major attention is dedicated to develop the nonlinear disturbance observer. To achieve better control performance, the observer-enhanced controller is designed by incorporating the disturbance observer into the control loop, benefits from the disturbance compensation are demonstrated, and also, the dependences of the disturbance observer performance on some important parameters are theoretically and numerically analyzed.

  13. 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.

  14. 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.

  15. 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

  16. Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

    Directory of Open Access Journals (Sweden)

    Isabelle Karine da Costa Nunes

    Full Text Available Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448 presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral, 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma.

  17. 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.

  18. 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.

  19. Condensins Exert Force on Chromatin-Nuclear Envelope Tethers to Mediate Nucleoplasmic Reticulum Formation in Drosophila melanogaster

    Science.gov (United States)

    Bozler, Julianna; Nguyen, Huy Q.; Rogers, Gregory C.; Bosco, Giovanni

    2014-01-01

    Although the nuclear envelope is known primarily for its role as a boundary between the nucleus and cytoplasm in eukaryotes, it plays a vital and dynamic role in many cellular processes. Studies of nuclear structure have revealed tissue-specific changes in nuclear envelope architecture, suggesting that its three-dimensional structure contributes to its functionality. Despite the importance of the nuclear envelope, the factors that regulate and maintain nuclear envelope shape remain largely unexplored. The nuclear envelope makes extensive and dynamic interactions with the underlying chromatin. Given this inexorable link between chromatin and the nuclear envelope, it is possible that local and global chromatin organization reciprocally impact nuclear envelope form and function. In this study, we use Drosophila salivary glands to show that the three-dimensional structure of the nuclear envelope can be altered with condensin II-mediated chromatin condensation. Both naturally occurring and engineered chromatin-envelope interactions are sufficient to allow chromatin compaction forces to drive distortions of the nuclear envelope. Weakening of the nuclear lamina further enhanced envelope remodeling, suggesting that envelope structure is capable of counterbalancing chromatin compaction forces. Our experiments reveal that the nucleoplasmic reticulum is born of the nuclear envelope and remains dynamic in that they can be reabsorbed into the nuclear envelope. We propose a model where inner nuclear envelope-chromatin tethers allow interphase chromosome movements to change nuclear envelope morphology. Therefore, interphase chromatin compaction may be a normal mechanism that reorganizes nuclear architecture, while under pathological conditions, such as laminopathies, compaction forces may contribute to defects in nuclear morphology. PMID:25552604

  20. Condensins exert force on chromatin-nuclear envelope tethers to mediate nucleoplasmic reticulum formation in Drosophila melanogaster.

    Science.gov (United States)

    Bozler, Julianna; Nguyen, Huy Q; Rogers, Gregory C; Bosco, Giovanni

    2014-12-30

    Although the nuclear envelope is known primarily for its role as a boundary between the nucleus and cytoplasm in eukaryotes, it plays a vital and dynamic role in many cellular processes. Studies of nuclear structure have revealed tissue-specific changes in nuclear envelope architecture, suggesting that its three-dimensional structure contributes to its functionality. Despite the importance of the nuclear envelope, the factors that regulate and maintain nuclear envelope shape remain largely unexplored. The nuclear envelope makes extensive and dynamic interactions with the underlying chromatin. Given this inexorable link between chromatin and the nuclear envelope, it is possible that local and global chromatin organization reciprocally impact nuclear envelope form and function. In this study, we use Drosophila salivary glands to show that the three-dimensional structure of the nuclear envelope can be altered with condensin II-mediated chromatin condensation. Both naturally occurring and engineered chromatin-envelope interactions are sufficient to allow chromatin compaction forces to drive distortions of the nuclear envelope. Weakening of the nuclear lamina further enhanced envelope remodeling, suggesting that envelope structure is capable of counterbalancing chromatin compaction forces. Our experiments reveal that the nucleoplasmic reticulum is born of the nuclear envelope and remains dynamic in that they can be reabsorbed into the nuclear envelope. We propose a model where inner nuclear envelope-chromatin tethers allow interphase chromosome movements to change nuclear envelope morphology. Therefore, interphase chromatin compaction may be a normal mechanism that reorganizes nuclear architecture, while under pathological conditions, such as laminopathies, compaction forces may contribute to defects in nuclear morphology. Copyright © 2015 Bozler et al.

  1. 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.

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

    Science.gov (United States)

    Heberlé, G; de Azevedo, W F

    2011-01-01

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

  3. 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

  4. 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.

  5. Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs.

    Science.gov (United States)

    Shen, Lu; Decker, Caitlin G; Maynard, Heather D; Levine, Alex J

    2016-09-01

    We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands.

  6. A Simple Flight Mill for the Study of Tethered Flight in Insects.

    Science.gov (United States)

    Attisano, Alfredo; Murphy, James T; Vickers, Andrew; Moore, Patricia J

    2015-12-10

    Flight in insects can be long-range migratory flights, intermediate-range dispersal flights, or short-range host-seeking flights. Previous studies have shown that flight mills are valuable tools for the experimental study of insect flight behavior, allowing researchers to examine how factors such as age, host plants, or population source can influence an insects' propensity to disperse. Flight mills allow researchers to measure components of flight such as speed and distance flown. Lack of detailed information about how to build such a device can make their construction appear to be prohibitively complex. We present a simple and relatively inexpensive flight mill for the study of tethered flight in insects. Experimental insects can be tethered with non-toxic adhesives and revolve around an axis by means of a very low friction magnetic bearing. The mill is designed for the study of flight in controlled conditions as it can be used inside an incubator or environmental chamber. The strongest points are the very simple electronic circuitry, the design that allows sixteen insects to fly simultaneously allowing the collection and analysis of a large number of samples in a short time and the potential to use the device in a very limited workspace. This design is extremely flexible, and we have adjusted the mill to accommodate different species of insects of various sizes.

  7. Comparison of standard, prone and cine MRI in the evaluation of tethered cord

    International Nuclear Information System (INIS)

    Singh, Sukhjinder; Kline-Fath, Beth; Racadio, Judy M.; Bierbrauer, Karin; Salisbury, Shelia; Macaluso, Maurizio; Jackson, Elizabeth C.; Egelhoff, John C.

    2012-01-01

    Tethered cord syndrome (TCS) is defined by abnormal traction on the spinal cord that confines its movement. Surgical cord release usually stops neurological deterioration; therefore, early and accurate neuroradiological diagnosis is important. Supine MRI is the imaging modality of choice, but prone MRI and cine MRI can demonstrate cord movement. We compared the diagnostic accuracies of standard MRI, prone MRI and cine MRI in patients with clinical suspicion of TCS and evaluated inter-reader reliability for MR imaging. Children who underwent MRI for suspicion of TCS were retrospectively identified. Supine, prone and cine MRI studies were re-read by two pediatric neuroradiologists. Conus level, filum appearance and cord movement were documented. Thirteen of 49 children had tethered cord documented at surgery. Conus level had the highest diagnostic accuracy (sensitivity 69-77%, specificity 94%, positive predictive value 82-83%, negative predictive value 89-92%, correct diagnosis 88-90%) and highest between-reader concordance (98%). Prone and cine MRI did not add to the accuracy of the supine imaging. Conus level provides the highest diagnostic accuracy and inter-reader reliability in TCS. Until a larger series is evaluated, it remains questionable whether prone or cine MRI provides enough additional diagnostic information to warrant routine use. (orig.)

  8. Comparison of standard, prone and cine MRI in the evaluation of tethered cord

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Sukhjinder [Cohen Children' s Medical Center, Department of Radiology, New Hyde Park, NY (United States); Kline-Fath, Beth; Racadio, Judy M. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Bierbrauer, Karin [Cincinnati Children' s Hospital Medical Center, Department of Neurosurgery, Cincinnati, OH (United States); Salisbury, Shelia; Macaluso, Maurizio [Cincinnati Children' s Hospital Medical Center, Division of Biostatistics and Epidemiology, Cincinnati, OH (United States); Jackson, Elizabeth C. [Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, Division of Nephrology, Cincinnati, OH (United States); Egelhoff, John C. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Phoenix Children' s Hospital, Department of Radiology, Phoenix, AZ (United States)

    2012-06-15

    Tethered cord syndrome (TCS) is defined by abnormal traction on the spinal cord that confines its movement. Surgical cord release usually stops neurological deterioration; therefore, early and accurate neuroradiological diagnosis is important. Supine MRI is the imaging modality of choice, but prone MRI and cine MRI can demonstrate cord movement. We compared the diagnostic accuracies of standard MRI, prone MRI and cine MRI in patients with clinical suspicion of TCS and evaluated inter-reader reliability for MR imaging. Children who underwent MRI for suspicion of TCS were retrospectively identified. Supine, prone and cine MRI studies were re-read by two pediatric neuroradiologists. Conus level, filum appearance and cord movement were documented. Thirteen of 49 children had tethered cord documented at surgery. Conus level had the highest diagnostic accuracy (sensitivity 69-77%, specificity 94%, positive predictive value 82-83%, negative predictive value 89-92%, correct diagnosis 88-90%) and highest between-reader concordance (98%). Prone and cine MRI did not add to the accuracy of the supine imaging. Conus level provides the highest diagnostic accuracy and inter-reader reliability in TCS. Until a larger series is evaluated, it remains questionable whether prone or cine MRI provides enough additional diagnostic information to warrant routine use. (orig.)

  9. Feasibility study of Tethered Capsule Endomicroscopy (TCE) deployment in the small intestine (Conference Presentation)

    Science.gov (United States)

    Otuya, David O.; Verma, Yogesh; Dong, Jing; Gora, Michalina J.; Tearney, Guillermo J.

    2017-02-01

    Environmental enteric dysfunction (EED) is a poorly understood disease of the small intestine that causes nutrient malabsorption in children, predominantly from low and middle income countries. The clinical importance of EED is neurological and growth stunting that remains as the child grows into adulthood. Tethered capsule endomicroscopy (TCE) has the potential to improve the understanding of EED and could be used to determine the effectiveness of EED interventions. TCE in the adult esophagus and the duodenum has been demonstrated for Barrett`s esophagus and celiac disease diagnosis, respectively. While adult subjects can independently swallow these capsules, it is likely that infants will not, and, as a result, new strategies for introducing these devices in young children aged 0.5-2 years need to be investigated. Our first approach will be to introduce the TCE devices in infants under the aid of endoscopic guidance. To determine the most effective method, we have tested endoscopic approaches for introducing TCE devices into the small intestine of living swine. These methods will be compared and contrasted to discuss the most effective means for endoscopic tethered capsule introduction into the small intestine.

  10. 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.

  11. Multifunctional inulin tethered silver-graphene quantum dots nanotheranostic module for pancreatic cancer therapy.

    Science.gov (United States)

    Nigam Joshi, Preeti; Agawane, Sachin; Athalye, Meghana C; Jadhav, Vrushali; Sarkar, Dhiman; Prakash, Rajiv

    2017-09-01

    Cancer nanotechnology is an emerging area of cancer diagnosis and therapy. Although considerable progress has been made for targeted drug delivery systems to deliver anticancer agents to particular site of interest, new nanomaterials are frequently being developed and explored for better drug delivery efficiency. In the present work, we have explored a novel nanoformulation based on silver-graphene quantum dots (Ag-GQDs) nanocomposite for its successful implementation for pancreatic cancer specific drug delivery in wistar rats. Carboxymethyl inulin (CMI); a modified variant of natural polysaccharide inulin is tethered with the nanocomposite via carbodiimide coupling to enhance the biocompatibility of nanoformulation. Experiments are performed to investigate the cytotoxicity reduction of silver nanoparticles after inulin tethering as well as anticancer efficacy of the system using 5-Fluorouracil (5-FU) as model drug. SEM, TEM, FT-IR, UV-vis, photoluminescence and anti proliferative assays (MTT) are performed for characterisation of the nanocomposite. Hyaluronic acid (HA) is conjugated as targeting moiety for CD-44 (cancer stem cell marker) to fabricate a complete targeted drug delivery vehicle specific for pancreatic cancer. In the present work two prime objectives were achieved; mitigation the toxicity of silver nanoparticles by inulin coating and it's in vivo application for pancreatic cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Optimizing fluorescently tethered Hsp90 inhibitor dose for maximal specific uptake by breast tumors

    Science.gov (United States)

    Crouch, Brian T.; Duer, Joy; Wang, Roujia; Gallagher, Jennifer; Hall, Allison; Soo, Mary Scott; Hughes, Philip; Haystead, Timothy A. J.; Ramanujam, Nirmala

    2018-03-01

    Despite improvements in surgical resection, 20-40% of patients undergoing breast conserving surgery require at least one additional re-excision. Leveraging the unique surface expression of heat shock protein 90 (Hsp90), a chaperone protein involved in several key hallmarks of cancer, in breast cancer provides an exciting opportunity to identify residual disease during surgery. We developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens using a fluorescence microendoscope with a field of view of 750 μm and subcellular resolution of 4 μm. HS-27 consists of an FDA approved Hsp90 inhibitor tethered to fluorescein isothiocyanate (EX 488nm, EM 525nm). Here, we optimized ex vivo HS-27 administration in pre-clinical breast cancer models and validated our approach on 21 patients undergoing standard of care ultrasound guided core needle biopsy. HS-27 administration time was fixed at 1- minute to minimize imaging impact on clinical workflow. HS-27 and HS-217 (non-specific control) doses were modulated from 1 μM up to 100 μM to identify the dose maximizing the ratio of specific uptake (HS-27 fluorescence) to non-specific uptake (HS-217 fluorescence). The specificity ratio was maximized at 100 μM and was significantly greater than all other doses (pcancer makes this technology attractive for assessing tumor margins, as one agent can be used for all subtypes.

  13. 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).

  14. ARM Tethered Balloon System & AALCO Activities at AMF3 Site at Oliktok Point, AK

    Science.gov (United States)

    Hardesty, J.; Dexheimer, D.; Mei, F.; Roesler, E. L.; Longbottom, C.; Hillman, B. R.

    2017-12-01

    Sandia National Laboratories (SNL) has operated the Atmospheric Radiation Measurement program's (ARM) third ARM Mobile Facility (AMF3) and the restricted airspace associated with it at Oliktok Point, Alaska, since October 2013. The site hosts ground-based instrumentation which collects a variety of continuous atmospheric measurements as well as user-conducted unmanned aircraft and tethered balloon campaigns. SNL has operated ARM's tethered balloon system (TBS) as part of the Inaugural Campaigns for ARM Research using Unmanned Systems (ICARUS) since 2016. AALCO (Aerial Assessment of Liquid in Clouds at Oliktok), is an ARM Intensive Operations Period conducted by SNL at the AMF3 since 2016. The operation of the TBS during ICARUS and AALCO to altitudes above 4,000' AGL in a variety of seasons and conditions is addressed. A Distributed Temperature Sensing (DTS) system and supercooled liquid water content (SLWC) sensors have been deployed under both campaigns. The performance of these sensors is discussed and results are presented. DTS measurements and their relationship to concurrent temperature measurements from unmanned aircraft and radiosondes are shown. SLWC sensor in situ measurements are compared with microwave radiometer and radiosonde-derived measurements. Preliminary analysis of using Large Eddy Simulations to compare with the SLWC measurements reveals three-dimensional properties of the observed clouds.

  15. 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.

  16. 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.

  17. Relative Contribution of Arms and Legs in 30 s Fully Tethered Front Crawl Swimming

    Directory of Open Access Journals (Sweden)

    Pedro G. Morouço

    2015-01-01

    Full Text Available The relative contribution of arm stroke and leg kicking to maximal fully tethered front crawl swimming performance remains to be solved. Twenty-three national level young swimmers (12 male and 11 female randomly performed 3 bouts of 30 s fully tethered swimming (using the whole body, only the arm stroke, and only the leg kicking. A load-cell system permitted the continuous measurement of the exerted forces, and swimming velocity was calculated from the time taken to complete a 50 m front crawl swim. As expected, with no restrictions swimmers were able to exert higher forces than that using only their arm stroke or leg kicking. Estimated relative contributions of arm stroke and leg kicking were 70.3% versus 29.7% for males and 66.6% versus 33.4% for females, with 15.6% and 13.1% force deficits, respectively. To obtain higher velocities, male swimmers are highly dependent on the maximum forces they can exert with the arm stroke (r=0.77, P<0.01, whereas female swimmers swimming velocity is more related to whole-body mean forces (r=0.81, P<0.01. The obtained results point that leg kicking plays an important role over short duration high intensity bouts and that the used methodology may be useful to identify strength and/or coordination flaws.

  18. 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.

  19. Waste Isolation Pilot Plant TruDock crane system analysis

    International Nuclear Information System (INIS)

    Morris, B.C.; Carter, M.

    1996-10-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  1. 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.

  2. 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.

  3. "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.

  4. 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 ...

  5. 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 .

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Application of tethered balloon for studying vertical distribution of air pollutants within lower tropsphere of Shanghai

    Science.gov (United States)

    Zhang, K.; Wang, D.; Fu, Q.; Xiu, G.; Duan, Y.

    2016-12-01

    Tethered balloon-based measurement campaign of particle number concentration (PNC) and particle number size distribution (PNSD) in the range of 15.7-661.2 nm was conducted within the lower troposphere of 1000 m in Shanghai, a Chinses megacity, in December 2015. The meteorological condition, PNC, and PNSD were synchronous measured at ground-based station as well as on the tethered balloon. Overall, the mixing layer height (MLH) showed a peak at about LST 14:00-15:00. On ground level, the 88.2 nm particles had the highest number concentration. The Pearson correlation analysis based on the ground level data shows the Pearson correlation coefficient between PNC and NO2was 0.774. The synchronous measurement of PNC and PNSD on ground level and on the tethered balloon showed the 15.7-200 nm particles had higher PNC on ground level, but the PNC of 200-661.2 nm particles are higher at 400 m. And the wind condition showed a strong influence on PNC.The vertical profiles of meteorological parameters and air pollutants was observed. The particle mass concentration, ozone concentration, temperature, and humidity all showed a quick change when the balloon across the atmosphere boundary layer. One episodic haze event (Dec 22nd-Dec 23rd) was selected with specific focus on the variation of PNSD and PNC vertical profiles. Before the haze, the PNC at ground was 9281 cm-3. The MaxDm (the particle diameter with the highest number concentration) was 53.3 nm at that time. Due to the shallow MLH, the MaxDm changed rapidly to 126.3 nm at 321 m. During the haze, the MaxDm and the PNC on ground level was 126.3 nm and 18515 cm-3 respectively. And a quick drop of PNC was observed at 553 m. This may due to the change of wind direction, temperature, and relative humidity. At the end of haze, the MaxDm and the PNC on ground level was 126.3 nm and 10711 cm-3 respectively. The highest MaxDm during those three launches all appeared at a high altitude, usually above 300 m. This result is consisted

  15. Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

    Science.gov (United States)

    2017-05-01

    ligand localization . These molecules will be tested as imaging agents in mouse models of breast cancer. 15. SUBJECT TERMS Radiodination, tethered...annually leading to the diagnosis and surgical resection of breast cancer or breast carcinoma in situ in over 250,000 women respectively. Unfortunately

  16. 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....

  17. Space vehicle with customizable payload and docking station

    Science.gov (United States)

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

    2018-01-30

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

  18. Diagnosis and surgical treatment of terminal syringomyelia within spinal cord combined with tethered cord syndrome

    Directory of Open Access Journals (Sweden)

    Jing-cheng XIE

    2016-04-01

    Full Text Available Objective To summarize the clinical manifestations, imaging characteristics and experience of surgical treatment of spinal cord terminal syringomyelia with tethered cord syndrome (TCS.  Methods and Results Clinical data of 10 patients with spinal cord syringomyelia combined with TCS surgically treated under microscope from January 1999 to March 2014 in our hospital were retrospectively analyzed. There were 3 males and 7 females with average age of 15.06 years old (ranged from 2 to 35 years old. The course of disease ranged from 3 months to 20 years (average 42.17 months. Among those patients, one patient presented hydromyelia, 8 patients suffered from meningeal cyst within the sacral canal, and one patient were concurrent with sacral dermal sinus. The weakness of lower extremities, especially distal limbs, was the main clinical manifestation. Five patients were accompanied with bowel and bladder dysfunction and 5 patients with sensory disturbance below the level of syringomyelia, especially hypesthesia. Preoperative MRI showed conus medullaris disappeared at the end of spinal cord, and there was fluid signal in the lower spinal cord with hypo-intensity signal in T1WI and hyper-intensity signal in T2WI without enhancement. All patients underwent surgical procedures. Under microscope, filum terminale was cut off, drainage was performed, meningeal cyst within the sacral canal was removed, and tethered cord was released. The success rate of operations was 100%. The duration of surgery ranged from 1.52 to 3.07 h (average 2.15 h, with average intraoperative blood loss 220 ml (ranged from 100 to 410 ml. The tethering filum had been totally resected and histological examination showed typical filum tissue in all cases. No operative complication was found. Visual Analogue Scale (VAS score was decreased, and the lower limbs weakness as well as bowel and bladder dysfunction was gradually relieved after operation. The period of follow-up was ranged from 6

  19. Quantifying parenchymal tethering in a finite element simulation of a human lung slice under bronchoconstriction.

    Science.gov (United States)

    Breen, Barbara J; Donovan, Graham M; Sneyd, James; Tawhai, Merryn H

    2012-08-15

    Airway hyper-responsiveness (AHR), a hallmark of asthma, is a highly complex phenomenon characterised by multiple processes manifesting over a large range of length and time scales. Multiscale computational models have been derived to embody the experimental understanding of AHR. While current models differ in their derivation, a common assumption is that the increase in parenchymal tethering pressure P(teth) during airway constriction can be described using the model proposed by Lai-Fook (1979), which is based on intact lung experimental data for elastic moduli over a range of inflation pressures. Here we reexamine this relationship for consistency with a nonlinear elastic material law that has been parameterised to the pressure-volume behaviour of the intact lung. We show that the nonlinear law and Lai-Fook's relationship are consistent for small constrictions, but diverge when the constriction becomes large. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.

    Science.gov (United States)

    Keedy, Daniel A; Hill, Zachary B; Biel, Justin T; Kang, Emily; Rettenmaier, T Justin; Brandao-Neto, Jose; Pearce, Nicholas M; von Delft, Frank; Wells, James A; Fraser, James S

    2018-06-07

    Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function. © 2018, Keedy et al.

  1. Optimization of motion control laws for tether crawler or elevator systems

    Science.gov (United States)

    Swenson, Frank R.; Von Tiesenhausen, Georg

    1988-01-01

    Based on the proposal of a motion control law by Lorenzini (1987), a method is developed for optimizing motion control laws for tether crawler or elevator systems in terms of the performance measures of travel time, the smoothness of acceleration and deceleration, and the maximum values of velocity and acceleration. The Lorenzini motion control law, based on powers of the hyperbolic tangent function, is modified by the addition of a constant-velocity section, and this modified function is then optimized by parameter selections to minimize the peak acceleration value for a selected travel time or to minimize travel time for the selected peak values of velocity and acceleration. It is shown that the addition of a constant-velocity segment permits further optimization of the motion control law performance.

  2. A practical concept for powered or tethered weight-lifting LTA vehicles

    Science.gov (United States)

    Balleyguier, M. A.

    1975-01-01

    A concept for a multi-hull weightlifting airship is presented. The concept is based upon experience in the design and handling of gas-filled balloons for commercial purposes, it was first tested in April, 1972. In the flight test, two barrage balloons were joined side-by-side, with an intermediate frame, and launched in captive flight. The success of this flight test led to plans for a development program calling for a powered, piloted prototype, a follow-on 40 ton model, and a 400 ton transport model. All of these airships utilize a tetrehedric three-line tethering method for loading and unloading phases of flight, which bypasses many of the difficulties inherent in the handling of a conventional airship near the ground. Both initial and operating costs per ton of lift capability are significantly less for the subject design than for either helicopters or airships of conventional mono-hull design.

  3. Differences between tethered polyelectrolyte chains adsorbed onto bare mica and hydrophobically modified mica, comparison with theory.

    Science.gov (United States)

    Balastre, Marc; Tamashiro, Mario N.; Hernandez, Ernesto; Pincus, Philip; Tirrell, Matthew

    2001-03-01

    End-grafted polymers generated from the adsorption of asymmetric diblock copolymers on solid surface play an important role in many areas of science and technology. While the small insoluble block acts as an anchor, the charged soluble block confers useful properties to the surface. This study looks at tethered layers of poly(styrene sulfonate)/poly(t-butyl styrene) (PtBS-PSS) adsorbed on both mica (hydrophilic) and octadecyltriethoxysilane (OTE) modified mica (hydrophobic). Normal compressing forces at two different constant grafting densities (bare and modified mica) were measured with the surface force apparatus and compared with theoretical prediction. The effect of salt concentration (Cs) upon the thickness of the self-assembled layers (Lo) was measured in each case. For adsorption of diblock copolymers onto OTE the resulting scaling relationship is much closer to the brush theory, Lo Cs-1/3. This result suggests that the adsorbed amount on mica is not high enough to form a brush.

  4. Development programme update for a socket solution offering a highly efficient termination of polyester mooring tethers

    International Nuclear Information System (INIS)

    Firth, Kevin M.; Calverley, Steve; Quintas, Manuel Pedro

    2000-01-01

    Bridon have previously developed a patented 'Socket and Spike' design for polyester tethers comprising a parallel array of seven sub-ropes. This phase of the development was successfully completed, subsequently Bridon have embarked on a new phase which aims to increase the efficiency of the socket and address the assembly problems that have been identified. The development has continued with the 'Socket and Spike' principle but a unique termination method has been devised such that each sub-rope is terminated in it is own mini-socket and pre-loaded prior to fitting into the main socket ensuring zero slippage and equal transfer of the mooring load. The sub-ropes are nested into the main socket body resulting in a socket termination that lighter, more efficient and easier to handle than the current method of spliced eye incorporating a steel spool and shackle. (author)

  5. Tethered particle analysis of supercoiled circular DNA using peptide nucleic acid handles

    DEFF Research Database (Denmark)

    Norregaard, Kamilla; Andersson, Magnus; Nielsen, Peter Eigil

    2014-01-01

    This protocol describes how to monitor individual naturally supercoiled circular DNA plasmids bound via peptide nucleic acid (PNA) handles between a bead and a surface. The protocol was developed for single-molecule investigation of the dynamics of supercoiled DNA, and it allows the investigation...... of both the dynamics of the molecule itself and of its interactions with a regulatory protein. Two bis-PNA clamps designed to bind with extremely high affinity to predetermined homopurine sequence sites in supercoiled DNA are prepared: one conjugated with digoxigenin for attachment to an anti......-digoxigenin-coated glass cover slide, and one conjugated with biotin for attachment to a submicron-sized streptavidin-coated polystyrene bead. Plasmids are constructed, purified and incubated with the PNA handles. The dynamics of the construct is analyzed by tracking the tethered bead using video microscopy: less...

  6. Sponges with covalently tethered amines for high-efficiency carbon capture

    KAUST Repository

    Qi, Genggeng

    2014-12-12

    © 2014 Macmillan Publishers Limited. All rights reserved. Adsorption using solid amine sorbents is an attractive emerging technology for energy-efficient carbon capture. Current syntheses for solid amine sorbents mainly based on physical impregnation or grafting-to methods (for example, aminosilane-grafting) lead to limited sorbent performance in terms of stability and working capacity, respectively. Here we report a family of solid amine sorbents using a grafting-from synthesis approach and synthesized by cationic polymerization of oxazolines on mesoporous silica. The sorbent with high amount of covalently tethered amines shows fast adsorption rate, high amine efficiency and sorbent capacity well exceeding the highest value reported to date for lowerature carbon dioxide sorbents under simulated flue gas conditions. The demonstrated efficiency of the new amine-immobilization chemistry may open up new avenues in the development of advanced carbon dioxide sorbents, as well as other nitrogen-functionalized systems.

  7. Single molecular switch based on thiol tethered iron(II)clathrochelate on gold

    Energy Technology Data Exchange (ETDEWEB)

    Viswanathan, Subramanian [Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn (Poland); Voloshin, Yan Z. [Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, 119991 Moscow (Russian Federation); Radecka, Hanna [Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn (Poland); Radecki, Jerzy [Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn (Poland)], E-mail: radecki@pan.olsztyn.pl

    2009-09-30

    Molecular electronics has been associated with high density nano-electronic devices. Developments of molecular electronic devices were based on reversible switching of molecules between the two conductive states. In this paper, self-assembled monolayers of dodecanethiol (DDT) and thiol tethered iron(II)clathrochelate (IC) have been prepared on gold film. The electrochemical and electronic properties of IC molecules inserted into the dodecanethiol monolayer (IC-DDT SAM) were investigated using voltammetric, electrochemical impedance spectroscopy (EIS), scanning tunneling microscopy (STM) and cross-wire tunneling measurements. The voltage triggered switching behaviour of IC molecules on mixed SAM was demonstrated. Deposition of polyaniline on the redox sites of IC-DDT SAM using electrochemical polymerization of aniline was performed in order to confirm that this monolayer acts as nano-patterned semiconducting electrode surface.

  8. Linear Viscoelasticity of Spherical SiO 2 Nanoparticle-Tethered Poly(butyl acrylate) Hybrids

    KAUST Repository

    Goel, Vivek; Pietrasik, Joanna; Matyjaszewski, Krzysztof; Krishnamoorti, Ramanan

    2010-01-01

    The melt state linear viscoelastic properties of spherical silica nanoparticles with grafted poly(n-butyl acrylate) chains of varying molecular weight were probed using linear small amplitude dynamic oscillatory measurements and complementary linear stress relaxation measurements. While the pure silica-tethered-polymer hybrids with no added homopolymer exhibit solid-like response, addition of matched molecular weight free matrix homopolymer chains to this hybrid, at low concentrations of added homopolymer, maintains the solid-like response with a lowered modulus that can be factored into a silica concentration dependence and a molecular weight dependence. While the silica concentration dependence of the modulus is strong, the dependence on molecular weight is weak. On the other hand, increasing the amount of added homopolymer changes the viscoelastic response to that of a liquid with a relaxation time that scales exponentially with hybrid concentration. © 2010 American Chemical Society.

  9. A new class of tunable hypersonic phononic crystals based on polymer-tethered colloids.

    Science.gov (United States)

    Alonso-Redondo, E; Schmitt, M; Urbach, Z; Hui, C M; Sainidou, R; Rembert, P; Matyjaszewski, K; Bockstaller, M R; Fytas, G

    2015-09-22

    The design and engineering of hybrid materials exhibiting tailored phononic band gaps are fundamentally relevant to innovative material technologies in areas ranging from acoustics to thermo-optic devices. Phononic hybridization gaps, originating from the anti-crossing between local resonant and propagating modes, have attracted particular interest because of their relative robustness to structural disorder and the associated benefit to 'manufacturability'. Although hybridization gap materials are well known, their economic fabrication and efficient control of the gap frequency have remained elusive because of the limited property variability and expensive fabrication methodologies. Here we report a new strategy to realize hybridization gap materials by harnessing the 'anisotropic elasticity' across the particle-polymer interface in densely polymer-tethered colloidal particles. Theoretical and Brillouin scattering analysis confirm both the robustness to disorder and the tunability of the resulting hybridization gap and provide guidelines for the economic synthesis of new materials with deliberately controlled gap position and width frequencies.

  10. Surface Ocean Dispersion Observations from the Ship-Tethered Aerostat Remote Sensing System

    DEFF Research Database (Denmark)

    Carlson, Daniel Frazier; Ozgokmen, Tamay; Novelli, Guillaume

    2018-01-01

    Oil slicks and sheens reside at the air-sea interface, a region of the ocean that is notoriously difficult to measure and, therefore, little is known about the velocity field at the sea surface. The Ship-Tethered Aerostat Remote Sensing System (STARSS) was developed to measure Lagrangian velocities...... of experiments in the northern Gulf of Mexico in January- February 2016. STARSS was equipped with a GPS and inertial navigation system (INS) that was used to directly georectify the aerial images. A relative rectification technique was developed that translates and rotates the drift cards to minimize the total...... movement of all drift cards from one frame to the next. Rectified drift card positions were used to quantify scale-dependent dispersion by computing relative dispersion, relative diffusivity, and velocity structure functions. STARSS was part of a nested observational framework, which included deployments...

  11. A new class of tunable hypersonic phononic crystals based on polymer-tethered colloids

    Science.gov (United States)

    Alonso-Redondo, E.; Schmitt, M.; Urbach, Z.; Hui, C. M.; Sainidou, R.; Rembert, P.; Matyjaszewski, K.; Bockstaller, M. R.; Fytas, G.

    2015-09-01

    The design and engineering of hybrid materials exhibiting tailored phononic band gaps are fundamentally relevant to innovative material technologies in areas ranging from acoustics to thermo-optic devices. Phononic hybridization gaps, originating from the anti-crossing between local resonant and propagating modes, have attracted particular interest because of their relative robustness to structural disorder and the associated benefit to `manufacturability'. Although hybridization gap materials are well known, their economic fabrication and efficient control of the gap frequency have remained elusive because of the limited property variability and expensive fabrication methodologies. Here we report a new strategy to realize hybridization gap materials by harnessing the `anisotropic elasticity' across the particle-polymer interface in densely polymer-tethered colloidal particles. Theoretical and Brillouin scattering analysis confirm both the robustness to disorder and the tunability of the resulting hybridization gap and provide guidelines for the economic synthesis of new materials with deliberately controlled gap position and width frequencies.

  12. Linear Viscoelasticity of Spherical SiO 2 Nanoparticle-Tethered Poly(butyl acrylate) Hybrids

    KAUST Repository

    Goel, Vivek

    2010-12-01

    The melt state linear viscoelastic properties of spherical silica nanoparticles with grafted poly(n-butyl acrylate) chains of varying molecular weight were probed using linear small amplitude dynamic oscillatory measurements and complementary linear stress relaxation measurements. While the pure silica-tethered-polymer hybrids with no added homopolymer exhibit solid-like response, addition of matched molecular weight free matrix homopolymer chains to this hybrid, at low concentrations of added homopolymer, maintains the solid-like response with a lowered modulus that can be factored into a silica concentration dependence and a molecular weight dependence. While the silica concentration dependence of the modulus is strong, the dependence on molecular weight is weak. On the other hand, increasing the amount of added homopolymer changes the viscoelastic response to that of a liquid with a relaxation time that scales exponentially with hybrid concentration. © 2010 American Chemical Society.

  13. Tethered balloons for radio detection of ultra high energy cosmic neutrinos in Antarctica

    Energy Technology Data Exchange (ETDEWEB)

    Besson, D. [Department of Physics and Astronomy, University of Kansas, Lawrence 66045, KS (United States); Dagkesamanskii, R.; Kravchenko, E. [Radio Astronomy Observatory LPI RAS, Pushchino 142290, Moscow Region (Russian Federation); Kravchenko, I., E-mail: ikrav@cern.ch [Department of Physics and Astronomy, University of Nebraska, Lincoln, 68588, NE (United States); Zheleznykh, I. [Institute for Nuclear Research RAS, Moscow 117312 (Russian Federation)

    2012-01-11

    We present a brief overview of experimental efforts in Antarctica to search for radio pulses from electron-hadron cascades produced by cosmic ultrahigh-energy neutrinos in Antarctic ice. Thus far, the essential features (energy thresholds, effective recording volumes, etc.) of Antarctic neutrino radio experiments can be classified according to the deployment scheme employed: either (1) on the surface of the glacier - RAMAND-type, (2) in holes in the ice at depths of several hundred meters - RICE-type or (3) on board of a stratospheric balloon at an altitude of 40 km - ANITA-type. We herein propose an alternative possibility, namely to use tethered balloons for placing the radio antennas at modest (compared to ANITA) altitudes above the ice surface (1-2 km). This configuration of antennas will reduce (as compared to ANITA) the energy threshold for detection of neutrinos and increase the observation time.

  14. Tethered balloons for radio detection of ultra high energy cosmic neutrinos in Antarctica

    International Nuclear Information System (INIS)

    Besson, D.; Dagkesamanskii, R.; Kravchenko, E.; Kravchenko, I.; Zheleznykh, I.

    2012-01-01

    We present a brief overview of experimental efforts in Antarctica to search for radio pulses from electron-hadron cascades produced by cosmic ultrahigh-energy neutrinos in Antarctic ice. Thus far, the essential features (energy thresholds, effective recording volumes, etc.) of Antarctic neutrino radio experiments can be classified according to the deployment scheme employed: either (1) on the surface of the glacier - RAMAND-type, (2) in holes in the ice at depths of several hundred meters - RICE-type or (3) on board of a stratospheric balloon at an altitude of 40 km - ANITA-type. We herein propose an alternative possibility, namely to use tethered balloons for placing the radio antennas at modest (compared to ANITA) altitudes above the ice surface (1-2 km). This configuration of antennas will reduce (as compared to ANITA) the energy threshold for detection of neutrinos and increase the observation time.

  15. Subunit Organisation of In Vitro Reconstituted HOPS and CORVET Multisubunit Membrane Tethering Complexes

    Science.gov (United States)

    Guo, Zhong; Johnston, Wayne; Kovtun, Oleksiy; Mureev, Sergey; Bröcker, Cornelia; Ungermann, Christian; Alexandrov, Kirill

    2013-01-01

    Biochemical and structural analysis of macromolecular protein assemblies remains challenging due to technical difficulties in recombinant expression, engineering and reconstitution of multisubunit complexes. Here we use a recently developed cell-free protein expression system based on the protozoan Leishmania tarentolae to produce in vitro all six subunits of the 600 kDa HOPS and CORVET membrane tethering complexes. We demonstrate that both subcomplexes and the entire HOPS complex can be reconstituted in vitro resulting in a comprehensive subunit interaction map. To our knowledge this is the largest eukaryotic protein complex in vitro reconstituted to date. Using the truncation and interaction analysis, we demonstrate that the complex is assembled through short hydrophobic sequences located in the C-terminus of the individual Vps subunits. Based on this data we propose a model of the HOPS and CORVET complex assembly that reconciles the available biochemical and structural data. PMID:24312556

  16. 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.

  17. BENTUK KERJASAMA PUBLIC-PRIVATE PEMBANGUNAN GRAVING DOCK DAN MANAJEMEN GALANGAN KAPAL DENGAN METODE ANALYTICAL HIERARCHI PROCESS (AHP

    Directory of Open Access Journals (Sweden)

    Hartono Hartono

    2012-08-01

    Full Text Available In paper Development of port infrastructure in Indonesia is now no longer the responsibility of centralgovernment, along with limited funds and the government's insistence seaport infrastructure needs. Toaccelerate economic growth, the government issued Government Regulation as a legal umbrella. The purpose ofthis study was to examine public-private partnership opportunities in the construction of graving dock andshipyard management. Targets do is review, the criteria are prioritized cooperation and cooperationpriorities.This study used qualitative and quantitative approach, a descriptive qualitative approach throughinterviews used to assess the normative aspect. The quantitative approach used to assess the priority criteriaforms of cooperation and public-private partnership in development graving dock and shipyard management byusing the Analytical Hierarchy Process (AHP. Based on the AHP analysis can be concluded that the expertsdisagree about the priority criteria of cooperation, where the majority of them choose the duration as the maincriterion. As for the analysis of priorities of the cooperation of all experts choose Built-Operate-Transfer (BOT,which is deemed suitable for long-term investment of up to 30 years. BOT puts private partners to more freely tofinance, construct, operate, anticipated rate of return on capital (rate of return and the risks of commercial andregulatory aspects

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

    Directory of Open Access Journals (Sweden)

    A. P. Karpenko

    2014-01-01

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

  19. Fluorosilicone multi-block copolymers tethering quaternary ammonium salt groups for antimicrobial purpose

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Fang; Qin, Xiaoshuai; Li, Yancai; Ren, Lixia; Zhao, Yunhui, E-mail: zhaoyunhui@tju.edu.cn; Yuan, Xiaoyan

    2015-08-30

    Highlights: • QAS-containing fluorosilicone multi-block copolymers were synthesized. • The block length of PHFBMA in the copolymers was tailored via RAFT polymerization. • Surface roughness of the copolymers decreased with the increased PHFBMA content. • A certain length of PHFBMA block enhanced C−N{sup +} percentage on the surface. - Abstract: Symmetrically structured fluorosilicone multi-block copolymers containing poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(hexafluorobutyl methacrylate) (PHFBMA) were sequentially synthesized via reversible addition–fragmentation chain transfer polymerization, using a polydimethylsiloxane (PDMS) chain transfer agent with dithiocarbonate groups at both ends. Then, the CBABC-type block copolymers were quaternized with n-octyliodide to tether quaternary ammonium salt (QAS) groups in the PDMAEMA blocks for the antimicrobial use. The obtained fluorosilicone copolymers showed clear variations in the C-N{sup +} composition and surface morphology on their films depending on the content of the PHFBMA blocks, which were characterized by X-ray photoelectron spectroscopy and atomic force microscopy, respectively. The results indicated that the symmetrical CBABC structure favored PDMS and QAS tethered blocks migrating to the film surface. With the mass percentage of the PHFBMA increased from 0 to 32.5%, the surface roughness of the copolymer film decreased gradually with a tendency to form a smooth surface. Owing to the surface properties, fluorosilicone multi-block copolymers containing a certain amount of PHFBMA with higher C-N{sup +} content and relatively smooth morphology demonstrated obvious antimicrobial activity against Gram-positive bacteria, Bacillus subtilis and Gram-negative bacteria, Escherichia coli. The functionalized multi-block copolymers based on fluorosilicone and QAS groups would have potential applications in antimicrobial coatings.

  20. Multiple Hydrogen Bond Tethers for Grazing Formic Acid in Its Complexes with Phenylacetylene.

    Science.gov (United States)

    Karir, Ginny; Kumar, Gaurav; Kar, Bishnu Prasad; Viswanathan, K S

    2018-03-01

    Complexes of phenylacetylene (PhAc) and formic acid (FA) present an interesting picture, where the two submolecules are tethered, sometimes multiply, by hydrogen bonds. The multiple tentacles adopted by PhAc-FA complexes stem from the fact that both submolecules can, in the same complex, serve as proton acceptors and/or proton donors. The acetylenic and phenyl π systems of PhAc can serve as proton acceptors, while the ≡C-H or -C-H of the phenyl ring can act as a proton donor. Likewise, FA also is amphiprotic. Hence, more than 10 hydrogen-bonded structures, involving O-H···π, C-H···π, and C-H···O contacts, were indicated by our computations, some with multiple tentacles. Interestingly, despite the multiple contacts in the complexes, the barrier between some of the structures is small, and hence, FA grazes around PhAc, even while being tethered to it, with hydrogen bonds. We used matrix isolation infrared spectroscopy to experimentally study the PhAc-FA complexes, with which we located global and a few local minima, involving primarily an O-H···π interaction. Experiments were corroborated by ab initio computations, which were performed using MP2 and M06-2X methods, with 6-311++G (d,p) and aug-cc-pVDZ basis sets. Single-point energy calculations were also done at MP2/CBS and CCSD(T)/CBS levels. The nature, strength, and origin of these noncovalent interactions were studied using AIM, NBO, and LMO-EDA analysis.

  1. Fluorosilicone multi-block copolymers tethering quaternary ammonium salt groups for antimicrobial purpose

    International Nuclear Information System (INIS)

    Zhou, Fang; Qin, Xiaoshuai; Li, Yancai; Ren, Lixia; Zhao, Yunhui; Yuan, Xiaoyan

    2015-01-01

    Highlights: • QAS-containing fluorosilicone multi-block copolymers were synthesized. • The block length of PHFBMA in the copolymers was tailored via RAFT polymerization. • Surface roughness of the copolymers decreased with the increased PHFBMA content. • A certain length of PHFBMA block enhanced C−N + percentage on the surface. - Abstract: Symmetrically structured fluorosilicone multi-block copolymers containing poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(hexafluorobutyl methacrylate) (PHFBMA) were sequentially synthesized via reversible addition–fragmentation chain transfer polymerization, using a polydimethylsiloxane (PDMS) chain transfer agent with dithiocarbonate groups at both ends. Then, the CBABC-type block copolymers were quaternized with n-octyliodide to tether quaternary ammonium salt (QAS) groups in the PDMAEMA blocks for the antimicrobial use. The obtained fluorosilicone copolymers showed clear variations in the C-N + composition and surface morphology on their films depending on the content of the PHFBMA blocks, which were characterized by X-ray photoelectron spectroscopy and atomic force microscopy, respectively. The results indicated that the symmetrical CBABC structure favored PDMS and QAS tethered blocks migrating to the film surface. With the mass percentage of the PHFBMA increased from 0 to 32.5%, the surface roughness of the copolymer film decreased gradually with a tendency to form a smooth surface. Owing to the surface properties, fluorosilicone multi-block copolymers containing a certain amount of PHFBMA with higher C-N + content and relatively smooth morphology demonstrated obvious antimicrobial activity against Gram-positive bacteria, Bacillus subtilis and Gram-negative bacteria, Escherichia coli. The functionalized multi-block copolymers based on fluorosilicone and QAS groups would have potential applications in antimicrobial coatings

  2. International survey on the management of skin stigmata and suspected tethered cord.

    Science.gov (United States)

    Ponger, Penina; Ben-Sira, Liat; Beni-Adani, Liana; Steinbok, Paul; Constantini, Shlomi

    2010-12-01

    We designed a survey to investigate current international management trends of neonates with lumbar midline skin stigmata suspicious of tethered cord, among pediatric neurosurgeons, focusing on the lower risk stigmata, simple dimples, deviated gluteal folds, and discolorations. Our findings will enable physicians to assess their current diagnosis routine and aid in clarifying management controversies. A questionnaire on the proposed diagnostic evaluation of seven case reports, each accompanied by relevant imaging, was distributed by e-mail to members of the International Society for Pediatric Neurosurgery, the European Society for Pediatric Neurosurgery, and via the PEDS server list between March and August 2008. Sixty-two questionnaires, completed by experienced professionals with a rather uniform distribution of experience levels, were analyzed. Forty-eight percent do not recommend any imaging of simple dimples, 30% recommend US screening and 22% recommend MR. Seventy-nine percent recommend imaging of deviated gluteal fold with 30% recommending MR. Ninety-two percent recommend imaging infants with hemangiomas with 74% recommending MR. MR for sinus tracts is recommended by 90% if sacral and by 98% if lumber. Eighty-four percent recommend MR for filar cyst. Our survey demonstrates that management of low-risk skin stigmata, simple dimple, deviated gluteal fold, and discolorations lacks consensus. In addition, a significant sector of the professional community proposes a work-up of simple dimples, sacral tracts, and filar cysts that contradicts established recommendations. A simple classification system is needed to attain a better approach, enabling correct diagnosis of tethered cord without exposing neonates to unnecessary examinations.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Hongjian Li

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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. 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

  15. HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Manjeet; Kaur, Supinder; Nazir, Aamir; Tripathi, Raj Kamal, E-mail: rajkamalcdri@gmail.com

    2016-05-20

    HIV-1 Nef modulates cellular function that enhances viral replication in vivo which culminate into AIDS pathogenesis. With no enzymatic activity, Nef regulates cellular function through host protein interaction. Interestingly, trans-cellular introduction of recombinant Nef protein in Caenorhabditis elegans results in AIDS like pathogenesis which might share common pathophysiology because the gene sequence of C. elegans and humans share considerable homology. Therefore employing C. elegans based initial screen complemented with sequence based homology search we identified GCC185 as novel host protein interacting with HIV-1 Nef. The detailed molecular characterization revealed N-terminal EEEE{sub 65} acidic domain of Nef as key region for interaction. GCC185 is a tethering protein that binds with Rab9 transport vesicles. Our results show that Nef-GCC185 interaction disrupts Rab9 interaction resulting in delocalization of CI-MPR (cation independent Mannose 6 phosphate receptor) resulting in elevated secretion of hexosaminidase. In agreement with this, our studies identified novel host GCC185 protein that interacts with Nef EEEE65 acidic domain interfering GCC185-Rab9 vesicle membrane fusion responsible for retrograde vesicular transport of CI-MPR from late endosomes to TGN. In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis. -- Highlights: •Nef, an accessory protein of HIV-1 interacts with host factor and culminates into AIDS pathogenesis. •Using Caenorhabditis elegans based screen system, novel Nef interacting cellular protein GCC185 was identified. •Molecular characterization of Nef and human protein GCC185 revealed Nef EEEE{sub 65} key region interacted with full length GCC185. •Nef impeded the GCC185-Rab 9 interaction and

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

    Directory of Open Access Journals (Sweden)

    Huai-Chun Chen

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

  17. Next-generation site-directed transgenesis in the malaria vector mosquito Anopheles gambiae: self-docking strains expressing germline-specific phiC31 integrase.

    Directory of Open Access Journals (Sweden)

    Janet M Meredith

    Full Text Available Diseases transmitted by mosquitoes have a devastating impact on global health and the situation is complicated due to difficulties with both existing control measures and the impact of climate change. Genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. The Streptomyces phage phiC31 integrase system has been successfully adapted for site-directed transgene integration in a range of insects, thus overcoming many limitations due to size constraints and random integration associated with transposon-mediated transformation. Using this technology, we previously published the first site-directed transformation of Anopheles gambiae, the principal vector of human malaria. Mosquitoes were initially engineered to incorporate the phiC31 docking site at a defined genomic location. A second phase of genetic modification then achieved site-directed integration of an anti-malarial effector gene. In the current publication we report improved efficiency and utility of the phiC31 integrase system following the generation of Anopheles gambiae self-docking strains. Four independent strains, with docking sites at known locations on three different chromosome arms, were engineered to express integrase under control of the regulatory regions of the nanos gene from Anopheles gambiae. The resulting protein accumulates in the posterior oocyte to provide integrase activity at the site of germline development. Two self-docking strains, exhibiting significantly different levels of integrase expression, were assessed for site-directed transgene integration and found to demonstrate greatly improved survival and efficiency of transformation. In the fight against malaria, it is imperative to establish a broad repertoire of both anti-malarial effector genes and tissue-specific promoters to regulate their expression, enabling those offering maximum effect with minimum fitness

  18. 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.

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

    KAUST Repository

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

    2013-01-01

    ) conformations in the top positions is still an open problem. Herein we present CONSRANK, a simple and effective tool to rank multiple docking solutions, which relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. First

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

    Data.gov (United States)

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