Switch loop flexibility affects substrate transport of the AcrB efflux pump

DOE PAGES

Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea; ...

2017-10-05

The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutionsmore » on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.« less

Switch loop flexibility affects substrate transport of the AcrB efflux pump

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea

The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutionsmore » on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.« less

Control of a flexible link by shaping the closed loop frequency response function through optimised feedback filters

NASA Astrophysics Data System (ADS)

Del Vescovo, D.; D'Ambrogio, W.

1995-01-01

A frequency domain method is presented to design a closed-loop control for vibration reduction flexible mechanisms. The procedure is developed on a single-link flexible arm, driven by one rotary degree of freedom servomotor, although the same technique may be applied to similar systems such as supports for aerospace antennae or solar panels. The method uses the structural frequency response functions (FRFs), thus avoiding system identification, that produces modeling uncertainties. Two closed-loops are implemented: the inner loop uses acceleration feedback with the aim of making the FRF similar to that of an equivalent rigid link; the outer loop feeds back displacements to achieve a fast positioning response and null steady state error. In both cases, the controller type is established a priori, while actual characteristics are defined by an optimisation procedure in which the relevant FRF is constrained into prescribed bounds and stability is taken into account.

Experimental determination of frequency response function estimates for flexible joint industrial manipulators with serial kinematics

NASA Astrophysics Data System (ADS)

Saupe, Florian; Knoblach, Andreas

2015-02-01

Two different approaches for the determination of frequency response functions (FRFs) are used for the non-parametric closed loop identification of a flexible joint industrial manipulator with serial kinematics. The two applied experiment designs are based on low power multisine and high power chirp excitations. The main challenge is to eliminate disturbances of the FRF estimates caused by the numerous nonlinearities of the robot. For the experiment design based on chirp excitations, a simple iterative procedure is proposed which allows exploiting the good crest factor of chirp signals in a closed loop setup. An interesting synergy of the two approaches, beyond validation purposes, is pointed out.

Maneuvering and control of flexible space robots

NASA Technical Reports Server (NTRS)

Meirovitch, Leonard; Lim, Seungchul

1994-01-01

This paper is concerned with a flexible space robot capable of maneuvering payloads. The robot is assumed to consist of two hinge-connected flexible arms and a rigid end-effector holding a payload; the robot is mounted on a rigid platform floating in space. The equations of motion are nonlinear and of high order. Based on the assumption that the maneuvering motions are one order of magnitude larger than the elastic vibrations, a perturbation approach permits design of controls for the two types of motion separately. The rigid-body maneuvering is carried out open loop, but the elastic motions are controlled closed loop, by means of discrete-time linear quadratic regulator theory with prescribed degree of stability. A numerical example demonstrates the approach. In the example, the controls derived by the perturbation approach are applied to the original nonlinear system and errors are found to be relatively small.

Flexibility of the Cu,Zn superoxide dismutase structure investigated at 0.57 GPa.

PubMed

Ascone, Isabella; Savino, Carmelinda; Kahn, Richard; Fourme, Roger

2010-06-01

The 2 A resolution crystal structure of bovine erythrocyte Cu,Zn superoxide dismutase (CuZnSOD) has been determined by X-ray diffraction at high pressure (0.57 GPa) and room temperature. At 0.57 GPa the secondary, tertiary and quaternary structures are similar to other previously determined bovine erythrocyte CuZnSOD structures. Nevertheless, pressure has a localized impact on the atomic coordinates of C(alpha) atoms and on side chains. The compression of the crystal and of the protein backbone is anisotropic. This anisotropy is discussed, taking into account intermolecular contacts and protein conformation. Pressure perturbation highlights the more flexible zones in the protein such as the electrostatic loop. At 0.57 GPa, a global shift of the dimetallic sites in both subunits and changes in the oxidation state of Cu were observed. The flexibility of the electrostatic loop may be useful for the interaction of different metal carriers in the copper-uptake process, whereas the flexibility of the metal sites involved in the activity of the protein could contribute to explaining the ubiquitous character of CuZnSODs, which are found in organisms living in very different conditions, including the deep-sea environment. This work illustrates the potential of combining X-ray crystallography with high pressure to promote and stabilize higher energy conformational substates.

Analysis of flexible aircraft longitudinal dynamics and handling qualities. Volume 2: Data

NASA Technical Reports Server (NTRS)

Waszak, M. R.; Schmidt, D. K.

1985-01-01

Two analysis methods are applied to a family of flexible aircraft in order to investigate how and when structural (especially dynamic aeroelastic) effects affect the dynamic characteristics of aircraft. The first type of analysis is an open loop modal analysis technique. This method considers the effect of modal residue magnitudes on determining vehicle handling qualities. The second method is a pilot in the loop analysis procedure that considers several closed loop system characteristics. Both analyses indicated that dynamic aeroelastic effects caused a degradation in vehicle tracking performance, based on the evaluation of some simulation results. Volume 2 consists of the presentation of the state variable models of the flexible aircraft configurations used in the analysis applications mode shape plots for the structural modes, numerical results from the modal analysis frequency response plots from the pilot in the loop analysis and a listing of the modal analysis computer program.

Modified nonlinear amplifying loop mirror for mode-locked fibre oscillators with record-high energy and high-average-power pulsed output

NASA Astrophysics Data System (ADS)

Kobtsev, Sergey; Ivanenko, Alexey; Smirnov, Sergey; Kokhanovsky, Alexey

2018-02-01

The present work proposes and studies approaches for development of new modified non-linear amplifying loop mirror (NALM) allowing flexible and dynamic control of their non-linear properties within a relatively broad range of radiation powers. Using two independently pumped active media in the loop reflector constitutes one of the most promising approaches to development of better NALM with nonlinear properties controllable independently of the intra-cavity radiation power. This work reports on experimental and theoretical studies of the proposed redesigned NALM allowing both a higher level of energy parameters of output generated by mode-locked fibre oscillators and new possibilities of switching among different mode-locked regimes.

Proteins with Novel Structure, Function and Dynamics

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2014-01-01

Recently, a small enzyme that ligates two RNA fragments with the rate of 10(exp 6) above background was evolved in vitro (Seelig and Szostak, Nature 448:828-831, 2007). This enzyme does not resemble any contemporary protein (Chao et al., Nature Chem. Biol. 9:81-83, 2013). It consists of a dynamic, catalytic loop, a small, rigid core containing two zinc ions coordinated by neighboring amino acids, and two highly flexible tails that might be unimportant for protein function. In contrast to other proteins, this enzyme does not contain ordered secondary structure elements, such as alpha-helix or beta-sheet. The loop is kept together by just two interactions of a charged residue and a histidine with a zinc ion, which they coordinate on the opposite side of the loop. Such structure appears to be very fragile. Surprisingly, computer simulations indicate otherwise. As the coordinating, charged residue is mutated to alanine, another, nearby charged residue takes its place, thus keeping the structure nearly intact. If this residue is also substituted by alanine a salt bridge involving two other, charged residues on the opposite sides of the loop keeps the loop in place. These adjustments are facilitated by high flexibility of the protein. Computational predictions have been confirmed experimentally, as both mutants retain full activity and overall structure. These results challenge our notions about what is required for protein activity and about the relationship between protein dynamics, stability and robustness. We hypothesize that small, highly dynamic proteins could be both active and fault tolerant in ways that many other proteins are not, i.e. they can adjust to retain their structure and activity even if subjected to mutations in structurally critical regions. This opens the doors for designing proteins with novel functions, structures and dynamics that have not been yet considered.

Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification

PubMed Central

Jeliazkov, Jeliazko R.; Sljoka, Adnan; Kuroda, Daisuke; Tsuchimura, Nobuyuki; Katoh, Naoki; Tsumoto, Kouhei; Gray, Jeffrey J.

2018-01-01

Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity. PMID:29545810

Central safety factor and β N control on NSTX-U via beam power and plasma boundary shape modification, using TRANSP for closed loop simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyer, M. D.; Andre, R.; Gates, D. A.

The high-performance operational goals of NSTX-U will require development of advanced feedback control algorithms, including control of ßN and the safety factor profile. In this work, a novel approach to simultaneously controlling ßN and the value of the safety factor on the magnetic axis, q0, through manipulation of the plasma boundary shape and total beam power, is proposed. Simulations of the proposed scheme show promising results and motivate future experimental implementation and eventual integration into a more complex current profile control scheme planned to include actuation of individual beam powers, density, and loop voltage. As part of this work, amore » flexible framework for closed loop simulations within the high-fidelity code TRANSP was developed. The framework, used here to identify control-design-oriented models and to tune and test the proposed controller, exploits many of the predictive capabilities of TRANSP and provides a means for performing control calculations based on user-supplied data (controller matrices, target waveforms, etc.). The flexible framework should enable high-fidelity testing of a variety of control algorithms, thereby reducing the amount of expensive experimental time needed to implement new control algorithms on NSTX-U and other devices.« less

Central safety factor and βN control on NSTX-U via beam power and plasma boundary shape modification, using TRANSP for closed loop simulations

NASA Astrophysics Data System (ADS)

Boyer, M. D.; Andre, R.; Gates, D. A.; Gerhardt, S.; Goumiri, I. R.; Menard, J.

2015-05-01

The high-performance operational goals of NSTX-U will require development of advanced feedback control algorithms, including control of βN and the safety factor profile. In this work, a novel approach to simultaneously controlling βN and the value of the safety factor on the magnetic axis, q0, through manipulation of the plasma boundary shape and total beam power, is proposed. Simulations of the proposed scheme show promising results and motivate future experimental implementation and eventual integration into a more complex current profile control scheme planned to include actuation of individual beam powers, density, and loop voltage. As part of this work, a flexible framework for closed loop simulations within the high-fidelity code TRANSP was developed. The framework, used here to identify control-design-oriented models and to tune and test the proposed controller, exploits many of the predictive capabilities of TRANSP and provides a means for performing control calculations based on user-supplied data (controller matrices, target waveforms, etc). The flexible framework should enable high-fidelity testing of a variety of control algorithms, thereby reducing the amount of expensive experimental time needed to implement new control algorithms on NSTX-U and other devices.

RosettaRemodel: A Generalized Framework for Flexible Backbone Protein Design

PubMed Central

Huang, Po-Ssu; Ban, Yih-En Andrew; Richter, Florian; Andre, Ingemar; Vernon, Robert; Schief, William R.; Baker, David

2011-01-01

We describe RosettaRemodel, a generalized framework for flexible protein design that provides a versatile and convenient interface to the Rosetta modeling suite. RosettaRemodel employs a unified interface, called a blueprint, which allows detailed control over many aspects of flexible backbone protein design calculations. RosettaRemodel allows the construction and elaboration of customized protocols for a wide range of design problems ranging from loop insertion and deletion, disulfide engineering, domain assembly, loop remodeling, motif grafting, symmetrical units, to de novo structure modeling. PMID:21909381

Closed Loop System Identification with Genetic Algorithms

NASA Technical Reports Server (NTRS)

Whorton, Mark S.

2004-01-01

High performance control design for a flexible space structure is challenging since high fidelity plant models are di.cult to obtain a priori. Uncertainty in the control design models typically require a very robust, low performance control design which must be tuned on-orbit to achieve the required performance. Closed loop system identi.cation is often required to obtain a multivariable open loop plant model based on closed-loop response data. In order to provide an accurate initial plant model to guarantee convergence for standard local optimization methods, this paper presents a global parameter optimization method using genetic algorithms. A minimal representation of the state space dynamics is employed to mitigate the non-uniqueness and over-parameterization of general state space realizations. This control-relevant system identi.cation procedure stresses the joint nature of the system identi.cation and control design problem by seeking to obtain a model that minimizes the di.erence between the predicted and actual closed-loop performance.

Real-time dynamics simulation of the Cassini spacecraft using DARTS. Part 1: Functional capabilities and the spatial algebra algorithm

NASA Technical Reports Server (NTRS)

Jain, A.; Man, G. K.

1993-01-01

This paper describes the Dynamics Algorithms for Real-Time Simulation (DARTS) real-time hardware-in-the-loop dynamics simulator for the National Aeronautics and Space Administration's Cassini spacecraft. The spacecraft model consists of a central flexible body with a number of articulated rigid-body appendages. The demanding performance requirements from the spacecraft control system require the use of a high fidelity simulator for control system design and testing. The DARTS algorithm provides a new algorithmic and hardware approach to the solution of this hardware-in-the-loop simulation problem. It is based upon the efficient spatial algebra dynamics for flexible multibody systems. A parallel and vectorized version of this algorithm is implemented on a low-cost, multiprocessor computer to meet the simulation timing requirements.

High Performance, Robust Control of Flexible Space Structures: MSFC Center Director's Discretionary Fund

NASA Technical Reports Server (NTRS)

Whorton, M. S.

1998-01-01

Many spacecraft systems have ambitious objectives that place stringent requirements on control systems. Achievable performance is often limited because of difficulty of obtaining accurate models for flexible space structures. To achieve sufficiently high performance to accomplish mission objectives may require the ability to refine the control design model based on closed-loop test data and tune the controller based on the refined model. A control system design procedure is developed based on mixed H2/H(infinity) optimization to synthesize a set of controllers explicitly trading between nominal performance and robust stability. A homotopy algorithm is presented which generates a trajectory of gains that may be implemented to determine maximum achievable performance for a given model error bound. Examples show that a better balance between robustness and performance is obtained using the mixed H2/H(infinity) design method than either H2 or mu-synthesis control design. A second contribution is a new procedure for closed-loop system identification which refines parameters of a control design model in a canonical realization. Examples demonstrate convergence of the parameter estimation and improved performance realized by using the refined model for controller redesign. These developments result in an effective mechanism for achieving high-performance control of flexible space structures.

A digitalized silicon microgyroscope based on embedded FPGA.

PubMed

Xia, Dunzhu; Yu, Cheng; Wang, Yuliang

2012-09-27

This paper presents a novel digital miniaturization method for a prototype silicon micro-gyroscope (SMG) with the symmetrical and decoupled structure. The schematic blocks of the overall system consist of high precision analog front-end interface, high-speed 18-bit analog to digital convertor, a high-performance core Field Programmable Gate Array (FPGA) chip and other peripherals such as high-speed serial ports for transmitting data. In drive mode, the closed-loop drive circuit are implemented by automatic gain control (AGC) loop and software phase-locked loop (SPLL) based on the Coordinated Rotation Digital Computer (CORDIC) algorithm. Meanwhile, the sense demodulation module based on varying step least mean square demodulation (LMSD) are addressed in detail. All kinds of algorithms are simulated by Simulink and DSPbuilder tools, which is in good agreement with the theoretical design. The experimental results have fully demonstrated the stability and flexibility of the system.

A Digitalized Silicon Microgyroscope Based on Embedded FPGA

PubMed Central

Xia, Dunzhu; Yu, Cheng; Wang, Yuliang

2012-01-01

This paper presents a novel digital miniaturization method for a prototype silicon micro-gyroscope (SMG) with the symmetrical and decoupled structure. The schematic blocks of the overall system consist of high precision analog front-end interface, high-speed 18-bit analog to digital convertor, a high-performance core Field Programmable Gate Array (FPGA) chip and other peripherals such as high-speed serial ports for transmitting data. In drive mode, the closed-loop drive circuit are implemented by automatic gain control (AGC) loop and software phase-locked loop (SPLL) based on the Coordinated Rotation Digital Computer (CORDIC) algorithm. Meanwhile, the sense demodulation module based on varying step least mean square demodulation (LMSD) are addressed in detail. All kinds of algorithms are simulated by Simulink and DSPbuilder tools, which is in good agreement with the theoretical design. The experimental results have fully demonstrated the stability and flexibility of the system. PMID:23201990

Flexible stator control on the Galileo spacecraft

NASA Technical Reports Server (NTRS)

Kopf, E. H.; Brown, T. K.; Marsh, E. L.

1979-01-01

Galileo is a dual-spin spacecraft designed to deliver a probe to Jupiter and then orbit the planet. The stator, or despun section, contains four flexible modes below 10 Hz and the despun actuator is separated from the inertial sensors by this flexibility. Control loop separation by bandwidth proved unacceptable due to performance requirements. To obtain the desired performance, a control scheme was devised which consists of three parts. First, flexibility damping and control notch filtering are accomplished by phase locked loop techniques. Second, slewing maneuvers are produced by torque profiles which are nonexcitatory to the structure. Finally, a low bandwidth perturbation controller is supplied to remove spacecraft disturbances.

Plastic flexible films waste management - A state of art review.

PubMed

Horodytska, O; Valdés, F J; Fullana, A

2018-04-21

Plastic flexible films are increasingly used in many applications due to their lightness and versatility. In 2014, the amount of plastic films represented 34% of total plastic packaging produced in UK. The flexible film waste generation rises according to the increase in number of applications. Currently, in developed countries, about 50% of plastics in domestic waste are films. Moreover, about 615,000 tonnes of agricultural flexible waste are generated in the EU every year. A review of plastic films recycling has been conducted in order to detect the shortcomings and establish guidelines for future research. This paper reviews plastic films waste management technologies from two different sources: post-industrial and post-consumer. Clean and homogeneous post-industrial waste is recycled through closed-loop or open-loop mechanical processes. The main differences between these methods are the quality and the application of the recycled materials. Further research should be focused on closing the loops to obtain the highest environmental benefits of recycling. This could be accomplished through minimizing the material degradation during mechanical processes. Regarding post-consumer waste, flexible films from agricultural and packaging sectors have been assessed. The agricultural films and commercial and industrial flexible packaging are recycled through open-loop mechanical recycling due to existing selective waste collection routes. Nevertheless, the contamination from the use phase adversely affects the quality of recycled plastics. Therefore, upgrading of current washing lines is required. On the other hand, household flexible packaging shows the lowest recycling rates mainly because of inefficient sorting technologies. Delamination and compatibilization methods should be further developed to ensure the recycling of multilayer films. Finally, Life Cycle Assessment (LCA) studies on waste management have been reviewed. A lack of thorough LCA on plastic films waste management systems was identified. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficient Computation of Closed-loop Frequency Response for Large Order Flexible Systems

NASA Technical Reports Server (NTRS)

Maghami, Peiman G.; Giesy, Daniel P.

1997-01-01

An efficient and robust computational scheme is given for the calculation of the frequency response function of a large order, flexible system implemented with a linear, time invariant control system. Advantage is taken of the highly structured sparsity of the system matrix of the plant based on a model of the structure using normal mode coordinates. The computational time per frequency point of the new computational scheme is a linear function of system size, a significant improvement over traditional, full-matrix techniques whose computational times per frequency point range from quadratic to cubic functions of system size. This permits the practical frequency domain analysis of systems of much larger order than by traditional, full-matrix techniques. Formulations are given for both open and closed loop loop systems. Numerical examples are presented showing the advantages of the present formulation over traditional approaches, both in speed and in accuracy. Using a model with 703 structural modes, a speed-up of almost two orders of magnitude was observed while accuracy improved by up to 5 decimal places.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Wei; Leal, Walter S.

Pheromone-binding proteins (PBPs) are involved in the uptake of pheromones from pores on the antennae, transport through an aqueous environment surrounding the olfactory receptor neurons, and fast delivery to pheromone receptors. We tested the hypothesis that a C-terminal segment and a flexible loop are involved in the release of pheromones to membrane-bound receptors. We expressed in Escherichia coli 11 mutants of the PBP from the silkworm moth, BmorPBP, taking into consideration structural differences between the forms with high and low binding affinity. The N-terminus was truncated and His-69, His-70 and His-95 at the base of a flexible loop, and amore » cluster of acidic residues at the C-terminus were mutated. Binding assays and circular dichroism analyses support a mechanism involving protonation of acidic residues Asp-132 and Glu-141 at the C-terminus and histidines, His-70 and His-95, in the base of a loop covering the binding pocket. The former leads to the formation of a new {alpha}-helix, which competes with pheromone for the binding pocket, whereas positive charge repulsion of the histidines opens the opposite side of the binding pocket.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Qiaozhen; Krug, Robert M.; Tao, Yizhi Jane

Influenza A viruses pose a serious threat to world public health, particularly the currently circulating avian H5N1 viruses. The influenza viral nucleoprotein forms the protein scaffold of the helical genomic ribonucleoprotein complexes, and has a critical role in viral RNA replication. Here we report a 3.2 Angstrom crystal structure of this nucleoprotein, the overall shape of which resembles a crescent with a head and a body domain, with a protein fold different compared with that of the rhabdovirus nucleoprotein. Oligomerization of the influenza virus nucleoprotein is mediated by a flexible tail loop that is inserted inside a neighboring molecule. Thismore » flexibility in the tail loop enables the nucleoprotein to form loose polymers as well as rigid helices, both of which are important for nucleoprotein functions. Single residue mutations in the tail loop result in the complete loss of nucleoprotein oligomerization. An RNA-binding groove, which is found between the head and body domains at the exterior of the nucleoprotein oligomer, is lined with highly conserved basic residues widely distributed in the primary sequence. The nucleoprotein structure shows that only one of two proposed nuclear localization signals are accessible, and suggests that the body domain of nucleoprotein contains the binding site for the viral polymerase. Our results identify the tail loop binding pocket as a potential target for antiviral development.« less

Analysis of virtual passive controllers for flexible space structures

NASA Technical Reports Server (NTRS)

Williams, Trevor W.

1992-01-01

The dynamics of flexible spacecraft are not usually well known before launch. This makes it important to develop controllers for such systems that can never be destabilized by perturbations in the structural model. Virtual passive controllers, or active vibration absorbers, possess this guaranteed stability property; they mimic a fictitious flexible structure attached to the true physical one. This report analyzes the properties of such controllers, and shows that disturbance absorption behavior can be naturally described in terms of a set of virtual zeros that they introduce into the closed-loop dynamics of the system. Based on this analysis, techniques are then derived for selecting the active vibration absorber internal parameters, i.e., the gain matrices of such controllers, so as to achieve specified control objectives. Finally, the effects on closed-loop stability of small delays in the feedback loop are investigated. Such delays would typically be introduced by a digital implementation of an active vibration absorber. It is shown that these delays only affect the real parts of the eigenvalues of a lightly-damped structure. Furthermore, it is only the high-frequency modes that are destabilized by delays; low-frequency modes are actually made more heavily damped. Eigenvalue perturbation methods are used to obtain accurate predictions of the critical delay at which a given system will become unstable; these methods also determine which mode is critical.

Energy Conversion Loop: A Testbed for Nuclear Hybrid Energy Systems Use in Biomass Pyrolysis

NASA Astrophysics Data System (ADS)

Verner, Kelley M.

Nuclear hybrid energy systems are a possible solution for contemporary energy challenges. Nuclear energy produces electricity without greenhouse gas emissions. However, nuclear power production is not as flexible as electrical grids demand and renewables create highly variable electricity. Nuclear hybrid energy systems are able to address both of these problems. Wasted heat can be used in processes such as desalination, hydrogen production, or biofuel production. This research explores the possible uses of nuclear process heat in bio-oil production via biomass pyrolysis. The energy conversion loop is a testbed designed and built to mimic the heat from a nuclear reactor. Small scale biomass pyrolysis experiments were performed and compared to results from the energy conversion loop tests to determine future pyrolysis experimentation with the energy conversion loop. Further improvements must be made to the energy conversion loop before more complex experiments may be performed. The current conditions produced by the energy conversion loop are not conducive for current biomass pyrolysis experimentation.tion.

Smart Braid Feedback for the Closed-Loop Control of Soft Robotic Systems.

PubMed

Felt, Wyatt; Chin, Khai Yi; Remy, C David

2017-09-01

This article experimentally investigates the potential of using flexible, inductance-based contraction sensors in the closed-loop motion control of soft robots. Accurate motion control remains a highly challenging task for soft robotic systems. Precise models of the actuation dynamics and environmental interactions are often unavailable. This renders open-loop control impossible, while closed-loop control suffers from a lack of suitable feedback. Conventional motion sensors, such as linear or rotary encoders, are difficult to adapt to robots that lack discrete mechanical joints. The rigid nature of these sensors runs contrary to the aspirational benefits of soft systems. As truly soft sensor solutions are still in their infancy, motion control of soft robots has so far relied on laboratory-based sensing systems such as motion capture, electromagnetic (EM) tracking, or Fiber Bragg Gratings. In this article, we used embedded flexible sensors known as Smart Braids to sense the contraction of McKibben muscles through changes in inductance. We evaluated closed-loop control on two systems: a revolute joint and a planar, one degree of freedom continuum manipulator. In the revolute joint, our proposed controller compensated for elasticity in the actuator connections. The Smart Braid feedback allowed motion control with a steady-state root-mean-square (RMS) error of [1.5]°. In the continuum manipulator, Smart Braid feedback enabled tracking of the desired tip angle with a steady-state RMS error of [1.25]°. This work demonstrates that Smart Braid sensors can provide accurate position feedback in closed-loop motion control suitable for field applications of soft robotic systems.

Initial Binding of Ions to the Interhelical Loops of Divalent Ion Transporter CorA: Replica Exchange Molecular Dynamics Simulation Study

PubMed Central

Zhang, Tong; Mu, Yuguang

2012-01-01

Crystal structures of Thermotoga maritima magnesium transporter CorA, reported in 2006, revealed its homo-pentameric constructions. However, the structure of the highly conserved extracellular interhelical loops remains unsolved, due to its high flexibility. We have explored the configurations of the loops through extensive replica exchange molecular dynamics simulations in explicit solvent model with the presence of either Co(III) Hexamine ions or Mg2+ ions. We found that there are multiple binding sites available on the interhelical loops in which the negatively charged residues, E316 and E320, are located notably close to the positively charged ions during the simulations. Our simulations resolved the distinct binding patterns of the two kinds of ions: Co(III) Hexamine ions were found to bind stronger with the loop than Mg2+ ions with binding free energy −7.3 kJ/mol lower, which is nicely consistent with the previous data. Our study provides an atomic basis description of the initial binding process of Mg2+ ions on the extracellular interhelical loops of CorA and the detailed inhibition mechanism of Co(III) Hexamine ions on CorA ions transportation. PMID:22952795

Vibration suppression in flexible structures via the sliding-mode control approach

NASA Technical Reports Server (NTRS)

Drakunov, S.; Oezguener, Uemit

1994-01-01

Sliding mode control became very popular recently because it makes the closed loop system highly insensitive to external disturbances and parameter variations. Sliding algorithms for flexible structures have been used previously, but these were based on finite-dimensional models. An extension of this approach for differential-difference systems is obtained. That makes if possible to apply sliding-mode control algorithms to the variety of nondispersive flexible structures which can be described as differential-difference systems. The main idea of using this technique for dispersive structures is to reduce the order of the controlled part of the system by applying an integral transformation. We can say that transformation 'absorbs' the dispersive properties of the flexible structure as the controlled part becomes dispersive.

Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis

PubMed Central

O’Brien, Darragh P.; Durand, Dominique; Voegele, Alexis; Hourdel, Véronique; Davi, Marilyne; Chamot-Rooke, Julia; Vachette, Patrice; Brier, Sébastien; Ladant, Daniel

2017-01-01

Once translocated into the cytosol of target cells, the catalytic domain (AC) of the adenylate cyclase toxin (CyaA), a major virulence factor of Bordetella pertussis, is potently activated by binding calmodulin (CaM) to produce supraphysiological levels of cAMP, inducing cell death. Using a combination of small-angle X-ray scattering (SAXS), hydrogen/deuterium exchange mass spectrometry (HDX-MS), and synchrotron radiation circular dichroism (SR-CD), we show that, in the absence of CaM, AC exhibits significant structural disorder, and a 75-residue-long stretch within AC undergoes a disorder-to-order transition upon CaM binding. Beyond this local folding, CaM binding induces long-range allosteric effects that stabilize the distant catalytic site, whilst preserving catalytic loop flexibility. We propose that the high enzymatic activity of AC is due to a tight balance between the CaM-induced decrease of structural flexibility around the catalytic site and the preservation of catalytic loop flexibility, allowing for fast substrate binding and product release. The CaM-induced dampening of AC conformational disorder is likely relevant to other CaM-activated enzymes. PMID:29287065

NMR studies of the backbone flexibility and structure of human growth hormone: a comparison of high and low pH conformations.

PubMed

Kasimova, Marina R; Kristensen, Søren M; Howe, Peter W A; Christensen, Thorkild; Matthiesen, Finn; Petersen, Jørgen; Sørensen, Hans H; Led, Jens J

2002-05-03

(15)N NMR relaxation parameters and amide (1)H/(2)H-exchange rates have been used to characterize the structural flexibility of human growth hormone (rhGH) at neutral and acidic pH. Our results show that the rigidity of the molecule is strongly affected by the solution conditions. At pH 7.0 the backbone dynamics parameters of rhGH are uniform along the polypeptide chain and their values are similar to those of other folded proteins. In contrast, at pH 2.7 the overall backbone flexibility increases substantially compared to neutral pH and the average order parameter approaches the lower limit expected for a folded protein. However, a significant variation of the backbone dynamics through the molecule indicates that under acidic conditions the mobility of the residues becomes more dependent on their location within the secondary structure units. In particular, the order parameters of certain loop regions decrease dramatically and become comparable to those found in unfolded proteins. Furthermore, the HN-exchange rates at low pH reveal that the residues most protected from exchange are clustered at one end of the helical bundle, forming a stable nucleus. We suggest that this nucleus maintains the overall fold of the protein under destabilizing conditions. We therefore conclude that the acid state of rhGH consists of a structurally conserved, but dynamically more flexible helical core surrounded by an aura of highly mobile, unstructured loops. However, in spite of its prominent flexibility the acid state of rhGH cannot be considered a "molten globule" state because of its high stability. It appears from our work that under certain conditions, a protein can tolerate a considerable increase in flexibility of its backbone, along with an increased penetration of water into its core, while still maintaining a stable folded conformation.

Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 Å resolution

PubMed Central

Tu, Chao; Tan, Yu-Hong; Shaw, Gary; Zhou, Zheng; Bai, Yawen; Luo, Ray; Ji, Xinhua

2008-01-01

Tumor suppressor p53 is a sequence-specific DNA-binding protein and its central DNA-binding domain (DBD) harbors six hotspots (Arg175, Gly245, Arg248, Arg249, Arg273 and Arg282) for human cancers. Here, the crystal structure of a low-frequency hotspot mutant, p53DBD(R282Q), is reported at 1.54 Å resolution together with the results of molecular-dynamics simulations on the basis of the structure. In addition to eliminating a salt bridge, the R282Q mutation has a significant impact on the properties of two DNA-binding loops (L1 and L3). The L1 loop is flexible in the wild type, but it is not flexible in the mutant. The L3 loop of the wild type is not flexible, whereas it assumes two conformations in the mutant. Molecular-dynamics simulations indicated that both conformations of the L3 loop are accessible under biological conditions. It is predicted that the elimination of the salt bridge and the inversion of the flexibility of L1 and L3 are directly or indirectly responsible for deactivating the tumor suppressor p53. PMID:18453682

The flexibility of a distant loop modulates active site motion and product release in ribonuclease A.

PubMed

Doucet, Nicolas; Watt, Eric D; Loria, J Patrick

2009-08-04

The role of the flexible loop 1 in protein conformational motion and in the dissociation of enzymatic product from ribonuclease A (RNase A) was investigated by creation of a chimeric enzyme in which a 6-residue loop 1 from the RNase A homologue, eosinophil cationic protein (ECP), replaced the 12-residue loop 1 in RNase A. The chimera (RNase A(ECP)) experiences only local perturbations in NMR backbone chemical shifts compared to WT RNase A. Many of the flexible residues that were previously identified in WT as involved in an important conformational change now experience no NMR-detected millisecond motions in the chimera. Likewise, binding of the product analogue, 3'-CMP, to RNase A(ECP) results in only minor chemical shift changes in the enzyme similar to what is observed for the H48A mutant of RNase A and in contrast to WT enzyme. For both RNase A(ECP) and H48A there is a 10-fold decrease in the product release rate constant, k(off), compared to WT, in agreement with previous studies indicating the importance of flexibility in RNase A in the overall rate-limiting product release step. Together, these NMR and biochemical experiments provide additional insight into the mechanism of millisecond motions in the RNase A catalytic cycle.

Higgs mass prediction in the MSSM at three-loop level in a pure \\overline{{ {DR}}} context

NASA Astrophysics Data System (ADS)

Harlander, Robert V.; Klappert, Jonas; Voigt, Alexander

2017-12-01

The impact of the three-loop effects of order α _tα _s^2 on the mass of the light CP-even Higgs boson in the { {MSSM}} is studied in a pure \\overline{{ {DR}}} context. For this purpose, we implement the results of Kant et al. (JHEP 08:104, 2010) into the C++ module Himalaya and link it to FlexibleSUSY, a Mathematica and C++ package to create spectrum generators for BSM models. The three-loop result is compared to the fixed-order two-loop calculations of the original FlexibleSUSY and of FeynHiggs, as well as to the result based on an EFT approach. Aside from the expected reduction of the renormalization scale dependence with respect to the lower-order results, we find that the three-loop contributions significantly reduce the difference from the EFT prediction in the TeV-region of the { {SUSY}} scale {M_S}. Himalaya can be linked also to other two-loop \\overline{{ {DR}}} codes, thus allowing for the elevation of these codes to the three-loop level.

Intracellular segment between transmembrane helices S0 and S1 of BK channel α subunit contains two amphipathic helices connected by a flexible loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Pan; High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui, 230031; Li, Dong

2013-08-02

Highlights: •The loop between S0 and S1 of BK channel was overexpressed and purified in DPC. •NMR studies indicated BK-IS1 contained two helices connected by a flexible loop. •Mg{sup 2+} titration of BK-IS1 indicated two possible binding sites of divalent ions. -- Abstract: The BK channel, a tetrameric potassium channel with very high conductance, has a central role in numerous physiological functions. The BK channel can be activated by intracellular Ca{sup 2+} and Mg{sup 2+}, as well as by membrane depolarization. Unlike other tetrameric potassium channels, the BK channel has seven transmembrane helices (S0–S6) including an extra helix S0. Themore » intracellular segment between S0 and S1 (BK-IS1) is essential to BK channel functions and Asp99 in BK-IS1 is reported to be responsible for Mg{sup 2+} coordination. In this study, BK-IS1 (44–113) was over-expressed using a bacterial system and purified in the presence of detergent micelles for multidimensional heteronuclear nuclear magnetic resonance (NMR) structural studies. Backbone resonance assignment and secondary structure analysis showed that BK-IS1 contains two amphipathic helices connected by a 36-residue loop. Amide {sup 1}H–{sup 15}N heteronuclear NOE analysis indicated that the loop is very flexible, while the two amphipathic helices are possibly stabilized through interaction with the membrane. A solution NMR-based titration assay of BK-IS1 was performed with various concentrations of Mg{sup 2+}. Two residues (Thr45 and Leu46) with chemical shift changes were observed but no, or very minor, chemical shift difference was observed for Asp99, indicating a possible site for binding divalent ions or other modulation partners.« less

A fast and flexible panoramic virtual reality system for behavioural and electrophysiological experiments.

PubMed

Takalo, Jouni; Piironen, Arto; Honkanen, Anna; Lempeä, Mikko; Aikio, Mika; Tuukkanen, Tuomas; Vähäsöyrinki, Mikko

2012-01-01

Ideally, neuronal functions would be studied by performing experiments with unconstrained animals whilst they behave in their natural environment. Although this is not feasible currently for most animal models, one can mimic the natural environment in the laboratory by using a virtual reality (VR) environment. Here we present a novel VR system based upon a spherical projection of computer generated images using a modified commercial data projector with an add-on fish-eye lens. This system provides equidistant visual stimulation with extensive coverage of the visual field, high spatio-temporal resolution and flexible stimulus generation using a standard computer. It also includes a track-ball system for closed-loop behavioural experiments with walking animals. We present a detailed description of the system and characterize it thoroughly. Finally, we demonstrate the VR system's performance whilst operating in closed-loop conditions by showing the movement trajectories of the cockroaches during exploratory behaviour in a VR forest.

Impact of magnetic isolation on pointing system performance in the presence of structural flexibility

NASA Technical Reports Server (NTRS)

Seller, J.

1985-01-01

The inertial pointing stability of a gimbal pointing system (AGS) was compared with a magnetic pointing/gimbal followup system (ASPS), under certain conditions of system structural flexibility and disturbance inputs from the gimbal support structure. Separate 3 degree-of-freedom (3DOF) linear models based on NASTRAN modal flexibility data for the gimbal and support structures were generated for the ASPS configurations. Using the models inertial pointing control loops providing 6dB of gain margin and 45 deg of phase margin were defined for each configuration. The pointing loop bandwidth obtained for the ASPS is more than twice the level achieved for the AGS configuration. The AGS limit is attributed to the gimbal and support structure flexibility. As a result of the higher ASPS pointing loop bandwidth and the disturbance rejection provided by the magnetic isolation ASPS pointing performane is significantly better than that of the AGS system. The low frequency peak of the ASPS transfer function from base disturbance to payload angular motion is almost 60dB lower than AGS low frequency peak.

Design of dissipative low-authority controllers using an eigensystem assignment technique

NASA Technical Reports Server (NTRS)

Maghami, P. G.; Gupta, S.; Joshi, S. M.

1992-01-01

A novel method for the design of dissipative, low-authority controllers has been developed. The method uses a sequential approach along with eigensystem assignment to compute rate and position gain matrices that assign a number of closed-loop poles of the system to desired locations. Because the feedback gain matrices are symmetric and nonnegative definite, the closed-loop stability is always guaranteed regardless of the model order or parameter inaccuracies. The resulting (nominal) closed-loop system can have specified damping ratios for m modes, which makes the plant amenable to high-authority controller design, using methods such as LQG/LTR or H-infinity. A numerical example is worked out for a flexible structure in order to demonstrate the proposed technique.

Structure and Dynamics Analysis on Plexin-B1 Rho GTPase Binding Domain as a Monomer and Dimer

PubMed Central

2015-01-01

Plexin-B1 is a single-pass transmembrane receptor. Its Rho GTPase binding domain (RBD) can associate with small Rho GTPases and can also self-bind to form a dimer. In total, more than 400 ns of NAMD molecular dynamics simulations were performed on RBD monomer and dimer. Different analysis methods, such as root mean squared fluctuation (RMSF), order parameters (S2), dihedral angle correlation, transfer entropy, principal component analysis, and dynamical network analysis, were carried out to characterize the motions seen in the trajectories. RMSF results show that after binding, the L4 loop becomes more rigid, but the L2 loop and a number of residues in other regions become slightly more flexible. Calculating order parameters (S2) for CH, NH, and CO bonds on both backbone and side chain shows that the L4 loop becomes essentially rigid after binding, but part of the L1 loop becomes slightly more flexible. Backbone dihedral angle cross-correlation results show that loop regions such as the L1 loop including residues Q25 and G26, the L2 loop including residue R61, and the L4 loop including residues L89–R91, are highly correlated compared to other regions in the monomer form. Analysis of the correlated motions at these residues, such as Q25 and R61, indicate two signal pathways. Transfer entropy calculations on the RBD monomer and dimer forms suggest that the binding process should be driven by the L4 loop and C-terminal. However, after binding, the L4 loop functions as the motion responder. The signal pathways in RBD were predicted based on a dynamical network analysis method using the pathways predicted from the dihedral angle cross-correlation calculations as input. It is found that the shortest pathways predicted from both inputs can overlap, but signal pathway 2 (from F90 to R61) is more dominant and overlaps all of the routes of pathway 1 (from F90 to P111). This project confirms the allosteric mechanism in signal transmission inside the RBD network, which was in part proposed in the previous experimental study. PMID:24901636

High-temperature self-circulating thermoacoustic heat exchanger

NASA Astrophysics Data System (ADS)

Backhaus, S.; Swift, G. W.; Reid, R. S.

2005-07-01

Thermoacoustic and Stirling engines and refrigerators use heat exchangers to transfer heat between the oscillating flow of their thermodynamic working fluids and external heat sources and sinks. An acoustically driven heat-exchange loop uses an engine's own pressure oscillations to steadily circulate its own thermodynamic working fluid through a physically remote high-temperature heat source without using moving parts, allowing for a significant reduction in the cost and complexity of thermoacoustic and Stirling heat exchangers. The simplicity and flexibility of such heat-exchanger loops will allow thermoacoustic and Stirling machines to access diverse heat sources and sinks. Measurements of the temperatures at the interface between such a heat-exchange loop and the hot end of a thermoacoustic-Stirling engine are presented. When the steady flow is too small to flush out the mixing chamber in one acoustic cycle, the heat transfer to the regenerator is excellent, with important implications for practical use.

Structure Analysis of Jungle-Gym-Type Gels by Brownian Dynamics Simulation

NASA Astrophysics Data System (ADS)

Ohta, Noriyoshi; Ono, Kohki; Takasu, Masako; Furukawa, Hidemitsu

2008-02-01

We investigated the structure and the formation process of two kinds of gels by Brownian dynamics simulation. The effect of flexibility of main chain oligomer was studied. From our results, hard gel with rigid main chain forms more homogeneous network structure than soft gel with flexible main chain. In soft gel, many small loops are formed, and clusters tend to shrink. This heterogeneous network structure may be caused by microgels. In the low density case, soft gel shows more heterogeneity than the high density case.

Characterizing Solution Surface Loop Conformational Flexibility of the GM2 Activator Protein

PubMed Central

2015-01-01

GM2AP has a β-cup topology with numerous X-ray structures showing multiple conformations for some of the surface loops, revealing conformational flexibility that may be related to function, where function is defined as either membrane binding associated with ligand binding and extraction or interaction with other proteins. Here, site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and molecular dynamic (MD) simulations are used to characterize the mobility and conformational flexibility of various structural regions of GM2AP. A series of 10 single cysteine amino acid substitutions were generated, and the constructs were chemically modified with the methanethiosulfonate spin label. Continuous wave (CW) EPR line shapes were obtained and subsequently simulated using the microscopic order macroscopic disorder (MOMD) program. Line shapes for sites that have multiple conformations in the X-ray structures required two spectral components, whereas spectra of the remaining sites were adequately fit with single-component parameters. For spin labeled sites L126C and I66C, spectra were acquired as a function of temperature, and simulations provided for the determination of thermodynamic parameters associated with conformational change. Binding to GM2 ligand did not alter the conformational flexibility of the loops, as evaluated by EPR and NMR spectroscopies. These results confirm that the conformational flexibility observed in the surface loops of GM2AP crystals is present in solution and that the exchange is slow on the EPR time scale (>ns). Furthermore, MD simulation results are presented and agree well with the conformational heterogeneity revealed by SDSL. PMID:25127419

A control system design approach for flexible spacecraft

NASA Technical Reports Server (NTRS)

Silverberg, L. M.

1985-01-01

A control system design approach for flexible spacecraft is presented. The control system design is carried out in two steps. The first step consists of determining the ideal control system in terms of a desirable dynamic performance. The second step consists of designing a control system using a limited number of actuators that possess a dynamic performance that is close to the ideal dynamic performance. The effects of using a limited number of actuators is that the actual closed-loop eigenvalues differ from the ideal closed-loop eigenvalues. A method is presented to approximate the actual closed-loop eigenvalues so that the calculation of the actual closed-loop eigenvalues can be avoided. Depending on the application, it also may be desirable to apply the control forces as impulses. The effect of digitizing the control to produce the appropriate impulses is also examined.

Control and trajectory design of a highly flexible air vehicle with a distributed sensing architecture

NASA Astrophysics Data System (ADS)

Pachikara, Abraham James

Next generational aircraft are becoming very flexible due to efforts to reduce weight and increase aerodynamic efficiency. As a result, flight control systems and trajectories that were designed with traditional rigid body assumptions may no longer become valid. When an aircraft becomes more flexible, the shape of the aircraft can deform significantly due to the aeroservoelastic dynamics. No longer are few sensors located at the CG and elsewhere will be enough to maximize performance. Instead, a full suite of sensors will be needed all throughout the aircraft to accurately measure the complete aerodynamic distribution and dynamics. First, a parametric study will be conducted to understand how flexibility impacts both the open-loop and closed-loop dynamics of a generic micro air vehicle (MAV). Once the impact of flexibility on the MAV's aeroservoelastic dynamics is well understood, an aeroservoelastic flight controller will be designed that leverages a "Fly-By-Feel" sensor architecture. A sensor architecture will be developed that uses several sensors to estimate the MAV's full aerodynamic and inertial distribution along with inertial sensors at the CG. A modal filtering approach will be used for the relevant sensor management and to extract useful modal characteristics from the sensor data. Once that is done, a controller will be designed for maneuver tracking. Once a flight controller has been designed, a set of representative motion primitives for the MAV can be developed that model how the aircraft moves for trajectory generation. Then trajectories can be developed for the flexible vehicle. Analysis will then be conducted to understand how flexibility impacts the creation of trajectories and MAV performance metrics.

Crystal structure analysis, covalent docking, and molecular dynamics calculations reveal a conformational switch in PhaZ7 PHB depolymerase.

PubMed

Kellici, Tahsin F; Mavromoustakos, Thomas; Jendrossek, Dieter; Papageorgiou, Anastassios C

2017-07-01

An open and a closed conformation of a surface loop in PhaZ7 extracellular poly(3-hydroxybutyrate) depolymerase were identified in two high-resolution crystal structures of a PhaZ7 Y105E mutant. Molecular dynamics (MD) simulations revealed high root mean square fluctuations (RMSF) of the 281-295 loop, in particular at residue Asp289 (RMSF 7.62 Å). Covalent docking between a 3-hydroxybutyric acid trimer and the catalytic residue Ser136 showed that the binding energy of the substrate is significantly more favorable in the open loop conformation compared to that in the closed loop conformation. MD simulations with the substrate covalently bound depicted 1 Å RMSF higher values for the residues 281-295 in comparison to the apo (substrate-free) form. In addition, the presence of the substrate in the active site enhanced the ability of the loop to adopt a closed form. Taken together, the analysis suggests that the flexible loop 281-295 of PhaZ7 depolymerase can act as a lid domain to control substrate access to the active site of the enzyme. Proteins 2017; 85:1351-1361. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Molecular basis of thermal stability in truncated (2/2) hemoglobins.

PubMed

Bustamante, Juan P; Bonamore, Alessandra; Nadra, Alejandro D; Sciamanna, Natascia; Boffi, Alberto; Estrin, Darío A; Boechi, Leonardo

2014-07-01

Understanding the molecular mechanism through which proteins are functional at extreme high and low temperatures is one of the key issues in structural biology. To investigate this phenomenon, we have focused on two instructive truncated hemoglobins from Thermobifida fusca (Tf-trHbO) and Mycobacterium tuberculosis (Mt-trHbO); although the two proteins are structurally nearly identical, only the former is stable at high temperatures. We used molecular dynamics simulations at different temperatures as well as thermal melting profile measurements of both wild type proteins and two mutants designed to interchange the amino acid residue, either Pro or Gly, at E3 position. The results show that the presence of a Pro at the E3 position is able to increase (by 8°) or decrease (by 4°) the melting temperature of Mt-trHbO and Tf-trHbO, respectively. We observed that the ProE3 alters the structure of the CD loop, making it more flexible. This gain in flexibility allows the protein to concentrate its fluctuations in this single loop and avoid unfolding. The alternate conformations of the CD loop also favor the formation of more salt-bridge interactions, together augmenting the protein's thermostability. These results indicate a clear structural and dynamical role of a key residue for thermal stability in truncated hemoglobins. Copyright © 2014 Elsevier B.V. All rights reserved.

Two-dimensional vanadium-doped ZnO nanosheet-based flexible direct current nanogenerator.

PubMed

Gupta, Manoj Kumar; Lee, Ju-Hyuck; Lee, Keun Young; Kim, Sang-Woo

2013-10-22

Here, we report the synthesis of lead-free single-crystalline two-dimensional (2D) vanadium(V)-doped ZnO nanosheets (NSs) and their application for high-performance flexible direct current (DC) power piezoelectric nanogenerators (NGs). The vertically aligned ZnO nanorods (NRs) converted to NS networks by V doping. Piezoresponse force microscopy studies reveal that vertical V-doped ZnO NS exhibit typical ferroelectricity with clear phase loops, butterfly, and well-defined hysteresis loops with a piezoelectric charge coefficient of up to 4 pm/V, even in 2D nanostructures. From pristine ZnO NR-based NGs, alternating current (AC)-type output current was observed, while from V-doped ZnO NS-based NGs, a DC-type output current density of up to 1.0 μAcm(-2) was surprisingly obtained under the same vertical compressive force. The growth mechanism, ferroelectric behavior, charge inverted phenomena, and high piezoelectric output performance observed from the V-doped ZnO NS are discussed in terms of the formation of an ionic layer of [V(OH)4(-)], permanent electric dipole, and the doping-induced resistive behavior of ZnO NS.

Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models

NASA Astrophysics Data System (ADS)

Dodani, Sheel C.; Kiss, Gert; Cahn, Jackson K. B.; Su, Ye; Pande, Vijay S.; Arnold, Frances H.

2016-05-01

The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.

Proline Restricts Loop I Conformation of the High Affinity WW Domain from Human Nedd4-1 to a Ligand Binding-Competent Type I β-Turn.

PubMed

Schulte, Marianne; Panwalkar, Vineet; Freischem, Stefan; Willbold, Dieter; Dingley, Andrew J

2018-04-19

Sequence alignment of the four WW domains from human Nedd4-1 (neuronal precursor cell expressed developmentally down-regulated gene 4-1) reveals that the highest sequence diversity exists in loop I. Three residues in this type I β-turn interact with the PPxY motif of the human epithelial Na + channel (hENaC) subunits, indicating that peptide affinity is defined by the loop I sequence. The third WW domain (WW3*) has the highest ligand affinity and unlike the other three hNedd4-1 WW domains or other WW domains studied contains the highly statistically preferred proline at the ( i + 1) position found in β-turns. In this report, molecular dynamics simulations and experimental data were combined to characterize loop I stability and dynamics. Exchange of the proline to the equivalent residue in WW4 (Thr) results in the presence of a predominantly open seven residue Ω loop rather than the type I β-turn conformation for the wild-type apo-WW3*. In the presence of the ligand, the structure of the mutated loop I is locked into a type I β-turn. Thus, proline in loop I ensures a stable peptide binding-competent β-turn conformation, indicating that amino acid sequence modulates local flexibility to tune binding preferences and stability of dynamic interaction motifs.

Loop engineering reveals the importance of active-site-decorating loops and gating residue in substrate affinity modulation of arginine deiminase (an anti-tumor enzyme).

PubMed

Cheng, Feng; Yang, Jianhua; Bocola, Marco; Schwaneberg, Ulrich; Zhu, Leilei

2018-05-05

Protein engineering of enzyme loop regions is an effective strategy to improve enzymatic properties. Previous studies that aimed to boost the activity of PpADI (an arginine deiminase from Pseudomonas plecoglossicida) under physiological conditions yielded several significantly improved variants that harbor substitutions predominantly located in active-site-decorating loops. A multi-site saturation mutagenesis at four positions in loop 1 (37, 38, 42, and 43) and three positions in loop 4 (402, 403, and 404) was performed to elucidate the importance of these loops in modulating the substrate affinity of PpADI. The identified "best" variant (M6-L1-4) showed a decreased S 0.5 ('K M ') of 0.48 mM compared with the parent M6 (0.81 mM). Subsequently, a rational design to recombine beneficial substitutions within loops 1 and 4 yielded variant L6 with a substantially decreased S 0.5 value (0.17 mM). A comprehensive simulation analysis resulted in a conclusion that high loop flexibility (especially the gating residue Arg400) is beneficial for substrate affinity due to less efficient blocking of the active site. Copyright © 2018 Elsevier Inc. All rights reserved.

40 CFR 63.11417 - What are the compliance requirements for new and existing sources?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Flexible Polyurethane Foam Production and Fabrication Area Sources Standards and Compliance Requirements... a slabstock flexible polyurethane foam production affected source, you must comply with the... affected source, or a loop slitter at a flexible polyurethane foam fabrication affected source you must...

40 CFR 63.11417 - What are the compliance requirements for new and existing sources?

Code of Federal Regulations, 2012 CFR

2012-07-01

... Flexible Polyurethane Foam Production and Fabrication Area Sources Standards and Compliance Requirements... a slabstock flexible polyurethane foam production affected source, you must comply with the... affected source, or a loop slitter at a flexible polyurethane foam fabrication affected source you must...

40 CFR 63.11417 - What are the compliance requirements for new and existing sources?

Code of Federal Regulations, 2011 CFR

2011-07-01

... Flexible Polyurethane Foam Production and Fabrication Area Sources Standards and Compliance Requirements... a slabstock flexible polyurethane foam production affected source, you must comply with the... affected source, or a loop slitter at a flexible polyurethane foam fabrication affected source you must...

40 CFR 63.11417 - What are the compliance requirements for new and existing sources?

Code of Federal Regulations, 2014 CFR

2014-07-01

... Flexible Polyurethane Foam Production and Fabrication Area Sources Standards and Compliance Requirements... a slabstock flexible polyurethane foam production affected source, you must comply with the... affected source, or a loop slitter at a flexible polyurethane foam fabrication affected source you must...

40 CFR 63.11417 - What are the compliance requirements for new and existing sources?

Code of Federal Regulations, 2013 CFR

2013-07-01

... Flexible Polyurethane Foam Production and Fabrication Area Sources Standards and Compliance Requirements... a slabstock flexible polyurethane foam production affected source, you must comply with the... affected source, or a loop slitter at a flexible polyurethane foam fabrication affected source you must...

Thermal Vacuum Testing of a Proto-flight Miniature Loop Heat Pipe with Two Evaporators and Two Condensers

NASA Technical Reports Server (NTRS)

Ku, Jentung; Ottenstein, Laura

2011-01-01

This paper describes thermal vacuum testing of a proto-flight miniature loop heat pipe (MLHP) with two evaporators and two condensers designed for future small systems applications requiring low mass, low power and compactness. Each evaporator contains a wick with an outer diameter of 6.35 mm, and each has its own integral compensation chamber (CC). Miniaturization of the loop components reduces the volume and mass of the thermal system. Multiple evaporators provide flexibility for placement of instruments that need to be maintained at the same temperature, and facilitate heat load sharing among instruments, reducing the auxiliary heater power requirement. A flow regulator is used to regulate heat dissipations between the two condensers, allowing flexible placement of radiators on the spacecraft. A thermoelectric converter (TEC) is attached to each CC for control of the operating temperature and enhancement of start-up success. Tests performed include start-up, power cycle, sink temperature cycle, high power and low power operation, heat load sharing, and operating temperature control. The proto-flight MLHP demonstrated excellent performance in the thermal vacuum test. The loop started successfully and operated stably under various evaporator heat loads and condenser sink temperatures. The TECs were able to maintain the loop operating temperature within b1K of the desired set point temperature at all power levels and all sink temperatures. The un-powered evaporator would automatically share heat from the other powered evaporator. The flow regulator was able to regulate the heat dissipation among the radiators and prevent vapor from flowing into the liquid line.

Coupling between Catalytic Loop Motions and Enzyme Global Dynamics

PubMed Central

Kurkcuoglu, Zeynep; Bakan, Ahmet; Kocaman, Duygu; Bahar, Ivet; Doruker, Pemra

2012-01-01

Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops. Our dataset includes a total of 117 crystal structures for ten enzymes of different sizes and oligomerization states. Each enzyme contains a specific functional/catalytic loop (10–21 residues long) that closes over the active site during catalysis. Principal component analysis (PCA) of the available crystal structures (including apo and ligand-bound forms) for each enzyme revealed the dominant conformational changes taking place in these loops upon substrate binding. These experimentally observed loop reconfigurations are shown to be predominantly driven by energetically favored modes of motion intrinsically accessible to the enzyme in the absence of its substrate. The analysis suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site. PMID:23028297

Adsorption of finite semiflexible polymers and their loop and tail distributions

NASA Astrophysics Data System (ADS)

Kampmann, Tobias A.; Kierfeld, Jan

2017-07-01

We discuss the adsorption of semiflexible polymers to a planar attractive wall and focus on the questions of the adsorption threshold for polymers of finite length and their loop and tail distributions using both Monte Carlo simulations and analytical arguments. For the adsorption threshold, we find three regimes: (i) a flexible or Gaussian regime if the persistence length is smaller than the adsorption potential range, (ii) a semiflexible regime if the persistence length is larger than the potential range, and (iii) for finite polymers, a novel crossover to a rigid rod regime if the deflection length exceeds the contour length. In the flexible and semiflexible regimes, finite size corrections arise because the correlation length exceeds the contour length. In the rigid rod regime, however, it is essential how the global orientational or translational degrees of freedom are restricted by grafting or confinement. We discuss finite size corrections for polymers grafted to the adsorbing surface and for polymers confined by a second (parallel) hard wall. Based on these results, we obtain a method to analyze adsorption data for finite semiflexible polymers such as filamentous actin. For the loop and tail distributions, we find power laws with an exponential decay on length scales exceeding the correlation length. We derive and confirm the loop and tail power law exponents for flexible and semiflexible polymers. This allows us to explain that, close to the transition, semiflexible polymers have significantly smaller loops and both flexible and semiflexible polymers desorb by expanding their tail length. The tail distribution allows us to extract the free energy per length of adsorption for actin filaments from experimental data [D. Welch et al., Soft Matter 11, 7507 (2015)].

Experimental Study of Flexible Plate Vibration Control by Using Two-Loop Sliding Mode Control Strategy

NASA Astrophysics Data System (ADS)

Yang, Jingyu; Lin, Jiahui; Liu, Yuejun; Yang, Kang; Zhou, Lanwei; Chen, Guoping

2017-08-01

It is well known that intelligent control theory has been used in many research fields, novel modeling method (DROMM) is used for flexible rectangular active vibration control, and then the validity of new model is confirmed by comparing finite element model with new model. In this paper, taking advantage of the dynamics of flexible rectangular plate, a two-loop sliding mode (TSM) MIMO approach is introduced for designing multiple-input multiple-output continuous vibration control system, which can overcome uncertainties, disturbances or unstable dynamics. An illustrative example is given in order to show the feasibility of the method. Numerical simulations and experiment confirm the effectiveness of the proposed TSM MIMO controller.

Modular high-voltage bias generator powered by dual-looped self-adaptive wireless power transmission.

PubMed

Xie, Kai; Huang, An-Feng; Li, Xiao-Ping; Guo, Shi-Zhong; Zhang, Han-Lu

2015-04-01

We proposed a modular high-voltage (HV) bias generator powered by a novel transmitter-sharing inductive coupled wireless power transmission technology, aimed to extend the generator's flexibility and configurability. To solve the problems caused through an uncertain number of modules, a dual-looped self-adaptive control method is proposed that is capable of tracking resonance frequency while maintaining a relatively stable induction voltage for each HV module. The method combines a phase-locked loop and a current feedback loop, which ensures an accurate resonance state and a relatively constant boost ratio for each module, simplifying the architecture of the boost stage and improving the total efficiency. The prototype was built and tested. The input voltage drop of each module is less than 14% if the module number varies from 3 to 10; resonance tracking is completed within 60 ms. The efficiency of the coupling structure reaches up to 95%, whereas the total efficiency approaches 73% for a rated output. Furthermore, this technology can be used in various multi-load wireless power supply applications.

High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations

PubMed Central

Chen, Alan A.; García, Angel E.

2013-01-01

We report the de novo folding of three hyperstable RNA tetraloops to 1–3 Å rmsd from their experimentally determined structures using molecular dynamics simulations initialized in the unfolded state. RNA tetraloops with loop sequences UUCG, GCAA, or CUUG are hyperstable because of the formation of noncanonical loop-stabilizing interactions, and they are all faithfully reproduced to angstrom-level accuracy in replica exchange molecular dynamics simulations, including explicit solvent and ion molecules. This accuracy is accomplished using unique RNA parameters, in which biases that favor rigid, highly stacked conformations are corrected to accurately capture the inherent flexibility of ssRNA loops, accurate base stacking energetics, and purine syn-anti interconversions. In a departure from traditional quantum chemistrycentric approaches to force field optimization, our parameters are calibrated directly from thermodynamic and kinetic measurements of intra- and internucleotide structural transitions. The ability to recapitulate the signature noncanonical interactions of the three most abundant hyperstable stem loop motifs represents a significant milestone to the accurate prediction of RNA tertiary structure using unbiased all-atom molecular dynamics simulations. PMID:24043821

DNA sequence-dependent mechanics and protein-assisted bending in repressor-mediated loop formation

PubMed Central

Boedicker, James Q.; Garcia, Hernan G.; Johnson, Stephanie; Phillips, Rob

2014-01-01

As the chief informational molecule of life, DNA is subject to extensive physical manipulations. The energy required to deform double-helical DNA depends on sequence, and this mechanical code of DNA influences gene regulation, such as through nucleosome positioning. Here we examine the sequence-dependent flexibility of DNA in bacterial transcription factor-mediated looping, a context for which the role of sequence remains poorly understood. Using a suite of synthetic constructs repressed by the Lac repressor and two well-known sequences that show large flexibility differences in vitro, we make precise statistical mechanical predictions as to how DNA sequence influences loop formation and test these predictions using in vivo transcription and in vitro single-molecule assays. Surprisingly, sequence-dependent flexibility does not affect in vivo gene regulation. By theoretically and experimentally quantifying the relative contributions of sequence and the DNA-bending protein HU to DNA mechanical properties, we reveal that bending by HU dominates DNA mechanics and masks intrinsic sequence-dependent flexibility. Such a quantitative understanding of how mechanical regulatory information is encoded in the genome will be a key step towards a predictive understanding of gene regulation at single-base pair resolution. PMID:24231252

Structural Insights into the Role of the Cyclic Backbone in a Squash Trypsin Inhibitor*

PubMed Central

Daly, Norelle L.; Thorstholm, Louise; Greenwood, Kathryn P.; King, Gordon J.; Rosengren, K. Johan; Heras, Begoña; Martin, Jennifer L.; Craik, David J.

2013-01-01

MCoTI-II is a head-to-tail cyclic peptide with potent trypsin inhibitory activity and, on the basis of its exceptional proteolytic stability, is a valuable template for the design of novel drug leads. Insights into inhibitor dynamics and interactions with biological targets are critical for drug design studies, particularly for protease targets. Here, we show that the cyclization and active site loops of MCoTI-II are flexible in solution, but when bound to trypsin, the active site loop converges to a single well defined conformation. This finding of reduced flexibility on binding is in contrast to a recent study on the homologous peptide MCoTI-I, which suggested that regions of the peptide are more flexible upon binding to trypsin. We provide a possible explanation for this discrepancy based on degradation of the complex over time. Our study also unexpectedly shows that the cyclization loop, not present in acyclic homologues, facilitates potent trypsin inhibitory activity by engaging in direct binding interactions with trypsin. PMID:24169696

Active vibration suppression of self-excited structures using an adaptive LMS algorithm

NASA Astrophysics Data System (ADS)

Danda Roy, Indranil

The purpose of this investigation is to study the feasibility of an adaptive feedforward controller for active flutter suppression in representative linear wing models. The ability of the controller to suppress limit-cycle oscillations in wing models having root springs with freeplay nonlinearities has also been studied. For the purposes of numerical simulation, mathematical models of a rigid and a flexible wing structure have been developed. The rigid wing model is represented by a simple three-degree-of-freedom airfoil while the flexible wing is modelled by a multi-degree-of-freedom finite element representation with beam elements for bending and rod elements for torsion. Control action is provided by one or more flaps attached to the trailing edge and extending along the entire wing span for the rigid model and a fraction of the wing span for the flexible model. Both two-dimensional quasi-steady aerodynamics and time-domain unsteady aerodynamics have been used to generate the airforces in the wing models. An adaptive feedforward controller has been designed based on the filtered-X Least Mean Squares (LMS) algorithm. The control configuration for the rigid wing model is single-input single-output (SISO) while both SISO and multi-input multi-output (MIMO) configurations have been applied on the flexible wing model. The controller includes an on-line adaptive system identification scheme which provides the LMS controller with a reasonably accurate model of the plant. This enables the adaptive controller to track time-varying parameters in the plant and provide effective control. The wing models in closed-loop exhibit highly damped responses at airspeeds where the open-loop responses are destructive. Simulations with the rigid and the flexible wing models in a time-varying airstream show a 63% and 53% increase, respectively, over their corresponding open-loop flutter airspeeds. The ability of the LMS controller to suppress wing store flutter in the two models has also been investigated. With 10% measurement noise introduced in the flexible wing model, the controller demonstrated good robustness to the extraneous disturbances. In the examples studied it is found that adaptation is rapid enough to successfully control flutter at accelerations in the airstream of up to 15 ft/sec2 for the rigid wing model and 9 ft/sec2 for the flexible wing model.

Crystal structure of native and a mutant of Lampyris turkestanicus luciferase implicate in bioluminescence color shift.

PubMed

Kheirabadi, Mitra; Sharafian, Zohreh; Naderi-Manesh, Hossein; Heineman, Udo; Gohlke, Ulrich; Hosseinkhani, Saman

2013-12-01

Firefly bioluminescence reaction in the presence of Mg(2+), ATP and molecular oxygen is carried out by luciferase. The luciferase structure alterations or modifications of assay conditions determine the bioluminescence color of firefly luciferase. Among different beetle luciferases, Phrixothrix hirtus railroad worm emits either yellow or red bioluminescence color. Sequence alignment analysis shows that the red-emitter luciferase from Phrixothrix hirtus has an additional arginine residue at 353 that is absent in other firefly luciferases. It was reported that insertion of Arg in an important flexible loop350-359 showed changes in bioluminescence color from green to red and the optimum temperature activity was also increased. To explain the color tuning mechanism of firefly luciferase, the structure of native and a mutant (E354R/356R/H431Y) of Lampyris turkestanicus luciferase is determined at 2.7Å and 2.2Å resolutions, respectively. The comparison of structure of both types of Lampyris turkestanicus luciferases reveals that the conformation of this flexible loop is significantly changed by addition of two Arg in this region. Moreover, its surface accessibility is affected considerably and some ionic bonds are made by addition of two positive charge residues. Furthermore, we noticed that the hydrogen bonding pattern of His431 with the flexible loop is changed by replacing this residue with Tyr at this position. Juxtaposition of a flexible loop (residues 351-359) in firefly luciferase and corresponding ionic and hydrogen bonds are essential for color emission. © 2013.

New Insights into the Role of T3 Loop in Determining Catalytic Efficiency of GH28 Endo-Polygalacturonases

PubMed Central

Tu, Tao; Meng, Kun; Luo, Huiying; Turunen, Ossi; Zhang, Lujia; Cheng, Yanli; Su, Xiaoyun; Ma, Rui; Shi, Pengjun; Wang, Yaru; Yang, Peilong; Yao, Bin

2015-01-01

Intramolecular mobility and conformational changes of flexible loops have important roles in the structural and functional integrity of proteins. The Achaetomium sp. Xz8 endo-polygalacturonase (PG8fn) of glycoside hydrolase (GH) family 28 is distinguished for its high catalytic activity (28,000 U/mg). Structure modeling indicated that PG8fn has a flexible T3 loop that folds partly above the substrate in the active site, and forms a hydrogen bond to the substrate by a highly conserved residue Asn94 in the active site cleft. Our research investigates the catalytic roles of Asn94 in T3 loop which is located above the catalytic residues on one side of the substrate. Molecular dynamics simulation performed on the mutant N94A revealed the loss of the hydrogen bond formed by the hydroxyl group at O34 of pentagalacturonic acid and the crucial ND2 of Asn94 and the consequent detachment and rotation of the substrate away from the active site, and that on N94Q caused the substrate to drift away from its place due to the longer side chain. In line with the simulations, site-directed mutagenesis at this site showed that this position is very sensitive to amino acid substitutions. Except for the altered K m values from 0.32 (wild type PG8fn) to 0.75–4.74 mg/ml, all mutants displayed remarkably lowered k cat (~3–20,000 fold) and k cat/K m (~8–187,500 fold) values and significantly increased △(△G) values (5.92–33.47 kJ/mol). Taken together, Asn94 in the GH28 T3 loop has a critical role in positioning the substrate in a correct way close to the catalytic residues. PMID:26327390

Plasticity of 150-loop in influenza neuraminidase explored by Hamiltonian replica exchange molecular dynamics simulations.

PubMed

Han, Nanyu; Mu, Yuguang

2013-01-01

Neuraminidase (NA) of influenza is a key target for antiviral inhibitors, and the 150-cavity in group-1 NA provides new insight in treating this disease. However, NA of 2009 pandemic influenza (09N1) was found lacking this cavity in a crystal structure. To address the issue of flexibility of the 150-loop, Hamiltonian replica exchange molecular dynamics simulations were performed on different groups of NAs. Free energy landscape calculated based on the volume of 150-cavity indicates that 09N1 prefers open forms of 150-loop. The turn A (residues 147-150) of the 150-loop is discovered as the most dynamical motif which induces the inter-conversion of this loop among different conformations. In the turn A, the backbone dynamic of residue 149 is highly related with the shape of 150-loop, thus can function as a marker for the conformation of 150-loop. As a contrast, the closed conformation of 150-loop is more energetically favorable in N2, one of group-2 NAs. The D147-H150 salt bridge is found having no correlation with the conformation of 150-loop. Instead the intimate salt bridge interaction between the 150 and 430 loops in N2 variant contributes the stabilizing factor for the closed form of 150-loop. The clustering analysis elaborates the structural plasticity of the loop. This enhanced sampling simulation provides more information in further structural-based drug discovery on influenza virus.

Plasticity of 150-Loop in Influenza Neuraminidase Explored by Hamiltonian Replica Exchange Molecular Dynamics Simulations

PubMed Central

Han, Nanyu; Mu, Yuguang

2013-01-01

Neuraminidase (NA) of influenza is a key target for antiviral inhibitors, and the 150-cavity in group-1 NA provides new insight in treating this disease. However, NA of 2009 pandemic influenza (09N1) was found lacking this cavity in a crystal structure. To address the issue of flexibility of the 150-loop, Hamiltonian replica exchange molecular dynamics simulations were performed on different groups of NAs. Free energy landscape calculated based on the volume of 150-cavity indicates that 09N1 prefers open forms of 150-loop. The turn A (residues 147–150) of the 150-loop is discovered as the most dynamical motif which induces the inter-conversion of this loop among different conformations. In the turn A, the backbone dynamic of residue 149 is highly related with the shape of 150-loop, thus can function as a marker for the conformation of 150-loop. As a contrast, the closed conformation of 150-loop is more energetically favorable in N2, one of group-2 NAs. The D147-H150 salt bridge is found having no correlation with the conformation of 150-loop. Instead the intimate salt bridge interaction between the 150 and 430 loops in N2 variant contributes the stabilizing factor for the closed form of 150-loop. The clustering analysis elaborates the structural plasticity of the loop. This enhanced sampling simulation provides more information in further structural-based drug discovery on influenza virus. PMID:23593372

Spiral vane bioreactor

NASA Technical Reports Server (NTRS)

Morrison, Dennis R. (Inventor)

1991-01-01

A spiral vane bioreactor of a perfusion type is described in which a vertical chamber, intended for use in a microgravity condition, has a central rotating filter assembly and has flexible membranes disposed to rotate annularly about the filter assembly. The flexible members have end portions disposed angularly with respect to one another. A fluid replenishment medium is input from a closed loop liquid system to a completely liquid filled chamber containing microcarrier beads, cells and a fluid medium. Output of spent medium is to the closed loop. In the closed loop, the output and input parameters are sensed by sensors. A manifold permits recharging of the nutrients and pH adjustment. Oxygen is supplied and carbon dioxide and bubbles are removed and the system is monitored and controlled by a microprocessor.

Creating stable stem regions for loop elongation in Fcabs — Insights from combining yeast surface display, in silico loop reconstruction and molecular dynamics simulations

PubMed Central

Hasenhindl, Christoph; Lai, Balder; Delgado, Javier; Traxlmayr, Michael W.; Stadlmayr, Gerhard; Rüker, Florian; Serrano, Luis; Oostenbrink, Chris; Obinger, Christian

2014-01-01

Fcabs (Fc antigen binding) are crystallizable fragments of IgG where the C-terminal structural loops of the CH3 domain are engineered for antigen binding. For the design of libraries it is beneficial to know positions that will permit loop elongation to increase the potential interaction surface with antigen. However, the insertion of additional loop residues might impair the immunoglobulin fold. In the present work we have probed whether stabilizing mutations flanking the randomized and elongated loop region improve the quality of Fcab libraries. In detail, 13 libraries were constructed having the C-terminal part of the EF loop randomized and carrying additional residues (1, 2, 3, 5 or 10, respectively) in the absence and presence of two flanking mutations. The latter have been demonstrated to increase the thermal stability of the CH3 domain of the respective solubly expressed proteins. Assessment of the stability of the libraries expressed on the surface of yeast cells by flow cytometry demonstrated that loop elongation was considerably better tolerated in the stabilized libraries. By using in silico loop reconstruction and mimicking randomization together with MD simulations the underlying molecular dynamics were investigated. In the presence of stabilizing stem residues the backbone flexibility of the engineered EF loop as well as the fluctuation between its accessible conformations were decreased. In addition the CD loop (but not the AB loop) and most of the framework regions were rigidified. The obtained data are discussed with respect to the design of Fcabs and available data on the relation between flexibility and affinity of CDR loops in Ig-like molecules. PMID:24792385

Creating stable stem regions for loop elongation in Fcabs - insights from combining yeast surface display, in silico loop reconstruction and molecular dynamics simulations.

PubMed

Hasenhindl, Christoph; Lai, Balder; Delgado, Javier; Traxlmayr, Michael W; Stadlmayr, Gerhard; Rüker, Florian; Serrano, Luis; Oostenbrink, Chris; Obinger, Christian

2014-09-01

Fcabs (Fc antigen binding) are crystallizable fragments of IgG where the C-terminal structural loops of the CH3 domain are engineered for antigen binding. For the design of libraries it is beneficial to know positions that will permit loop elongation to increase the potential interaction surface with antigen. However, the insertion of additional loop residues might impair the immunoglobulin fold. In the present work we have probed whether stabilizing mutations flanking the randomized and elongated loop region improve the quality of Fcab libraries. In detail, 13 libraries were constructed having the C-terminal part of the EF loop randomized and carrying additional residues (1, 2, 3, 5 or 10, respectively) in the absence and presence of two flanking mutations. The latter have been demonstrated to increase the thermal stability of the CH3 domain of the respective solubly expressed proteins. Assessment of the stability of the libraries expressed on the surface of yeast cells by flow cytometry demonstrated that loop elongation was considerably better tolerated in the stabilized libraries. By using in silico loop reconstruction and mimicking randomization together with MD simulations the underlying molecular dynamics were investigated. In the presence of stabilizing stem residues the backbone flexibility of the engineered EF loop as well as the fluctuation between its accessible conformations were decreased. In addition the CD loop (but not the AB loop) and most of the framework regions were rigidified. The obtained data are discussed with respect to the design of Fcabs and available data on the relation between flexibility and affinity of CDR loops in Ig-like molecules. Copyright © 2014. Published by Elsevier B.V.

Adaptive control strategies for flexible robotic arm

NASA Technical Reports Server (NTRS)

Bialasiewicz, Jan T.

1993-01-01

The motivation of this research came about when a neural network direct adaptive control scheme was applied to control the tip position of a flexible robotic arm. Satisfactory control performance was not attainable due to the inherent non-minimum phase characteristics of the flexible robotic arm tip. Most of the existing neural network control algorithms are based on the direct method and exhibit very high sensitivity if not unstable closed-loop behavior. Therefore a neural self-tuning control (NSTC) algorithm is developed and applied to this problem and showed promising results. Simulation results of the NSTC scheme and the conventional self-tuning (STR) control scheme are used to examine performance factors such as control tracking mean square error, estimation mean square error, transient response, and steady state response.

Fabrication of flexible oriented magnetic thin films with large in-plane uniaxial anisotropy by roll-to-roll nanoimprint lithography

NASA Astrophysics Data System (ADS)

Thantirige, Rukshan M.; John, Jacob; Pradhan, Nihar R.; Carter, Kenneth R.; Tuominen, Mark T.

2016-06-01

Here, we report wafer scale fabrication of densely packed Fe nanostripe-based magnetic thin films on a flexible substrate and their magnetic anisotropy properties. We find that Fe nanostripes exhibit large in-plane uniaxial anisotropy and nearly square hysteresis loops with energy products (BHmax) exceeding 3 MGOe at room temperature. High density Fe nanostripes were fabricated on 70 nm flexible polyethylene terephthalate (PET) gratings, which were made by a roll-to-roll (R2R) UV nanoimprint lithography technique. We observed large in-plane uniaxial anisotropies along the long dimension of nanostripes that can be attributed to the shape. Temperature dependent hysteresis measurements confirm that the magnetization reversal is driven by non-coherent rotation reversal processes.

Two strategies to engineer flexible loops for improved enzyme thermostability

PubMed Central

Yu, Haoran; Yan, Yihan; Zhang, Cheng; Dalby, Paul A.

2017-01-01

Flexible sites are potential targets for engineering the stability of enzymes. Nevertheless, the success rate of the rigidifying flexible sites (RFS) strategy is still low due to a limited understanding of how to determine the best mutation candidates. In this study, two parallel strategies were applied to identify mutation candidates within the flexible loops of Escherichia coli transketolase (TK). The first was a “back to consensus mutations” approach, and the second was computational design based on ΔΔG calculations in Rosetta. Forty-nine single variants were generated and characterised experimentally. From these, three single-variants I189H, A282P, D143K were found to be more thermostable than wild-type TK. The combination of A282P with H192P, a variant constructed previously, resulted in the best all-round variant with a 3-fold improved half-life at 60 °C, 5-fold increased specific activity at 65 °C, 1.3-fold improved kcat and a Tm increased by 5 °C above that of wild type. Based on a statistical analysis of the stability changes for all variants, the qualitative prediction accuracy of the Rosetta program reached 65.3%. Both of the two strategies investigated were useful in guiding mutation candidates to flexible loops, and had the potential to be used for other enzymes. PMID:28145457

The Natively Disordered Loop of Bcl-2 Undergoes Phosphorylation-Dependent Conformational Change and Interacts with Pin1

PubMed Central

Kang, CongBao; Bharatham, Nagakumar; Chia, Joel; Mu, Yuguang; Baek, Kwanghee; Yoon, Ho Sup

2012-01-01

Bcl-2 plays a central role in the regulation of apoptosis. Structural studies of Bcl-2 revealed the presence of a flexible and natively disordered loop that bridges the Bcl-2 homology motifs, BH3 and BH4. This loop is phosphorylated on multiple sites in response to a variety of external stimuli, including the microtubule-targeting drugs, paclitaxel and colchicine. Currently, the underlying molecular mechanism of Bcl-2 phosphorylation and its biological significance remain elusive. In this study, we investigated the molecular characteristics of this anti-apoptotic protein. To this end, we generated synthetic peptides derived from the Bcl-2 loop, and multiple Bcl-2 loop truncation mutants that include the phosphorylation sites. Our results demonstrate that S87 in the flexible loop of Bcl-2 is the primary phosphorylation site for JNK and ERK2, suggesting some sequence or structural specificity for the phosphorylation by these kinases. Our NMR studies and molecular dynamics simulation studies support indicate that phosphorylation of S87 induces a conformational change in the peptide. Finally, we show that the phosphorylated peptides of the Bcl-2 loop can bind Pin1, further substantiating the phosphorylation-mediated conformation change of Bcl-2. PMID:23272207

Cascaded VLSI neural network architecture for on-line learning

NASA Technical Reports Server (NTRS)

Thakoor, Anilkumar P. (Inventor); Duong, Tuan A. (Inventor); Daud, Taher (Inventor)

1992-01-01

High-speed, analog, fully-parallel, and asynchronous building blocks are cascaded for larger sizes and enhanced resolution. A hardware compatible algorithm permits hardware-in-the-loop learning despite limited weight resolution. A computation intensive feature classification application was demonstrated with this flexible hardware and new algorithm at high speed. This result indicates that these building block chips can be embedded as an application specific coprocessor for solving real world problems at extremely high data rates.

Cascaded VLSI neural network architecture for on-line learning

NASA Technical Reports Server (NTRS)

Duong, Tuan A. (Inventor); Daud, Taher (Inventor); Thakoor, Anilkumar P. (Inventor)

1995-01-01

High-speed, analog, fully-parallel and asynchronous building blocks are cascaded for larger sizes and enhanced resolution. A hardware-compatible algorithm permits hardware-in-the-loop learning despite limited weight resolution. A comparison-intensive feature classification application has been demonstrated with this flexible hardware and new algorithm at high speed. This result indicates that these building block chips can be embedded as application-specific-coprocessors for solving real-world problems at extremely high data rates.

Conformational Changes in a Hyperthermostable Glycoside Hydrolase: Enzymatic Activity Is a Consequence of the Loop Dynamics and Protonation Balance

PubMed Central

de Oliveira, Leandro C.; da Silva, Viviam M.; Colussi, Francieli; Cabral, Aline D.; de Oliveira Neto, Mario; Squina, Fabio M.; Garcia, Wanius

2015-01-01

Endo-β-1, 4-mannanase from Thermotoga petrophila (TpMan) is a modular hyperthermostable enzyme involved in the degradation of mannan-containing polysaccharides. The degradation of these polysaccharides represents a key step for several industrial applications. Here, as part of a continuing investigation of TpMan, the region corresponding to the GH5 domain (TpManGH5) was characterized as a function of pH and temperature. The results indicated that the enzymatic activity of the TpManGH5 is pH-dependent, with its optimum activity occurring at pH 6. At pH 8, the studies demonstrated that TpManGH5 is a molecule with a nearly spherical tightly packed core displaying negligible flexibility in solution, and with size and shape very similar to crystal structure. However, TpManGH5 experiences an increase in radius of gyration in acidic conditions suggesting expansion of the molecule. Furthermore, at acidic pH values, TpManGH5 showed a less globular shape, probably due to a loop region slightly more expanded and flexible in solution (residues Y88 to A105). In addition, molecular dynamics simulations indicated that conformational changes caused by pH variation did not change the core of the TpManGH5, which means that only the above mentioned loop region presents high degree of fluctuations. The results also suggested that conformational changes of the loop region may facilitate polysaccharide and enzyme interaction. Finally, at pH 6 the results indicated that TpManGH5 is slightly more flexible at 65°C when compared to the same enzyme at 20°C. The biophysical characterization presented here is well correlated with the enzymatic activity and provide new insight into the structural basis for the temperature and pH-dependent activity of the TpManGH5. Also, the data suggest a loop region that provides a starting point for a rational design of biotechnological desired features. PMID:25723179

Single link flexible beam testbed project. Thesis

NASA Technical Reports Server (NTRS)

Hughes, Declan

1992-01-01

This thesis describes the single link flexible beam testbed at the CLaMS laboratory in terms of its hardware, software, and linear model, and presents two controllers, each including a hub angle proportional-derivative (PD) feedback compensator and one augmented by a second static gain full state feedback loop, based upon a synthesized strictly positive real (SPR) output, that increases specific flexible mode pole damping ratios w.r.t the PD only case and hence reduces unwanted residual oscillation effects. Restricting full state feedback gains so as to produce a SPR open loop transfer function ensures that the associated compensator has an infinite gain margin and a phase margin of at least (-90, 90) degrees. Both experimental and simulation data are evaluated in order to compare some different observer performance when applied to the real testbed and to the linear model when uncompensated flexible modes are included.

Unbiased, scalable sampling of protein loop conformations from probabilistic priors.

PubMed

Zhang, Yajia; Hauser, Kris

2013-01-01

Protein loops are flexible structures that are intimately tied to function, but understanding loop motion and generating loop conformation ensembles remain significant computational challenges. Discrete search techniques scale poorly to large loops, optimization and molecular dynamics techniques are prone to local minima, and inverse kinematics techniques can only incorporate structural preferences in adhoc fashion. This paper presents Sub-Loop Inverse Kinematics Monte Carlo (SLIKMC), a new Markov chain Monte Carlo algorithm for generating conformations of closed loops according to experimentally available, heterogeneous structural preferences. Our simulation experiments demonstrate that the method computes high-scoring conformations of large loops (>10 residues) orders of magnitude faster than standard Monte Carlo and discrete search techniques. Two new developments contribute to the scalability of the new method. First, structural preferences are specified via a probabilistic graphical model (PGM) that links conformation variables, spatial variables (e.g., atom positions), constraints and prior information in a unified framework. The method uses a sparse PGM that exploits locality of interactions between atoms and residues. Second, a novel method for sampling sub-loops is developed to generate statistically unbiased samples of probability densities restricted by loop-closure constraints. Numerical experiments confirm that SLIKMC generates conformation ensembles that are statistically consistent with specified structural preferences. Protein conformations with 100+ residues are sampled on standard PC hardware in seconds. Application to proteins involved in ion-binding demonstrate its potential as a tool for loop ensemble generation and missing structure completion.

Unbiased, scalable sampling of protein loop conformations from probabilistic priors

PubMed Central

2013-01-01

Background Protein loops are flexible structures that are intimately tied to function, but understanding loop motion and generating loop conformation ensembles remain significant computational challenges. Discrete search techniques scale poorly to large loops, optimization and molecular dynamics techniques are prone to local minima, and inverse kinematics techniques can only incorporate structural preferences in adhoc fashion. This paper presents Sub-Loop Inverse Kinematics Monte Carlo (SLIKMC), a new Markov chain Monte Carlo algorithm for generating conformations of closed loops according to experimentally available, heterogeneous structural preferences. Results Our simulation experiments demonstrate that the method computes high-scoring conformations of large loops (>10 residues) orders of magnitude faster than standard Monte Carlo and discrete search techniques. Two new developments contribute to the scalability of the new method. First, structural preferences are specified via a probabilistic graphical model (PGM) that links conformation variables, spatial variables (e.g., atom positions), constraints and prior information in a unified framework. The method uses a sparse PGM that exploits locality of interactions between atoms and residues. Second, a novel method for sampling sub-loops is developed to generate statistically unbiased samples of probability densities restricted by loop-closure constraints. Conclusion Numerical experiments confirm that SLIKMC generates conformation ensembles that are statistically consistent with specified structural preferences. Protein conformations with 100+ residues are sampled on standard PC hardware in seconds. Application to proteins involved in ion-binding demonstrate its potential as a tool for loop ensemble generation and missing structure completion. PMID:24565175

Reduction of Urease Activity by Interaction with the Flap Covering the Active Site

PubMed Central

Macomber, Lee; Minkara, Mona S.; Hausinger, Robert P.; Merz, Kenneth M.

2015-01-01

With the increasing appreciation for the human microbiome coupled with the global rise of antibiotic resistant organisms, it is imperative that new methods be developed to specifically target pathogens. To that end, a novel computational approach was devised to identify compounds that reduce the activity of urease, a medically important enzyme of Helicobacter pylori, Proteus mirabilis, and many other microorganisms. Urease contains a flexible loop that covers its active site; Glide was used to identify small molecules predicted to lock this loop in an open conformation. These compounds were screened against the model urease from Klebsiella aerogenes and the natural products epigallocatechin and quercetin were shown to inhibit at low and high micromolar concentrations, respectively. These molecules exhibit a strong time-dependent inactivation of urease that was not due to their oxygen sensitivity. Rather, these compounds appear to inactivate urease by reacting with a specific Cys residue located on the flexible loop. Substitution of this cysteine by alanine in the C319A variant increased the urease resistance to both epigallocatechin and quercetin, as predicted by the computational studies. Protein dynamics are integral to the function of many enzymes; thus, identification of compounds that lock an enzyme into a single conformation presents a useful approach to define potential inhibitors. PMID:25594724

Conformation of receptor-bound visual arrestin.

PubMed

Kim, Miyeon; Vishnivetskiy, Sergey A; Van Eps, Ned; Alexander, Nathan S; Cleghorn, Whitney M; Zhan, Xuanzhi; Hanson, Susan M; Morizumi, Takefumi; Ernst, Oliver P; Meiler, Jens; Gurevich, Vsevolod V; Hubbell, Wayne L

2012-11-06

Arrestin-1 (visual arrestin) binds to light-activated phosphorylated rhodopsin (P-Rh*) to terminate G-protein signaling. To map conformational changes upon binding to the receptor, pairs of spin labels were introduced in arrestin-1 and double electron-electron resonance was used to monitor interspin distance changes upon P-Rh* binding. The results indicate that the relative position of the N and C domains remains largely unchanged, contrary to expectations of a "clam-shell" model. A loop implicated in P-Rh* binding that connects β-strands V and VI (the "finger loop," residues 67-79) moves toward the expected location of P-Rh* in the complex, but does not assume a fully extended conformation. A striking and unexpected movement of a loop containing residue 139 away from the adjacent finger loop is observed, which appears to facilitate P-Rh* binding. This change is accompanied by smaller movements of distal loops containing residues 157 and 344 at the tips of the N and C domains, which correspond to "plastic" regions of arrestin-1 that have distinct conformations in monomers of the crystal tetramer. Remarkably, the loops containing residues 139, 157, and 344 appear to have high flexibility in both free arrestin-1 and the P-Rh*complex.

Flexibility and mutagenic resiliency of glycosyltransferases.

PubMed

Bay, Marie Lund; Cuesta-Seijo, Jose A; Weadge, Joel T; Persson, Mattias; Palcic, Monica M

2014-10-01

The human blood group A and B antigens are synthesized by two highly homologous enzymes, glycosyltransferase A (GTA) and glycosyltransferase B (GTB), respectively. These enzymes catalyze the transfer of either GalNAc or Gal from their corresponding UDP-donors to αFuc1-2βGal-R terminating acceptors. GTA and GTB differ at only four of 354 amino acids (R176G, G235S, L266M, G268A), which alter the donor specificity from UDP-GalNAc to UDP-Gal. Blood type O individuals synthesize truncated or non-functional enzymes. The cloning, crystallization and X-ray structure elucidations for GTA and GTB have revealed key residues responsible for donor discrimination and acceptor binding. Structural studies suggest that numerous conformational changes occur during the catalytic cycle. Over 300 ABO alleles are tabulated in the blood group antigen mutation database (BGMUT) that provides a framework for structure-function studies. Natural mutations are found in all regions of GTA and GTB from the active site, flexible loops, stem region and surfaces remote from the active site. Our characterizations of natural mutants near a flexible loop (V175M), on a remote surface site (P156L), in the metal binding motif (M212V) and near the acceptor binding site (L232P) demonstrate the resiliency of GTA and GTB to mutagenesis.

Transposon Mutagenesis of the Zika Virus Genome Highlights Regions Essential for RNA Replication and Restricted for Immune Evasion.

PubMed

Fulton, Benjamin O; Sachs, David; Schwarz, Megan C; Palese, Peter; Evans, Matthew J

2017-08-01

The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the ZIKV MR766 genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle. The ZIKV structural genes showed the highest degree of insertional tolerance. Although the envelope (E) protein exhibited particular flexibility, the highly conserved envelope domain II (EDII) fusion loop of the E protein was intolerant of transposon insertions. The fusion loop is also a target of pan-flavivirus antibodies that are generated against other flaviviruses and neutralize a broad range of dengue virus and ZIKV isolates. The genetic restrictions identified within the epitopes in the EDII fusion loop likely explain the sequence and antigenic conservation of these regions in ZIKV and among multiple flaviviruses. Thus, our results provide insights into the genetic restrictions on ZIKV that may affect the evolution of this virus. IMPORTANCE Zika virus recently emerged as a significant human pathogen. Determining the genetic constraints on Zika virus is important for understanding the factors affecting viral evolution. We used a genome-wide transposon mutagenesis screen to identify where mutations were tolerated in replicating viruses. We found that the genetic regions involved in RNA replication were mostly intolerant of mutations. The genes coding for structural proteins were more permissive to mutations. Despite the flexibility observed in these regions, we found that epitopes bound by broadly reactive antibodies were genetically constrained. This finding may explain the genetic conservation of these epitopes among flaviviruses. Copyright © 2017 American Society for Microbiology.

High speed, precision motion strategies for lightweight structures

NASA Technical Reports Server (NTRS)

Book, Wayne J.

1987-01-01

Abstracts of published papers and dissertations generated during the reporting period are compiled. Work on fine motion control was completed. Specifically, real time control of flexible manipulator vibrations were experimentally investigated. A linear model based on the application of Lagrangian dynamics to a rigid body mode and a series of separable flexible modes was examined with respect to model order requirements, and modal candidate selection. State feedback control laws were implemented based upon linear quadratic regulator design. Specification of the closed loop poles in the regulator design process was obtained by inclusion of a prescribed degree of stability in the manipulator model. Work on gross motion planning and control is also summarized. A systematic method to symbolically derive the full nonlinear dynamic equations of motion of multi-link flexible manipulators was developed.

Fault Accommodation in Control of Flexible Systems

NASA Technical Reports Server (NTRS)

Maghami, Peiman G.; Sparks, Dean W., Jr.; Lim, Kyong B.

1998-01-01

New synthesis techniques for the design of fault accommodating controllers for flexible systems are developed. Three robust control design strategies, static dissipative, dynamic dissipative and mu-synthesis, are used in the approach. The approach provides techniques for designing controllers that maximize, in some sense, the tolerance of the closed-loop system against faults in actuators and sensors, while guaranteeing performance robustness at a specified performance level, measured in terms of the proximity of the closed-loop poles to the imaginary axis (the degree of stability). For dissipative control designs, nonlinear programming is employed to synthesize the controllers, whereas in mu-synthesis, the traditional D-K iteration is used. To demonstrate the feasibility of the proposed techniques, they are applied to the control design of a structural model of a flexible laboratory test structure.

Variation of wave speed determined by the PU-loop with proximity to a reflection site.

PubMed

Li, Ye; Borlotti, Alessandra; Parker, Kim H; Khir, Ashraf W

2011-01-01

Wave speed is directly related to arterial distensibility and is widely used by clinicians to assess arterial stiffness. The PU-loop method for determining wave speed is based on the water hammer equation for flow in flexible tubes and artery using the method of characteristics. This technique determines wave speed using simultaneous measurements of pressure and velocity at a single point. The method shows that during the early part of systole, the relationship between pressure and velocity is generally linear, and the initial slope of the PU-loop is proportional to wave speed. In this work, we designed an in-vitro experiment to investigate the effect of proximity to a reflection site on the wave speed determined by the PU-loop through varying the distance between the measurement and reflection sites. Measurements were made in a flexible tube with a reflection site at the distal end formed by joining the tube to another tube with a different diameter and material properties. Six different flexible tubes were used to generate both positive and negative reflection coefficients of different magnitudes. We found that the wave speed determined by the PU-loop did not change when the measurement site was far from the reflection site but did change as the distance to the reflection site decreased. The calculated wave speed increased with positive reflections and decreased with negative reflections. The magnitude of the change in wave speed at a fixed distance from the reflection site increased with increasing the value of the reflection coefficient.

Monitoring transients in low inductance circuits

DOEpatents

Guilford, Richard P.; Rosborough, John R.

1987-01-01

A pair of flat cable transmission lines are monitored for transient current spikes by using a probe connected to a current transformer by a pickup loop and monitoring the output of the current transformer. The approach utilizes a U-shaped pickup probe wherein the pair of flat cable transmission lines are received between the legs of the U-shaped probe. The U-shaped probe is preferably formed of a flat coil conductor adhered to one side of a flexible substrate. On the other side of the flexible substrate there is a copper foil shield. The copper foil shield is connected to one end of the flat conductor coil and connected to one leg of the pickup loop which passes through the current transformer. The other end of the flat conductor coil is connected to the other leg of the pickup loop.

Speckle interferometry using fiber optic phase stepping

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Beheim, Glenn

1989-01-01

A system employing closed-loop phase-stepping is used to measure the out-of-plane deformation of a diffusely reflecting object. Optical fibers are used to provide reference and object beam illumination for a standard two-beam speckle interferometer, providing set-up flexibility and ease of alignment. Piezoelectric fiber-stretchers and a phase-measurement/servo system are used to provide highly accurate phase steps. Intensity data is captured with a charge-injection-device camera, and is converted into a phase map using a desktop computer. The closed-loop phase-stepping system provides 90 deg phase steps which are accurate to 0.02 deg, greatly improving this system relative to open-loop interferometers. The system is demonstrated on a speckle interferometer, measuring the rigid-body translation of a diffusely reflecting object with an accuracy + or - 10 deg, or roughly + or - 15 nanometers. This accuracy is achieved without the use of a pneumatically mounted optics table.

Development of a Turbofan Engine Simulation in a Graphical Simulation Environment

NASA Technical Reports Server (NTRS)

Parker, Khary I.; Guo, Ten-Heui

2003-01-01

This paper presents the development of a generic component level model of a turbofan engine simulation with a digital controller, in an advanced graphical simulation environment. The goal of this effort is to develop and demonstrate a flexible simulation platform for future research in propulsion system control and diagnostic technology. A previously validated FORTRAN-based model of a modern, high-performance, military-type turbofan engine is being used to validate the platform development. The implementation process required the development of various innovative procedures, which are discussed in the paper. Open-loop and closed-loop comparisons are made between the two simulations. Future enhancements that are to be made to the modular engine simulation are summarized.

Conformational Flexibility of Human Casein Kinase Catalytic Subunit Explored by Metadynamics

PubMed Central

Gouron, Aurélie; Milet, Anne; Jamet, Helene

2014-01-01

Casein kinase CK2 is an essential enzyme in higher organisms, catalyzing the transfer of the γ phosphate from ATP to serine and threonine residues on protein substrates. In a number of animal tumors, CK2 activity has been shown to escape normal cellular control, making it a potential target for cancer therapy. Several crystal structures of human CK2 have been published with different conformations for the CK2α catalytic subunit. This variability reflects a high flexibility for two regions of CK2α: the interdomain hinge region, and the glycine-rich loop (p-loop). Here, we present a computational study simulating the equilibrium between three conformations involving these regions. Simulations were performed using well-tempered metadynamics combined with a path collective variables approach. This provides a reference pathway describing the conformational changes being studied, based on analysis of free energy surfaces. The free energies of the three conformations were found to be close and the paths proposed had low activation barriers. Our results indicate that these conformations can exist in water. This information should be useful when designing inhibitors specific to one conformation. PMID:24606937

Conformation of receptor-bound visual arrestin

PubMed Central

Kim, Miyeon; Vishnivetskiy, Sergey A.; Van Eps, Ned; Alexander, Nathan S.; Cleghorn, Whitney M.; Zhan, Xuanzhi; Hanson, Susan M.; Morizumi, Takefumi; Ernst, Oliver P.; Meiler, Jens; Gurevich, Vsevolod V.; Hubbell, Wayne L.

2012-01-01

Arrestin-1 (visual arrestin) binds to light-activated phosphorylated rhodopsin (P-Rh*) to terminate G-protein signaling. To map conformational changes upon binding to the receptor, pairs of spin labels were introduced in arrestin-1 and double electron–electron resonance was used to monitor interspin distance changes upon P-Rh* binding. The results indicate that the relative position of the N and C domains remains largely unchanged, contrary to expectations of a “clam-shell” model. A loop implicated in P-Rh* binding that connects β-strands V and VI (the “finger loop,” residues 67–79) moves toward the expected location of P-Rh* in the complex, but does not assume a fully extended conformation. A striking and unexpected movement of a loop containing residue 139 away from the adjacent finger loop is observed, which appears to facilitate P-Rh* binding. This change is accompanied by smaller movements of distal loops containing residues 157 and 344 at the tips of the N and C domains, which correspond to “plastic” regions of arrestin-1 that have distinct conformations in monomers of the crystal tetramer. Remarkably, the loops containing residues 139, 157, and 344 appear to have high flexibility in both free arrestin-1 and the P-Rh*complex. PMID:23091036

A dynamically reconfigurable multi-functional PLL for SRAM-based FPGA in 65nm CMOS technology

NASA Astrophysics Data System (ADS)

Yang, Mingqian; Chen, Lei; Li, Xuewu; Zhang, Yanlong

2018-04-01

Phase-locked loops (PLL) have been widely utilized in FPGA as an important module for clock management. PLL with dynamic reconfiguration capability is always welcomed in FPGA design as it is able to decrease power consumption and simultaneously improve flexibility. In this paper, a multi-functional PLL with dynamic reconfiguration capability for 65nm SRAM-based FPGA is proposed. Firstly, configurable charge pump and loop filter are utilized to optimize the loop bandwidth. Secondly, the PLL incorporates a VCO with dual control voltages to accelerate the adjustment of oscillation frequency. Thirdly, three configurable dividers are presented for flexible frequency synthesis. Lastly, a configuration block with dynamic reconfiguration function is proposed. Simulation results demonstrate that the proposed multi-functional PLL can output clocks with configurable division ratio, phase shift and duty cycle. The PLL can also be dynamically reconfigured without affecting other parts' running or halting the FPGA device.

Hard real-time closed-loop electrophysiology with the Real-Time eXperiment Interface (RTXI)

PubMed Central

George, Ansel; Dorval, Alan D.; Christini, David J.

2017-01-01

The ability to experimentally perturb biological systems has traditionally been limited to static pre-programmed or operator-controlled protocols. In contrast, real-time control allows dynamic probing of biological systems with perturbations that are computed on-the-fly during experimentation. Real-time control applications for biological research are available; however, these systems are costly and often restrict the flexibility and customization of experimental protocols. The Real-Time eXperiment Interface (RTXI) is an open source software platform for achieving hard real-time data acquisition and closed-loop control in biological experiments while retaining the flexibility needed for experimental settings. RTXI has enabled users to implement complex custom closed-loop protocols in single cell, cell network, animal, and human electrophysiology studies. RTXI is also used as a free and open source, customizable electrophysiology platform in open-loop studies requiring online data acquisition, processing, and visualization. RTXI is easy to install, can be used with an extensive range of external experimentation and data acquisition hardware, and includes standard modules for implementing common electrophysiology protocols. PMID:28557998

AGARD (Advisory Group for Aerospace Research & Development) Index of Publications, 1986-1988

DTIC Science & Technology

1989-08-01

measurements are used in forming the navigation and the baro-inertial loop as well The system communicates with equations to solve for the user position...processing techniques in the tracking ROBERT P. DENARO and G JEFFREY GEIER In AGARD, The loops . and later in the navigation processing ot the Kalman...avionics investigations to predict the dynamic structural response of flexible assessment. The current status of real time, pilot-in-the- loop flight

Structures of apo IRF-3 and IRF-7 DNA binding domains: effect of loop L1 on DNA binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Ioannes, Pablo; Escalante, Carlos R.; Aggarwal, Aneel K.

2013-11-20

Interferon regulatory factors IRF-3 and IRF-7 are transcription factors essential in the activation of interferon-{beta} (IFN-{beta}) gene in response to viral infections. Although, both proteins recognize the same consensus IRF binding site AANNGAAA, they have distinct DNA binding preferences for sites in vivo. The X-ray structures of IRF-3 and IRF-7 DNA binding domains (DBDs) bound to IFN-{beta} promoter elements revealed flexibility in the loops (L1-L3) and the residues that make contacts with the target sequence. To characterize the conformational changes that occur on DNA binding and how they differ between IRF family members, we have solved the X-ray structures ofmore » IRF-3 and IRF-7 DBDs in the absence of DNA. We found that loop L1, carrying the conserved histidine that interacts with the DNA minor groove, is disordered in apo IRF-3 but is ordered in apo IRF-7. This is reflected in differences in DNA binding affinities when the conserved histidine in loop L1 is mutated to alanine in the two proteins. The stability of loop L1 in IRF-7 derives from a unique combination of hydrophobic residues that pack against the protein core. Together, our data show that differences in flexibility of loop L1 are an important determinant of differential IRF-DNA binding.« less

Aircraft Thermal Management Using Loop Heat Pipes

DTIC Science & Technology

2009-03-01

flexible copper-water arterial wick heat pipe subjected to transverse acceleration using a centrifuge table. Evaporator heat loads up to Qin = 150 W and...acceleration. Yerkes and Beam (1992) examined the same flexible copper-water arterial wick heat pipe as Ponnappan et al. under transient transverse...examined the same flexible copper-water arterial wick heat pipe as Ponnappan et al. with evaporator heat loads from Qin = 75 to 150 W, condenser

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

PubMed

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

2009-10-13

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

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

PubMed Central

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

2009-01-01

Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and “noise” that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds. PMID:20160879

The Recombinant Inhibitor of DNA Binding Id2 Forms Multimeric Structures via the Helix-Loop-Helix Domain and the Nuclear Export Signal.

PubMed

Roschger, Cornelia; Schubert, Mario; Regl, Christof; Andosch, Ancuela; Marquez, Augusto; Berger, Thomas; Huber, Christian G; Lütz-Meindl, Ursula; Cabrele, Chiara

2018-04-07

The inhibitor of DNA binding and cell differentiation 2 (Id2) is a helix-loop-helix (HLH) protein that acts as negative dominant regulator of basic-HLH transcription factors during development and in cancer. The structural properties of Id2 have been investigated so far by using synthetic or recombinant fragments reproducing single domains (N-terminus, HLH, C-terminus): the HLH domain tends to dimerize into a four-helix bundle, whereas the flanking regions are flexible. In this work, the intact protein was expressed in E. coli , solubilized from inclusion bodies with urea, purified and dissolved in water at pH~4. Under these conditions, Id2 was obtained with both cysteine residues disulfide-bonded to β-mercaptoethanol that was present during the solubilization process. Moreover, it existed in a self-assembled state, in which the N-terminus remained highly flexible, while the HLH domain and, surprisingly, part of the C-terminus, which corresponds to the nuclear export signal (NES), both were involved in slowly tumbling, rigid structures. The protein oligomers also formed twisted fibrils that were several micrometers long and up to 80 nm thick. These results show that self-assembly decreases the backbone flexibility of those two protein regions (HLH and NES) that are important for interaction with basic-HLH transcription factors or for nucleocytoplasmic shuttling.

Guaranteed cost control with poles assignment for a flexible air-breathing hypersonic vehicle

NASA Astrophysics Data System (ADS)

Li, Hongyi; Si, Yulin; Wu, Ligang; Hu, Xiaoxiang; Gao, Huijun

2011-05-01

This article investigates the problem of guaranteed cost control for a flexible air-breathing hypersonic vehicle (FAHV). The FAHV includes intricate coupling between the engine and flight dynamics as well as complex interplay between flexible and rigid modes, which results in an intractable system for the control design. A longitudinal model is adopted for control design due to the complexity of the vehicle. First, for a highly nonlinear and coupled FAHV, a linearised model is established around the trim condition, which includes the state of altitude, velocity, angle of attack, pitch angle and pitch rate, etc. Secondly, by using the Lyapunov approach, performance analysis is carried out for the resulting closed-loop FAHV system, whose criterion with respect to guaranteed performance cost and poles assignment is expressed in the framework of linear matrix inequalities (LMIs). The established criterion exhibits a kind of decoupling between the Lyapunov positive-definite matrices to be determined and the FAHV system matrices, which is enabled by the introduction of additional slack matrix variables. Thirdly, a convex optimisation problem with LMI constraints is formulated for designing an admissible controller, which guarantees a prescribed performance cost with the simultaneous consideration of poles assignment for the resulting closed-loop system. Finally, some simulation results are provided to show that the guaranteed cost controller could assign the poles into the desired regional and achieve excellent reference altitude and velocity tracking performance.

Analysis of TMT primary mirror control-structure interaction

NASA Astrophysics Data System (ADS)

MacMynowski, Douglas G.; Thompson, Peter M.; Sirota, Mark J.

2008-07-01

The primary mirror control system (M1CS) keeps the 492 segments of the Thirty Meter Telescope primary mirror aligned in the presence of disturbances. A global position control loop uses feedback from inter-segment edge sensors to three actuators behind each segment that control segment piston, tip and tilt. If soft force actuators are used (e.g. voice-coil), then in addition to the global position loop there will be a local servo loop to provide stiffness. While the M1 control system at Keck compensates only for slow disturbances such as gravity and thermal variations, the M1CS for TMT will need to provide some compensation for higher frequency wind disturbances in order to meet stringent error budget targets. An analysis of expected high-wavenumber wind forces on M1 suggests that a 1Hz control bandwidth is required for the global feedback of segment edge-sensorbased position information in order to minimize high spatial frequency segment response for both seeing-limited and adaptive optics performance. A much higher bandwidth is required from the local servo loop to provide adequate stiffness to wind or acoustic disturbances. A related paper presents the control designs for the local actuator servo loops. The disturbance rejection requirements would not be difficult to achieve for a single segment, but the structural coupling between segments mounted on a flexible mirror cell results in controlstructure interaction (CSI) that limits the achievable bandwidth. Using a combination of simplified modeling to build intuition and the full telescope finite element model for verification, we present designs and analysis for both the local servo loop and global loop demonstrating sufficient bandwidth and resulting wind-disturbance rejection despite the presence of CSI.

Negative Factor from SIV Binds to the Catalytic Subunit of the V-ATPase to Internalize CD4 and to Increase Viral Infectivity

PubMed Central

Mandic, Robert; Fackler, Oliver T.; Geyer, Matthias; Linnemann, Thomas; Zheng, Yong-Hui; Peterlin, B. Matija

2001-01-01

The accessory protein negative factor (Nef) from human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is required for optimal viral infectivity and the progression to acquired immunodeficiency syndrome (AIDS). Nef interacts with the endocytic machinery, resulting in the down-regulation of cluster of differentiation antigen 4 (CD4) and major histocompatibility complex class I (MHCI) molecules on the surface of infected cells. Mutations in the C-terminal flexible loop of Nef result in a lower rate of internalization by this viral protein. However, no loop-dependent binding of Nef to adaptor protein-2 (AP-2), which is the adaptor protein complex that is required for the internalization of proteins from the plasma membrane, could be demonstrated. In this study we investigated the relevance of different motifs in Nef from SIVmac239 for its internalization, CD4 down-regulation, binding to components of the trafficking machinery, and viral infectivity. Our data suggest that the binding of Nef to the catalytic subunit H of the vacuolar membrane ATPase (V-ATPase) facilitates its internalization. This binding depends on the integrity of the whole flexible loop. Subsequent studies on Nef mutant viruses revealed that the flexible loop is essential for optimal viral infectivity. Therefore, our data demonstrate how Nef contacts the endocytic machinery in the absence of its direct binding to AP-2 and suggest an important role for subunit H of the V-ATPase in viral infectivity. PMID:11179428

Active control of flexible structures using a fuzzy logic algorithm

NASA Astrophysics Data System (ADS)

Cohen, Kelly; Weller, Tanchum; Ben-Asher, Joseph Z.

2002-08-01

This study deals with the development and application of an active control law for the vibration suppression of beam-like flexible structures experiencing transient disturbances. Collocated pairs of sensors/actuators provide active control of the structure. A design methodology for the closed-loop control algorithm based on fuzzy logic is proposed. First, the behavior of the open-loop system is observed. Then, the number and locations of collocated actuator/sensor pairs are selected. The proposed control law, which is based on the principles of passivity, commands the actuator to emulate the behavior of a dynamic vibration absorber. The absorber is tuned to a targeted frequency, whereas the damping coefficient of the dashpot is varied in a closed loop using a fuzzy logic based algorithm. This approach not only ensures inherent stability associated with passive absorbers, but also circumvents the phenomenon of modal spillover. The developed controller is applied to the AFWAL/FIB 10 bar truss. Simulated results using MATLAB© show that the closed-loop system exhibits fairly quick settling times and desirable performance, as well as robustness characteristics. To demonstrate the robustness of the control system to changes in the temporal dynamics of the flexible structure, the transient response to a considerably perturbed plant is simulated. The modal frequencies of the 10 bar truss were raised as well as lowered substantially, thereby significantly perturbing the natural frequencies of vibration. For these cases, too, the developed control law provides adequate settling times and rates of vibrational energy dissipation.

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.

PubMed

Blaha-Nelson, David; Krüger, Dennis M; Szeler, Klaudia; Ben-David, Moshe; Kamerlin, Shina Caroline Lynn

2017-01-25

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k cat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1's active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar "gating loop" or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates.

A Printed Organic Amplification System for Wearable Potentiometric Electrochemical Sensors.

PubMed

Shiwaku, Rei; Matsui, Hiroyuki; Nagamine, Kuniaki; Uematsu, Mayu; Mano, Taisei; Maruyama, Yuki; Nomura, Ayako; Tsuchiya, Kazuhiko; Hayasaka, Kazuma; Takeda, Yasunori; Fukuda, Takashi; Kumaki, Daisuke; Tokito, Shizuo

2018-03-02

Electrochemical sensor systems with integrated amplifier circuits play an important role in measuring physiological signals via in situ human perspiration analysis. Signal processing circuitry based on organic thin-film transistors (OTFTs) have significant potential in realizing wearable sensor devices due to their superior mechanical flexibility and biocompatibility. Here, we demonstrate a novel potentiometric electrochemical sensing system comprised of a potassium ion (K + ) sensor and amplifier circuits employing OTFT-based pseudo-CMOS inverters, which have a highly controllable switching voltage and closed-loop gain. The ion concentration sensitivity of the fabricated K + sensor was 34 mV/dec, which was amplified to 160 mV/dec (by a factor of 4.6) with high linearity. The developed system is expected to help further the realization of ultra-thin and flexible wearable sensor devices for healthcare applications.

Thermal and Mechanical Microspacecraft Technologies for X-2000 Future Deliveries

NASA Technical Reports Server (NTRS)

Birur, Gaj; Bruno, Robin

1999-01-01

Thermal and mechanical technologies are an important part of the X-2000 Future Delivery (X-2000 FD) microspacecraft. A wide range of future space missions are expected to utilize the technologies and the architecture developed by the X-2000 FD. These technologies, besides being small in physical size, make the tiny spacecraft robust and flexible. The X2000 FD architecture is designed to be highly reliable and suitable for a wide range of missions such as planetary landers/orbiters/flybys, earth orbiters, cometary flybys/landers/sample returns, etc. One of the key ideas used in the development of these technologies and architecture is that several functions be in included in each of the thermal and mechanical elements. One of the thermal architecture being explored for the X-2000 FD microspacecraft is integrated thermal energy management of the complete spacecraft using a fluid loop. The robustness and the simplicity of the loop and the flexibility with which it can be integrated in the spacecraft have made it attractive for applications to X-2000 FD. Some of the thermal technologies to be developed as a part of this architecture are passive and active cooling loops, electrically variable emittance surfaces, miniature thermal switches, and specific high density electronic cooling technologies. In the mechanical area, multifunction architecture for the structural elements will be developed. The multifunction aspect is expected to substantially reduce the mass and volume of the spacecraft. Some of the technologies that will be developed are composite material panels incorporating electronics, cabling, and thermal elements in them. The paper to be presented at the 1999 conference, will describe the progress made so far in the microspacecraft thermal and mechanical technologies and approaches for the X2000 Future Deliveries microspacecraft.

A decoupled recursive approach for constrained flexible multibody system dynamics

NASA Technical Reports Server (NTRS)

Lai, Hao-Jan; Kim, Sung-Soo; Haug, Edward J.; Bae, Dae-Sung

1989-01-01

A variational-vector calculus approach is employed to derive a recursive formulation for dynamic analysis of flexible multibody systems. Kinematic relationships for adjacent flexible bodies are derived in a companion paper, using a state vector notation that represents translational and rotational components simultaneously. Cartesian generalized coordinates are assigned for all body and joint reference frames, to explicitly formulate deformation kinematics under small deformation kinematics and an efficient flexible dynamics recursive algorithm is developed. Dynamic analysis of a closed loop robot is performed to illustrate efficiency of the algorithm.

Heterodimer Autorepression Loop: A Robust and Flexible Pulse-Generating Genetic Module

NASA Astrophysics Data System (ADS)

Lannoo, B.; Carlon, E.; Lefranc, M.

2016-07-01

We investigate the dynamics of the heterodimer autorepression loop (HAL), a small genetic module in which a protein A acts as an autorepressor and binds to a second protein B to form an A B dimer. For suitable values of the rate constants, the HAL produces pulses of A alternating with pulses of B . By means of analytical and numerical calculations, we show that the duration of A pulses is extremely robust against variation of the rate constants while the duration of the B pulses can be flexibly adjusted. The HAL is thus a minimal genetic module generating robust pulses with a tunable duration, an interesting property for cellular signaling.

Flexible High-Performance Lead-Free Na0.47K0.47Li0.06NbO3 Microcube-Structure-Based Piezoelectric Energy Harvester.

PubMed

Gupta, Manoj Kumar; Kim, Sang-Woo; Kumar, Binay

2016-01-27

Lead-free piezoelectric nano- and microstructure-based generators have recently attracted much attention due to the continuous demand of self-powered body implantable devices. We report the fabrication of a high-performance flexible piezoelectric microgenerator based on lead-free inorganic piezoelectric Na0.47K0.47Li0.06NbO3 (NKLN) microcubes for the first time. The composite generator is fabricated using NKLN microcubes and polydimethylsiloxane (PDMS) polymer on a flexible substrate. The flexible device exhibits excellent performance with a large recordable piezoelectric output voltage of 48 V and output current density of 0.43 μA/cm(2) under vertical compressive force of 2 kgf, for which an energy conversion efficiency of about 11% has been achieved. Piezoresponse and ferroelectric studies reveal that NKLN microcubes exhibited high piezoelectric charge coefficient (d33) as high as 460 pC/N and a well-defined hysteresis loops with remnant polarization and coercive field of 13.66 μC/cm(2) and 19.45 kV/cm, respectively. The piezoelectric charge generation mechanism from NKLN microgenerator are discussed in the light of the high d33 and alignment of electric dipoles in polymer matrix and dielectric constant of NKLN microcubes. It has been demonstrated that the developed power generator has the potential to generate high electric output power under mechanical vibration for powering biomedical devices in the near future.

Control-structure interaction in precision pointing servo loops

NASA Technical Reports Server (NTRS)

Spanos, John T.

1989-01-01

The control-structure interaction problem is addressed via stability analysis of a generic linear servo loop model. With the plant described by the rigid body mode and a single elastic mode, structural flexibility is categorized into one of three types: (1) appendage, (2) in-the-loop minimum phase, and (3) in-the-loop nonminimum phase. Closing the loop with proportional-derivative (PD) control action and introducing sensor roll-off dynamics in the feedback path, stability conditions are obtained. Trade studies are conducted with modal frequency, modal participation, modal damping, loop bandwidth, and sensor bandwidth treated as free parameters. Results indicate that appendage modes are most likely to produce instability if they are near the sensor rolloff, whereas in-the-loop modes are most dangerous near the loop bandwidth. The main goal of this paper is to provide a fundamental understanding of the control-structure interaction problem so that it may benefit the design of complex spacecraft and pointing system servo loops. In this framework, the JPL Pathfinder gimbal pointer is considered as an example.

An evaluation of some strategies for vibration control of flexible rotors

NASA Technical Reports Server (NTRS)

Burrows, C. R.

1992-01-01

There is evidence that the reliability of magnetic bearings has achieved an acceptable level in applications when high cost can be tolerated. This acceptability would be enhanced if the inherent capability of magnetic bearings as active control elements were fully used. The technological and commercial promise of magnetic bearings will be fulfilled only if attention is focussed on the control problems associated with their use. The open loop adaptive control algorithm provides an efficient method of controlling the vibration of rotors without the need of a prior knowledge of parameter values. It overcomes the disadvantages normally associated with open loop control while avoiding the problem of instability associated with closed loop control algorithms. The algorithm is conceptually satisfying because it uses the capability of magnetic bearings as fully active vibration control elements rather than limiting them to act as adjustable stiffness and damping elements, as is the case when they are used with local position and velocity feedback.

Robust fuel- and time-optimal control of uncertain flexible space structures

NASA Technical Reports Server (NTRS)

Wie, Bong; Sinha, Ravi; Sunkel, John; Cox, Ken

1993-01-01

The problem of computing open-loop, fuel- and time-optimal control inputs for flexible space structures in the face of modeling uncertainty is investigated. Robustified, fuel- and time-optimal pulse sequences are obtained by solving a constrained optimization problem subject to robustness constraints. It is shown that 'bang-off-bang' pulse sequences with a finite number of switchings provide a practical tradeoff among the maneuvering time, fuel consumption, and performance robustness of uncertain flexible space structures.

A family of asymptotically stable control laws for flexible robots based on a passivity approach

NASA Technical Reports Server (NTRS)

Lanari, Leonardo; Wen, John T.

1991-01-01

A general family of asymptotically stabilizing control laws is introduced for a class of nonlinear Hamiltonian systems. The inherent passivity property of this class of systems and the Passivity Theorem are used to show the closed-loop input/output stability which is then related to the internal state space stability through the stabilizability and detectability condition. Applications of these results include fully actuated robots, flexible joint robots, and robots with link flexibility.

Metal Oxide Silicon /MOS/ transistors protected from destructive damage by wire

NASA Technical Reports Server (NTRS)

Deboo, G. J.; Devine, E. J.

1966-01-01

Loop of flexible, small diameter, nickel wire protects metal oxide silicon /MOS/ transistors from a damaging electrostatic potential. The wire is attached to a music-wire spring, slipped over the MOS transistor case, and released so the spring tensions the wire loop around all the transistor leads, shorting them together. This allows handling without danger of damage.

Conformational flexibility of human casein kinase catalytic subunit explored by metadynamics.

PubMed

Gouron, Aurélie; Milet, Anne; Jamet, Helene

2014-03-04

Casein kinase CK2 is an essential enzyme in higher organisms, catalyzing the transfer of the γ phosphate from ATP to serine and threonine residues on protein substrates. In a number of animal tumors, CK2 activity has been shown to escape normal cellular control, making it a potential target for cancer therapy. Several crystal structures of human CK2 have been published with different conformations for the CK2α catalytic subunit. This variability reflects a high flexibility for two regions of CK2α: the interdomain hinge region, and the glycine-rich loop (p-loop). Here, we present a computational study simulating the equilibrium between three conformations involving these regions. Simulations were performed using well-tempered metadynamics combined with a path collective variables approach. This provides a reference pathway describing the conformational changes being studied, based on analysis of free energy surfaces. The free energies of the three conformations were found to be close and the paths proposed had low activation barriers. Our results indicate that these conformations can exist in water. This information should be useful when designing inhibitors specific to one conformation. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A dihydropyridine receptor alpha1s loop region critical for skeletal muscle contraction is intrinsically unstructured and binds to a SPRY domain of the type 1 ryanodine receptor.

PubMed

Cui, Yanfang; Tae, Han-Shen; Norris, Nicole C; Karunasekara, Yamuna; Pouliquin, Pierre; Board, Philip G; Dulhunty, Angela F; Casarotto, Marco G

2009-03-01

The II-III loop of the dihydropyridine receptor (DHPR) alpha(1s) subunit is a modulator of the ryanodine receptor (RyR1) Ca(2+) release channel in vitro and is essential for skeletal muscle contraction in vivo. Despite its importance, the structure of this loop has not been reported. We have investigated its structure using a suite of NMR techniques which revealed that the DHPR II-III loop is an intrinsically unstructured protein (IUP) and as such belongs to a burgeoning structural class of functionally important proteins. The loop does not possess a stable tertiary fold: it is highly flexible, with a strong N-terminal helix followed by nascent helical/turn elements and unstructured segments. Its residual structure is loosely globular with the N and C termini in close proximity. The unstructured nature of the II-III loop may allow it to easily modify its interaction with RyR1 following a surface action potential and thus initiate rapid Ca(2+) release and contraction. The in vitro binding partner for the II-III was investigated. The II-III loop interacts with the second of three structurally distinct SPRY domains in RyR1, whose function is unknown. This interaction occurs through two preformed N-terminal alpha-helical regions and a C-terminal hydrophobic element. The A peptide corresponding to the helical N-terminal region is a common probe of RyR function and binds to the same SPRY domain as the full II-III loop. Thus the second SPRY domain is an in vitro binding site for the II-III loop. The possible in vivo role of this region is discussed.

Flight control synthesis for flexible aircraft using Eigenspace assignment

NASA Technical Reports Server (NTRS)

Davidson, J. B.; Schmidt, D. K.

1986-01-01

The use of eigenspace assignment techniques to synthesize flight control systems for flexible aircraft is explored. Eigenspace assignment techniques are used to achieve a specified desired eigenspace, chosen to yield desirable system impulse residue magnitudes for selected system responses. Two of these are investigated. The first directly determines constant measurement feedback gains that will yield a close-loop system eigenspace close to a desired eigenspace. The second technique selects quadratic weighting matrices in a linear quadratic control synthesis that will asymptotically yield the close-loop achievable eigenspace. Finally, the possibility of using either of these techniques with state estimation is explored. Application of the methods to synthesize integrated flight-control and structural-mode-control laws for a large flexible aircraft is demonstrated and results discussed. Eigenspace selection criteria based on design goals are discussed, and for the study case it would appear that a desirable eigenspace can be obtained. In addition, the importance of state-space selection is noted along with problems with reduced-order measurement feedback. Since the full-state control laws may be implemented with dynamic compensation (state estimation), the use of reduced-order measurement feedback is less desirable. This is especially true since no change in the transient response from the pilot's input results if state estimation is used appropriately. The potential is also noted for high actuator bandwidth requirements if the linear quadratic synthesis approach is utilized. Even with the actuator pole location selected, a problem with unmodeled modes is noted due to high bandwidth. Some suggestions for future research include investigating how to choose an eigenspace that will achieve certain desired dynamics and stability robustness, determining how the choice of measurements effects synthesis results, and exploring how the phase relationships between desired eigenvector elements effects the synthesis results.

Adaptive super twisting vibration control of a flexible spacecraft with state rate estimation

NASA Astrophysics Data System (ADS)

Malekzadeh, Maryam; Karimpour, Hossein

2018-05-01

The robust attitude and vibration control of a flexible spacecraft trying to perform accurate maneuvers in spite of various sources of uncertainty is addressed here. Difficulties for achieving precise and stable pointing arise from noisy onboard sensors, parameters indeterminacy, outer disturbances as well as un-modeled or hidden dynamics interactions. Based on high-order sliding-mode methods, the non-minimum phase nature of the problem is dealt with through output redefinition. An adaptive super-twisting algorithm (ASTA) is incorporated with its observer counterpart on the system under consideration to get reliable attitude and vibration control in the presence of sensor noise and momentum coupling. The closed-loop efficiency is verified through simulations under various indeterminate situations and got compared to other methods.

A random-walk/giant-loop model for interphase chromosomes.

PubMed Central

Sachs, R K; van den Engh, G; Trask, B; Yokota, H; Hearst, J E

1995-01-01

Fluorescence in situ hybridization data on distances between defined genomic sequences are used to construct a quantitative model for the overall geometric structure of a human chromosome. We suggest that the large-scale geometry during the G0/G1 part of the cell cycle may consist of flexible chromatin loops, averaging approximately 3 million bp, with a random-walk backbone. A fully explicit, three-parametric polymer model of this random-walk/giant-loop structure can account well for the data. More general models consistent with the data are briefly discussed. PMID:7708711

Simple and Flexible Self-Reproducing Structures in Asynchronous Cellular Automata and Their Dynamics

NASA Astrophysics Data System (ADS)

Huang, Xin; Lee, Jia; Yang, Rui-Long; Zhu, Qing-Sheng

2013-03-01

Self-reproduction on asynchronous cellular automata (ACAs) has attracted wide attention due to the evident artifacts induced by synchronous updating. Asynchronous updating, which allows cells to undergo transitions independently at random times, might be more compatible with the natural processes occurring at micro-scale, but the dark side of the coin is the increment in the complexity of an ACA in order to accomplish stable self-reproduction. This paper proposes a novel model of self-timed cellular automata (STCAs), a special type of ACAs, where unsheathed loops are able to duplicate themselves reliably in parallel. The removal of sheath cannot only allow various loops with more flexible and compact structures to replicate themselves, but also reduce the number of cell states of the STCA as compared to the previous model adopting sheathed loops [Y. Takada, T. Isokawa, F. Peper and N. Matsui, Physica D227, 26 (2007)]. The lack of sheath, on the other hand, often tends to cause much more complicated interactions among loops, when all of them struggle independently to stretch out their constructing arms at the same time. In particular, such intense collisions may even cause the emergence of a mess of twisted constructing arms in the cellular space. By using a simple and natural method, our self-reproducing loops (SRLs) are able to retract their arms successively, thereby disentangling from the mess successfully.

A microcontroller platform for the rapid prototyping of functional electrical stimulation-based gait neuroprostheses.

PubMed

Luzio de Melo, Paulo; da Silva, Miguel Tavares; Martins, Jorge; Newman, Dava

2015-05-01

Functional electrical stimulation (FES) has been used over the last decades as a method to rehabilitate lost motor functions of individuals with spinal cord injury, multiple sclerosis, and post-stroke hemiparesis. Within this field, researchers in need of developing FES-based control solutions for specific disabilities often have to choose between either the acquisition and integration of high-performance industry-level systems, which are rather expensive and hardly portable, or develop custom-made portable solutions, which despite their lower cost, usually require expert-level electronic skills. Here, a flexible low-cost microcontroller-based platform for rapid prototyping of FES neuroprostheses is presented, designed for reduced execution complexity, development time, and production cost. For this reason, the Arduino open-source microcontroller platform was used, together with off-the-shelf components whenever possible. The developed system enables the rapid deployment of portable FES-based gait neuroprostheses, being flexible enough to allow simple open-loop strategies but also more complex closed-loop solutions. The system is based on a modular architecture that allows the development of optimized solutions depending on the desired FES applications, even though the design and testing of the platform were focused toward drop foot correction. The flexibility of the system was demonstrated using two algorithms targeting drop foot condition within different experimental setups. Successful bench testing of the device in healthy subjects demonstrated these neuroprosthesis platform capabilities to correct drop foot. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Highly flexible pulse programmer for NMR applications

NASA Technical Reports Server (NTRS)

Dart, J.; Burum, D. P.; Rhim, W. K.

1980-01-01

A pulse generator for NMR application is described. Eighteen output channels are provided to allow use in single and double resonance experiments. Complex pulse sequences may be generated by loading instructions into a 256-word by 16-bit program memory. Features of the pulse generator include programmable time delays from 0.5 micros to 1000 s, branching and looping instructions, and the ability to be loaded and operated either manually or from a PDP-11/10 computer.

Optical interferometer testbed

NASA Technical Reports Server (NTRS)

Blackwood, Gary H.

1991-01-01

Viewgraphs on optical interferometer testbed presented at the MIT Space Research Engineering Center 3rd Annual Symposium are included. Topics covered include: space-based optical interferometer; optical metrology; sensors and actuators; real time control hardware; controlled structures technology (CST) design methodology; identification for MIMO control; FEM/ID correlation for the naked truss; disturbance modeling; disturbance source implementation; structure design: passive damping; low authority control; active isolation of lightweight mirrors on flexible structures; open loop transfer function of mirror; and global/high authority control.

Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons

PubMed Central

Müller, Jan; Bakkum, Douglas J.; Hierlemann, Andreas

2012-01-01

We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

X-56A MUTT: Aeroservoelastic Modeling

NASA Technical Reports Server (NTRS)

Ouellette, Jeffrey A.

2015-01-01

For the NASA X-56a Program, Armstrong Flight Research Center has been developing a set of linear states space models that integrate the flight dynamics and structural dynamics. These high order models are needed for the control design, control evaluation, and test input design. The current focus has been on developing stiff wing models to validate the current modeling approach. The extension of the modeling approach to the flexible wings requires only a change in the structural model. Individual subsystems models (actuators, inertial properties, etc.) have been validated by component level ground tests. Closed loop simulation of maneuvers designed to validate the flight dynamics of these models correlates very well flight test data. The open loop structural dynamics are also shown to correlate well to the flight test data.

Adaptive optics based non-null interferometry for optical free form surfaces test

NASA Astrophysics Data System (ADS)

Zhang, Lei; Zhou, Sheng; Li, Jingsong; Yu, Benli

2018-03-01

An adaptive optics based non-null interferometry (ANI) is proposed for optical free form surfaces testing, in which an open-loop deformable mirror (DM) is employed as a reflective compensator, to compensate various low-order aberrations flexibly. The residual wavefront aberration is treated by the multi-configuration ray tracing (MCRT) algorithm. The MCRT algorithm based on the simultaneous ray tracing for multiple system models, in which each model has different DM surface deformation. With the MCRT algorithm, the final figure error can be extracted together with the surface misalignment aberration correction after the initial system calibration. The flexible test for free form surface is achieved with high accuracy, without auxiliary device for DM deformation monitoring. Experiments proving the feasibility, repeatability and high accuracy of the ANI were carried out to test a bi-conic surface and a paraboloidal surface, with a high stable ALPAOTM DM88. The accuracy of the final test result of the paraboloidal surface was better than 1/20 Μ PV value. It is a successful attempt in research of flexible optical free form surface metrology and would have enormous potential in future application with the development of the DM technology.

Flexible Metal-Fabric Radiators

NASA Technical Reports Server (NTRS)

Cross, Cynthia; Nguyen, Hai D.; Ruemmele, Warren; Andish, Kambiz K.; McCalley, Sean

2005-01-01

Flexible metal-fabric radiators have been considered as alternative means of dissipating excess heat from spacecraft and space suits. The radiators also may be useful in such special terrestrial applications as rejecting heat from space-suit-like protective suits worn in hot work environments. In addition to flexibility and consequent ease of deployment and installation on objects of varying sizes and shapes, the main advantages of these radiators over conventional rigid radiators are that they weigh less and occupy less volume for a given amount of cooling capacity. A radiator of this type includes conventional stainless-steel tubes carrying a coolant fluid. The main radiating component consists of a fabric of interwoven aluminum-foil strips bonded to the tubes by use of a proprietary process. The strip/tube bonds are strong and highly thermally conductive. Coolant is fed to and from the tubes via flexible stainless-steel manifolds designed to accommodate flexing of, and minimize bending forces on, the fabric. The manifolds are sized to minimize pressure drops and distribute the flow of coolant evenly to all the tubes. The tubes and manifolds are configured in two independent flow loops for operational flexibility and protective redundancy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandao, T.; Robinson, H; Johnson, S

Catalysis by the Yersinia protein-tyrosine phosphatase YopH is significantly impaired by the mutation of the conserved Trp354 residue to Phe. Though not a catalytic residue, this Trp is a hinge residue in a conserved flexible loop (the WPD-loop) that must close during catalysis. To learn why this seemingly conservative mutation reduces catalysis by 2 orders of magnitude, we have solved high-resolution crystal structures for the W354F YopH in the absence and in the presence of tungstate and vanadate. Oxyanion binding to the P-loop in W354F is analogous to that observed in the native enzyme. However, the WPD-loop in the presencemore » of oxyanions assumes a half-closed conformation, in contrast to the fully closed state observed in structures of the native enzyme. This observation provides an explanation for the impaired general acid catalysis observed in kinetic experiments with Trp mutants. A 1.4 Angstroms structure of the W354F mutant obtained in the presence of vanadate reveals an unusual divanadate species with a cyclic [VO]2 core, which has precedent in small molecules but has not been previously reported in a protein crystal structure.« less

A time domain inverse dynamic method for the end point tracking control of a flexible manipulator

NASA Technical Reports Server (NTRS)

Kwon, Dong-Soo; Book, Wayne J.

1991-01-01

The inverse dynamic equation of a flexible manipulator was solved in the time domain. By dividing the inverse system equation into the causal part and the anticausal part, we calculated the torque and the trajectories of all state variables for a given end point trajectory. The interpretation of this method in the frequency domain was explained in detail using the two-sided Laplace transform and the convolution integral. The open loop control of the inverse dynamic method shows an excellent result in simulation. For real applications, a practical control strategy is proposed by adding a feedback tracking control loop to the inverse dynamic feedforward control, and its good experimental performance is presented.

Relevance of Internal Friction and Structural Constraints for the Dynamics of Denatured Bovine Serum Albumin.

PubMed

Ameseder, Felix; Radulescu, Aurel; Holderer, Olaf; Falus, Peter; Richter, Dieter; Stadler, Andreas M

2018-05-17

A general property of disordered proteins is their structural expansion that results in a high molecular flexibility. The structure and dynamics of bovine serum albumin (BSA) denatured by guanidinium hydrochloride (GndCl) were investigated using small-angle neutron scattering (SANS) and neutron spin-echo spectroscopy (NSE). SANS experiments demonstrated the relevance of intrachain interactions for structural expansion. Using NSE experiments, we observed a high internal flexibility of denatured BSA in addition to center-of-mass diffusion detected by dynamic light scattering. Internal motions measured by NSE were described using concepts based on polymer theory. The contribution of residue-solvent friction was accounted for using the Zimm model including internal friction (ZIF). Disulfide bonds forming loops of amino acids of the peptide backbone have a major impact on internal dynamics that can be interpreted with a reduced set of Zimm modes.

Modeling and control for vibration suppression of a flexible smart structure

NASA Technical Reports Server (NTRS)

Dosch, J.; Leo, D.; Inman, D.

1993-01-01

Theoretical and experimental results of the modeling and control of a flexible ribbed antenna are presented. The antenna consists of eight flexible ribs which constitutes a smart antenna in the sense that the actuator and sensors are an integral part of the structure. The antenna exhibits closely space and repeated modes, thus multi-input multi-output (MIMO) control is necessary for controllability and observability of the structure. The structure also exhibits mode localization phenomenon and contains post buckled members making an accurate finite element model of the structure difficult to obtain. An identified MIMO minimum order model of the antenna is synthesized from identified single-input single-output (SISO) transfer functions curve fit in the frequency domain. The identified model is used to design a positive position feedback (PPF) controller that increases damping in all of the modes in the targeted frequency range. Due to the accuracy of the open loop model of the antenna, the closed loop response predicted by the identified model correlates well wtih experimental results.

Vibration suppression using a proofmass actuator operating in stroke/force saturation

NASA Technical Reports Server (NTRS)

Lindner, D. K.; Celano, T. P.; Ide, E. N.

1991-01-01

The design of the control-loop structure for a feedback control system which contains a proofmass actuator for suppressing vibration is discussed. The loop structure is composed of inner control loops, which determine the frequency of the actuator and which are directly related to the actuator and the outer loops which add damping to the structure. When the frequency response of the actuator is matched to the stroke/force saturation curve, the actuator is most effective in the vibration suppression loops, and, since the stroke/force saturation curve is characterized by the stroke length, the mass of the proofmass, and the maximum current delivered by the motor electronics, the size of the actuator can be easily determined. The results of the loop-structure model calculations are verified by examining linear DC motors as proofmass actuators for the Mast in NASA's Control of Flexible Structures program.

Development of High-power LED Lighting Luminaires Using Loop Heat Pipe

NASA Astrophysics Data System (ADS)

Huang, Bin-Juine; Huang, Huan-Hsiang; Chen, Chun-Wei; Wu, Min-Sheng

High-power LED should reject about 6 times of heat of the conventional lighting device and keep the LED junction temperature below 80°C to assure reliability and low light decay. In addition, no fan is allowed and the heat dissipation design should not interfere with the industrial design of lighting fixture and have a light weight. This thus creates an extreme thermal management problem. The present study has shown that, using a special heat dissipation technology (loop heat pipe), the high-power LED lighting luminaire with input power from 36 to 150W for outdoor and indoor applications can be achieved with light weight, among 0.96 to 1.57 kg per 1,000 lumen of net luminous flux output from the luminaire. The loop heat pipe uses a flexible connecting pipe as the condenser which can be wounded around the reflector of the luminaire to dissipate the heat to the ambient air by natural convection. For roadway or street lighting application, the present study shows that a better optical design of LED lamps can further result in power consumption reduction, based on the same illumination on road surface. The high-power LED luminaries developed in the present study have shown that the energy saving is > 50% in road lighting applications as compared to sodium light or > 70% compared to mercury light.

The dynamics and control of large flexible space structures - 12, supplement 11

NASA Technical Reports Server (NTRS)

Bainum, Peter M.; Reddy, A. S. S. R.; Li, Feiyue; Xu, Jianke

1989-01-01

The rapid 2-D slewing and vibrational control of the unsymmetrical flexible SCOLE (Spacecraft Control Laboratory Experiment) with multi-bounded controls is considered. Pontryagin's Maximum Principle is applied to the nonlinear equations of the system to derive the necessary conditions for the optimal control. The resulting two point boundary value problem is then solved by using the quasilinearization technique, and the near minimum time is obtained by sequentially shortening the slewing time until the controls are near the bang-bang type. The tradeoff between the minimum time and the minimum flexible amplitude requirements is discussed. The numerical results show that the responses of the nonlinear system are significantly different from those of the linearized system for rapid slewing. The SCOLE station-keeping closed loop dynamics are re-examined by employing a slightly different method for developing the equations of motion in which higher order terms in the expressions for the mast modal shape functions are now included. A preliminary study on the effect of actuator mass on the closed loop dynamics of large space systems is conducted. A numerical example based on a coupled two-mass two-spring system illustrates the effect of changes caused in the mass and stiffness matrices on the closed loop system eigenvalues. In certain cases the need for redesigning control laws previously synthesized, but not accounting for actuator masses, is indicated.

Locking the Active Conformation of c-Src Kinase through the Phosphorylation of the Activation Loop

PubMed Central

Meng, Yilin; Roux, Benoît

2013-01-01

Molecular dynamics umbrella sampling simulations are used to compare the relative stability of the active conformation of the catalytic domain of c-Src kinase while the tyrosine 416 in the activation loop (A-loop) is either unphosphorylated or phosphorylated. When the A-loop is unphosphorylated, there is considerable flexiblity of the kinase. While the active conformation of the kinase is not forbidden and can be visited transiently, it is not the predominant state. This is consistent with the view that c-Src displays some catalytic activity even when the A-loop is unphosphorylated. In contrast, phosphorylation of the A-loop contributes to stabilize several structural features that are critical for catalysis, such as the hydrophobic regulatory spine, the HRD motif, and the electrostatic switch. In summary, the free energy landscape calculations demonstrate that phosphorylation of tyrosine 416 in the A-loop essentially “locks” the kinase into its catalytically competent conformation. PMID:24103328

Using in-cell SHAPE-Seq and simulations to probe structure–function design principles of RNA transcriptional regulators

PubMed Central

Takahashi, Melissa K.; Watters, Kyle E.; Gasper, Paul M.; Abbott, Timothy R.; Carlson, Paul D.; Chen, Alan A.

2016-01-01

Antisense RNA-mediated transcriptional regulators are powerful tools for controlling gene expression and creating synthetic gene networks. RNA transcriptional repressors derived from natural mechanisms called attenuators are particularly versatile, though their mechanistic complexity has made them difficult to engineer. Here we identify a new structure–function design principle for attenuators that enables the forward engineering of new RNA transcriptional repressors. Using in-cell SHAPE-Seq to characterize the structures of attenuator variants within Escherichia coli, we show that attenuator hairpins that facilitate interaction with antisense RNAs require interior loops for proper function. Molecular dynamics simulations of these attenuator variants suggest these interior loops impart structural flexibility. We further observe hairpin flexibility in the cellular structures of natural RNA mechanisms that use antisense RNA interactions to repress translation, confirming earlier results from in vitro studies. Finally, we design new transcriptional attenuators in silico using an interior loop as a structural requirement and show that they function as desired in vivo. This work establishes interior loops as an important structural element for designing synthetic RNA gene regulators. We anticipate that the coupling of experimental measurement of cellular RNA structure and function with computational modeling will enable rapid discovery of structure–function design principles for a diverse array of natural and synthetic RNA regulators. PMID:27103533

Neural self-tuning adaptive control of non-minimum phase system

NASA Technical Reports Server (NTRS)

Ho, Long T.; Bialasiewicz, Jan T.; Ho, Hai T.

1993-01-01

The motivation of this research came about when a neural network direct adaptive control scheme was applied to control the tip position of a flexible robotic arm. Satisfactory control performance was not attainable due to the inherent non-minimum phase characteristics of the flexible robotic arm tip. Most of the existing neural network control algorithms are based on the direct method and exhibit very high sensitivity, if not unstable, closed-loop behavior. Therefore, a neural self-tuning control (NSTC) algorithm is developed and applied to this problem and showed promising results. Simulation results of the NSTC scheme and the conventional self-tuning (STR) control scheme are used to examine performance factors such as control tracking mean square error, estimation mean square error, transient response, and steady state response.

Robust control of flexible space vehicles with minimum structural excitation: On-off pulse control of flexible space vehicles

NASA Technical Reports Server (NTRS)

Wie, Bong; Liu, Qiang

1992-01-01

Both feedback and feedforward control approaches for uncertain dynamical systems (in particular, with uncertainty in structural mode frequency) are investigated. The control objective is to achieve a fast settling time (high performance) and robustness (insensitivity) to plant uncertainty. Preshaping of an ideal, time optimal control input using a tapped-delay filter is shown to provide a fast settling time with robust performance. A robust, non-minimum-phase feedback controller is synthesized with particular emphasis on its proper implementation for a non-zero set-point control problem. It is shown that a properly designed, feedback controller performs well, as compared with a time optimal open loop controller with special preshaping for performance robustness. Also included are two separate papers by the same authors on this subject.

Ethoscopes: An open platform for high-throughput ethomics.

PubMed

Geissmann, Quentin; Garcia Rodriguez, Luis; Beckwith, Esteban J; French, Alice S; Jamasb, Arian R; Gilestro, Giorgio F

2017-10-01

Here, we present the use of ethoscopes, which are machines for high-throughput analysis of behavior in Drosophila and other animals. Ethoscopes provide a software and hardware solution that is reproducible and easily scalable. They perform, in real-time, tracking and profiling of behavior by using a supervised machine learning algorithm, are able to deliver behaviorally triggered stimuli to flies in a feedback-loop mode, and are highly customizable and open source. Ethoscopes can be built easily by using 3D printing technology and rely on Raspberry Pi microcomputers and Arduino boards to provide affordable and flexible hardware. All software and construction specifications are available at http://lab.gilest.ro/ethoscope.

Conformational and dynamics changes induced by bile acids binding to chicken liver bile acid binding protein.

PubMed

Eberini, Ivano; Guerini Rocco, Alessandro; Ientile, Anna Rita; Baptista, António M; Gianazza, Elisabetta; Tomaselli, Simona; Molinari, Henriette; Ragona, Laura

2008-06-01

The correlation between protein motions and function is a central problem in protein science. Several studies have demonstrated that ligand binding and protein dynamics are strongly correlated in intracellular lipid binding proteins (iLBPs), in which the high degree of flexibility, principally occurring at the level of helix-II, CD, and EF loops (the so-called portal area), is significantly reduced upon ligand binding. We have recently investigated by NMR the dynamic properties of a member of the iLBP family, chicken liver bile acid binding protein (cL-BABP), in its apo and holo form, as a complex with two bile salts molecules. Binding was found to be regulated by a dynamic process and a conformational rearrangement was associated with this event. We report here the results of molecular dynamics (MD) simulations performed on apo and holo cL-BABP with the aim of further characterizing the protein regions involved in motion propagation and of evaluating the main molecular interactions stabilizing bound ligands. Upon binding, the root mean square fluctuation values substantially decrease for CD and EF loops while increase for the helix-loop-helix region, thus indicating that the portal area is the region mostly affected by complex formation. These results nicely correlate with backbone dynamics data derived from NMR experiments. Essential dynamics analysis of the MD trajectories indicates that the major concerted motions involve the three contiguous structural elements of the portal area, which however are dynamically coupled in different ways whether in the presence or in the absence of the ligands. Motions of the EF loop and of the helical region are part of the essential space of both apo and holo-BABP and sample a much wider conformational space in the apo form. Together with NMR results, these data support the view that, in the apo protein, the flexible EF loop visits many conformational states including those typical of the holo state and that the ligand acts stabilizing one of these pre-existing conformations. The present results, in agreement with data reported for other iLBPs, sharpen our knowledge on the binding mechanism for this protein family. (c) 2008 Wiley-Liss, Inc.

Flexible graphene-PZT ferroelectric nonvolatile memory.

PubMed

Lee, Wonho; Kahya, Orhan; Toh, Chee Tat; Ozyilmaz, Barbaros; Ahn, Jong-Hyun

2013-11-29

We report the fabrication of a flexible graphene-based nonvolatile memory device using Pb(Zr0.35,Ti0.65)O3 (PZT) as the ferroelectric material. The graphene and PZT ferroelectric layers were deposited using chemical vapor deposition and sol–gel methods, respectively. Such PZT films show a high remnant polarization (Pr) of 30 μC cm−2 and a coercive voltage (Vc) of 3.5 V under a voltage loop over ±11 V. The graphene–PZT ferroelectric nonvolatile memory on a plastic substrate displayed an on/off current ratio of 6.7, a memory window of 6 V and reliable operation. In addition, the device showed one order of magnitude lower operation voltage range than organic-based ferroelectric nonvolatile memory after removing the anti-ferroelectric behavior incorporating an electrolyte solution. The devices showed robust operation in bent states of bending radii up to 9 mm and in cycling tests of 200 times. The devices exhibited remarkable mechanical properties and were readily integrated with plastic substrates for the production of flexible circuits.

Numerical Analysis of a Flexible Dual Loop Coil and its Experimental Validation for pre-Clinical Magnetic Resonance Imaging of Rodents at 7 T

NASA Astrophysics Data System (ADS)

Solis-Najera, S.; Vazquez, F.; Hernandez, R.; Marrufo, O.; Rodriguez, A. O.

2016-12-01

A surface radio frequency coil was developed for small animal image acquisition in a pre-clinical magnetic resonance imaging system at 7 T. A flexible coil composed of two circular loops was developed to closely cover the object to be imaged. Electromagnetic numerical simulations were performed to evaluate its performance before the coil construction. An analytical expression of the mutual inductance for the two circular loops as a function of the separation between them was derived and used to validate the simulations. The RF coil is composed of two circular loops with a 5 cm external diameter and was tuned to 300 MHz and 50 Ohms matched. The angle between the loops was varied and the Q factor was obtained from the S11 simulations for each angle. B1 homogeneity was also evaluated using the electromagnetic simulations. The coil prototype was designed and built considering the numerical simulation results. To show the feasibility of the coil and its performance, saline-solution phantom images were acquired. A correlation of the simulations and imaging experimental results was conducted showing a concordance of 0.88 for the B1 field. The best coil performance was obtained at the 90° aperture angle. A more realistic phantom was also built using a formaldehyde-fixed rat phantom for ex vivo imaging experiments. All images showed a good image quality revealing clearly defined anatomical details of an ex vivo rat.

Electrostatic Interactions between OmpG Nanopore and Analyte Protein Surface Can Distinguish between Glycosylated Isoforms.

PubMed

Fahie, Monifa A; Chen, Min

2015-08-13

The flexible loops decorating the entrance of OmpG nanopore move dynamically during ionic current recording. The gating caused by these flexible loops changes when a target protein is bound. The gating is characterized by parameters including frequency, duration, and open-pore current, and these features combine to reveal the identity of a specific analyte protein. Here, we show that OmpG nanopore equipped with a biotin ligand can distinguish glycosylated and deglycosylated isoforms of avidin by their differences in surface charge. Our studies demonstrate that the direct interaction between the nanopore and analyte surface, induced by the electrostatic attraction between the two molecules, is essential for protein isoform detection. Our technique is remarkably sensitive to the analyte surface, which may provide a useful tool for glycoprotein profiling.

A passivity based control methodology for flexible joint robots with application to a simplified shuttle RMS arm

NASA Technical Reports Server (NTRS)

Sicard, Pierre; Wen, John T.

1991-01-01

The main goal is to develop a general theory for the control of flexible robots, including flexible joint robots, flexible link robots, rigid bodies with flexible appendages, etc. As part of the validation, the theory is applied to the control law development for a test example which consists of a three-link arm modeled after the shoulder yaw joint of the space shuttle remote manipulator system (RMS). The performance of the closed loop control system is then compared with the performance of the existing RMS controller to demonstrate the effectiveness of the proposed approach. The theoretical foundation of this new approach to the control of flexible robots is presented and its efficacy is demonstrated through simulation results on the three-link test arm.

Large planar maneuvers for articulated flexible manipulators

NASA Technical Reports Server (NTRS)

Huang, Jen-Kuang; Yang, Li-Farn

1988-01-01

An articulated flexible manipulator carried on a translational cart is maneuvered by an active controller to perform certain position control tasks. The nonlinear dynamics of the articulated flexible manipulator are derived and a transformation matrix is formulated to localize the nonlinearities within the inertia matrix. Then a feedback linearization scheme is introduced to linearize the dynamic equations for controller design. Through a pole placement technique, a robust controller design is obtained by properly assigning a set of closed-loop desired eigenvalues to meet performance requirements. Numerical simulations for the articulated flexible manipulators are given to demonstrate the feasibility and effectiveness of the proposed position control algorithms.

Human ER Oxidoreductin-1α (Ero1α) Undergoes Dual Regulation through Complementary Redox Interactions with Protein-Disulfide Isomerase.

PubMed

Kanemura, Shingo; Okumura, Masaki; Yutani, Katsuhide; Ramming, Thomas; Hikima, Takaaki; Appenzeller-Herzog, Christian; Akiyama, Shuji; Inaba, Kenji

2016-11-11

In the mammalian endoplasmic reticulum, oxidoreductin-1α (Ero1α) generates protein disulfide bonds and transfers them specifically to canonical protein-disulfide isomerase (PDI) to sustain oxidative protein folding. This oxidative process is coupled to the reduction of O 2 to H 2 O 2 on the bound flavin adenine dinucleotide cofactor. Because excessive thiol oxidation and H 2 O 2 generation cause cell death, Ero1α activity must be properly regulated. In addition to the four catalytic cysteines (Cys 94 , Cys 99 , Cys 104 , and Cys 131 ) that are located in the flexible active site region, the Cys 208 -Cys 241 pair located at the base of another flexible loop is necessary for Ero1α regulation, although the mechanistic basis is not fully understood. The present study revealed that the Cys 208 -Cys 241 disulfide was reduced by PDI and other PDI family members during PDI oxidation. Differential scanning calorimetry and small angle X-ray scattering showed that mutation of Cys 208 and Cys 241 did not grossly affect the thermal stability or overall shape of Ero1α, suggesting that redox regulation of this cysteine pair serves a functional role. Moreover, the flexible loop flanked by Cys 208 and Cys 241 provides a platform for functional interaction with PDI, which in turn enhances the oxidative activity of Ero1α through reduction of the Cys 208 -Cys 241 disulfide. We propose a mechanism of dual Ero1α regulation by dynamic redox interactions between PDI and the two Ero1α flexible loops that harbor the regulatory cysteines. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A voice coil actuator driven active vibration isolation system with the consideration of flexible modes.

PubMed

Park, Kyihwan; Choi, Dongyoub; Ozer, Abdullah; Kim, Sangyoo; Lee, Yongkwan; Joo, Dongik

2008-06-01

We develop a four-mount active vibration isolation system (AVIS) using voice coil actuators. The flexible body modes in the upper plate of the AVIS can cause an instability problem due to control signal whose frequency is close to the resonant frequency of the flexible modes. The loop shaping technique is applied to reduce the amplitude of the control signal. We investigate the performances of the active vibration isolation system proposed in the word in the time domain and frequency domain by comparing to the passive isolation system.

Analysis of the bacterial luciferase mobile loop by replica-exchange molecular dynamics.

PubMed

Campbell, Zachary T; Baldwin, Thomas O; Miyashita, Osamu

2010-12-15

Bacterial luciferase contains an extended 29-residue mobile loop. Movements of this loop are governed by binding of either flavin mononucleotide (FMNH2) or polyvalent anions. To understand this process, loop dynamics were investigated using replica-exchange molecular dynamics that yielded conformational ensembles in either the presence or absence of FMNH2. The resulting data were analyzed using clustering and network analysis. We observed the closed conformations that are visited only in the simulations with the ligand. Yet the mobile loop is intrinsically flexible, and FMNH2 binding modifies the relative populations of conformations. This model provides unique information regarding the function of a crystallographically disordered segment of the loop near the binding site. Structures at or near the fringe of this network were compatible with flavin binding or release. Finally, we demonstrate that the crystallographically observed conformation of the mobile loop bound to oxidized flavin was influenced by crystal packing. Thus, our study has revealed what we believe are novel conformations of the mobile loop and additional context for experimentally determined structures. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Submembranous recruitment of creatine kinase B supports formation of dynamic actin-based protrusions of macrophages and relies on its C-terminal flexible loop.

PubMed

Venter, Gerda; Polling, Saskia; Pluk, Helma; Venselaar, Hanka; Wijers, Mietske; Willemse, Marieke; Fransen, Jack A M; Wieringa, Bé

2015-02-01

Subcellular partitioning of creatine kinase contributes to the formation of patterns in intracellular ATP distribution and the fuelling of cellular processes with a high and sudden energy demand. We have previously shown that brain-type creatine kinase (CK-B) accumulates at the phagocytic cup in macrophages where it is involved in the compartmentalized generation of ATP for actin remodeling. Here, we report that CK-B catalytic activity also helps in the formation of protrusive ruffle structures which are actin-dependent and abundant on the surface of both unstimulated and LPS-activated macrophages. Recruitment of CK-B to these structures occurred transiently and inhibition of the enzyme's catalytic activity with cyclocreatine led to a general smoothening of surface morphology as visualized by scanning electron microscopy. Comparison of the dynamics of distribution of YFP-tagged CK-mutants and isoforms by live imaging revealed that amino acid residues in the C-terminal segment (aa positions 323-330) that forms one of the protein's two mobile loops are involved in partitioning over inner regions of the cytosol and nearby sites where membrane protrusions occur during induction of phagocytic cup formation. Although wt CK-B, muscle-type CK (CK-M), and a catalytically dead CK-B-E232Q mutant with intact loop region were normally recruited from the cytosolic pool, no dynamic transition to the phagocytic cup area was seen for the CK-homologue arginine kinase and a CK-B-D326A mutant protein. Bioinformatics analysis helped us to predict that conformational flexibility of the C-terminal loop, independent of conformational changes induced by substrate binding or catalytic activity, is likely involved in exposing the enzyme for binding at or near the sites of membrane protrusion formation. Copyright © 2014 Elsevier GmbH. All rights reserved.

Effects of ligand binding on the dynamics of rice nonspecific lipid transfer protein 1: a model from molecular simulations.

PubMed

Lai, Yen-Ting; Cheng, Chao-Sheng; Liu, Yu-Nan; Liu, Yaw-Jen; Lyu, Ping-Chiang

2008-09-01

Plant nonspecific lipid transfer proteins (nsLTPs) are small, basic proteins constituted mainly of alpha-helices and stabilized by four conserved disulfide bridges. They are characterized by the presence of a tunnel-like hydrophobic cavity, capable of transferring various lipid molecules between lipid bilayers in vitro. In this study, molecular dynamics (MD) simulations were performed at room temperature to investigate the effects of lipid binding on the dynamic properties of rice nsLTP1. Rice nsLTP1, either in the free form or complexed with one or two lipids was subjected to MD simulations. The C-terminal loop was very flexible both before and after lipid binding, as revealed by calculating the root-mean-square fluctuation. After lipid binding, the flexibility of some residues that were not in direct contact with lipid molecules increased significantly, indicating an increase of entropy in the region distal from the binding site. Essential dynamics analysis revealed clear differences in motion between unliganded and liganded rice nsLTP1s. In the free form of rice nsLTP1, loop1 exhibited the largest directional motion. This specific essential motion mode diminished after binding one or two lipid molecules. To verify the origin of the essential motion observed in the free form of rice nsLTP1, we performed multiple sequence alignments to probe the intrinsic motion encoded in the primary sequence. We found that the amino acid sequence of loop1 is highly conserved among plant nsLTP1s, thus revealing its functional importance during evolution. Furthermore, the sequence of loop1 is composed mainly of amino acids with short side chains. In this study, we show that MD simulations, together with essential dynamics analysis, can be used to determine structural and dynamic differences of rice nsLTP1 upon lipid binding. 2008 Wiley-Liss, Inc.

Multifunctional transducer

NASA Technical Reports Server (NTRS)

Feldstein, C.; Lewis, G. W.; Culler, V. H.; Merrbaum, S. (Inventor)

1981-01-01

Several parameters of a small region of a muscle tissue or other object, can be simultaneously measured using with minimal traumatizing or damage of the object, a trifunctional transducer which can determine the force applied by a muscle fiber, the displacement of the fiber, and the change in thickness of the fiber. The transducer has three legs with inner ends joined together and outer ends formed to piece the tissue and remain within it. Two of the legs are relatively stiff, to measure force applied by the tissue, and a third leg is relatively flexible to measure displacement of the tissue relative to one or both stiff legs, and with the three legs lying in a common plane so that the force and displacement measurements all relate to the same direction of muscle movements. A flexible loop is attached to one of the stiff legs to measure changes in muscle thickness, with the upper end of the loop fixed to the leg and the lower end of the loop bearing against the surface of the tissue and being free to slide on the leg.

Resolved single-molecule detection of individual species within a mixture of anti-biotin antibodies using an engineered monomeric nanopore.

PubMed

Fahie, Monifa; Chisholm, Christina; Chen, Min

2015-02-24

Oligomeric protein nanopores with rigid structures have been engineered for the purpose of sensing a wide range of analytes including small molecules and biological species such as proteins and DNA. We chose a monomeric β-barrel porin, OmpG, as the platform from which to derive the nanopore sensor. OmpG is decorated with seven flexible loops that move dynamically to create a distinct gating pattern when ionic current passes through the pore. Biotin was chemically tethered to the most flexible one of these loops. The gating characteristic of the loop's movement in and out of the porin was substantially altered by analyte protein binding. The gating characteristics of the pore with bound targets were remarkably sensitive to molecular identity, even providing the ability to distinguish between homologues within an antibody mixture. A total of five gating parameters were analyzed for each analyte to create a unique fingerprint for each biotin-binding protein. Our exploitation of gating noise as a molecular identifier may allow more sophisticated sensor design, while OmpG's monomeric structure greatly simplifies nanopore production.

Virtual solar field - An opportunity to optimize transient processes in line-focus CSP power plants

NASA Astrophysics Data System (ADS)

Noureldin, Kareem; Hirsch, Tobias; Pitz-Paal, Robert

2017-06-01

Optimizing solar field operation and control is a key factor to improve the competitiveness of line-focus solar thermal power plants. However, the risks of assessing new and innovative control strategies on operational power plants hinder such optimizations and result in applying more conservative control schemes. In this paper, we describe some applications for a whole solar field transient in-house simulation tool developed at the German Aerospace Centre (DLR), the Virtual Solar Field (VSF). The tool offers a virtual platform to simulate real solar fields while coupling the thermal and hydraulic conditions of the field with high computational efficiency. Using the tool, developers and operator can probe their control strategies and assess the potential benefits while avoiding the high risks and costs. In this paper, we study the benefits gained from controlling the loop valves and of using direct normal irradiance maps and forecasts for the field control. Loop valve control is interesting for many solar field operators since it provides a high degree of flexibility to the control of the solar field through regulating the flow rate in each loop. This improves the reaction to transient condition, such as passing clouds and field start-up in the morning. Nevertheless, due to the large number of loops and the sensitivity of the field control to the valve settings, this process needs to be automated and the effect of changing the setting of each valve on the whole field control needs to be taken into account. We used VSF to implement simple control algorithms to control the loop valves and to study the benefits that could be gained from using active loop valve control during transient conditions. Secondly, we study how using short-term highly spatially-resolved DNI forecasts provided by cloud cameras could improve the plant energy yield. Both cases show an improvement in the plant efficiency and outlet temperature stability. This paves the road for further investigations of new control strategies or for optimizations of the currently implemented ones.

Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse.

PubMed

Zhang, Xu; Diekwisch, Thomas G H; Luan, Xianghong

2011-12-01

The functional significance of extracellular matrix proteins in the life of vertebrates is underscored by a high level of sequence variability in tandem with a substantial degree of conservation in terms of cell-cell and cell-matrix adhesion interactions. Many extracellular matrix proteins feature multiple adhesion domains for successful attachment to substrates, such as integrin, CD63, and heparin. Here we have used homology and ab initio modeling algorithms to compare mouse ameloblastin (mAMBN) and human ameloblastin (hABMN) isoforms and to analyze their potential for cell adhesion and interaction with other matrix molecules as well as calcium binding. Sequence comparison between mAMBN and hAMBN revealed a 26-amino-acid deletion in mAMBN, corresponding to a helix-loop-helix frameshift. The human AMBN domain (174Q-201G), homologous to the mAMBN 157E-178I helix-loop-helix region, formed a helix-loop motif with an extended loop, suggesting a higher degree of flexibility of hAMBN compared with mAMBN, as confirmed by molecular dynamics simulation. Heparin-binding domains, CD63-interaction domains, and calcium-binding sites in both hAMBN and mAMBN support the concept of AMBN as an extracellular matrix protein. The high level of conservation between AMBN functional domains related to adhesion and differentiation was remarkable when compared with only 61% amino acid sequence homology. © 2011 Eur J Oral Sci.

Megawatt-Scale Power Hardware-in-the-Loop Simulation Testing of a Power Conversion Module for Naval Applications

DTIC Science & Technology

2015-06-21

problem was detected . Protection elements were implemented to trigger on over- voltage , over-current, over/under-frequency, and zero-sequence voltage ...power hardware in the loop simulation of distribution networks with photovoltaic generation,” International Journal of Renewable Energy Research...source modules were intended to support both emulation of a representative gas turbine generator set, as well as a flexible, controllable voltage source

Integrated Reconfigurable Intelligent Systems (IRIS) for Complex Naval Systems

DTIC Science & Technology

2009-12-31

written. The new implementation supports the XML dialect called dashML. The plug-in is written in Java script using a flexible extension of the...human in the loop control was improved and documented, and the script for integration was developed; further study on theoretical framework for...reference damage controller was developed and tested; the model of human in the loop control was improved and documented, and the script for integrating

A High-Sensitivity Flexible Eddy Current Array Sensor for Crack Monitoring of Welded Structures under Varying Environment.

PubMed

Chen, Tao; He, Yuting; Du, Jinqiang

2018-06-01

This paper develops a high-sensitivity flexible eddy current array (HS-FECA) sensor for crack monitoring of welded structures under varying environment. Firstly, effects of stress, temperature and crack on output signals of the traditional flexible eddy current array (FECA) sensor were investigated by experiments that show both stress and temperature have great influences on the crack monitoring performance of the sensor. A 3-D finite element model was established using Comsol AC/DC module to analyze the perturbation effects of crack on eddy currents and output signals of the sensor, which showed perturbation effect of cracks on eddy currents is reduced by the current loop when crack propagates. Then, the HS-FECA sensor was proposed to boost the sensitivity to cracks. Simulation results show that perturbation effect of cracks on eddy currents excited by the HS-FECA sensor gradually grows stronger when the crack propagates, resulting in much higher sensitivity to cracks. Experimental result further shows that the sensitivity of the new sensor is at least 19 times that of the original one. In addition, both stress and temperature variations have little effect on signals of the new sensor.

Molecular characterization and application of lipase from Bacillus sp. PU1 and investigation of structural changes based on pH and temperature using MD simulation.

PubMed

Esakkiraj, Palanichamy; Antonyraj, Christian Bharathi; Meleppat, Balraj; Ankaiah, Dasari; Ayyanna, Repally; Ahamed, Syed Ibrahim Basheer; Arul, Venkatesan

2017-10-01

A gene coding lipase from Bacillus sp. PU1 was cloned and expressed in E. coli BL21(DE3) pLysS. The purified lipase has a molecular weight of 23kDa, is highly alkaline (pH range 8-10) and mesophilic (20-50°C). Three dimensional structure of the lipase was modeled by comparative homology and identified as a typical serine lipase by the presence of conserved Ser77, Asp133, His156. The molecular stability and behavior of the lipase was carried out using MD simulation studies at different pH and temperature was performed in comparison with biochemical analysis. Structural modifications of the lipase under these conditions were trapped by dihedral based FEL analysis and the functional loops (loop-H5/B4 and loop-H6/B5 of lipase) are identified which would cause the catalytic behavior of the lipase by high flexibility. Further characteristic feature of lipase are observed as follows; SDS completely inhibits the lipase activity and enzyme activity is enhanced with non-ionic surfactants. The lipase was highly stable in different organic solvents and also it could tolerate NaCl (0.4-0.8M). This enzyme was found to disrupt the biofilm of tested pathogenic bacterial strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Closing loop base pairs in RNA loop-loop complexes: structural behavior, interaction energy and solvation analysis through molecular dynamics simulations.

PubMed

Golebiowski, Jérôme; Antonczak, Serge; Fernandez-Carmona, Juan; Condom, Roger; Cabrol-Bass, Daniel

2004-12-01

Nanosecond molecular dynamics using the Ewald summation method have been performed to elucidate the structural and energetic role of the closing base pair in loop-loop RNA duplexes neutralized by Mg2+ counterions in aqueous phases. Mismatches GA, CU and Watson-Crick GC base pairs have been considered for closing the loop of an RNA in complementary interaction with HIV-1 TAR. The simulations reveal that the mismatch GA base, mediated by a water molecule, leads to a complex that presents the best compromise between flexibility and energetic contributions. The mismatch CU base pair, in spite of the presence of an inserted water molecule, is too short to achieve a tight interaction at the closing-loop junction and seems to force TAR to reorganize upon binding. An energetic analysis has allowed us to quantify the strength of the interactions of the closing and the loop-loop pairs throughout the simulations. Although the water-mediated GA closing base pair presents an interaction energy similar to that found on fully geometry-optimized structure, the water-mediated CU closing base pair energy interaction reaches less than half the optimal value.

Vibration and Control of Flexible Rotor Supported by Magnetic Bearings

NASA Technical Reports Server (NTRS)

Nonami, Kenzou

1988-01-01

Active vibration control of flexible rotors supported by magnetic bearings is discussed. Using a finite-element method for a mathematical model of the flexible rotor, the eigenvalue problem is formulated taking into account the interaction between a mechanical system of the flexible rotor and an electrical system of the magnetic bearings and the controller. However, for the sake of simplicity, gyroscopic effects are disregarded. It is possible to adapt this formulation to a general flexible rotor-magnetic bearing system. Controllability with and without collocation sensors and actuators located at the same distance along the rotor axis is discussed for the higher order flexible modes of the test rig. In conclusion, it is proposed that it is necessary to add new active control loops for the higher flexible modes even in the case of collocation. Then it is possible to stabilize for the case of uncollocation by means of this method.

Control of large flexible systems via eigenvalue relocation

NASA Technical Reports Server (NTRS)

Denman, E. D.; Jeon, G. J.

1985-01-01

For the vibration control of large flexible systems, a control scheme by which the eigenvalues of the closed-loop systems are assigned to predetermined locations within the feasible region through velocity-only feedback is presented. Owing to the properties of second-order lambda-matrices and an efficient model decoupling technique, the control scheme makes it possible that selected modes are damped with the rest of the modes unchanged.

Thermal and Mechanical Microspacecraft Technologies for Deep Space Systems Program X2000 Future Deliveries

NASA Technical Reports Server (NTRS)

Birur, Gajanana C.; Bruno, Robin J.

1999-01-01

Thermal and mechanical technologies are an important part of the Deep Space Systems Technology (DSST) Program X2000 Future Deliveries (FD) microspacecraft. A wide range of future space missions are expected to utilize the technologies and the architecture developed by DSST FD. These technologies, besides being small in physical size, make the tiny spacecraft robust and flexible. The DSST FD architecture is designed to be highly reliable and suitable for a wide range of missions such as planetary landers/orbiters/flybys, earth orbiters, cometary flybys/landers/sample returns, etc. Two of the key ideas used in the development of thermal and mechanical technologies and architectures are: 1) to include several of the thermal and mechanical functions in any given single spacecraft element and 2) the architecture be modular so that it can easily be adapted to any of the future missions. One of the thermal architectures being explored for the DSST FD microspacecraft is the integrated thermal energy management of the complete spacecraft using a fluid loop. The robustness and the simplicity of the loop and the flexibility with which it can be integrated in the spacecraft have made it attractive for applications to DSST FD. Some of the thermal technologies to be developed as a part of this architecture are passive and active cooling loops, electrically variable emittance surfaces, miniature thermal switches, and specific high density electronic cooling technologies. In the mechanical area, multifunction architecture for the structural elements will be developed. The multifunction aspect is expected to substantially reduce the mass and volume of the spacecraft. Some of the technologies that will be developed are composite material panels incorporating electronics, cabling, and thermal elements in them. The paper describes the current state of the technologies and progress to be made in the thermal and mechanical technologies and approaches for the DSST Future Deliveries microspacecraft.

A double-headed cathepsin B inhibitor devoid of warhead

PubMed Central

Schenker, Patricia; Alfarano, Pietro; Kolb, Peter; Caflisch, Amedeo; Baici, Antonio

2008-01-01

Most synthetic inhibitors of peptidases have been targeted to the active site for inhibiting catalysis through reversible competition with the substrate or by covalent modification of catalytic groups. Cathepsin B is unique among the cysteine peptidase for the presence of a flexible segment, known as the occluding loop, which can block the primed subsites of the substrate binding cleft. With the occluding loop in the open conformation cathepsin B acts as an endopeptidase, and it acts as an exopeptidase when the loop is closed. We have targeted the occluding loop of human cathepsin B at its surface, outside the catalytic center, using a high-throughput docking procedure. The aim was to identify inhibitors that would interact with the occluding loop thereby modulating enzyme activity without the help of chemical warheads against catalytic residues. From a large library of compounds, the in silico approach identified [2-[2-(2,4-dioxo-1,3-thiazolidin-3-yl)ethylamino]-2-oxoethyl] 2-(furan-2-carbonylamino) acetate, which fulfills the working hypothesis. This molecule possesses two distinct binding moieties and behaves as a reversible, double-headed competitive inhibitor of cathepsin B by excluding synthetic and protein substrates from the active center. The kinetic mechanism of inhibition suggests that the occluding loop is stabilized in its closed conformation, mainly by hydrogen bonds with the inhibitor, thus decreasing endoproteolytic activity of the enzyme. Furthermore, the dioxothiazolidine head of the compound sterically hinders binding of the C-terminal residue of substrates resulting in inhibition of the exopeptidase activity of cathepsin B in a physiopathologically relevant pH range. PMID:18796695

On the feasibility of closed-loop control of intra-aortic balloon pumping

NASA Technical Reports Server (NTRS)

Clark, J. W., Jr.; Bourland, H. M.; Kane, G. R.

1973-01-01

A closed-loop control scheme for the control of intra-aortic balloon pumping has been developed and tested in dog experiments. A performance index reflecting the general objectives of balloon-assist pumping is developed and a modified steepest ascent control algorithm is utilized for the selection of a proper operating point for the balloon during its pumping cycle. This paper attempts to indicate the feasibility of closed-loop control of balloon pumping, and particularly its flexibility in achieving both diastolic augmentation of mean aortic pressure and control of the level of end-diastolic pressure (EDP) an important factor in reducing heart work.

Evaluation of inertial devices for the control of large, flexible, space-based telerobotic arms

NASA Technical Reports Server (NTRS)

Montgomery, Raymond C.; Kenny, Sean P.; Ghosh, Dave; Shenhar, Joram

1993-01-01

Inertial devices, including sensors and actuators, offer the potential of improving the tracking of telerobotic commands for space-based robots by smoothing payload motions and suppressing vibrations. In this paper, inertial actuators (specifically, torque-wheels and reaction-masses) are studied for that potential application. Batch simulation studies are presented which show that torque-wheels can reduce the overshoot in abrupt stop commands by 82 percent for a two-link arm. For man-in-the-loop evaluation, a real-time simulator has been developed which samples a hand-controller, solves the nonlinear equations of motion, and graphically displays the resulting motion on a computer workstation. Currently, two manipulator models, a two-link, rigid arm and a single-link, flexible arm, have been studied. Results are presented which show that, for a single-link arm, a reaction-mass/torque-wheel combination at the payload end can yield a settling time of 3 s for disturbances in the first flexible mode as opposed to 10 s using only a hub motor. A hardware apparatus, which consists of a single-link, highly flexible arm with a hub motor and a torque-wheel, has been assembled to evaluate the concept and is described herein.

Evaluation of inertial devices for the control of large, flexible, space-based telerobotic arms

NASA Astrophysics Data System (ADS)

Montgomery, Raymond C.; Kenny, Sean P.; Ghosh, Dave; Shenhar, Joram

1993-02-01

Inertial devices, including sensors and actuators, offer the potential of improving the tracking of telerobotic commands for space-based robots by smoothing payload motions and suppressing vibrations. In this paper, inertial actuators (specifically, torque-wheels and reaction-masses) are studied for that potential application. Batch simulation studies are presented which show that torque-wheels can reduce the overshoot in abrupt stop commands by 82 percent for a two-link arm. For man-in-the-loop evaluation, a real-time simulator has been developed which samples a hand-controller, solves the nonlinear equations of motion, and graphically displays the resulting motion on a computer workstation. Currently, two manipulator models, a two-link, rigid arm and a single-link, flexible arm, have been studied. Results are presented which show that, for a single-link arm, a reaction-mass/torque-wheel combination at the payload end can yield a settling time of 3 s for disturbances in the first flexible mode as opposed to 10 s using only a hub motor. A hardware apparatus, which consists of a single-link, highly flexible arm with a hub motor and a torque-wheel, has been assembled to evaluate the concept and is described herein.

Application of the LQG/LTR technique to robust controller synthesis for a large flexible space antenna

NASA Technical Reports Server (NTRS)

Joshi, S. M.; Armstrong, E. S.; Sundararajan, N.

1986-01-01

The problem of synthesizing a robust controller is considered for a large, flexible space-based antenna by using the linear-quadratic-Gaussian (LQG)/loop transfer recovery (LTR) method. The study is based on a finite-element model of the 122-m hoop/column antenna, which consists of three rigid-body rotational modes and the first 10 elastic modes. A robust compensator design for achieving the required performance bandwidth in the presence of modeling uncertainties is obtained using the LQG/LTR method for loop-shaping in the frequency domain. Different sensor actuator locations are analyzed in terms of the pole/zero locations of the multivariable systems and possible best locations are indicated. The computations are performed by using the LQG design package ORACLS augmented with frequency domain singular value analysis software.

On actuator placement for robust time-optimal control of uncertain flexible spacecraft

NASA Technical Reports Server (NTRS)

Wie, Bong; Sinha, Ravi; Liu, Qiang

1992-01-01

The problem of computing open-loop, on-off jet firing logic for flexible spacecraft in the face of plant modeling uncertainty is investigated. The primary control objective is to achieve a fast maneuvering time with a minimum of structural vibrations during and/or after a maneuver. This paper is also concerned with the problem of selecting a proper pair of jets for practical trade-offs among the maneuvering time, fuel consumption, structural mode excitation, and performance robustness. A time-optimal control problem subject to parameter robustness constraints is formulated. A three-mass-spring model of flexible spacecraft with a rigid-body mode and two flexible modes is used to illustrate the concept.

Using in-cell SHAPE-Seq and simulations to probe structure-function design principles of RNA transcriptional regulators.

PubMed

Takahashi, Melissa K; Watters, Kyle E; Gasper, Paul M; Abbott, Timothy R; Carlson, Paul D; Chen, Alan A; Lucks, Julius B

2016-06-01

Antisense RNA-mediated transcriptional regulators are powerful tools for controlling gene expression and creating synthetic gene networks. RNA transcriptional repressors derived from natural mechanisms called attenuators are particularly versatile, though their mechanistic complexity has made them difficult to engineer. Here we identify a new structure-function design principle for attenuators that enables the forward engineering of new RNA transcriptional repressors. Using in-cell SHAPE-Seq to characterize the structures of attenuator variants within Escherichia coli, we show that attenuator hairpins that facilitate interaction with antisense RNAs require interior loops for proper function. Molecular dynamics simulations of these attenuator variants suggest these interior loops impart structural flexibility. We further observe hairpin flexibility in the cellular structures of natural RNA mechanisms that use antisense RNA interactions to repress translation, confirming earlier results from in vitro studies. Finally, we design new transcriptional attenuators in silico using an interior loop as a structural requirement and show that they function as desired in vivo. This work establishes interior loops as an important structural element for designing synthetic RNA gene regulators. We anticipate that the coupling of experimental measurement of cellular RNA structure and function with computational modeling will enable rapid discovery of structure-function design principles for a diverse array of natural and synthetic RNA regulators. © 2016 Takahashi et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Relative stability of the open and closed conformations of the active site loop of streptavidin

NASA Astrophysics Data System (ADS)

Ignacio J., General; Meirovitch, Hagai

2011-01-01

The eight-residue surface loop, 45-52 (Ser, Ala, Val, Gly, Asn, Ala, Glu, Ser), of the homotetrameric protein streptavidin has a "closed" conformation in the streptavidin-biotin complex, where the corresponding binding affinity is one of the strongest found in nature (ΔG ˜ -18 kcal/mol). However, in most of the crystal structures of apo (unbound) streptavidin, the loop conformation is "open" and typically exhibits partial disorder and high B-factors. Thus, it is plausible to assume that the loop structure is changed from open to closed upon binding of biotin, and the corresponding difference in free energy, ΔF = Fopen - Fclosed in the unbound protein, should therefore be considered in the total absolute free energy of binding. ΔF (which has generally been neglected) is calculated here using our "hypothetical scanning molecular-dynamics" (HSMD) method. We use a protein model in which only the atoms closest to the loop are considered (the "template") and they are fixed in the x-ray coordinates of the free protein; the x-ray conformation of the closed loop is attached to the same (unbound) template and both systems are capped with the same sphere of TIP3P water. Using the force field of the assisted model building with energy refinement (AMBER), we carry out two separate MD simulations (at temperature T = 300 K), starting from the open and closed conformations, where only the atoms of the loop and water are allowed to move (the template-water and template-loop interactions are considered). The absolute Fopen and Fclosed (of loop + water) are calculated from these trajectories, where the loop and water contributions are obtained by HSMD and a thermodynamic integration (TI) process, respectively. The combined HSMD-TI procedure leads to total (loop + water) ΔF = -27.1 ± 2.0 kcal/mol, where the entropy TΔS constitutes 34% of ΔF, meaning that the effect of S is significant and should not be ignored. Also, ΔS is positive, in accord with the high flexibility of the open loop observed in crystal structures, while the energy ΔE is unexpectedly negative, thus also adding to the stability of the open loop. The loop and the 250 capped water molecules are the largest system studied thus far, which constitutes a test for the efficiency of HSMD-TI; this efficiency and technical issues related to the implementation of the method are also discussed. Finally, the result for ΔF is a prediction that will be considered in the calculation of the absolute free energy of binding of biotin to streptavidin, which constitutes our next project.

Mapping epitopes and antigenicity by site-directed masking

NASA Astrophysics Data System (ADS)

Paus, Didrik; Winter, Greg

2006-06-01

Here we describe a method for mapping the binding of antibodies to the surface of a folded antigen. We first created a panel of mutant antigens (-lactamase) in which single surface-exposed residues were mutated to cysteine. We then chemically tethered the cysteine residues to a solid phase, thereby masking a surface patch centered on each cysteine residue and blocking the binding of antibodies to this region of the surface. By these means we mapped the epitopes of several mAbs directed to -lactamase. Furthermore, by depleting samples of polyclonal antisera to the masked antigens and measuring the binding of each depleted sample of antisera to unmasked antigen, we mapped the antigenicity of 23 different epitopes. After immunization of mice and rabbits with -lactamase in Freund's adjuvant, we found that the antisera reacted with both native and denatured antigen and that the antibody response was mainly directed to an exposed and flexible loop region of the native antigen. By contrast, after immunization in PBS, we found that the antisera reacted only weakly with denatured antigen and that the antibody response was more evenly distributed over the antigenic surface. We suggest that denatured antigen (created during emulsification in Freund's adjuvant) elicits antibodies that bind mainly to the flexible regions of the native protein and that this explains the correlation between antigenicity and backbone flexibility. Denaturation of antigen during vaccination or natural infections would therefore be expected to focus the antibody response to the flexible loops. backbone flexibility | Freund's adjuvant | conformational epitope | antisera

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1

PubMed Central

2016-01-01

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70–81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1’s lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1’s lactonase activity is minimal, whereas the kcat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1’s active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar “gating loop” or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates. PMID:28026940

Crystallographic and Molecular Dynamics Analysis of Loop Motions Unmasking the Peptidoglycan-Binding Site in Stator Protein MotB of Flagellar Motor

PubMed Central

Nahar, Musammat F.; Buckle, Ashley M.; Roujeinikova, Anna

2011-01-01

Background The C-terminal domain of MotB (MotB-C) shows high sequence similarity to outer membrane protein A and related peptidoglycan (PG)-binding proteins. It is believed to anchor the power-generating MotA/MotB stator unit of the bacterial flagellar motor to the peptidoglycan layer of the cell wall. We previously reported the first crystal structure of this domain and made a puzzling observation that all conserved residues that are thought to be essential for PG recognition are buried and inaccessible in the crystal structure. In this study, we tested a hypothesis that peptidoglycan binding is preceded by, or accompanied by, some structural reorganization that exposes the key conserved residues. Methodology/Principal Findings We determined the structure of a new crystalline form (Form B) of Helicobacter pylori MotB-C. Comparisons with the existing Form A revealed conformational variations in the petal-like loops around the carbohydrate binding site near one end of the β-sheet. These variations are thought to reflect natural flexibility at this site required for insertion into the peptidoglycan mesh. In order to understand the nature of this flexibility we have performed molecular dynamics simulations of the MotB-C dimer. The results are consistent with the crystallographic data and provide evidence that the three loops move in a concerted fashion, exposing conserved MotB residues that have previously been implicated in binding of the peptide moiety of peptidoglycan. Conclusion/Significance Our structural analysis provides a new insight into the mechanism by which MotB inserts into the peptidoglycan mesh, thus anchoring the power-generating complex to the cell wall. PMID:21533052

Measuring Pressure Volume Loops in the Mouse.

PubMed

Townsend, DeWayne

2016-05-02

Understanding the causes and progression of heart disease presents a significant challenge to the biomedical community. The genetic flexibility of the mouse provides great potential to explore cardiac function at the molecular level. The mouse's small size does present some challenges in regards to performing detailed cardiac phenotyping. Miniaturization and other advancements in technology have made many methods of cardiac assessment possible in the mouse. Of these, the simultaneous collection of pressure and volume data provides a detailed picture of cardiac function that is not available through any other modality. Here a detailed procedure for the collection of pressure-volume loop data is described. Included is a discussion of the principles underlying the measurements and the potential sources of error. Anesthetic management and surgical approaches are discussed in great detail as they are both critical to obtaining high quality hemodynamic measurements. The principles of hemodynamic protocol development and relevant aspects of data analysis are also addressed.

Ethoscopes: An open platform for high-throughput ethomics

PubMed Central

Geissmann, Quentin; Garcia Rodriguez, Luis; Beckwith, Esteban J.; French, Alice S.; Jamasb, Arian R.

2017-01-01

Here, we present the use of ethoscopes, which are machines for high-throughput analysis of behavior in Drosophila and other animals. Ethoscopes provide a software and hardware solution that is reproducible and easily scalable. They perform, in real-time, tracking and profiling of behavior by using a supervised machine learning algorithm, are able to deliver behaviorally triggered stimuli to flies in a feedback-loop mode, and are highly customizable and open source. Ethoscopes can be built easily by using 3D printing technology and rely on Raspberry Pi microcomputers and Arduino boards to provide affordable and flexible hardware. All software and construction specifications are available at http://lab.gilest.ro/ethoscope. PMID:29049280

How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA.

PubMed

Hur, Sun; Stroud, Robert M

2007-04-27

Translational accuracy and efficiency depend upon modification of uridines in the tRNA anticodon stem loop (ASL) by a highly conserved pseudouridine synthase TruA. TruA specifically modifies uridines at positions 38, 39, and/or 40 of tRNAs with highly divergent sequences and structures through a poorly characterized mechanism that differs from previously studied RNA-modifying enzymes. The molecular basis for the site and substrate "promiscuity" was studied by determining the crystal structures of E. coli TruA in complex with two different leucyl tRNAs in conjunction with functional assays and computer simulation. The structures capture three stages of the TruA*tRNA reaction, revealing the mechanism by which TruA selects the target site. We propose that TruA utilizes the intrinsic flexibility of the ASL for site promiscuity and also to select against intrinsically stable tRNAs to avoid their overstabilization through pseudouridylation, thereby maintaining the balance between the flexibility and stability required for its biological function.

Integrated and flexible multichannel interface for electrotactile stimulation

NASA Astrophysics Data System (ADS)

Štrbac, Matija; Belić, Minja; Isaković, Milica; Kojić, Vladimir; Bijelić, Goran; Popović, Igor; Radotić, Milutin; Došen, Strahinja; Marković, Marko; Farina, Dario; Keller, Thierry

2016-08-01

Objective. The aim of the present work was to develop and test a flexible electrotactile stimulation system to provide real-time feedback to the prosthesis user. The system requirements were to accommodate the capabilities of advanced multi-DOF myoelectric hand prostheses and transmit the feedback variables (proprioception and force) using intuitive coding, with high resolution and after minimal training. Approach. We developed a fully-programmable and integrated electrotactile interface supporting time and space distributed stimulation over custom designed flexible array electrodes. The system implements low-level access to individual stimulation channels as well as a set of high-level mapping functions translating the state of a multi-DoF prosthesis (aperture, grasping force, wrist rotation) into a set of predefined dynamic stimulation profiles. The system was evaluated using discrimination tests employing spatial and frequency coding (10 able-bodied subjects) and dynamic patterns (10 able-bodied and 6 amputee subjects). The outcome measure was the success rate (SR) in discrimination. Main results. The more practical electrode with the common anode configuration performed similarly to the more usual concentric arrangement. The subjects could discriminate six spatial and four frequency levels with SR >90% after a few minutes of training, whereas the performance significantly deteriorated for more levels. The dynamic patterns were intuitive for the subjects, although amputees showed lower SR than able-bodied individuals (86% ± 10% versus 99% ± 3%). Significance. The tests demonstrated that the system was easy to setup and apply. The design and resolution of the multipad electrode was evaluated. Importantly, the novel dynamic patterns, which were successfully tested, can be superimposed to transmit multiple feedback variables intuitively and simultaneously. This is especially relevant for closing the loop in modern multifunction prostheses. Therefore, the proposed system is convenient for practical applications and can be used to implement sensory perception training and/or closed-loop control of myoelectric prostheses, providing grasping force and proprioceptive feedback.

Flexible pile thermal barrier insulator

NASA Technical Reports Server (NTRS)

Anderson, G. E.; Fell, D. M.; Tesinsky, J. S. (Inventor)

1978-01-01

A flexible pile thermal barrier insulator included a plurality of upstanding pile yarns. A generally planar backing section supported the upstanding pile yarns. The backing section included a plurality of filler yarns forming a mesh in a first direction. A plurality of warp yarns were looped around said filler yarns and pile yarns in the backing section and formed a mesh in a second direction. A binder prevented separation of the yarns in the backing section.

A convenient method for large-scale STM mapping of freestanding atomically thin conductive membranes

NASA Astrophysics Data System (ADS)

Uder, B.; Hartmann, U.

2017-06-01

Two-dimensional atomically flat sheets with a high flexibility are very attractive as ultrathin membranes but are also inherently challenging for microscopic investigations. We report on a method using Scanning Tunneling Microscopy (STM) under ultra-high vacuum conditions for large-scale mapping of several-micrometer-sized freestanding single and multilayer graphene membranes. This is achieved by operating the STM at unusual parameters. We found that large-scale scanning on atomically thin membranes delivers valuable results using very high tip-scan speeds combined with high feedback-loop gain and low tunneling currents. The method ultimately relies on the particular behavior of the freestanding membrane in the STM which is much different from that of a solid substrate.

HRD Motif as the Central Hub of the Signaling Network for Activation Loop Autophosphorylation in Abl Kinase.

PubMed

La Sala, Giuseppina; Riccardi, Laura; Gaspari, Roberto; Cavalli, Andrea; Hantschel, Oliver; De Vivo, Marco

2016-11-08

A number of structural factors modulate the activity of Abelson (Abl) tyrosine kinase, whose deregulation is often related to oncogenic processes. First, only the open conformation of the Abl kinase domain's activation loop (A-loop) favors ATP binding to the catalytic cleft. In this regard, the trans-autophosphorylation of the Y412 residue, which is located along the A-loop, favors the stability of the open conformation, in turn enhancing Abl activity. Another key factor for full Abl activity is the formation of active conformations of the catalytic DFG motif in the Abl kinase domain. Furthermore, binding of the SH2 domain to the N-lobe of the Abl kinase was recently demonstrated to have a long-range allosteric effect on the stabilization of the A-loop open state. Intriguingly, these distinct structural factors imply a complex signal transmission network for controlling the A-loop's flexibility and conformational preference for optimal Abl function. However, the exact dynamical features of this signal transmission network structure remain unclear. Here, we report on microsecond-long molecular dynamics coupled with enhanced sampling simulations of multiple Abl model systems, in the presence or absence of the SH2 domain and with the DFG motif flipped in two ways (in or out conformation). Through comparative analysis, our simulations augment the interpretation of the existing Abl experimental data, revealing a dynamical network of interactions that interconnect SH2 domain binding with A-loop plasticity and Y412 autophosphorylation in Abl. This signaling network engages the DFG motif and, importantly, other conserved structural elements of the kinase domain, namely, the EPK-ELK H-bond network and the HRD motif. Our results show that the signal propagation for modulating the A-loop spatial localization is highly dependent on the HRD motif conformation, which thus acts as the central hub of this (allosteric) signaling network controlling Abl activation and function.

Reactivation of mutant p53: Constraints on mechanism highlighted by principal component analysis of the DNA binding domain.

PubMed

Ouaray, Zahra; ElSawy, Karim M; Lane, David P; Essex, Jonathan W; Verma, Chandra

2016-10-01

Most p53 mutations associated with cancer are located in its DNA binding domain (DBD). Many structures (X-ray and NMR) of this domain are available in the protein data bank (PDB) and a vast conformational heterogeneity characterizes the various free and complexed states. The major difference between the apo and the holo-complexed states appears to lie in the L1 loop. In particular, the conformations of this loop appear to depend intimately on the sequence of DNA to which it binds. This conclusion builds upon recent observations that implicate the tetramerization and the C-terminal domains (respectively TD and Cter) in DNA binding specificity. Detailed PCA analysis of the most recent collection of DBD structures from the PDB have been carried out. In contrast to recommendations that small molecules/drugs stabilize the flexible L1 loop to rescue mutant p53, our study highlights a need to retain the flexibility of the p53 DNA binding surface (DBS). It is the adaptability of this region that enables p53 to engage in the diverse interactions responsible for its functionality. Proteins 2016; 84:1443-1461. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A 2.2 sq m /24 sq ft/ self-controlled deployable heat pipe radiator - Design and test

NASA Technical Reports Server (NTRS)

Edelstein, F.

1975-01-01

An all heat pipe, deployable radiator has been developed which can effectively control pumped fluid loop temperatures under varying loads using variable conductance panel heat pipes. The 2.2 sq m (24 sq ft) aluminum panel can be coupled to either a fluid header or a flexible heat pipe header capable of transporting 850 watts in a 90-deg bent configuration. Test results support the feasibility of using this system to passively control Freon-21 loop temperatures.

Functional Loop Dynamics of the Streptavidin-Biotin Complex

PubMed Central

Song, Jianing; Li, Yongle; Ji, Changge; Zhang, John Z. H.

2015-01-01

Accelerated molecular dynamics (aMD) simulation is employed to study the functional dynamics of the flexible loop3-4 in the strong-binding streptavidin-biotin complex system. Conventional molecular (cMD) simulation is also performed for comparison. The present study reveals the following important properties of the loop dynamics: (1) The transition of loop3-4 from open to closed state is observed in 200 ns aMD simulation. (2) In the absence of biotin binding, the open-state streptavidin is more stable, which is consistent with experimental evidences. The free energy (ΔG) difference is about 5 kcal/mol between two states. But with biotin binding, the closed state is more stable due to electrostatic and hydrophobic interactions between the loop3-4 and biotin. (3) The closure of loop3-4 is concerted to the stable binding of biotin to streptavidin. When the loop3-4 is in its open-state, biotin moves out of the binding pocket, indicating that the interactions between the loop3-4 and biotin are essential in trapping biotin in the binding pocket. (4) In the tetrameric streptavidin system, the conformational change of the loop3-4 in each monomer is independent of each other. That is, there is no cooperative binding for biotin bound to the four subunits of the tetramer. PMID:25601277

Falcon: a highly flexible open-source software for closed-loop neuroscience.

PubMed

Ciliberti, Davide; Kloosterman, Fabian

2017-08-01

Closed-loop experiments provide unique insights into brain dynamics and function. To facilitate a wide range of closed-loop experiments, we created an open-source software platform that enables high-performance real-time processing of streaming experimental data. We wrote Falcon, a C++ multi-threaded software in which the user can load and execute an arbitrary processing graph. Each node of a Falcon graph is mapped to a single thread and nodes communicate with each other through thread-safe buffers. The framework allows for easy implementation of new processing nodes and data types. Falcon was tested both on a 32-core and a 4-core workstation. Streaming data was read from either a commercial acquisition system (Neuralynx) or the open-source Open Ephys hardware, while closed-loop TTL pulses were generated with a USB module for digital output. We characterized the round-trip latency of our Falcon-based closed-loop system, as well as the specific latency contribution of the software architecture, by testing processing graphs with up to 32 parallel pipelines and eight serial stages. We finally deployed Falcon in a task of real-time detection of population bursts recorded live from the hippocampus of a freely moving rat. On Neuralynx hardware, round-trip latency was well below 1 ms and stable for at least 1 h, while on Open Ephys hardware latencies were below 15 ms. The latency contribution of the software was below 0.5 ms. Round-trip and software latencies were similar on both 32- and 4-core workstations. Falcon was used successfully to detect population bursts online with ~40 ms average latency. Falcon is a novel open-source software for closed-loop neuroscience. It has sub-millisecond intrinsic latency and gives the experimenter direct control of CPU resources. We envisage Falcon to be a useful tool to the neuroscientific community for implementing a wide variety of closed-loop experiments, including those requiring use of complex data structures and real-time execution of computationally intensive algorithms, such as population neural decoding/encoding from large cell assemblies.

Falcon: a highly flexible open-source software for closed-loop neuroscience

NASA Astrophysics Data System (ADS)

Ciliberti, Davide; Kloosterman, Fabian

2017-08-01

Objective. Closed-loop experiments provide unique insights into brain dynamics and function. To facilitate a wide range of closed-loop experiments, we created an open-source software platform that enables high-performance real-time processing of streaming experimental data. Approach. We wrote Falcon, a C++ multi-threaded software in which the user can load and execute an arbitrary processing graph. Each node of a Falcon graph is mapped to a single thread and nodes communicate with each other through thread-safe buffers. The framework allows for easy implementation of new processing nodes and data types. Falcon was tested both on a 32-core and a 4-core workstation. Streaming data was read from either a commercial acquisition system (Neuralynx) or the open-source Open Ephys hardware, while closed-loop TTL pulses were generated with a USB module for digital output. We characterized the round-trip latency of our Falcon-based closed-loop system, as well as the specific latency contribution of the software architecture, by testing processing graphs with up to 32 parallel pipelines and eight serial stages. We finally deployed Falcon in a task of real-time detection of population bursts recorded live from the hippocampus of a freely moving rat. Main results. On Neuralynx hardware, round-trip latency was well below 1 ms and stable for at least 1 h, while on Open Ephys hardware latencies were below 15 ms. The latency contribution of the software was below 0.5 ms. Round-trip and software latencies were similar on both 32- and 4-core workstations. Falcon was used successfully to detect population bursts online with ~40 ms average latency. Significance. Falcon is a novel open-source software for closed-loop neuroscience. It has sub-millisecond intrinsic latency and gives the experimenter direct control of CPU resources. We envisage Falcon to be a useful tool to the neuroscientific community for implementing a wide variety of closed-loop experiments, including those requiring use of complex data structures and real-time execution of computationally intensive algorithms, such as population neural decoding/encoding from large cell assemblies.

Flight simulation software at NASA Dryden Flight Research Center

NASA Technical Reports Server (NTRS)

Norlin, Ken A.

1995-01-01

The NASA Dryden Flight Research Center has developed a versatile simulation software package that is applicable to a broad range of fixed-wing aircraft. This package has evolved in support of a variety of flight research programs. The structure is designed to be flexible enough for use in batch-mode, real-time pilot-in-the-loop, and flight hardware-in-the-loop simulation. Current simulations operate on UNIX-based platforms and are coded with a FORTRAN shell and C support routines. This paper discusses the features of the simulation software design and some basic model development techniques. The key capabilities that have been included in the simulation are described. The NASA Dryden simulation software is in use at other NASA centers, within industry, and at several universities. The straightforward but flexible design of this well-validated package makes it especially useful in an engineering environment.

ChIA-PET2: a versatile and flexible pipeline for ChIA-PET data analysis

PubMed Central

Li, Guipeng; Chen, Yang; Snyder, Michael P.; Zhang, Michael Q.

2017-01-01

ChIA-PET2 is a versatile and flexible pipeline for analyzing different types of ChIA-PET data from raw sequencing reads to chromatin loops. ChIA-PET2 integrates all steps required for ChIA-PET data analysis, including linker trimming, read alignment, duplicate removal, peak calling and chromatin loop calling. It supports different kinds of ChIA-PET data generated from different ChIA-PET protocols and also provides quality controls for different steps of ChIA-PET analysis. In addition, ChIA-PET2 can use phased genotype data to call allele-specific chromatin interactions. We applied ChIA-PET2 to different ChIA-PET datasets, demonstrating its significantly improved performance as well as its ability to easily process ChIA-PET raw data. ChIA-PET2 is available at https://github.com/GuipengLi/ChIA-PET2. PMID:27625391

Crystal Structure of MpPR-1i, a SCP/TAPS protein from Moniliophthora perniciosa, the fungus that causes Witches’ Broom Disease of Cacao

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baroni, Renata M.; Luo, Zhipu; Darwiche, Rabih

The pathogenic fungi Moniliophthora perniciosa causes Witches’ Broom Disease (WBD) of cacao. The structure of MpPR-1i, a protein expressed by M. perniciosa when it infects cacao, are presented. This is the first reported de novo structure determined by single-wavelength anomalous dispersion phasing upon soaking with selenourea. Each monomer has flexible loop regions linking the core alpha-beta-alpha sandwich topology that comprise ~50% of the structure, making it difficult to generate an accurate homology model of the protein. MpPR-1i is monomeric in solution but is packed as a high ~70% solvent content, crystallographic heptamer. The greatest conformational flexibility between monomers is foundmore » in loops exposed to the solvent channel that connect the two longest strands. MpPR-1i lacks the conserved CAP tetrad and is incapable of binding divalent cations. MpPR-1i has the ability to bind lipids, which may have roles in its infection of cacao. These lipids likely bind in the palmitate binding cavity as observed in tablysin-15, since MpPR-1i binds palmitate with comparable affinity as tablysin-15. Further studies are required to clarify the possible roles and underlying mechanisms of neutral lipid binding, as well as their effects on the pathogenesis of M. perniciosa so as to develop new interventions for WBD.« less

A flexible algorithm for calculating pair interactions on SIMD architectures

NASA Astrophysics Data System (ADS)

Páll, Szilárd; Hess, Berk

2013-12-01

Calculating interactions or correlations between pairs of particles is typically the most time-consuming task in particle simulation or correlation analysis. Straightforward implementations using a double loop over particle pairs have traditionally worked well, especially since compilers usually do a good job of unrolling the inner loop. In order to reach high performance on modern CPU and accelerator architectures, single-instruction multiple-data (SIMD) parallelization has become essential. Avoiding memory bottlenecks is also increasingly important and requires reducing the ratio of memory to arithmetic operations. Moreover, when pairs only interact within a certain cut-off distance, good SIMD utilization can only be achieved by reordering input and output data, which quickly becomes a limiting factor. Here we present an algorithm for SIMD parallelization based on grouping a fixed number of particles, e.g. 2, 4, or 8, into spatial clusters. Calculating all interactions between particles in a pair of such clusters improves data reuse compared to the traditional scheme and results in a more efficient SIMD parallelization. Adjusting the cluster size allows the algorithm to map to SIMD units of various widths. This flexibility not only enables fast and efficient implementation on current CPUs and accelerator architectures like GPUs or Intel MIC, but it also makes the algorithm future-proof. We present the algorithm with an application to molecular dynamics simulations, where we can also make use of the effective buffering the method introduces.

Structure of GlnK1 with bound effectors indicates regulatory mechanism for ammonia uptake.

PubMed

Yildiz, Ozkan; Kalthoff, Christoph; Raunser, Stefan; Kühlbrandt, Werner

2007-01-24

A binary complex of the ammonia channel Amt1 from Methanococcus jannaschii and its cognate P(II) signalling protein GlnK1 has been produced and characterized. Complex formation is prevented specifically by the effector molecules Mg-ATP and 2-ketoglutarate. Single-particle electron microscopy of the complex shows that GlnK1 binds on the cytoplasmic side of Amt1. Three high-resolution X-ray structures of GlnK1 indicate that the functionally important T-loop has an extended, flexible conformation in the absence of Mg-ATP, but assumes a compact, tightly folded conformation upon Mg-ATP binding, which in turn creates a 2-ketoglutarate-binding site. We propose a regulatory mechanism by which nitrogen uptake is controlled by the binding of both effector molecules to GlnK1. At normal effector levels, a 2-ketoglutarate molecule binding at the apex of the compact T-loop would prevent complex formation, ensuring uninhibited ammonia uptake. At low levels of Mg-ATP, the extended loops would seal the ammonia channels in the complex. Binding of both effector molecules to P(II) signalling proteins may thus represent an effective feedback mechanism for regulating ammonium uptake through the membrane.

Speed-accuracy trade-off in skilled typewriting: decomposing the contributions of hierarchical control loops.

PubMed

Yamaguchi, Motonori; Crump, Matthew J C; Logan, Gordon D

2013-06-01

Typing performance involves hierarchically structured control systems: At the higher level, an outer loop generates a word or a series of words to be typed; at the lower level, an inner loop activates the keystrokes comprising the word in parallel and executes them in the correct order. The present experiments examined contributions of the outer- and inner-loop processes to the control of speed and accuracy in typewriting. Experiments 1 and 2 involved discontinuous typing of single words, and Experiments 3 and 4 involved continuous typing of paragraphs. Across experiments, typists were able to trade speed for accuracy but were unable to type at rates faster than 100 ms/keystroke, implying limits to the flexibility of the underlying processes. The analyses of the component latencies and errors indicated that the majority of the trade-offs were due to inner-loop processing. The contribution of outer-loop processing to the trade-offs was small, but it resulted in large costs in error rate. Implications for strategic control of automatic processes are discussed. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

PubMed

Suebsuwong, Chalada; Pinkas, Daniel M; Ray, Soumya S; Bufton, Joshua C; Dai, Bing; Bullock, Alex N; Degterev, Alexei; Cuny, Gregory D

2018-02-15

Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A Generic Guidance and Control Structure for Six-Degree-of-Freedom Conceptual Aircraft Design

NASA Technical Reports Server (NTRS)

Cotting, M. Christopher; Cox, Timothy H.

2005-01-01

A control system framework is presented for both real-time and batch six-degree-of-freedom simulation. This framework allows stabilization and control with multiple command options, from body rate control to waypoint guidance. Also, pilot commands can be used to operate the simulation in a pilot-in-the-loop environment. This control system framework is created by using direct vehicle state feedback with nonlinear dynamic inversion. A direct control allocation scheme is used to command aircraft effectors. Online B-matrix estimation is used in the control allocation algorithm for maximum algorithm flexibility. Primary uses for this framework include conceptual design and early preliminary design of aircraft, where vehicle models change rapidly and a knowledge of vehicle six-degree-of-freedom performance is required. A simulated airbreathing hypersonic vehicle and a simulated high performance fighter are controlled to demonstrate the flexibility and utility of the control system.

Dual-pump Kerr Micro-cavity Optical Frequency Comb with varying FSR spacing

PubMed Central

Wang, Weiqiang; Chu, Sai T.; Little, Brent E.; Pasquazi, Alessia; Wang, Yishan; Wang, Leiran; Zhang, Wenfu; Wang, Lei; Hu, Xiaohong; Wang, Guoxi; Hu, Hui; Su, Yulong; Li, Feitao; Liu, Yuanshan; Zhao, Wei

2016-01-01

In this paper, we demonstrate a novel dual-pump approach to generate robust optical frequency comb with varying free spectral range (FSR) spacing in a CMOS-compatible high-Q micro-ring resonator (MRR). The frequency spacing of the comb can be tuned by an integer number FSR of the MRR freely in our dual-pump scheme. The dual pumps are self-oscillated in the laser cavity loop and their wavelengths can be tuned flexibly by programming the tunable filter embedded in the cavity. By tuning the pump wavelength, broadband OFC with the bandwidth of >180 nm and the frequency-spacing varying from 6 to 46-fold FSRs is realized at a low pump power. This approach could find potential and practical applications in many areas, such as optical metrology, optical communication, and signal processing systems, for its excellent flexibility and robustness. PMID:27338250

Structural and functional characterization of methicillin-resistant Staphylococcus aureus's class IIb fructose 1,6-bisphosphate aldolase.

PubMed

Capodagli, Glenn C; Lee, Stephen A; Boehm, Kyle J; Brady, Kristin M; Pegan, Scott D

2014-12-09

Staphylococcus aureus is one of the most common nosocomial sources of soft-tissue and skin infections and has more recently become prevalent in the community setting as well. Since the use of penicillins to combat S. aureus infections in the 1940s, the bacterium has been notorious for developing resistances to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). With the persistence of MRSA as well as many other drug resistant bacteria and parasites, there is a growing need to focus on new pharmacological targets. Recently, class II fructose 1,6-bisphosphate aldolases (FBAs) have garnered attention to fill this role. Regrettably, scarce biochemical data and no structural data are currently available for the class II FBA found in MRSA (SaFBA). With the recent finding of a flexible active site zinc-binding loop (Z-Loop) in class IIa FBAs and its potential for broad spectrum class II FBA inhibition, the lack of information regarding this feature of class IIb FBAs, such as SaFBA, has been limiting for further Z-loop inhibitor development. Therefore, we elucidated the crystal structure of SaFBA to 2.1 Å allowing for a more direct structural analysis of SaFBA. Furthermore, we determined the KM for one of SaFBA's substrates, fructose 1,6-bisphosphate, as well as performed mode of inhibition studies for an inhibitor that takes advantage of the Z-loop's flexibility. Together the data offers insight into a class IIb FBA from a pervasively drug resistant bacterium and a comparison of Z-loops and other features between the different subtypes of class II FBAs.

Precise control of flexible manipulators

NASA Technical Reports Server (NTRS)

Cannon, R. H., Jr.; Bindford, T. O.; Schmitz, E.

1984-01-01

The design and experimental testing of end point position controllers for a very flexible one link lightweight manipulator are summarized. The latest upgraded version of the experimental set up, and the basic differences between conventional joint angle feedback and end point position feedback are described. A general procedure for application of modern control methods to the problem is outlined. The relationship between weighting parameters and the bandwidth and control stiffness of the resulting end point position closed loop system is shown. It is found that joint rate angle feedback in addition to the primary end point position sensor is essential for adequate disturbance rejection capability of the closed loop system. The use of a low order multivariable compensator design computer code; called Sandy is documented. A solution to the problem of control mode switching between position sensor sets is outlined. The proof of concept for endpoint position feedback for a one link flexible manipulator was demonstrated. The bandwidth obtained with the experimental end point position controller is about twice as fast as the beam's first natural cantilevered frequency, and comes within a factor of four of the absolute physical speed limit imposed by the wave propagation time of the beam.

Modeling the Lac repressor-operator assembly: The influence of DNA looping on Lac repressor conformation

PubMed Central

Swigon, David; Coleman, Bernard D.; Olson, Wilma K.

2006-01-01

Repression of transcription of the Escherichia coli Lac operon by the Lac repressor (LacR) is accompanied by the simultaneous binding of LacR to two operators and the formation of a DNA loop. A recently developed theory of sequence-dependent DNA elasticity enables one to relate the fine structure of the LacR–DNA complex to a wide range of heretofore-unconnected experimental observations. Here, that theory is used to calculate the configuration and free energy of the DNA loop as a function of its length and base-pair sequence, its linking number, and the end conditions imposed by the LacR tetramer. The tetramer can assume two types of conformations. Whereas a rigid V-shaped structure is observed in the crystal, EM images show extended forms in which two dimer subunits are flexibly joined. Upon comparing our computed loop configurations with published experimental observations of permanganate sensitivities, DNase I cutting patterns, and loop stabilities, we conclude that linear DNA segments of short-to-medium chain length (50–180 bp) give rise to loops with the extended form of LacR and that loops formed within negatively supercoiled plasmids induce the V-shaped structure. PMID:16785444

Interface Matters: The Stiffness Route to Stability of a Thermophilic Tetrameric Malate Dehydrogenase

PubMed Central

Kalimeri, Maria; Girard, Eric; Madern, Dominique; Sterpone, Fabio

2014-01-01

In this work we investigate by computational means the behavior of two orthologous bacterial proteins, a mesophilic and a thermophilic tetrameric malate dehydrogenase (MalDH), at different temperatures. Namely, we quantify how protein mechanical rigidity at different length- and time-scales correlates to protein thermophilicity as commonly believed. In particular by using a clustering analysis strategy to explore the conformational space of the folded proteins, we show that at ambient conditions and at the molecular length-scale the thermophilic variant is indeed more rigid that the mesophilic one. This rigidification is the result of more efficient inter-domain interactions, the strength of which is further quantified via ad hoc free energy calculations. When considered isolated, the thermophilic domain is indeed more flexible than the respective mesophilic one. Upon oligomerization, the induced stiffening of the thermophilic protein propagates from the interface to the active site where the loop, controlling the access to the catalytic pocket, anchors down via an extended network of ion-pairs. On the contrary in the mesophilic tetramer the loop is highly mobile. Simulations at high temperature, could not re-activate the mobility of the loop in the thermophile. This finding opens questions on the similarities of the binding processes for these two homologues at their optimal working temperature and suggests for the thermophilic variant a possible cooperative role of cofactor/substrate. PMID:25437494

Interface matters: the stiffness route to stability of a thermophilic tetrameric malate dehydrogenase.

PubMed

Kalimeri, Maria; Girard, Eric; Madern, Dominique; Sterpone, Fabio

2014-01-01

In this work we investigate by computational means the behavior of two orthologous bacterial proteins, a mesophilic and a thermophilic tetrameric malate dehydrogenase (MalDH), at different temperatures. Namely, we quantify how protein mechanical rigidity at different length- and time-scales correlates to protein thermophilicity as commonly believed. In particular by using a clustering analysis strategy to explore the conformational space of the folded proteins, we show that at ambient conditions and at the molecular length-scale the thermophilic variant is indeed more rigid that the mesophilic one. This rigidification is the result of more efficient inter-domain interactions, the strength of which is further quantified via ad hoc free energy calculations. When considered isolated, the thermophilic domain is indeed more flexible than the respective mesophilic one. Upon oligomerization, the induced stiffening of the thermophilic protein propagates from the interface to the active site where the loop, controlling the access to the catalytic pocket, anchors down via an extended network of ion-pairs. On the contrary in the mesophilic tetramer the loop is highly mobile. Simulations at high temperature, could not re-activate the mobility of the loop in the thermophile. This finding opens questions on the similarities of the binding processes for these two homologues at their optimal working temperature and suggests for the thermophilic variant a possible cooperative role of cofactor/substrate.

The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes.

PubMed

Knoch, Tobias A; Wachsmuth, Malte; Kepper, Nick; Lesnussa, Michael; Abuseiris, Anis; Ali Imam, A M; Kolovos, Petros; Zuin, Jessica; Kockx, Christel E M; Brouwer, Rutger W W; van de Werken, Harmen J G; van IJcken, Wilfred F J; Wendt, Kerstin S; Grosveld, Frank G

2016-01-01

The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function-the storage, expression, and replication of genetic information-is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture ( T2C ), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence. The genome is compacted into a chromatin quasi-fibre with ~5 ± 1 nucleosomes/11 nm, folded into stable ~30-100 kbp loops forming stable loop aggregates/rosettes connected by similar sized linkers. Minor but significant variations in the architecture are seen between cell types and functional states. The architecture and the DNA sequence show very similar fine-structured multi-scaling behaviour confirming their co-evolution and the above. This architecture, its dynamics, and accessibility, balance stability and flexibility ensuring genome integrity and variation enabling gene expression/regulation by self-organization of (in)active units already in proximity. Our results agree with the heuristics of the field and allow "architectural sequencing" at a genome mechanics level to understand the inseparable systems genomic properties.

Mapping flexible protein domains at subnanometer resolution with the atomic force microscope.

PubMed

Müller, D J; Fotiadis, D; Engel, A

1998-06-23

The mapping of flexible protein domains with the atomic force microscope is reviewed. Examples discussed are the bacteriorhodopsin from Halobacterium salinarum, the head-tail-connector from phage phi29, and the hexagonally packed intermediate layer from Deinococcus radiodurans which all were recorded in physiological buffer solution. All three proteins undergo reversible structural changes that are reflected in standard deviation maps calculated from aligned topographs of individual protein complexes. Depending on the lateral resolution (up to 0.8 nm) flexible surface regions can ultimately be correlated with individual polypeptide loops. In addition, multivariate statistical classification revealed the major conformations of the protein surface.

Applications of the hybrid coordinate method to the TOPS autopilot

NASA Technical Reports Server (NTRS)

Fleischer, G. E.

1978-01-01

Preliminary results are presented from the application of the hybrid coordinate method to modeling TOPS (thermoelectric outer planet spacecraft) structural dynamics. Computer simulated responses of the vehicle are included which illustrate the interaction of relatively flexible appendages with an autopilot control system. Comparisons were made between simplified single-axis models of the control loop, with spacecraft flexibility represented by hinged rigid bodies, and a very detailed three-axis spacecraft model whose flexible portions are described by modal coordinates. While single-axis system, root loci provided reasonable qualitative indications of stability margins in this case, they were quantitatively optimistic when matched against responses of the detailed model.

The Trade-Off Mechanism in Mammalian Circadian Clock Model with Two Time Delays

NASA Astrophysics Data System (ADS)

Yan, Jie; Kang, Xiaxia; Yang, Ling

Circadian clock is an autonomous oscillator which orchestrates the daily rhythms of physiology and behaviors. This study is devoted to explore how a positive feedback loop affects the dynamics of mammalian circadian clock. We simplify an experimentally validated mathematical model in our previous work, to a nonlinear differential equation with two time delays. This simplified mathematical model incorporates the pacemaker of mammalian circadian clock, a negative primary feedback loop, and a critical positive auxiliary feedback loop, Rev-erbα/Cry1 loop. We perform analytical studies of the system. Delay-dependent conditions for the asymptotic stability of the nontrivial positive steady state of the model are investigated. We also prove the existence of Hopf bifurcation, which leads to self-sustained oscillation of mammalian circadian clock. Our theoretical analyses show that the oscillatory regime is reduced upon the participation of the delayed positive auxiliary loop. However, further simulations reveal that the auxiliary loop can enable the circadian clock gain widely adjustable amplitudes and robust period. Thus, the positive auxiliary feedback loop may provide a trade-off mechanism, to use the small loss in the robustness of oscillation in exchange for adaptable flexibility in mammalian circadian clock. The results obtained from the model may gain new insights into the dynamics of biological oscillators with interlocked feedback loops.

Stringency of substrate specificity of Escherichia coli malate dehydrogenase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boernke, W. E.; Millard, C. S.; Stevens, P. W.

1995-09-10

Malate dehydrogenase and lactate dehydrogenase are members of the structurally and functionally homologous family of 2-ketoacid dehydrogenases. Both enzymes display high specificity for their respective keto substrates, oxaloacetate and pyruvate. Closer analysis of their specificity, however, reveals that the specificity of malate dehydrogenase is much stricter and less malleable than that of lactate dehydrogenase. Site-specific mutagenesis of the two enzymes in an attempt to reverse their specificity has met with contrary results. Conversion of a specific active-site glutamine to arginine in lactate dehydrogenase from Bacillus stearothermophilus generated an enzyme that displayed activity toward oxaloacetate equal to that of the nativemore » enzyme toward pyruvate (H. M. Wilks et al. (1988) Science 242, 1541-1544). We have constructed a series of mutants in the mobile, active site loop of the Escherichia coli malate dehydrogenase that incorporate the complementary change, conversion of arginine 81 to glutamine, to evaluate the role of charge distribution and conformational flexibility within this loop in defining the substrate specificity of these enzymes. Mutants incorporating the change R81Q all had reversed specificity, displaying much higher activity toward pyruvate than to the natural substrate, oxaloacetate. In contrast to the mutated lactate dehydrogenase, these reversed-specificity mutants were much less active than the native enzyme. Secondary mutations within the loop of the E. coli enzyme (A80N, A80P, A80P/M85E/D86T) had either no or only moderately beneficial effects on the activity of the mutant enzyme toward pyruvate. The mutation A80P, which can be expected to reduce the overall flexibility of the loop, modestly improved activity toward pyruvate. The possible physiological relevance of the stringent specificity of malate dehydrogenase was investigated. In normal strains of E. coli, fermentative metabolism was not affected by expression of the mutant malate dehydrogenase. However, when expressed in a strain of E. coli unable to ferment glucose, the mutant enzyme restored growth and produced lactic acid as the sole fermentation product.« less

Reduced modeling of flexible structures for decentralized control

NASA Technical Reports Server (NTRS)

Yousuff, A.; Tan, T. M.; Bahar, L. Y.; Konstantinidis, M. F.

1986-01-01

Based upon the modified finite element-transfer matrix method, this paper presents a technique for reduced modeling of flexible structures for decentralized control. The modeling decisions are carried out at (finite-) element level, and are dictated by control objectives. A simply supported beam with two sets of actuators and sensors (linear force actuator and linear position and velocity sensors) is considered for illustration. In this case, it is conjectured that the decentrally controlled closed loop system is guaranteed to be at least marginally stable.

Development and Evaluation of an Order-N Formulation for Multi-Flexible Body Space Systems

NASA Technical Reports Server (NTRS)

Ghosh, Tushar K.; Quiocho, Leslie J.

2013-01-01

This paper presents development of a generic recursive Order-N algorithm for systems with rigid and flexible bodies, in tree or closed-loop topology, with N being the number of bodies of the system. Simulation results are presented for several test cases to verify and evaluate the performance of the code compared to an existing efficient dense mass matrix-based code. The comparison brought out situations where Order-N or mass matrix-based algorithms could be useful.

Modal domain fiber optic sensor for closed loop vibration control of a flexible beam

NASA Technical Reports Server (NTRS)

Cox, D.; Thomas, D.; Reichard, K.; Lindner, D.; Claus, R. O.

1990-01-01

The use of a modal domain sensor in a vibration control experiment is described. An optical fiber is bonded along the length of a flexible beam. A control signal derived from the output of the modal domain sensor is used to suppress vibrations induced in the beam. A distributed effect model for the modal domain sensor is developed and combined with models of the beam and actuator dynamics to produce a system suitable for control design.

An improved output feedback control of flexible large space structures

NASA Technical Reports Server (NTRS)

Lin, Y. H.; Lin, J. G.

1980-01-01

A special output feedback control design technique for flexible large space structures is proposed. It is shown that the technique will increase both the damping and frequency of selected modes for more effective control. It is also able to effect integrated control of elastic and rigid-body modes and, in particular, closed-loop system stability and robustness to modal truncation and parameter variation. The technique is seen as marking an improvement over previous work concerning large space structures output feedback control.

40 CFR 63.8802 - What methods must I use to demonstrate compliance with the emission limitation for loop slitter...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Hazardous Air Pollutants: Flexible Polyurethane Foam Fabrication Operations Testing and Initial Compliance... for each material used in your foam fabrication operations, you must use one of the options in...

40 CFR 63.8802 - What methods must I use to demonstrate compliance with the emission limitation for loop slitter...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Hazardous Air Pollutants: Flexible Polyurethane Foam Fabrication Operations Testing and Initial Compliance... for each material used in your foam fabrication operations, you must use one of the options in...

40 CFR 63.8802 - What methods must I use to demonstrate compliance with the emission limitation for loop slitter...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Hazardous Air Pollutants: Flexible Polyurethane Foam Fabrication Operations Testing and Initial Compliance... for each material used in your foam fabrication operations, you must use one of the options in...

40 CFR 63.8802 - What methods must I use to demonstrate compliance with the emission limitation for loop slitter...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Hazardous Air Pollutants: Flexible Polyurethane Foam Fabrication Operations Testing and Initial Compliance... for each material used in your foam fabrication operations, you must use one of the options in...

40 CFR 63.8802 - What methods must I use to demonstrate compliance with the emission limitation for loop slitter...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Hazardous Air Pollutants: Flexible Polyurethane Foam Fabrication Operations Testing and Initial Compliance... for each material used in your foam fabrication operations, you must use one of the options in...

Control of Space-Based Electron Beam Free Form Fabrication

NASA Technical Reports Server (NTRS)

Seifzer. W. J.; Taminger, K. M.

2007-01-01

Engineering a closed-loop control system for an electron beam welder for space-based additive manufacturing is challenging. For earth and space based applications, components must work in a vacuum and optical components become occluded with metal vapor deposition. For extraterrestrial applications added components increase launch weight, increase complexity, and increase space flight certification efforts. Here we present a software tool that closely couples path planning and E-beam parameter controls into the build process to increase flexibility. In an environment where data collection hinders real-time control, another approach is considered that will still yield a high quality build.

HIV protease drug resistance and its impact on inhibitor design.

PubMed

Ala, P J; Rodgers, J D; Chang, C H

1999-07-01

The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.

Digital tracking loops for a programmable digital modem

NASA Technical Reports Server (NTRS)

Poklemba, John J.

1992-01-01

In this paper, an analysis and hardware emulation of the tracking loops for a very flexible programmable digital modem (PDM) will be presented. The modem is capable of being programmed for 2, 4, 8, 16-PSK, 16-QAM, MSK, and Offset-QPSK modulation schemes over a range of data rates from 2.34 to 300 Mbps with programmable spectral occupancy from 1.2 to 1.8 times the symbol rate; these operational parameters are executable in burst or continuous mode. All of the critical processing in both the modulator and demodulator is done at baseband with very high-speed digital hardware and memory. Quadrature analog front-ends are used for translation between baseband and the IF center frequency. The modulator is based on a table lookup approach, where precomputed samples are stored in memory and clocked out according to the incoming data pattern. The sample values are predistorted to counteract the effects of the other filtering functions in the link as well as any transmission impairments. The demodulator architecture was adapted from a joint estimator-detector (JED) mathematical analysis. Its structure is applicable to most signalling formats that can be represented in a two-dimensional space. The JED realization uses interdependent, mutually aiding tracking loops with post-detection data feedback. To expedite and provide for more reliable synchronization, initial estimates for these loops are computed in a parallel acquisition processor. The cornerstone of the demodulator realization is the pre-averager received data filter which allows operation over a broad range of data rates without any hardware changes and greatly simplifies the implementation complexity. The emulation results confirmed tracking loop operation over the entire range of operational parameters listed above, as well as the capability of achieving and maintaining synchronization at BER's in excess of 10(exp -1). The emulation results also showed very close agreement with the tracking loop analysis, and validated the resolution apportionment of the various hardware elements in the tracking loops.

Dynamics of the active site loops in catalyzing aminoacylation reaction in seryl and histidyl tRNA synthetases.

PubMed

Dutta, Saheb; Kundu, Soumya; Saha, Amrita; Nandi, Nilashis

2018-03-01

Aminoacylation reaction is the first step of protein biosynthesis. The catalytic reorganization at the active site of aminoacyl tRNA synthetases (aaRSs) is driven by the loop motions. There remain lacunae of understanding concerning the catalytic loop dynamics in aaRSs. We analyzed the functional loop dynamics in seryl tRNA synthetase from Methanopyrus kandleri ( mk SerRS) and histidyl tRNA synthetases from Thermus thermophilus ( tt HisRS), respectively, using molecular dynamics. Results confirm that the motif 2 loop and other active site loops are flexible spots within the catalytic domain. Catalytic residues of the loops form a network of interaction with the substrates to form a reactive state. The loops undergo transitions between closed state and open state and the relaxation of the constituent residues occurs in femtosecond to nanosecond time scale. Order parameters are higher for constituent catalytic residues which form a specific network of interaction with the substrates to form a reactive state compared to the Gly residues within the loop. The development of interaction is supported from mutation studies where the catalytic domain with mutated loop exhibits unfavorable binding energy with the substrates. During the open-close motion of the loops, the catalytic residues make relaxation by ultrafast librational motion as well as fast diffusive motion and subsequently relax rather slowly via slower diffusive motion. The Gly residues act as a hinge to facilitate the loop closing and opening by their faster relaxation behavior. The role of bound water is analyzed by comparing implicit solvent-based and explicit solvent-based simulations. Loops fail to form catalytically competent geometry in absence of water. The present result, for the first time reveals the nature of the active site loop dynamics in aaRS and their influence on catalysis.

Modal Filtering for Control of Flexible Aircraft

NASA Technical Reports Server (NTRS)

Suh, Peter M.; Mavris, Dimitri N.

2013-01-01

Modal regulators and deformation trackers are designed for an open-loop fluttering wing model. The regulators are designed with modal coordinate and accelerometer inputs respectively. The modal coordinates are estimated with simulated fiber optics. The robust stability of the closed-loop systems is compared in a structured singular-value vector analysis. Performance is evaluated and compared in a gust alleviation and flutter suppression simulation. For the same wing and flight condition two wing-shape-tracking control architectures are presented, which achieve deformation control at any point on the wing.

Dynamic modelling and adaptive robust tracking control of a space robot with two-link flexible manipulators under unknown disturbances

NASA Astrophysics Data System (ADS)

Yang, Xinxin; Ge, Shuzhi Sam; He, Wei

2018-04-01

In this paper, both the closed-form dynamics and adaptive robust tracking control of a space robot with two-link flexible manipulators under unknown disturbances are developed. The dynamic model of the system is described with assumed modes approach and Lagrangian method. The flexible manipulators are represented as Euler-Bernoulli beams. Based on singular perturbation technique, the displacements/joint angles and flexible modes are modelled as slow and fast variables, respectively. A sliding mode control is designed for trajectories tracking of the slow subsystem under unknown but bounded disturbances, and an adaptive sliding mode control is derived for slow subsystem under unknown slowly time-varying disturbances. An optimal linear quadratic regulator method is proposed for the fast subsystem to damp out the vibrations of the flexible manipulators. Theoretical analysis validates the stability of the proposed composite controller. Numerical simulation results demonstrate the performance of the closed-loop flexible space robot system.

Surface NMR imaging with simultaneously energized transmission loops

NASA Astrophysics Data System (ADS)

Irons, T. P.; Kass, A.; Parsekian, A.

2016-12-01

Surface nuclear magnetic resonance (sNMR) is a unique geophysical technique which allows for the direct detection of liquid-phase water. In saturated media the sNMR response also provides estimates of hydrologic properties including porosity and permeability. The most common survey deployment consists of a single coincident loop performing both transmission and receiving. Because the sNMR method is relatively slow, tomography using coincident loops is time-intensive. Surveys using multiple receiver loops (but a single transmitter) provide additional sensitivity; however, they still require iterating transmission over the loops, and do not decrease survey acquisition time. In medical rotating frame imaging, arrays of transmitters are employed in order to decrease acquisition time, whilst optimizing image resolving power-a concept which we extend to earth's field imaging. Using simultaneously energized transmission loops decreases survey time linearly with the number of channels. To demonstrate the efficacy and benefits of multiple transmission loops, we deployed simultaneous sNMR transmission arrays using minimally coupled loops and a specially modified instrument at the Red Buttes Hydrogeophysics Experiment Site-a well-characterized location near Laramie, Wyoming. The proposed survey proved capable of acquiring multiple-channel imaging data with comparable noise levels to figure-eight configurations. Finally, the channels can be combined after acquisition or inverted simultaneously to provide composite datasets and images. This capability leverages the improved near surface resolving power of small loops but retains sensitivity to deep media through the use of synthetic aperature receivers. As such, simultaneously acquired loop arrays provide a great deal of flexibility.

Characterization of the Interaction of Sclerostin with the Low Density Lipoprotein Receptor-related Protein (LRP) Family of Wnt Co-receptors*

PubMed Central

Holdsworth, Gill; Slocombe, Patrick; Doyle, Carl; Sweeney, Bernadette; Veverka, Vaclav; Le Riche, Kelly; Franklin, Richard J.; Compson, Joanne; Brookings, Daniel; Turner, James; Kennedy, Jeffery; Garlish, Rachael; Shi, Jiye; Newnham, Laura; McMillan, David; Muzylak, Mariusz; Carr, Mark D.; Henry, Alistair J.; Ceska, Thomas; Robinson, Martyn K.

2012-01-01

LRP5 and LRP6 are proteins predicted to contain four six-bladed β-propeller domains and both bind the bone-specific Wnt signaling antagonist sclerostin. Here, we report the crystal structure of the amino-terminal region of LRP6 and using NMR show that the ability of sclerostin to bind to this molecule is mediated by the central core of sclerostin and does not involve the amino- and carboxyl-terminal flexible arm regions. We show that this structured core region interacts with LRP5 and LRP6 via an NXI motif (found in the sequence PNAIG) within a flexible loop region (loop 2) within the central core region. This sequence is related closely to a previously identified motif in laminin that mediates its interaction with the β-propeller domain of nidogen. However, the NXI motif is not involved in the interaction of sclerostin with LRP4 (another β-propeller containing protein in the LRP family). A peptide derived from the loop 2 region of sclerostin blocked the interaction of sclerostin with LRP5/6 and also inhibited Wnt1 but not Wnt3A or Wnt9B signaling. This suggests that these Wnts interact with LRP6 in different ways. PMID:22696217

Experimental and Theoretical Study of the Movement of the Wpd Flexible Loop of Human Protein Tyrosine Phosphatase PTP1B in Complex with Halide Ions

NASA Astrophysics Data System (ADS)

Katz, Aline; Saenz-Méndez, Patricia; Cousido-Siah, Alexandra; Podjarny, Alberto D.; Ventura, Oscar N.

2012-11-01

Protein tyrosine phosphorylation is a post-translational modification mechanism, crucial for the regulation of nearly all aspects of cell life. This dynamic, reversible process is regulated by the balanced opposing activity of protein tyrosine kinases and protein tyrosine phosphatases. In particular, the protein tyrosine phosphatase 1B (PTP1B) is implicated in the regulation of the insulin-receptor activity, leptin-stimulated signal transduction pathways and other clinically relevant metabolic routes, and it has been found overexpressed or overregulated in human breasts, colon and ovary cancers. The WPD loop of the enzyme presents an inherent flexibility, and it plays a fundamental role in the enzymatic catalysis, turning it into a potential target in the design of new efficient PTP1B inhibitors. In order to determine the interactions that control the spatial conformation adopted by the WPD loop, complexes between the enzyme and halide ions (Br- and I- in particular) were crystallized and their crystallographic structure determined, and the collective movements of the aforementioned complexes were studied through Molecular Dynamics (MD) simulations. Both studies yielded concordant results, indicating the existence of a relationship between the identity of the ion present in the complex and the strength of the interactions it establishes with the surrounding protein residues.

The dynamics and control of large flexible space structures, 8

NASA Technical Reports Server (NTRS)

Bainum, P. M.; Reddy, A. S. S. R.; Diarra, C. M.; Ananthakrishnan, S.

1985-01-01

A development of the in plane open loop rotational equations of motion for the proposed Spacecraft Control Laboratory Experiment (SCOLE) in orbit configuration is presented based on an Eulerian formulation. The mast is considered to be a flexible beam connected to the (rigid) shuttle and the reflector. Frequencies and mode shapes are obtained for the mast vibrational appendage modes (assumed to be decoupled) for different boundary conditions based on continuum approaches and also preliminary results are obtained using a finite element representation of the mast reflector system. The linearized rotational in plane equation is characterized by periodic coefficients and open loop system stability can be examined with an application of the Floquet theorem. Numerical results are presented to illustrate the potential instability associated with actuator time delays even for delays which represent only a small fraction of the natural period of oscillation of the modes contained in the open loop model of the system. When plant and measurement noise effects are added to the previously designed deterministic model of the hoop column system, it is seen that both the system transient and steady state performance are degraded. Mission requirements can be satisfied by appropriate assignment of cost function weighting elements and changes in the ratio of plant noise to measurement noise.

Flexible Connectors between Capsomer Subunits that Regulate Capsid Assembly.

PubMed

Hasek, Mary L; Maurer, Joshua B; Hendrix, Roger W; Duda, Robert L

2017-08-04

Viruses build icosahedral capsids of specific size and shape by regulating the spatial arrangement of the hexameric and pentameric protein capsomers in the growing shell during assembly. In the T=7 capsids of Escherichia coli bacteriophage HK97 and other phages, 60 capsomers are hexons, while the rest are pentons that are correctly positioned during assembly. Assembly of the HK97 capsid to the correct size and shape has been shown to depend on specific ionic contacts between capsomers. We now describe additional ionic interactions within capsomers that also regulate assembly. Each is between the long hairpin, the "E-loop," that extends from one subunit to the adjacent subunit within the same capsomer. Glutamate E153 on the E-loop and arginine R210 on the adjacent subunit's backbone alpha-helix form salt bridges in hexamers and pentamers. Mutations that disrupt these salt bridges were lethal for virus production, because the mutant proteins assembled into tubes or sheets instead of capsids. X-ray structures show that the E153-R210 links are flexible and maintained during maturation despite radical changes in capsomer shape. The E153-R210 links appear to form early in assembly to enable capsomers to make programmed changes in their shape during assembly. The links also prevent flattening of capsomers and premature maturation. Mutant phenotypes and modeling support an assembly model in which flexible E153-R210 links mediate capsomer shape changes that control where pentons are placed to create normal-sized capsids. The E-loop may be conserved in other systems in order to play similar roles in regulating assembly. Copyright © 2017 Elsevier Ltd. All rights reserved.

STEREOSCOPIC OBSERVATION OF SLIPPING RECONNECTION IN A DOUBLE CANDLE-FLAME-SHAPED SOLAR FLARE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gou, Tingyu; Liu, Rui; Wang, Yuming

2016-04-20

The 2011 January 28 M1.4 flare exhibits two side-by-side candle-flame-shaped flare loop systems underneath a larger cusp-shaped structure during the decay phase, as observed at the northwestern solar limb by the Solar Dynamics Observatory . The northern loop system brightens following the initiation of the flare within the southern loop system, but all three cusp-shaped structures are characterized by ∼10 MK temperatures, hotter than the arch-shaped loops underneath. The “Ahead” satellite of the Solar Terrestrial Relations Observatory provides a top view, in which the post-flare loops brighten sequentially, with one end fixed while the other apparently slipping eastward. By performingmore » stereoscopic reconstruction of the post-flare loops in EUV and mapping out magnetic connectivities, we found that the footpoints of the post-flare loops are slipping along the footprint of a hyperbolic flux tube (HFT) separating the two loop systems and that the reconstructed loops share similarity with the magnetic field lines that are traced starting from the same HFT footprint, where the field lines are relatively flexible. These results argue strongly in favor of slipping magnetic reconnection at the HFT. The slipping reconnection was likely triggered by the flare and manifested as propagative dimmings before the loop slippage is observed. It may contribute to the late-phase peak in Fe xvi 33.5 nm, which is even higher than its main-phase counterpart, and may also play a role in the density and temperature asymmetry observed in the northern loop system through heat conduction.« less

Identifying Functional Requirements for Flexible Airspace Management Concept Using Human-In-The-Loop Simulations

NASA Technical Reports Server (NTRS)

Lee, Paul U.; Bender, Kim; Pagan, Danielle

2011-01-01

Flexible Airspace Management (FAM) is a mid- term Next Generation Air Transportation System (NextGen) concept that allows dynamic changes to airspace configurations to meet the changes in the traffic demand. A series of human-in-the-loop (HITL) studies have identified procedures and decision support requirements needed to implement FAM. This paper outlines a suggested FAM procedure and associated decision support functionality based on these HITL studies. A description of both the tools used to support the HITLs and the planned NextGen technologies available in the mid-term are presented and compared. The mid-term implementation of several NextGen capabilities, specifically, upgrades to the Traffic Management Unit (TMU), the initial release of an en route automation system, the deployment of a digital data communication system, a more flexible voice communications network, and the introduction of a tool envisioned to manage and coordinate networked ground systems can support the implementation of the FAM concept. Because of the variability in the overall deployment schedule of the mid-term NextGen capabilities, the dependency of the individual NextGen capabilities are examined to determine their impact on a mid-term implementation of FAM. A cursory review of the different technologies suggests that new functionality slated for the new en route automation system is a critical enabling technology for FAM, as well as the functionality to manage and coordinate networked ground systems. Upgrades to the TMU are less critical but important nonetheless for FAM to be fully realized. Flexible voice communications network and digital data communication system could allow more flexible FAM operations but they are not as essential.

Integrated Flight/Structural Mode Control for Very Flexible Aircraft Using L1 Adaptive Output Feedback Controller

NASA Technical Reports Server (NTRS)

Che, Jiaxing; Cao, Chengyu; Gregory, Irene M.

2012-01-01

This paper explores application of adaptive control architecture to a light, high-aspect ratio, flexible aircraft configuration that exhibits strong rigid body/flexible mode coupling. Specifically, an L(sub 1) adaptive output feedback controller is developed for a semi-span wind tunnel model capable of motion. The wind tunnel mount allows the semi-span model to translate vertically and pitch at the wing root, resulting in better simulation of an aircraft s rigid body motion. The control objective is to design a pitch control with altitude hold while suppressing body freedom flutter. The controller is an output feedback nominal controller (LQG) augmented by an L(sub 1) adaptive loop. A modification to the L(sub 1) output feedback is proposed to make it more suitable for flexible structures. The new control law relaxes the required bounds on the unmatched uncertainty and allows dependence on the state as well as time, i.e. a more general unmatched nonlinearity. The paper presents controller development and simulated performance responses. Simulation is conducted by using full state flexible wing models derived from test data at 10 different dynamic pressure conditions. An L(sub 1) adaptive output feedback controller is designed for a single test point and is then applied to all the test cases. The simulation results show that the L(sub 1) augmented controller can stabilize and meet the performance requirements for all 10 test conditions ranging from 30 psf to 130 psf dynamic pressure.

Assessing the effect of D59P mutation in the DE loop region in amyloid aggregation propensity of β2-microglobulin: A molecular dynamics simulation study.

PubMed

Narang, Simranjeet S; Shuaib, Suniba; Goyal, Deepti; Goyal, Bhupesh

2018-01-01

Dialysis-related amyloidosis (DRA) is a severe condition characterized by the accumulation of amyloidogenic β2-microglobulin (β2m) protein around skeletal joints and bones. The recent studies highlighted a critical role of the DE loop region for β2m stability and amyloid aggregation propensity. Despite significant efforts, the molecular mechanism of enhanced aggregation due to D59P mutation in the DE loop region remain elusive. In the present study, explicit-solvent molecular dynamics (MD) simulations were performed to examine the key changes in the structural and dynamic properties of wild type (wt) β2m upon D59P mutation. MD simulations reveal a decrease in the average number of hydrogen bonds in the loop regions on D59P mutation that enhances conformational flexibility, which lead to higher aggregation propensity of D59P as compare to wt β2m. The principal component analysis (PCA) highlight that D59P covers a larger region of phase space and display a higher trace value than wt β2m, which suggest an overall enhancement in the conformational flexibility. D59P display two minimum energy basins in the free energy landscape (FEL) that are associated with thermodynamically less stable conformational states as compare to single minimum energy basin in wt β2m. The present study provides theoretical insights into the molecular mechanism behind the higher aggregation propensity of D59P as compare to wt β2m. © 2017 Wiley Periodicals, Inc.

Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: Functional convergence of a common protein fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casados-Vázquez, Luz E.; Lara-González, Samuel; Brieb, Luis G.

Cysteine proteases (CP) are key pathogenesis and virulence determinants of protozoan parasites. Entamoeba histolytica contains at least 50 cysteine proteases; however, only three (EhCP1, EhCP2 and EhCP5) are responsible for approximately 90% of the cysteine protease activity in this parasite. CPs are expressed as inactive zymogens. Because the processed proteases are potentially cytotoxic, protozoan parasites have developed mechanisms to regulate their activity. Inhibitors of cysteine proteases (ICP) of the chagasin-like inhibitor family (MEROPS family I42) were recently identified in bacteria and protozoan parasites. E. histolytica contains two ICP-encoding genes of the chagasin-like inhibitor family. EhICP1 localizes to the cytosol, whereasmore » EhICP2 is targeted to phagosomes. Herein, we report two crystal structures of EhICP2. The overall structure of EhICP2 consists of eight {beta}-strands and closely resembles the immunoglobulin fold. A comparison between the two crystal forms of EhICP2 indicates that the conserved BC, DE and FG loops form a flexible wedge that may block the active site of CPs. The positively charged surface of the wedge-forming loops in EhICP2 contrasts with the neutral surface of the wedge-forming loops in chagasin. We postulate that the flexibility and positive charge observed in the DE and FG loops of EhICP2 may be important to facilitate the initial binding of this inhibitor to the battery of CPs present in E. histolytica.« less

Package architecture and component design for an implanted neural stimulator with closed loop control.

PubMed

Bjune, Caroline K; Marinis, Thomas F; Brady, Jeanne M; Moran, James; Wheeler, Jesse; Sriram, Tirunelveli S; Parks, Philip D; Widge, Alik S; Dougherty, Darin D; Eskandar, Emad N

2015-08-01

An implanted neural stimulator with closed loop control requires electrodes for stimulation pulses and recording neuron activity. Our system features arrays of 64 electrodes. Each electrode can be addressed through a cross bar switch, to enable it to be used for stimulation or recording. This electrode switch, a bank of low noise amplifiers with an integrated analog to digital converter, power conditioning electronics, and a communications and control gate array are co-located with the electrode array in a 14 millimeter diameter satellite package that is designed to be flush mounted in a skull burr hole. Our system features five satellite packages connected to a central hub processor-controller via ten conductor cables that terminate in a custom designed, miniaturized connector. The connector incorporates features of high reliability, military grade devices and utilizes three distinct seals to isolate the contacts from fluid permeation. The hub system is comprised of a connector header, hermetic electronics package, and rechargeable battery pack, which are mounted on and electrically interconnected by a flexible circuit board. The assembly is over molded with a compliant silicone rubber. The electronics package contains two antennas, a large coil, used for recharging the battery and a high bandwidth antenna that is used to download data and update software. The package is assembled from two machined alumina pieces, a flat base with brazed in, electrical feed through pins and a rectangular cover with rounded corners. Titanium seal rings are brazed onto these two pieces so that they can be sealed by laser welding. A third system antenna is incorporated in the flexible circuit board. It is used to communicate with an externally worn control package, which monitors the health of the system and allows both the user and clinician to control or modify various system function parameters.

Compensation for Unconstrained Catheter Shaft Motion in Cardiac Catheters

PubMed Central

Degirmenci, Alperen; Loschak, Paul M.; Tschabrunn, Cory M.; Anter, Elad; Howe, Robert D.

2016-01-01

Cardiac catheterization with ultrasound (US) imaging catheters provides real time US imaging from within the heart, but manually navigating a four degree of freedom (DOF) imaging catheter is difficult and requires extensive training. Existing work has demonstrated robotic catheter steering in constrained bench top environments. Closed-loop control in an unconstrained setting, such as patient vasculature, remains a significant challenge due to friction, backlash, and physiological disturbances. In this paper we present a new method for closed-loop control of the catheter tip that can accurately and robustly steer 4-DOF cardiac catheters and other flexible manipulators despite these effects. The performance of the system is demonstrated in a vasculature phantom and an in vivo porcine animal model. During bench top studies the robotic system converged to the desired US imager pose with sub-millimeter and sub-degree-level accuracy. During animal trials the system achieved 2.0 mm and 0.65° accuracy. Accurate and robust robotic navigation of flexible manipulators will enable enhanced visualization and treatment during procedures. PMID:27525170

Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD.

PubMed

Grande-García, Araceli; Lallous, Nada; Díaz-Tejada, Celsa; Ramón-Maiques, Santiago

2014-02-04

Upregulation of CAD, the multifunctional protein that initiates and controls the de novo biosynthesis of pyrimidines in animals, is essential for cell proliferation. Deciphering the architecture and functioning of CAD is of interest for its potential usage as an antitumoral target. However, there is no detailed structural information about CAD other than that it self-assembles into hexamers of ∼1.5 MDa. Here we report the crystal structure and functional characterization of the dihydroorotase domain of human CAD. Contradicting all assumptions, the structure reveals an active site enclosed by a flexible loop with two Zn²⁺ ions bridged by a carboxylated lysine and a third Zn coordinating a rare histidinate ion. Site-directed mutagenesis and functional assays prove the involvement of the Zn and flexible loop in catalysis. Comparison with homologous bacterial enzymes supports a reclassification of the DHOase family and provides strong evidence against current models of the architecture of CAD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ca-asp bound X-ray structure and inhibition of Bacillus anthracis dihydroorotase (DHOase).

PubMed

Rice, Amy J; Lei, Hao; Santarsiero, Bernard D; Lee, Hyun; Johnson, Michael E

2016-10-01

Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis pathway and is responsible for the reversible cyclization of carbamyl-aspartate (Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes based on several structural characteristics, one of which is the length of the flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the enzyme activity. Here, we present the crystal structure of Class I Bacillus anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone of glycine in the shorter loop forming the necessary hydrogen bonds with the substrate, in place of the two threonines found in Class II DHOases. Despite the differences in the catalytic loop, the structure confirms that the key interactions between the substrate and active site residues are similar between Class I and Class II DHOase enzymes, which we further validated by mutagenesis studies. B. anthracis DHOase is also a potential antibacterial drug target. In order to identify prospective inhibitors, we performed high-throughput screening against several libraries using a colorimetric enzymatic assay and an orthogonal fluorescence thermal binding assay. Surface plasmon resonance was used for determining binding affinity (KD) and competition analysis with Ca-asp. Our results highlight that the primary difference between Class I and Class II DHOase is the catalytic loop. We also identify several compounds that can potentially be further optimized as potential B. anthracis inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

A multi-mode operation control strategy for flexible microgrid based on sliding-mode direct voltage and hierarchical controls.

PubMed

Zhang, Qinjin; Liu, Yancheng; Zhao, Youtao; Wang, Ning

2016-03-01

Multi-mode operation and transient stability are two problems that significantly affect flexible microgrid (MG). This paper proposes a multi-mode operation control strategy for flexible MG based on a three-layer hierarchical structure. The proposed structure is composed of autonomous, cooperative, and scheduling controllers. Autonomous controller is utilized to control the performance of the single micro-source inverter. An adaptive sliding-mode direct voltage loop and an improved droop power loop based on virtual negative impedance are presented respectively to enhance the system disturbance-rejection performance and the power sharing accuracy. Cooperative controller, which is composed of secondary voltage/frequency control and phase synchronization control, is designed to eliminate the voltage/frequency deviations produced by the autonomous controller and prepare for grid connection. Scheduling controller manages the power flow between the MG and the grid. The MG with the improved hierarchical control scheme can achieve seamless transitions from islanded to grid-connected mode and have a good transient performance. In addition the presented work can also optimize the power quality issues and improve the load power sharing accuracy between parallel VSIs. Finally, the transient performance and effectiveness of the proposed control scheme are evaluated by theoretical analysis and simulation results. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Effect of various refining processes for Kenaf Bast non-wood pulp fibers suspensions on heat transfer coefficient in circular pipe heat exchanger

NASA Astrophysics Data System (ADS)

Ahmed, Syed Muzamil; Kazi, S. N.; Khan, Ghulamullah; Sadri, Rad; Dahari, Mahidzal; Zubir, M. N. M.; Sayuti, M.; Ahmad, Pervaiz; Ibrahim, Rushdan

2018-03-01

Heat transfer coefficients were obtained for a range of non-wood kenaf bast pulp fiber suspensions flowing through a circular pipe heat exchanger test loop. The data were produced over a selected temperature and range of flow rates from the flow loop. It was found that the magnitude of the heat transfer coefficient of a fiber suspension is dependent on characteristics, concentration and pulping method of fiber. It was observed that at low concentration and high flow rates, the heat transfer coefficient values of suspensions were observed higher than that of the heat transfer coefficient values of water, on the other hand the heat transfer coefficient values of suspensions decreases at low flow rates and with the increase of their concentration. The heat transfer were affected by varying fiber characteristics, such as fiber length, fiber flexibility, fiber chemical and mechanical treatment as well as different pulping methods used to liberate the fibers. Heat transfer coefficient was decreased with the increase of fiber flexibility which was also observed by previous researchers. In the present work, the characteristics of fibers are correlated with the heat transfer coefficient of suspensions of the fibers. Deviations in fiber properties can be monitored from the flowing fiber suspensions by measuring heat transfer coefficient to adjust the degree of fiber refining treatment so that papers made from those fibers will be more uniform, consistent, within the product specification and retard the paper production loss.

Iterative key-residues interrogation of a phytase with thermostability increasing substitutions identified in directed evolution.

PubMed

Shivange, Amol V; Roccatano, Danilo; Schwaneberg, Ulrich

2016-01-01

Bacterial phytases have attracted industrial interest as animal feed supplement due to their high activity and sufficient thermostability (required for feed pelleting). We devised an approach named KeySIDE,  an iterative Key-residues interrogation of the wild type with Substitutions Identified in Directed Evolution for improving Yersinia mollaretii phytase (Ymphytase) thermostability by combining key beneficial substitutions and elucidating their individual roles. Directed evolution yielded in a discovery of nine positions in Ymphytase and combined iteratively to identify key positions. The "best" combination (M6: T77K, Q154H, G187S, and K289Q) resulted in significantly improved thermal resistance; the residual activity improved from 35 % (wild type) to 89 % (M6) at 58 °C and 20-min incubation. Melting temperature increased by 3 °C in M6 without a loss of specific activity. Molecular dynamics simulation studies revealed reduced flexibility in the loops located next to helices (B, F, and K) which possess substitutions (Helix-B: T77K, Helix-F: G187S, and Helix-K: K289E/Q). Reduced flexibility in the loops might be caused by strengthened hydrogen bonding network (e.g., G187S and K289E/K289Q) and a salt bridge (T77K). Our results demonstrate a promising approach to design phytases in food research, and we hope that the KeySIDE might become an attractive approach for understanding of structure-function relationships of enzymes.

Probing the effect of the non-active-site mutation Y229W in New Delhi metallo-β-lactamase-1 by site-directed mutagenesis, kinetic studies, and molecular dynamics simulations.

PubMed

Chen, Jiao; Chen, Hui; Shi, Yun; Hu, Feng; Lao, Xingzhen; Gao, Xiangdong; Zheng, Heng; Yao, Wenbing

2013-01-01

New Delhi metallo-β-lactamase-1 (NDM-1) has attracted extensive attention for its high catalytic activities of hydrolyzing almost all β-lactam antibiotics. NDM-1 shows relatively higher similarity to subclass B1 metallo-β-lactamases (MβLs), but its residue at position 229 is identical to that of B2/B3 MβLs, which is a Tyr instead of a B1-MβL-conserved Trp. To elucidate the possible role of Y229 in the bioactivity of NDM-1, we performed mutagenesis study and molecular dynamics (MD) simulations. Although residue Y229 is spatially distant from the active site and not contacting directly with the substrate or zinc ions, the Y229W mutant was found to have higher kcat and Km values than those of wild-type NDM-1, resulting in 1 ∼ 7 fold increases in k(cat) /K(m) values against tested antibiotics. In addition, our MD simulations illustrated the enhanced flexibility of Loop 2 upon Y229W mutation, which could increase the kinetics of both substrate entrance (kon) and product egress (koff). The enhanced flexibility of Loop 2 might allow the enzyme to adjust the geometry of its active site to accommodate substrates with different structures, broadening its substrate spectrum. This study indicated the possible role of the residue at position 229 in the evolution of NDM-1.

Robust lateral blended-wing-body aircraft feedback control design using a parameterized LFR model and DGK-iteration

NASA Astrophysics Data System (ADS)

Schirrer, A.; Westermayer, C.; Hemedi, M.; Kozek, M.

2013-12-01

This paper shows control design results, performance, and limitations of robust lateral control law designs based on the DGK-iteration mixed-μ-synthesis procedure for a large, flexible blended wing body (BWB) passenger aircraft. The aircraft dynamics is preshaped by a low-complexity inner loop control law providing stabilization, basic response shaping, and flexible mode damping. The μ controllers are designed to further improve vibration damping of the main flexible modes by exploiting the structure of the arising significant parameter-dependent plant variations. This is achieved by utilizing parameterized Linear Fractional Representations (LFR) of the aircraft rigid and flexible dynamics. Designs with various levels of LFR complexity are carried out and discussed, showing the achieved performance improvement over the initial controller and their robustness and complexity properties.

Study of design and control of remote manipulators. Modeling manipulator arms with distributed flexibility for design and control

NASA Technical Reports Server (NTRS)

Book, W. J.

1974-01-01

The interactions of control system and distributed flexible structural dynamics is explored for mechanical arms. A modeling process using 4 x 4 transfer matrices is described which permits the closed loop response of many current arm configurations to be evaluated. Root locus, frequency response, modal shapes, and time impulse response have all been obtained from the digital computer implementation of this model, which is oriented to arm design and allows for easy variation of the arm configuration through data cards. The model corresponds with experimentally observed natural frequencies with an average error of less than 5% in the first three flexible modes in the seven cases considered. The model was used to explore the limits imposed by structural flexibility on a nondimensionalized two link arm with one and two joints for planar motion.

Gust alleviation of highly flexible UAVs with artificial hair sensors

NASA Astrophysics Data System (ADS)

Su, Weihua; Reich, Gregory W.

2015-04-01

Artificial hair sensors (AHS) have been recently developed in Air Force Research Laboratory (AFRL) using carbon nanotube (CNT). The deformation of CNT in air flow causes voltage and current changes in the circuit, which can be used to quantify the dynamic pressure and aerodynamic load along the wing surface. AFRL has done a lot of essential work in design, manufacturing, and measurement of AHSs. The work in this paper is to bridge the current AFRL's work on AHSs and their feasible applications in flight dynamics and control (e.g., the gust alleviation) of highly flexible aircraft. A highly flexible vehicle is modeled using a strain-based geometrically nonlinear beam formulation, coupled with finite-state inflow aerodynamics. A feedback control algorithm for the rejection of gust perturbations will be developed. A simplified Linear Quadratic Regulator (LQR) controller will be implemented based on the state-space representation of the linearized system. All AHS measurements will be used as the control input, i.e., wing sectional aerodynamic loads will be defined as the control output for designing the feedback gain. Once the controller is designed, closed-loop aeroelastic simulations will be performed to evaluate the performance of different controllers with the force feedback and be compared to traditional controller designs with the state feedback. From the study, the feasibility of AHSs in flight control will be assessed. The whole study will facilitate in building a fly-by-feel simulation environment for autonomous vehicles.

Pilot modeling and closed-loop analysis of flexible aircraft in the pitch tracking task

NASA Technical Reports Server (NTRS)

Schmidt, D. K.

1983-01-01

The issue addressed in the appropriate modeling technique for pilot vehicle analysis of large flexible aircraft, when the frequency separation between the rigid-body mode and the dynamic aeroelastic modes is reduced. This situation was shown to have significant effects on pitch-tracking performance and subjective rating of the task, obtained via fixed base simulation. Further, the dynamics in these cases are not well modeled with a rigid-body-like model obtained by including only 'static elastic' effects, for example. It is shown that pilot/vehicle analysis of this data supports the hypothesis that an appropriate pilot-model structure is an optimal-control pilot model of full order. This is in contrast to the contention that a representative model is of reduced order when the subject is controlling high-order dynamics as in a flexible vehicle. The key appears to be in the correct assessment of the pilot's objective of attempting to control 'rigid-body' vehicle response, a response that must be estimated by the pilot from observations contaminated by aeroelastic dynamics. Finally, a model-based metric is shown to correlate well with the pilot's subjective ratings.

Identifying the adaptive mechanism in globular proteins: Fluctuations in densely packed regions manipulate flexible parts

NASA Astrophysics Data System (ADS)

Yilmaz, Lutfu Safak; Atilgan, Ali Rana

2000-09-01

A low-resolution structural model based on the packing geometry of α-carbons is utilized to establish a connection between the flexible and rigid parts of a folded protein. The former commonly recognizes a complementing molecule for making a complex, while the latter manipulates the necessary conformational change for binding. We attempt analytically to distinguish this control architecture that intrinsically exists in globular proteins. First with two-dimensional simple models, then for a native protein, bovine pancreatic trypsin inhibitor, we explicitly demonstrate that inserting fluctuations in tertiary contacts supported by the stable core, one can regulate the displacement of residues on loop regions. The positional fluctuations of the flexible regions are annihilated by the rest of the protein in conformity with the Le Chatelier-Braun principle. The results indicate that the distortion of the principal nonbonded contacts between highly packed residues is accompanied by that of the slavery fluctuations that are widely distributed over the native structure. These positional arrangements do not appear in a reciprocal relation between a perturbation and the associated response; the effect of a movement of residue i on residue j is not equal to that of the same movement of residue j on residue i.

Dynamics and control of high precision magnetically levitated vibration isolation systems

NASA Technical Reports Server (NTRS)

Youcef-Toumi, K.; Yeh, T-J.

1992-01-01

Vibration control of flexible structures has received a great deal of interest in recent years. Several authors have investigated this topic in the areas of robot manipulators, space structures, and flexible rotors. Key issues associated with the dynamics and control of vibration isolation systems are addressed. Among other important issues to consider in the control of such systems, the location and number of actuators and sensors are essential to effectively control and suppress vibration. We first address the selection of proper actuator and sensor locations leading to a controllable and observable system. The Rayleigh-Ritz modal analysis method is used to develop a lumped-parameter model of a flexible vibration isolation table top. This model is then used to investigate the system's controllability and observability including the coupling effects introduced by the magnetic bearing. This analysis results in necessary and sufficient conditions for proper selection of actuator and sensor locations. These locations are also important for both controller system's complexity and stability of point of views. A favorable pole-zero plot of the open loop transfer functions is presented. Necessary and sufficient conditions for reducing the controller complexity are derived. The results are illustrated by examples using approximate mode shape functions.

A classical model for closed-loop diagrams of binary liquid mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnitzler, J.v.; Prausnitz, J.M.

1994-03-01

A classical lattice model for closed-loop temperature-composition phase diagrams has been developed. It considers the effect of specific interactions, such as hydrogen bonding, between dissimilar components. This van Laar-type model includes a Flory-Huggins term for the excess entropy of mixing. It is applied to several liquid-liquid equilibria of nonelectrolytes, where the molecules of the two components differ in size. The model is able to represent the observed data semi-quantitatively, but in most cases it is not flexible enough to predict all parts of the closed loop quantitatively. The ability of the model to represent different binary systems is discussed. Finally,more » attention is given to a correction term, concerning the effect of concentration fluctuations near the upper critical solution temperature.« less

Engineering the thermostability of β-glucuronidase from Penicillium purpurogenum Li-3 by loop transplant.

PubMed

Feng, Xudong; Tang, Heng; Han, Beijia; Zhang, Liang; Lv, Bo; Li, Chun

2016-12-01

In this study, we proposed a loop transplant strategy to improve the thermostability of Penicillium purpurogenum Li-3 β-glucuronidase expressed in Escherichia coli (abbreviated to PGUS-E). Firstly, three unstable surface loops of PGUS-E to be replaced were identified with regards to B-factor values and in-depth structure analysis: loops 205-211, 258-263, and 25-31. Then, based on B-factor analysis, eight stable loops for substitution were selected from two typical thermophilic glycosidases which had low homology with PGUS-E (less than 25 %). By analyzing the common features of these stable loops, it was found that they shared a common residue skeleton DXXTX(X)R, based on this, three chimera loops were also manually designed: RSQTSND, RSSTQRD, and DDQTSR. All these loops were introduced to replace the unstable loops of PGUS-E by homology structure modeling, and only mutants with increased hydrogen bonds number and good compatibility with the local mutated region were further subjected to experimental verification. By using this strategy, 10 mutants were experimentally generated, among which three mutants, M1, M3, and M8, were obtained which showed 11.8, 3.3, and 9.4 times higher half-life at 70 °C than that of wild-type (8.5 min). Finally, the MD simulation indicated that the increased hydrogen bonds, decreased flexibility of N-terminal, and increased π-π stacking interaction were responsible for the improved thermostability.

CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

PubMed

Mercurio, Flavia A; Scognamiglio, Pasqualina L; Di Natale, Concetta; Marasco, Daniela; Pellecchia, Maurizio; Leone, Marilisa

2014-11-01

The lipid phosphatase Ship2 is a protein that intervenes in several diseases such as diabetes, cancer, neurodegeneration, and atherosclerosis. It is made up of a catalytic domain and several protein docking modules such as a C-terminal Sam (Sterile alpha motif) domain. The Sam domain of Ship2 (Ship2-Sam) binds to the Sam domains of the EphA2 receptor (EphA2-Sam) and the PI3K effector protein Arap3 (Arap3-Sam). These heterotypic Sam-Sam interactions occur through formation of dimers presenting the canonical "Mid Loop/End Helix" binding mode. The central region of Ship2-Sam, spanning the C-terminal end of α2, the α3 and α4 helices together with the α2α3 and α3α4 interhelical loops, forms the Mid Loop surface that is needed to bind partners Sam domains. A peptide encompassing most of the Ship2-Sam Mid Loop interface (Shiptide) capable of binding to both EphA2-Sam and Arap3-Sam, was previously identified. Here we investigated the conformational features of this peptide, through solution CD and NMR studies in different conditions. These studies reveal that the peptide is highly flexible in aqueous buffer, while it adopts a helical conformation in presence of 2,2,2-trifluoroethanol. The discovered structural insights and in particular the identification of a helical motif, may lead to the design of more constrained and possibly cell permeable Shiptide analogs that could work as efficient antagonists of Ship2-Sam heterotypic interactions and embrace therapeutic applications. © 2014 Wiley Periodicals, Inc.

Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

PubMed

Nakashima, T; Yao, M; Kawamura, S; Iwasaki, K; Kimura, M; Tanaka, I

2001-05-01

Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic representation suggest that the concave surface and loop regions are involved in 5S rRNA binding. To identify amino acid residues responsible for 5S rRNA binding, we made use of Ala-scanning mutagenesis of evolutionarily conserved amino acids occurring in the beta-strands and loop regions. The mutations of Asn37 at the beta1-strand and Gln63 at the loop between helix 2 and beta3-strand as well as that of Phe77 at the tip of the loop structure between the beta2- and beta3-strands caused a significant reduction in 5S rRNA binding. In addition, the mutations of Thr90 on the beta3-strand and Ile141 and Asp144 at the loop between beta4- and beta5-strands moderately reduced the 5S rRNA-binding affinity. Comparison of these results with the more recently analyzed structure of the 50S subunit from Haloarcula marismortui suggests that there are significant differences in the structure at N- and C-terminal regions and probably in the 5S rRNA binding.

Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

PubMed Central

Nakashima, T; Yao, M; Kawamura, S; Iwasaki, K; Kimura, M; Tanaka, I

2001-01-01

Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic representation suggest that the concave surface and loop regions are involved in 5S rRNA binding. To identify amino acid residues responsible for 5S rRNA binding, we made use of Ala-scanning mutagenesis of evolutionarily conserved amino acids occurring in the beta-strands and loop regions. The mutations of Asn37 at the beta1-strand and Gln63 at the loop between helix 2 and beta3-strand as well as that of Phe77 at the tip of the loop structure between the beta2- and beta3-strands caused a significant reduction in 5S rRNA binding. In addition, the mutations of Thr90 on the beta3-strand and Ile141 and Asp144 at the loop between beta4- and beta5-strands moderately reduced the 5S rRNA-binding affinity. Comparison of these results with the more recently analyzed structure of the 50S subunit from Haloarcula marismortui suggests that there are significant differences in the structure at N- and C-terminal regions and probably in the 5S rRNA binding. PMID:11350033

Imaging and modeling new VETEM data

USGS Publications Warehouse

Wright, David L.; Smith, David V.; Abraham, Jared D.; Hutton, Raymond S.; Bond, E. Kent; Cui, Tie Jun; Aydiner, Alaeddin A.; Chew, Weng Cho

2000-01-01

In previously reported work (Wright and others, 2000) we found that the very early time electromagnetic (VETEM) prototype system produced data from which high resolution images of a buried former foundry site at the Denver Federal Center were made. The soil covering the site is about 30 mS/m conductivity, and is thus relatively unfavorable for ground penetrating radar (GPR) imaging. We have surveyed portions of this site again with new electric field dipole antennas and a new receiver designed for these antennas. Comparisons of the images produced using the loop antennas to those produced using the electric field dipole antennas illustrate that for this application the loop antennas produced more useful images. The larger man-made structures can be seen more clearly because they are not masked by dispersion and/or smaller scale variations as with the electric field dipole antennas. The VETEM system now contains an array of antennas with appropriate transmitters and receivers and can be operated as a low frequency time domain GPR or as a high frequency time domain electromagnetic (EM) system with several possible antenna spacings and polarizations. We plan to examine additional configurations. Numerical modeling of the perpendicular loop antenna configuration has been done and depth estimates produced. We conclude that, as with other GPR and time domain EM systems, the best choice of operating parameters depends on the application and the environment, but the inherent flexibility of the VETEM system allows a wide range of options.

Rigidification of the autolysis loop enhances Na[superscript +] binding to thrombin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pozzi, Nicola; Chen, Raymond; Chen, Zhiwei

2011-09-20

Binding of Na{sup +} to thrombin ensures high activity toward physiological substrates and optimizes the procoagulant and prothrombotic roles of the enzyme in vivo. Under physiological conditions of pH and temperature, the binding affinity of Na{sup +} is weak due to large heat capacity and enthalpy changes associated with binding, and the K{sub d} = 80 mM ensures only 64% saturation of the site at the concentration of Na{sup +} in the blood (140 mM). Residues controlling Na{sup +} binding and activation have been identified. Yet, attempts to improve the interaction of Na{sup +} with thrombin and possibly increase catalyticmore » activity under physiological conditions have so far been unsuccessful. Here we report how replacement of the flexible autolysis loop of human thrombin with the homologous rigid domain of the murine enzyme results in a drastic (up to 10-fold) increase in Na{sup +} affinity and a significant improvement in the catalytic activity of the enzyme. Rigidification of the autolysis loop abolishes the heat capacity change associated with Na{sup +} binding observed in the wild-type and also increases the stability of thrombin. These findings have general relevance to protein engineering studies of clotting proteases and trypsin-like enzymes.« less

Retargeting of existing FORTRAN program and development of parallel compilers

NASA Technical Reports Server (NTRS)

Agrawal, Dharma P.

1988-01-01

The software models used in implementing the parallelizing compiler for the B-HIVE multiprocessor system are described. The various models and strategies used in the compiler development are: flexible granularity model, which allows a compromise between two extreme granularity models; communication model, which is capable of precisely describing the interprocessor communication timings and patterns; loop type detection strategy, which identifies different types of loops; critical path with coloring scheme, which is a versatile scheduling strategy for any multicomputer with some associated communication costs; and loop allocation strategy, which realizes optimum overlapped operations between computation and communication of the system. Using these models, several sample routines of the AIR3D package are examined and tested. It may be noted that automatically generated codes are highly parallelized to provide the maximized degree of parallelism, obtaining the speedup up to a 28 to 32-processor system. A comparison of parallel codes for both the existing and proposed communication model, is performed and the corresponding expected speedup factors are obtained. The experimentation shows that the B-HIVE compiler produces more efficient codes than existing techniques. Work is progressing well in completing the final phase of the compiler. Numerous enhancements are needed to improve the capabilities of the parallelizing compiler.

Rational positive real approximations for LQG optimal compensators arising in active stabilization of flexible structures

NASA Technical Reports Server (NTRS)

Desantis, A.

1994-01-01

In this paper the approximation problem for a class of optimal compensators for flexible structures is considered. The particular case of a simply supported truss with an offset antenna is dealt with. The nonrational positive real optimal compensator transfer function is determined, and it is proposed that an approximation scheme based on a continued fraction expansion method be used. Comparison with the more popular modal expansion technique is performed in terms of stability margin and parameters sensitivity of the relative approximated closed loop transfer functions.

Vibration sensing in flexible structures using a distributed-effect modal domain optical fiber sensor

NASA Technical Reports Server (NTRS)

Reichard, Karl M.; Lindner, Douglas K.; Claus, Richard O.

1991-01-01

Modal domain optical fiber sensors have recently been employed in the implementation of system identification algorithms and the closed-loop control of vibrations in flexible structures. The mathematical model of the modal domain optical fiber sensor used in these applications, however, only accounted for the effects of strain in the direction of the fiber's longitudinal axis. In this paper, we extend this model to include the effects of arbitrary stress. Using this sensor model, we characterize the sensor's sensitivity and dynamic range.

Torque-balanced vibrationless rotary coupling

DOEpatents

Miller, Donald M.

1980-01-01

This disclosure describes a torque-balanced vibrationless rotary coupling for transmitting rotary motion without unwanted vibration into the spindle of a machine tool. A drive member drives a driven member using flexible connecting loops which are connected tangentially and at diametrically opposite connecting points through a free floating ring.

Noncolocated Structural Vibration Suppression Using Zero Annihilation Periodic Control

NASA Technical Reports Server (NTRS)

Bayard, David S.; Boussalis, Dhemetrios

1993-01-01

The Zero Annihilation Periodic (ZAP) controller is applied to the problem of vibration control of a noncolocated flexible structure. It is shown that even though the transfer function is nonminimum-phase, a plant inverse controller can be designed which elicits a deadbeat closed-loop response.

Carbon Dioxide Control System for a Mars Space Suit Life Support System

NASA Technical Reports Server (NTRS)

Alptekin, Gokhan; Jayaraman, Ambalavanan; Copeland, Robert; Parker, Amanda; Paul, Heather L.

2011-01-01

Carbon dioxide (CO2) control during Extravehicular Activities (EVAs) on Mars will be challenging. Lithium hydroxide (LiOH) canisters have impractical logistics penalties, and regenerable metal oxide (MetOx) canisters weigh too much. Cycling bed systems and permeable membranes that are regenerable in space vacuum cannot vent on Mars due to the high partial pressure of CO2 in the atmosphere. Although sweep gas regeneration is under investigation, the feasibility, logistics penalties, and failure modes associated with this technique have not been fully determined. TDA Research, Inc. is developing a durable, high-capacity regenerable adsorbent that can remove CO2 from the space suit ventilation loop. The system design allows sorbent regeneration at or above 6 torr, eliminating the potential for Martian atmosphere to leak into the regeneration bed and into the ventilation loop. Regeneration during EVA minimizes the amount of consumables to be brought from Earth and makes the mission more affordable, while providing great operational flexibility during EVA. The feasibility of the concept has been demonstrated in a series of bench-scale experiments and a preliminary system analysis. This paper presents the latest results from these sorbent and system development efforts.

Cable shield connecting device

DOEpatents

Silva, Frank A.

1979-01-01

A cable shield connecting device for installation on a high voltage cable of the type having a metallic shield, the device including a relatively conformable, looped metal bar for placement around a bared portion of the metallic shield to extend circumferentially around a major portion of the circumference of the metallic shield while being spaced radially therefrom, a plurality of relatively flexible metallic fingers affixed to the bar, projecting from the bar in an axial direction and spaced circumferentially along the bar, each finger being attached to the metallic shield at a portion located remote from the bar to make electrical contact with the metallic shield, and a connecting conductor integral with the bar.

OpenGeoSys-GEMS: Hybrid parallelization of a reactive transport code with MPI and threads

NASA Astrophysics Data System (ADS)

Kosakowski, G.; Kulik, D. A.; Shao, H.

2012-04-01

OpenGeoSys-GEMS is a generic purpose reactive transport code based on the operator splitting approach. The code couples the Finite-Element groundwater flow and multi-species transport modules of the OpenGeoSys (OGS) project (http://www.ufz.de/index.php?en=18345) with the GEM-Selektor research package to model thermodynamic equilibrium of aquatic (geo)chemical systems utilizing the Gibbs Energy Minimization approach (http://gems.web.psi.ch/). The combination of OGS and the GEM-Selektor kernel (GEMS3K) is highly flexible due to the object-oriented modular code structures and the well defined (memory based) data exchange modules. Like other reactive transport codes, the practical applicability of OGS-GEMS is often hampered by the long calculation time and large memory requirements. • For realistic geochemical systems which might include dozens of mineral phases and several (non-ideal) solid solutions the time needed to solve the chemical system with GEMS3K may increase exceptionally. • The codes are coupled in a sequential non-iterative loop. In order to keep the accuracy, the time step size is restricted. In combination with a fine spatial discretization the time step size may become very small which increases calculation times drastically even for small 1D problems. • The current version of OGS is not optimized for memory use and the MPI version of OGS does not distribute data between nodes. Even for moderately small 2D problems the number of MPI processes that fit into memory of up-to-date workstations or HPC hardware is limited. One strategy to overcome the above mentioned restrictions of OGS-GEMS is to parallelize the coupled code. For OGS a parallelized version already exists. It is based on a domain decomposition method implemented with MPI and provides a parallel solver for fluid and mass transport processes. In the coupled code, after solving fluid flow and solute transport, geochemical calculations are done in form of a central loop over all finite element nodes with calls to GEMS3K and consecutive calculations of changed material parameters. In a first step the existing MPI implementation was utilized to parallelize this loop. Calculations were split between the MPI processes and afterwards data was synchronized by using MPI communication routines. Furthermore, multi-threaded calculation of the loop was implemented with help of the boost thread library (http://www.boost.org). This implementation provides a flexible environment to distribute calculations between several threads. For each MPI process at least one and up to several dozens of worker threads are spawned. These threads do not replicate the complete OGS-GEM data structure and use only a limited amount of memory. Calculation of the central geochemical loop is shared between all threads. Synchronization between the threads is done by barrier commands. The overall number of local threads times MPI processes should match the number of available computing nodes. The combination of multi-threading and MPI provides an effective and flexible environment to speed up OGS-GEMS calculations while limiting the required memory use. Test calculations on different hardware show that for certain types of applications tremendous speedups are possible.

Vibration control of a manipulator tip on a flexible body

NASA Technical Reports Server (NTRS)

Xu, J.; Bainum, P. M.; Li, F.

1992-01-01

Vibration control of a rigid manipulator tip on a main flexible uniform beam is examined. It is proposed to add a compensator between the manipulator and the beam to rotate and extend/retrieve the manipulator during the control period. The 2D station-keeping maneuvers within the linear range without gravity and damping are considered. The compensatory open-loop control law, which depends on the amplitudes of the beam's flexible deformations at the connection joint, is synthesized using linear quadratic regulator techniques. After introducing the compensatory control into the system, system control is still stable, and the tip coordinates of the manipulator can be made to closely follow the rigid beam motion, which is assumed to be a desired motion.

Robust output feedback stabilization for a flexible marine riser system.

PubMed

Zhao, Zhijia; Liu, Yu; Guo, Fang

2017-12-06

The aim of this paper is to develop a boundary control for the vibration reduction of a flexible marine riser system in the presence of parametric uncertainties and system states obtained inaccurately. To this end, an adaptive output feedback boundary control is proposed to suppress the riser's vibration fusing with observer-based backstepping, high-gain observers and robust adaptive control theory. In addition, the parameter adaptive laws are designed to compensate for the system parametric uncertainties, and the disturbance observer is introduced to mitigate the effects of external environmental disturbance. The uniformly bounded stability of the closed-loop system is achieved through rigorous Lyapunov analysis without any discretisation or simplification of the dynamics in the time and space, and the state observer error is ensured to exponentially converge to zero as time grows to infinity. In the end, the simulation and comparison studies are carried out to illustrate the performance of the proposed control under the proper choice of the design parameters. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Energy 101: Geothermal Heat Pumps

ScienceCinema

None

2018-02-13

An energy-efficient heating and cooling alternative, the geothermal heat pump system moves heat from the ground to a building (or from a building to the ground) through a series of flexible pipe "loops" containing water. This edition of Energy 101 explores the benefits Geothermal and the science behind how it all comes together.

Soft container for explosive nuts

NASA Technical Reports Server (NTRS)

Glenn, D. C.; Drummond, W. E.; Miller, G.

1981-01-01

Flexible fabric fits over variety of assembly shapes to contain debris produced by detonations or safety tests. Bag material is woven multifilament polyamide or aramid. Belt loops hold bag to clamp. Ring supports explosive nut structure and detonator wires, and after nut is mounted, bag and clamp are slipped over ring and fastened.

A Notional Battlespace for Simulating and Testing Dynamic Wireless Networks

DTIC Science & Technology

2006-06-01

communications. The system is built with single and multiple-beam antenn provide more flexible coverage than its predecessor. The single steerable dish ante...The network recognizes inbound commercial satellite transmissions to the platoon are successful and through the relay back to the A-10s, the loop is

Computational simulations assessment of mutations impact on streptokinase (SK) from a group G streptococci with enhanced activity - insights into the functional roles of structural dynamics flexibility of SK and stabilization of SK-μplasmin catalytic complex.

PubMed

Kazemi, Faegheh; Arab, Seyed Shahriar; Mohajel, Nasir; Keramati, Malihe; Niknam, Niloofar; Aslani, Mohammad Mehdi; Roohvand, Farzin

2018-05-28

Streptokinase (SK), a plasminogen activator (PA) that converts inactive plasminogen (Pg) to plasmin (Pm), is a protein secreted by groups A, C, and G streptococci (GAS, GCS, and GGS, respectively), with high sequence divergence and functional heterogeneity. While roles of some residual changes in altered SK functionality are shown, the underlying structural mechanisms are less known. Herein, using computational approaches, we analyzed the conformational basis for the increased activity of SK from a GGS (SKG132) isolate with four natural residual substitutions (Ile33Phe, Arg45Gln, Asn228Lys, Phe287Ile) compared to the standard GCS (SKC). Using the crystal structure of SK.Pm catalytic complex as main template SKC.μPm catalytic complex was modeled through homology modeling process and validated by several online validation servers. Subsequently, SKG132.μPm structure was constructed by altering the corresponding residual substitutions. Results of three independent MD simulations showed increased RMSF values for SKG132.μPm, indicating the enhanced structural flexibility compared to SKC.μPm, specially in 170 and 250 loops and three regions: R1 (149-161), R2 (182-215) and R3 (224-229). In parallel, the average number of Hydrogen bonds in 170 loop, R2 and R3 (especially for Asn228Lys) of SKG132 compared to that of the SKC was decreased. Accordingly, residue interaction networks (RINs) analyses indicated that Asn228Lys might induce more level of structural flexibility by generation of free Lys256, while Phe287Ile and Ile33Phe enhanced the stabilization of the SKG132.μPm catalytic complex. These results denoted the potential role of the optimal dynamic state and stabilized catalytic complex for increased PA potencies of SK as a thrombolytic drug.

Evaluating the role of coherent delocalized phonon-like modes in DNA cyclization

DOE PAGES

Alexandrov, Ludmil B.; Rasmussen, Kim Ø.; Bishop, Alan R.; ...

2017-08-29

The innate flexibility of a DNA sequence is quantified by the Jacobson-Stockmayer’s J-factor, which measures the propensity for DNA loop formation. Recent studies of ultra-short DNA sequences revealed a discrepancy of up to six orders of magnitude between experimentally measured and theoretically predicted J-factors. These large differences suggest that, in addition to the elastic moduli of the double helix, other factors contribute to loop formation. We develop a new theoretical model that explores how coherent delocalized phonon-like modes in DNA provide single-stranded ”flexible hinges” to assist in loop formation. We also combine the Czapla-Swigon-Olson structural model of DNA with ourmore » extended Peyrard-Bishop-Dauxois model and, without changing any of the parameters of the two models, apply this new computational framework to 86 experimentally characterized DNA sequences. Our results demonstrate that the new computational framework can predict J-factors within an order of magnitude of experimental measurements for most ultra-short DNA sequences, while continuing to accurately describe the J-factors of longer sequences. Furthermore, we demonstrate that our computational framework can be used to describe the cyclization of DNA sequences that contain a base pair mismatch. Overall, our results support the conclusion that coherent delocalized phonon-like modes play an important role in DNA cyclization.« less

Closed Loop Software Control of the MIDEX Power System

NASA Technical Reports Server (NTRS)

Castell, Karen; Hernandez-Pellerano, Amri; Wismer, Margaret

1998-01-01

The Microwave Anisotropy Probe (MAP) is a follow-on to the Differential Microwave Radiometer (DMR) instrument on the Cosmic Background Explorer (COBE) spacecraft. The design and analysis of the MAP attitude control system (ACS) have been refined since work previously reported. The full spacecraft and instrument flexible model was developed in NASTRAN, and the resulting flexible modes were plotted and reduced with the Modal Significance Analysis Package (MSAP). The reduced-order model was used to perform the linear stability analysis for each control mode, the results of which are presented in this paper. Although MAP is going to a relatively disturbance-free Lissajous orbit around the Earth-Sun L2 Lagrange point, a detailed disturbance-torque analysis is required because there are only a small number of opportunities for momentum unloading each year. Environmental torques, including solar pressure at L2, and aerodynamic and gravity gradient during phasing-loop orbits, were calculated and simulated. A simple model of fuel slosh was derived to model its effect on the motion of the spacecraft. In addition, a thruster mode linear impulse controller was developed to meet the accuracy requirements of the phasing loop burns. A dynamic attitude error limiter was added to improve the performance of the ACS during large attitude slews. The result of this analysis is a stable ACS subsystem that meets all of the mission's requirements.

Evaluating the role of coherent delocalized phonon-like modes in DNA cyclization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexandrov, Ludmil B.; Rasmussen, Kim Ø.; Bishop, Alan R.

The innate flexibility of a DNA sequence is quantified by the Jacobson-Stockmayer’s J-factor, which measures the propensity for DNA loop formation. Recent studies of ultra-short DNA sequences revealed a discrepancy of up to six orders of magnitude between experimentally measured and theoretically predicted J-factors. These large differences suggest that, in addition to the elastic moduli of the double helix, other factors contribute to loop formation. We develop a new theoretical model that explores how coherent delocalized phonon-like modes in DNA provide single-stranded ”flexible hinges” to assist in loop formation. We also combine the Czapla-Swigon-Olson structural model of DNA with ourmore » extended Peyrard-Bishop-Dauxois model and, without changing any of the parameters of the two models, apply this new computational framework to 86 experimentally characterized DNA sequences. Our results demonstrate that the new computational framework can predict J-factors within an order of magnitude of experimental measurements for most ultra-short DNA sequences, while continuing to accurately describe the J-factors of longer sequences. Furthermore, we demonstrate that our computational framework can be used to describe the cyclization of DNA sequences that contain a base pair mismatch. Overall, our results support the conclusion that coherent delocalized phonon-like modes play an important role in DNA cyclization.« less

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

PubMed Central

Ramanathan, Arvind; Agarwal, Pratul K.

2011-01-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design. PMID:22087074

Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis.

PubMed

Ramanathan, Arvind; Agarwal, Pratul K

2011-11-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme-substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme-substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.

Takagi-Sugeno fuzzy model based robust dissipative control for uncertain flexible spacecraft with saturated time-delay input.

PubMed

Xu, Shidong; Sun, Guanghui; Sun, Weichao

2017-01-01

In this paper, the problem of robust dissipative control is investigated for uncertain flexible spacecraft based on Takagi-Sugeno (T-S) fuzzy model with saturated time-delay input. Different from most existing strategies, T-S fuzzy approximation approach is used to model the nonlinear dynamics of flexible spacecraft. Simultaneously, the physical constraints of system, like input delay, input saturation, and parameter uncertainties, are also taken care of in the fuzzy model. By employing Lyapunov-Krasovskii method and convex optimization technique, a novel robust controller is proposed to implement rest-to-rest attitude maneuver for flexible spacecraft, and the guaranteed dissipative performance enables the uncertain closed-loop system to reject the influence of elastic vibrations and external disturbances. Finally, an illustrative design example integrated with simulation results are provided to confirm the applicability and merits of the developed control strategy. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Structural and functional characterization of methicillin-resistant Staphylococcus aureus’s class IIb fructose 1,6-bisphosphate aldolase

DOE PAGES

Capodagli, Glenn C.; Lee, Stephen A.; Boehm, Kyle J.; ...

2014-11-12

Staphylococcus aureus is one of the most common nosocomial sources of soft-tissue and skin infections and has more recently become prevalent in the community setting as well. Since the use of penicillins to combat S. aureus infections in the 1940s, the bacterium has been notorious for developing resistances to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). With the persistence of MRSA as well as many other drug resistant bacteria and parasites, there is a growing need to focus on new pharmacological targets. Recently, class II fructose 1,6-bisphosphate aldolases (FBAs) have garnered attention to fill this role. Regrettably, scarce biochemical datamore » and no structural data are currently available for the class II FBA found in MRSA (SaFBA). With the recent finding of a flexible active site zinc-binding loop (Z-Loop) in class IIa FBAs and its potential for broad spectrum class II FBA inhibition, the lack of information regarding this feature of class IIb FBAs, such as SaFBA, has been limiting for further Z-loop inhibitor development. Therefore, we elucidated the crystal structure of SaFBA to 2.1 Å allowing for a more direct structural analysis of SaFBA. Furthermore, we determined the KM for one of SaFBA’s substrates, fructose 1,6-bisphosphate, as well as performed mode of inhibition studies for an inhibitor that takes advantage of the Z-loop’s flexibility. Altogether the data offers insight into a class IIb FBA from a pervasively drug resistant bacterium and a comparison of Z-loops and other features between the different subtypes of class II FBAs.« less

Multiple substitutions lead to increased loop flexibility and expanded specificity in Acinetobacter baumannii carbapenemase OXA-239.

PubMed

Harper, Thomas M; June, Cynthia M; Taracila, Magdalena A; Bonomo, Robert A; Powers, Rachel A; Leonard, David A

2018-01-11

OXA-239 is a class D carbapenemase isolated from an Acinetobacter baumannii strain found in Mexico. This enzyme is a variant of OXA-23 with three amino acid substitutions in or near the active site. These substitutions cause OXA-239 to hydrolyze late-generation cephalosporins and the monobactam aztreonam with greater efficiency than OXA-23. OXA-239 activity against the carbapenems doripenem and imipenem is reduced ∼3-fold and 20-fold, respectively. Further analysis demonstrated that two of the substitutions (P225S and D222N) are largely responsible for the observed alteration of kinetic parameters, while the third (S109L) may serve to stabilize the protein. Structures of OXA-239 with cefotaxime, doripenem and imipenem bound as acyl-intermediates were determined. These structures reveal that OXA-239 has increased flexibility in a loop that contains P225S and D222N. When carbapenems are bound, the conformation of this loop is essentially identical with that observed previously for OXA-23, with a narrow active site that makes extensive contacts to the ligand. When cefotaxime is bound, the loop can adopt a different conformation that widens the active site to allow binding of that bulky drug. This alternate conformation is made possible by P225S and further stabilized by D222N. Taken together, these results suggest that the three substitutions were selected to expand the substrate specificity profile of OXA-23 to cephalosporins and monobactams. The loss of activity against imipenem, however, suggests that there may be limits to the plasticity of class D enzymes with regard to evolving active sites that can effectively bind multiple classes of β-lactam drugs. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Structural and functional characterization of methicillin-resistant Staphylococcus aureus’s class IIb fructose 1,6-bisphosphate aldolase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capodagli, Glenn C.; Lee, Stephen A.; Boehm, Kyle J.

Staphylococcus aureus is one of the most common nosocomial sources of soft-tissue and skin infections and has more recently become prevalent in the community setting as well. Since the use of penicillins to combat S. aureus infections in the 1940s, the bacterium has been notorious for developing resistances to antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA). With the persistence of MRSA as well as many other drug resistant bacteria and parasites, there is a growing need to focus on new pharmacological targets. Recently, class II fructose 1,6-bisphosphate aldolases (FBAs) have garnered attention to fill this role. Regrettably, scarce biochemical datamore » and no structural data are currently available for the class II FBA found in MRSA (SaFBA). With the recent finding of a flexible active site zinc-binding loop (Z-Loop) in class IIa FBAs and its potential for broad spectrum class II FBA inhibition, the lack of information regarding this feature of class IIb FBAs, such as SaFBA, has been limiting for further Z-loop inhibitor development. Therefore, we elucidated the crystal structure of SaFBA to 2.1 Å allowing for a more direct structural analysis of SaFBA. Furthermore, we determined the KM for one of SaFBA’s substrates, fructose 1,6-bisphosphate, as well as performed mode of inhibition studies for an inhibitor that takes advantage of the Z-loop’s flexibility. Altogether the data offers insight into a class IIb FBA from a pervasively drug resistant bacterium and a comparison of Z-loops and other features between the different subtypes of class II FBAs.« less

Dynamics of knotted flexible loops settling under a constant force in a viscous fluid

NASA Astrophysics Data System (ADS)

Gruziel, Magdalena; Thyagarajan, Krishnan; Dietler, Giovanni; Szymczak, Piotr; Ekiel-Jezewska, Maria

2017-11-01

Sedimenting chains of metal beads knotted to a topology of a torus knot tend to stabilize in the form of extended, flat, tightly interwound loops. In this configuration they perform an oscillatory motion of the loops swirling periodically around each other. Stokesian dynamics simulations of elastic fibers confirm the long-lasting character of the traveling wave-like swirling motion and show also the accompanying rotation of the system. Moreover, the periodic motion shows striking resemblance to the stable solutions for the evolution of vortices of torus knot topology. Using the results of the simulations we study the dependence of the frequencies and sedimentation velocities on the length of the fiber. We also notice the dependence of the knot dynamics on the bending stiffness of the fiber and the knot rank. NCN-2015/19/D/ST8/03199.

SpalLoop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabau, Adrian; Wright, Ian

Boiler tubes in steam power plants experience tube blockages due to exfoliation of oxide grown on the inner side of the tubes. In extreme cases, significant tube blockages can lead to forced power plant outages. It is thus desired to predict through modeling the amount of tube blockage in order to inform power plant operators of possible forced outages. SpalLoop solves for the stress-strain equations in an axisymmetric geometry, tracking the stress/strain evolution during boiler operation including outages for the entire boiler tube length. At each operational outage, i.e., temperature excursions down to room temperature, the amount of exfoliated areamore » for the entire tube loop is estimated the amount of tube blockage is predicted based assumed blockage geometry and site. The SpaLLoop code contains modules developed for oxide growth, stress analysis, tube loop geometry, blockage area by taking into account the following phenomena and features, (a) Plant operation schedule with periodic alternate full-load and partial-load regimes and shut-downs, i.e., temperature excursions from high-load to room temperature, (b) axisymmetric formulation for cylindrical tubes, (c) oxide growth in a temperature gradient with multiple oxide layers, (d) geometry of a boiler tube with a single tube loop or two tube loops, (e) temperature variation along the tube length based on hot gas temperature distribution outside the tube and inlet steam temperature, (f) non-uniform oxide growth along the tube length according to the local steam tube temperature, (g) exfoliated area module: at each operational outage considered, the amount of exfoliated area and exfoliated volume along the tube is estimated, (h) blockage module: at each operational outage considered, the exfoliated volume/mass for each tube loop is estimated from which the amount of tube blockage is predicted based on given blockage geometry (length, location, and geometry). The computer program is written in FORTRAN90. Its modular structure was sought for allowing the best flexibility in updating the program by implementing new constitutive equations due to availability of new material property data and/or new physical phenomena.« less

HEPMath 1.4: A mathematica package for semi-automatic computations in high energy physics

NASA Astrophysics Data System (ADS)

Wiebusch, Martin

2015-10-01

This article introduces the Mathematica package HEPMath which provides a number of utilities and algorithms for High Energy Physics computations in Mathematica. Its functionality is similar to packages like FormCalc or FeynCalc, but it takes a more complete and extensible approach to implementing common High Energy Physics notations in the Mathematica language, in particular those related to tensors and index contractions. It also provides a more flexible method for the generation of numerical code which is based on new features for C code generation in Mathematica. In particular it can automatically generate Python extension modules which make the compiled functions callable from Python, thus eliminating the need to write any code in a low-level language like C or Fortran. It also contains seamless interfaces to LHAPDF, FeynArts, and LoopTools.

Mapping the Ca(2+) induced structural change in calreticulin.

PubMed

Boelt, Sanne Grundvad; Norn, Christoffer; Rasmussen, Morten Ib; André, Ingemar; Čiplys, Evaldas; Slibinskas, Rimantas; Houen, Gunnar; Højrup, Peter

2016-06-16

Calreticulin is a highly conserved multifunctional protein implicated in many different biological systems and has therefore been the subject of intensive research. It is primarily present in the endoplasmatic reticulum where its main functions are to regulate Ca(2+) homeostasis, act as a chaperone and stabilize the MHC class I peptide-loading complex. Although several high-resolution structures of calreticulin exist, these only cover three-quarters of the entire protein leaving the extended structures unsolved. Additionally, the structure of calreticulin is influenced by the presence of Ca(2+). The conformational changes induced by Ca(2+) have not been determined yet as they are hard to study with traditional approaches. Here, we investigated the Ca(2+)-induced conformational changes with a combination of chemical cross-linking, mass spectrometry, bioinformatics analysis and modelling in Rosetta. Using a bifunctional linker, we found a large Ca(2+)-induced change to the cross-linking pattern in calreticulin. Our results are consistent with a high flexibility in the P-loop, a stabilization of the acidic C-terminal and a relatively close interaction of the P-loop and the acidic C-terminal. The function of calreticulin, an endoplasmatic reticulin chaperone, is affected by fluctuations in Ca(2+)concentration, but the structural mechanism is unknown. The present work suggests that Ca(2+)-dependent regulation is caused by different conformations of a long proline-rich loop that changes the accessibility to the peptide/lectin-binding site. Our results indicate that the binding of Ca(2+) to calreticulin may thus not only just be a question of Ca(2+) storage but is likely to have an impact on the chaperone activity. Copyright © 2016 Elsevier B.V. All rights reserved.

High heat flux loop heat pipes

NASA Astrophysics Data System (ADS)

North, Mark T.; Sarraf, David B.; Rosenfeld, John H.; Maidanik, Yuri F.; Vershinin, Sergey

1997-01-01

Loop Heat Pipes (LHPs) can transport very large thermal power loads, over long distances, through flexible, small diameter tubes and against high gravitational heads. While recent LHPs have transported as much as 1500 W, the peak heat flux through a LHP's evaporator has been limited to about 0.07 MW/m2. This limitation is due to the arrangement of vapor passages next to the heat load which is one of the conditions necessary to ensure self priming of the device. This paper describes work aimed at raising this limit by threefold to tenfold. Two approaches were pursued. One optimized the vapor passage geometry for the high heat flux conditions. The geometry improved the heat flow into the wick and working fluid. This approach also employed a finer pored wick to support higher vapor flow losses. The second approach used a bidisperse wick material within the circumferential vapor passages. The bidisperse material increased the thermal conductivity and the evaporative surface area in the region of highest heat flux, while providing a flow path for the vapor. Proof-of-concept devices were fabricated and tested for each approach. Both devices operated as designed and both demonstrated operation at a heat flux of 0.70 MW/m2. This performance exceeded the known state of the art by a factor of more than six for both conventional heat pipes and for loop heat pipes using ammonia. In addition, the bidisperse-wick device demonstrated boiling heat transfer coefficients up to 100,000 W/m2.K, and the fine pored device demonstrated an orientation independence with its performance essentially unaffected by whether its evaporator was positioned above, below or level with the condenser.

The interaction between the yeast telomerase RNA and the Est1 protein requires three structural elements.

PubMed

Lubin, Johnathan W; Tucey, Timothy M; Lundblad, Victoria

2012-09-01

In the budding yeast Saccharomyces cerevisiae, the telomerase enzyme is composed of a 1.3-kb TLC1 RNA that forms a complex with Est2 (the catalytic subunit) and two regulatory proteins, Est1 and Est3. Previous work has identified a conserved 5-nt bulge, present in a long helical arm of TLC1, which mediates binding of Est1 to TLC1. However, increased expression of Est1 can bypass the consequences of removal of this RNA bulge, indicating that there are additional binding site(s) for Est1 on TLC1. We report here that a conserved single-stranded internal loop immediately adjacent to the bulge is also required for the Est1-RNA interaction; furthermore, a TLC1 variant that lacks this internal loop but retains the bulge cannot be suppressed by Est1 overexpression, arguing that the internal loop may be a more critical element for Est1 binding. An additional structural feature consisting of a single-stranded region at the base of the helix containing the bulge and internal loop also contributes to recognition of TLC1 by Est1, potentially by providing flexibility to this helical arm. Association of Est1 with each of these TLC1 motifs was assessed using a highly sensitive biochemical assay that simultaneously monitors the relative levels of the Est1 and Est2 proteins in the telomerase complex. The identification of three elements of TLC1 that are required for Est1 association provides a detailed view of this particular protein-RNA interaction.

A vision-based end-point control for a two-link flexible manipulator. M.S. Thesis

NASA Technical Reports Server (NTRS)

Obergfell, Klaus

1991-01-01

The measurement and control of the end-effector position of a large two-link flexible manipulator are investigated. The system implementation is described and an initial algorithm for static end-point positioning is discussed. Most existing robots are controlled through independent joint controllers, while the end-effector position is estimated from the joint positions using a kinematic relation. End-point position feedback can be used to compensate for uncertainty and structural deflections. Such feedback is especially important for flexible robots. Computer vision is utilized to obtain end-point position measurements. A look-and-move control structure alleviates the disadvantages of the slow and variable computer vision sampling frequency. This control structure consists of an inner joint-based loop and an outer vision-based loop. A static positioning algorithm was implemented and experimentally verified. This algorithm utilizes the manipulator Jacobian to transform a tip position error to a joint error. The joint error is then used to give a new reference input to the joint controller. The convergence of the algorithm is demonstrated experimentally under payload variation. A Landmark Tracking System (Dickerson, et al 1990) is used for vision-based end-point measurements. This system was modified and tested. A real-time control system was implemented on a PC and interfaced with the vision system and the robot.

Development Specification for the Portable Life Support System (PLSS) Thermal Loop Pump

NASA Technical Reports Server (NTRS)

Anchondo, Ian; Campbell, Colin

2017-01-01

The AEMU Thermal Loop Pump Development Specification establishes the requirements for design, performance, and testing of the Water Pump as part of the Thermal System of the Advanced Portable Life Support System (PLSS). It is envisioned that the Thermal Loop Pump is a positive displacement pump that provides a repeatable volume of flow against a given range of back-pressures provided by the various applications. The intention is to operate the pump at a fixed speed for the given application. The primary system is made up of two identical and redundant pumps of which only one is in operation at given time. The Auxiliary Loop Pump is an identical pump design to the primary pumps but is operated at half the flow rate. Inlet positive pressure to the pumps is provided by the upstream Flexible Supply Assembly (FSA-431 and FSA-531) which are physically located inside the suit volume and pressurized by suit pressure. An integrated relief valve, placed in parallel to the pump's inlet and outlet protects the pump and loop from over-pressurization. An integrated course filter is placed upstream of the pump's inlet to provide filtration and prevent potential debris from damaging the pump.

Organic printed photonics: From microring lasers to integrated circuits

PubMed Central

Zhang, Chuang; Zou, Chang-Ling; Zhao, Yan; Dong, Chun-Hua; Wei, Cong; Wang, Hanlin; Liu, Yunqi; Guo, Guang-Can; Yao, Jiannian; Zhao, Yong Sheng

2015-01-01

A photonic integrated circuit (PIC) is the optical analogy of an electronic loop in which photons are signal carriers with high transport speed and parallel processing capability. Besides the most frequently demonstrated silicon-based circuits, PICs require a variety of materials for light generation, processing, modulation, and detection. With their diversity and flexibility, organic molecular materials provide an alternative platform for photonics; however, the versatile fabrication of organic integrated circuits with the desired photonic performance remains a big challenge. The rapid development of flexible electronics has shown that a solution printing technique has considerable potential for the large-scale fabrication and integration of microsized/nanosized devices. We propose the idea of soft photonics and demonstrate the function-directed fabrication of high-quality organic photonic devices and circuits. We prepared size-tunable and reproducible polymer microring resonators on a wafer-scale transparent and flexible chip using a solution printing technique. The printed optical resonator showed a quality (Q) factor higher than 4 × 105, which is comparable to that of silicon-based resonators. The high material compatibility of this printed photonic chip enabled us to realize low-threshold microlasers by doping organic functional molecules into a typical photonic device. On an identical chip, this construction strategy allowed us to design a complex assembly of one-dimensional waveguide and resonator components for light signal filtering and optical storage toward the large-scale on-chip integration of microscopic photonic units. Thus, we have developed a scheme for soft photonic integration that may motivate further studies on organic photonic materials and devices. PMID:26601256

Organic printed photonics: From microring lasers to integrated circuits.

PubMed

Zhang, Chuang; Zou, Chang-Ling; Zhao, Yan; Dong, Chun-Hua; Wei, Cong; Wang, Hanlin; Liu, Yunqi; Guo, Guang-Can; Yao, Jiannian; Zhao, Yong Sheng

2015-09-01

A photonic integrated circuit (PIC) is the optical analogy of an electronic loop in which photons are signal carriers with high transport speed and parallel processing capability. Besides the most frequently demonstrated silicon-based circuits, PICs require a variety of materials for light generation, processing, modulation, and detection. With their diversity and flexibility, organic molecular materials provide an alternative platform for photonics; however, the versatile fabrication of organic integrated circuits with the desired photonic performance remains a big challenge. The rapid development of flexible electronics has shown that a solution printing technique has considerable potential for the large-scale fabrication and integration of microsized/nanosized devices. We propose the idea of soft photonics and demonstrate the function-directed fabrication of high-quality organic photonic devices and circuits. We prepared size-tunable and reproducible polymer microring resonators on a wafer-scale transparent and flexible chip using a solution printing technique. The printed optical resonator showed a quality (Q) factor higher than 4 × 10(5), which is comparable to that of silicon-based resonators. The high material compatibility of this printed photonic chip enabled us to realize low-threshold microlasers by doping organic functional molecules into a typical photonic device. On an identical chip, this construction strategy allowed us to design a complex assembly of one-dimensional waveguide and resonator components for light signal filtering and optical storage toward the large-scale on-chip integration of microscopic photonic units. Thus, we have developed a scheme for soft photonic integration that may motivate further studies on organic photonic materials and devices.

Flexible Environments for Grand-Challenge Simulation in Climate Science

NASA Astrophysics Data System (ADS)

Pierrehumbert, R.; Tobis, M.; Lin, J.; Dieterich, C.; Caballero, R.

2004-12-01

Current climate models are monolithic codes, generally in Fortran, aimed at high-performance simulation of the modern climate. Though they adequately serve their designated purpose, they present major barriers to application in other problems. Tailoring them to paleoclimate of planetary simulations, for instance, takes months of work. Theoretical studies, where one may want to remove selected processes or break feedback loops, are similarly hindered. Further, current climate models are of little value in education, since the implementation of textbook concepts and equations in the code is obscured by technical detail. The Climate Systems Center at the University of Chicago seeks to overcome these limitations by bringing modern object-oriented design into the business of climate modeling. Our ultimate goal is to produce an end-to-end modeling environment capable of configuring anything from a simple single-column radiative-convective model to a full 3-D coupled climate model using a uniform, flexible interface. Technically, the modeling environment is implemented as a Python-based software component toolkit: key number-crunching procedures are implemented as discrete, compiled-language components 'glued' together and co-ordinated by Python, combining the high performance of compiled languages and the flexibility and extensibility of Python. We are incrementally working towards this final objective following a series of distinct, complementary lines. We will present an overview of these activities, including PyOM, a Python-based finite-difference ocean model allowing run-time selection of different Arakawa grids and physical parameterizations; CliMT, an atmospheric modeling toolkit providing a library of 'legacy' radiative, convective and dynamical modules which can be knitted into dynamical models, and PyCCSM, a version of NCAR's Community Climate System Model in which the coupler and run-control architecture are re-implemented in Python, augmenting its flexibility and adaptability.

Structural domains and main-chain flexibility in prion proteins.

PubMed

Blinov, N; Berjanskii, M; Wishart, D S; Stepanova, M

2009-02-24

In this study we describe a novel approach to define structural domains and to characterize the local flexibility in both human and chicken prion proteins. The approach we use is based on a comprehensive theory of collective dynamics in proteins that was recently developed. This method determines the essential collective coordinates, which can be found from molecular dynamics trajectories via principal component analysis. Under this particular framework, we are able to identify the domains where atoms move coherently while at the same time to determine the local main-chain flexibility for each residue. We have verified this approach by comparing our results for the predicted dynamic domain systems with the computed main-chain flexibility profiles and the NMR-derived random coil indexes for human and chicken prion proteins. The three sets of data show excellent agreement. Additionally, we demonstrate that the dynamic domains calculated in this fashion provide a highly sensitive measure of protein collective structure and dynamics. Furthermore, such an analysis is capable of revealing structural and dynamic properties of proteins that are inaccessible to the conventional assessment of secondary structure. Using the collective dynamic simulation approach described here along with a high-temperature simulations of unfolding of human prion protein, we have explored whether locations of relatively low stability could be identified where the unfolding process could potentially be facilitated. According to our analysis, the locations of relatively low stability may be associated with the beta-sheet formed by strands S1 and S2 and the adjacent loops, whereas helix HC appears to be a relatively stable part of the protein. We suggest that this kind of structural analysis may provide a useful background for a more quantitative assessment of potential routes of spontaneous misfolding in prion proteins.

Solution NMR Structures of Pyrenophora tritici-repentis ToxB and Its Inactive Homolog Reveal Potential Determinants of Toxin Activity*

PubMed Central

Nyarko, Afua; Singarapu, Kiran K.; Figueroa, Melania; Manning, Viola A.; Pandelova, Iovanna; Wolpert, Thomas J.; Ciuffetti, Lynda M.; Barbar, Elisar

2014-01-01

Pyrenophora tritici-repentis Ptr ToxB (ToxB) is a proteinaceous host-selective toxin produced by Pyrenophora tritici-repentis (P. tritici-repentis), a plant pathogenic fungus that causes the disease tan spot of wheat. One feature that distinguishes ToxB from other host-selective toxins is that it has naturally occurring homologs in non-pathogenic P. tritici-repentis isolates that lack toxic activity. There are no high-resolution structures for any of the ToxB homologs, or for any protein with >30% sequence identity, and therefore what underlies activity remains an open question. Here, we present the NMR structures of ToxB and its inactive homolog Ptr toxb. Both proteins adopt a β-sandwich fold comprising three strands in each half that are bridged together by two disulfide bonds. The inactive toxb, however, shows higher flexibility localized to the sequence-divergent β-sandwich half. The absence of toxic activity is attributed to a more open structure in the vicinity of one disulfide bond, higher flexibility, and residue differences in an exposed loop that likely impacts interaction with putative targets. We propose that activity is regulated by perturbations in a putative active site loop and changes in dynamics distant from the site of activity. Interestingly, the new structures identify AvrPiz-t, a secreted avirulence protein produced by the rice blast fungus, as a structural homolog to ToxB. This homology suggests that fungal proteins involved in either disease susceptibility such as ToxB or resistance such as AvrPiz-t may have a common evolutionary origin. PMID:25063993

Effect of chain stiffness on the structure of single-chain polymer nanoparticles

NASA Astrophysics Data System (ADS)

Moreno, Angel J.; Bacova, Petra; Lo Verso, Federica; Arbe, Arantxa; Colmenero, Juan; Pomposo, José A.

2018-01-01

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by purely intramolecular cross-linking of single polymer chains. By means of computer simulations, we investigate the conformational properties of SCNPs as a function of the bending stiffness of their linear polymer precursors. We investigate a broad range of characteristic ratios from the fully flexible case to those typical of bulky synthetic polymers. Increasing stiffness hinders bonding of groups separated by short contour distances and increases looping over longer distances, leading to more compact nanoparticles with a structure of highly interconnected loops. This feature is reflected in a crossover in the scaling behaviour of several structural observables. The scaling exponents change from those characteristic for Gaussian chains or rings in θ-solvents in the fully flexible limit, to values resembling fractal or ‘crumpled’ globular behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are weakly deformable regions that can be seen as disordered analogues of domains in disordered proteins. Increasing stiffness leads to bigger and less deformable domains. Surprisingly, the scaling behaviour of the domains is in all cases similar to that of Gaussian chains or rings, irrespective of the stiffness and degree of cross-linking. It is the spatial arrangement of the domains which determines the global structure of the SCNP (sparse Gaussian-like object or crumpled globule). Since intramolecular stiffness can be varied through the specific chemistry of the precursor or by introducing bulky side groups in its backbone, our results propose a new strategy to tune the global structure of SCNPs.

An E-Learning Environment for Algorithmic: Toward an Active Construction of Skills

ERIC Educational Resources Information Center

Babori, Abdelghani; Fassi, Hicham Fihri; Hariri, Abdellah; Bideq, Mustapha

2016-01-01

Assimilating an algorithmic course is a persistent problem for many undergraduate students. The major problem faced by students is the lack of problem solving ability and flexibility. Therefore, students are generally passive, unmotivated and unable to mobilize all the acquired knowledge (loops, test, variables, etc.) to deal with new encountered…

Assessment and Innovation: One Darn Thing Leads to Another

ERIC Educational Resources Information Center

Rutz, Carol; Lauer-Glebov, Jacqulyn

2005-01-01

Using recent experience at Carleton College in Minnesota as a case history, the authors offer a model for assessment that provides more flexibility than the well-known assessment feedback loop, which assumes a linear progression within a hierarchical administrative structure. The proposed model is based on a double helix, with values and feedback…

Simultaneous structural and control optimization via linear quadratic regulator eigenstructure assignment

NASA Technical Reports Server (NTRS)

Becus, G. A.; Lui, C. Y.; Venkayya, V. B.; Tischler, V. A.

1987-01-01

A method for simultaneous structural and control design of large flexible space structures (LFSS) to reduce vibration generated by disturbances is presented. Desired natural frequencies and damping ratios for the closed loop system are achieved by using a combination of linear quadratic regulator (LQR) synthesis and numerical optimization techniques. The state and control weighing matrices (Q and R) are expressed in terms of structural parameters such as mass and stiffness. The design parameters are selected by numerical optimization so as to minimize the weight of the structure and to achieve the desired closed-loop eigenvalues. An illustrative example of the design of a two bar truss is presented.

Robust Assignment Of Eigensystems For Flexible Structures

NASA Technical Reports Server (NTRS)

Juang, Jer-Nan; Lim, Kyong B.; Junkins, John L.

1992-01-01

Improved method for placement of eigenvalues and eigenvectors of closed-loop control system by use of either state or output feedback. Applied to reduced-order finite-element mathematical model of NASA's MAST truss beam structure. Model represents deployer/retractor assembly, inertial properties of Space Shuttle, and rigid platforms for allocation of sensors and actuators. Algorithm formulated in real arithmetic for efficient implementation. Choice of open-loop eigenvector matrix and its closest unitary matrix believed suitable for generating well-conditioned eigensystem with small control gains. Implication of this approach is that element of iterative search for "optimal" unitary matrix appears unnecessary in practice for many test problems.

Spatial operator algebra framework for multibody system dynamics

NASA Technical Reports Server (NTRS)

Rodriguez, G.; Jain, Abhinandan; Kreutz, K.

1989-01-01

The Spatial Operator Algebra framework for the dynamics of general multibody systems is described. The use of a spatial operator-based methodology permits the formulation of the dynamical equations of motion of multibody systems in a concise and systematic way. The dynamical equations of progressively more complex grid multibody systems are developed in an evolutionary manner beginning with a serial chain system, followed by a tree topology system and finally, systems with arbitrary closed loops. Operator factorizations and identities are used to develop novel recursive algorithms for the forward dynamics of systems with closed loops. Extensions required to deal with flexible elements are also discussed.

Spatial Operator Algebra for multibody system dynamics

NASA Technical Reports Server (NTRS)

Rodriguez, G.; Jain, A.; Kreutz-Delgado, K.

1992-01-01

The Spatial Operator Algebra framework for the dynamics of general multibody systems is described. The use of a spatial operator-based methodology permits the formulation of the dynamical equations of motion of multibody systems in a concise and systematic way. The dynamical equations of progressively more complex grid multibody systems are developed in an evolutionary manner beginning with a serial chain system, followed by a tree topology system and finally, systems with arbitrary closed loops. Operator factorizations and identities are used to develop novel recursive algorithms for the forward dynamics of systems with closed loops. Extensions required to deal with flexible elements are also discussed.

A continuum model for dynamic analysis of the Space Station

NASA Technical Reports Server (NTRS)

Thomas, Segun

1989-01-01

Dynamic analysis of the International Space Station using MSC/NASTRAN had 1312 rod elements, 62 beam elements, 489 nodes and 1473 dynamic degrees of freedom. A realtime, man-in-the-loop simulation of such a model is impractical. This paper discusses the mathematical model for realtime dynamic simulation of the Space Station. Several key questions in structures and structural dynamics are addressed. First, to achieve a significant reduction in the number of dynamic degrees of freedom, a continuum equivalent representation of the Space Station truss structure which accounted for the unsymmetry of the basic configuration and resulted in the coupling of extensional and transverse deformation, is developed. Next, dynamic equations for the continuum equivalent of the Space Station truss structure are formulated using a matrix version of Kane's dynamical equations. Flexibility is accounted for by using a theory that accommodates extension, bending in two principal planes and shear displacement. Finally, constraint equations suitable for dynamic analysis of flexible bodies with closed loop configuration are developed and solution of the resulting system of equations is based on the zero eigenvalue theorem.

Insights into substrate binding and catalysis in bacterial type I dehydroquinase.

PubMed

Maneiro, María; Peón, Antonio; Lence, Emilio; Otero, José M; Van Raaij, Mark J; Thompson, Paul; Hawkins, Alastair R; González-Bello, Concepción

2014-09-15

Structural, biochemical and computational studies to study substrate binding and the role of the conserved residues of the DHQ1 (type I dehydroquinase) enzyme active site are reported in the present paper. The crystal structure of DHQ1 from Salmonella typhi in complex with (2R)-2-methyl-3-dehydroquinic acid, a substrate analogue, was solved at 1.5 Å. The present study reveals a previously unknown key role for conserved Glu46, Phe145 and Met205 and Gln236, Pro234 and Ala233 residues, with the latter three being located in the flexible substrate-covering loop. Gln236 was shown to be responsible for the folding of this loop and for the dramatic reduction of its flexibility, which triggers active site closure. Glu46 was found to be key in bringing the substrate close to the lysine/histidine catalytic pocket to initiate catalysis. The present study could be useful in the rational design of inhibitors of this challenging and recognized target for the development of novel herbicides and antimicrobial agents.

The C-terminal priming domain is strongly associated with the main body of bacteriophage ϕ6 RNA-dependent RNA polymerase.

PubMed

Sarin, L Peter; Wright, Sam; Chen, Qing; Degerth, Linda H; Stuart, David I; Grimes, Jonathan M; Bamford, Dennis H; Poranen, Minna M

2012-10-10

Double-stranded RNA viruses encode a single protein species containing RNA-dependent RNA polymerase (RdRP) motifs. This protein is responsible for RNA transcription and replication. The architecture of viral RdRPs resembles that of a cupped right hand with fingers, palm and thumb domains. Those using de novo initiation have a flexible structural elaboration that constitutes the priming platform. Here we investigate the properties of the C-terminal priming domain of bacteriophage ϕ6 to get insights into the role of an extended loop connecting this domain to the main body of the polymerase. Proteolyzed ϕ6 RdRP that possesses a nick in the hinge region of this loop was better suited for de novo initiation. The clipped C-terminus remained associated with the main body of the polymerase via the anchor helix. The structurally flexible hinge region appeared to be involved in the control of priming platform movement. Moreover, we detected abortive initiation products for a bacteriophage RdRP. Copyright © 2012 Elsevier Inc. All rights reserved.

Packing loops into annular cavities.

PubMed

Sobral, T A; Gomes, M A F

2017-02-01

The continuous packing of a flexible rod in two-dimensional cavities yields a countable set of interacting domains that resembles nonequilibrium cellular systems and belongs to a new class of lightweight material. However, the link between the length of the rod and the number of domains requires investigation, especially in the case of non-simply connected cavities, where the number of avoided regions emulates an effective topological temperature. In the present article we report the results of an experiment of injection of a single flexible rod into annular cavities in order to find the total length needed to insert a given number of loops (domains of one vertex). Using an exponential model to describe the experimental data we quite minutely analyze the initial conditions, the intermediary behavior, and the tight packing limit. This method allows the observation of a new fluctuation phenomenon associated with instabilities in the dynamic evolution of the packing process. Furthermore, the fractal dimension of the global pattern enters the discussion under a novel point of view. A comparison with the classical problems of the random close packing of disks and jammed disk packings is made.

Packing loops into annular cavities

NASA Astrophysics Data System (ADS)

Sobral, T. A.; Gomes, M. A. F.

2017-02-01

The continuous packing of a flexible rod in two-dimensional cavities yields a countable set of interacting domains that resembles nonequilibrium cellular systems and belongs to a new class of lightweight material. However, the link between the length of the rod and the number of domains requires investigation, especially in the case of non-simply connected cavities, where the number of avoided regions emulates an effective topological temperature. In the present article we report the results of an experiment of injection of a single flexible rod into annular cavities in order to find the total length needed to insert a given number of loops (domains of one vertex). Using an exponential model to describe the experimental data we quite minutely analyze the initial conditions, the intermediary behavior, and the tight packing limit. This method allows the observation of a new fluctuation phenomenon associated with instabilities in the dynamic evolution of the packing process. Furthermore, the fractal dimension of the global pattern enters the discussion under a novel point of view. A comparison with the classical problems of the random close packing of disks and jammed disk packings is made.

Managing Demand and Capacity Using Multi-Sector Planning and Flexible Airspace: Human-in-the-Loop Evaluation of NextGen

NASA Technical Reports Server (NTRS)

Lee, Paul U.; Smith, Nancy M.; Prevot, Thomas; Homola, Jeffrey R.

2010-01-01

When demand for an airspace sector exceeds capacity, the balance can be re-established by reducing the demand, increasing the capacity, or both. The Multi-Sector Planner (MSP) concept has been proposed to better manage traffic demand by modifying trajectories across multiple sectors. A complementary approach to MSP, called Flexible Airspace Management (FAM), reconfigures the airspace such that capacity can be reallocated dynamically to balance the traffic demand across multiple sectors, resulting in fewer traffic management initiatives. The two concepts have been evaluated with a series of human-in-the-loop simulations at the Airspace Operations Laboratory to examine and refine the roles of the human operators in these concepts, as well as their tools and procedural requirements. So far MSP and FAM functions have been evaluated individually but the integration of the two functions is desirable since there are significant overlaps in their goals, geographic/temporal scope of the problem space, and the implementation timeframe. Ongoing research is planned to refine the humans roles in the integrated concept.

A new crystal form of a hyperthermophilic endocellulase

PubMed Central

Kataoka, Misumi; Ishikawa, Kazuhiko

2014-01-01

The hyperthermophilic glycoside hydrolase family endocellulase 12 from the archaeon Pyrococcus furiosus (EGPf; Gene ID PF0854; EC 3.2.1.4) catalyzes the hydrolytic cleavage of the β-1,4-glucosidic linkage in β-glucan in lignocellulose biomass. A crystal of EGPf was previously prepared at pH 9.0 and its structure was determined at an atomic resolution of 1.07 Å. This article reports the crystallization of EGPf at the more physiologically relevant pH of 5.5. Structure determination showed that this new crystal form has the symmetry of space group C2. Two molecules of the enzyme are observed in the asymmetric unit. Crystal packing is weak at pH 5.5 owing to two flexible interfaces between symmetry-related molecules. Comparison of the EGPf structures obtained at pH 9.0 and pH 5.5 reveals a significant conformational difference at the active centre and in the surface loops. The interfaces in the vicinity of the flexible surface loops impact the quality of the EGPf crystal. PMID:25005081

Control and structural optimization for maneuvering large spacecraft

NASA Technical Reports Server (NTRS)

Chun, H. M.; Turner, J. D.; Yu, C. C.

1990-01-01

Presented here are the results of an advanced control design as well as a discussion of the requirements for automating both the structures and control design efforts for maneuvering a large spacecraft. The advanced control application addresses a general three dimensional slewing problem, and is applied to a large geostationary platform. The platform consists of two flexible antennas attached to the ends of a flexible truss. The control strategy involves an open-loop rigid body control profile which is derived from a nonlinear optimal control problem and provides the main control effort. A perturbation feedback control reduces the response due to the flexibility of the structure. Results are shown which demonstrate the usefulness of the approach. Software issues are considered for developing an integrated structures and control design environment.

Backbone ¹H, ¹³C, ¹⁵N NMR assignments of yeast OMP synthase in unliganded form and in complex with orotidine 5'-monophosphate.

PubMed

Hansen, Michael Riis; Harris, Richard; Barr, Eric W; Cheng, Hong; Girvin, Mark E; Grubmeyer, Charles

2014-04-01

The type I phosphoribosyltransferase OMP synthase (EC 2.4.2.10) is involved in de novo synthesis of pyrimidine nucleotides forming the UMP precursor orotidine 5'-monophosphate (OMP). The homodimeric enzyme has a Rossman α/β core topped by a base-enclosing "hood" domain and a flexible domain-swapped catalytic loop. High-resolution X-ray structures of the homologous Salmonella typhimurium and yeast enzymes show that a general compacting of the core as well as movement of the hood and a major disorder-to-order transition of the loop occur upon binding of ligands MgPRPP and orotate. Here we present backbone NMR assignments for the unliganded yeast enzyme (49 kDa) and its complex with product OMP. We were able to assign 212-213 of the 225 non-proline backbone (15)N and amide proton resonances. Significant difference in chemical shifts of the amide cross peaks occur in regions of the structure that undergo movement upon ligand occupancy in the S. typhimurium enzyme.

Across-Gimbal and Miniaturized Cryogenic Loop Heat Pipes

NASA Astrophysics Data System (ADS)

Bugby, D.; Marland, B.; Stouffer, C.; Kroliczek, E.

2003-01-01

This paper describes the development status of three advanced cryogenic loop heat pipes (CLHP) for solving important problems in cryogenic integration. The three devices described herein are: (1) an across-gimbal CLHP; (2) a short transport length miniaturized CLHP; and (3) a long transport length miniaturized CLHP. The across-gimbal CLHP, which is baselined for operation from 80-100 K with nitrogen, provides a low weight, low torque, high conductance solution for gimbaled cryogenic systems wishing to mount their cryocoolers off-gimbal. The short transport length miniaturized CLHP, which is baselined for operation near 35 K with neon, combines localized thermal transport, flexibility, and thermal switching into one device that can be directly mounted to a cryocooler cold head and a cryogenic component just a short distance (10-20 cm) away. The long transport length miniaturized CLHP, which is also baselined for operation near 35 K with neon, adds to the capabilities of the short transport length miniaturized CLHP by increasing the transport length to over 250 cm to meet cryogenic heat transport device requirements of future NASA and DoD spacecraft.

Stability and performance of notch filter control for unbalance response

NASA Technical Reports Server (NTRS)

Knospe, C. R.

1992-01-01

Many current applications of magnetic bearings for rotating machinery employ notch filters in the feedback control loop to reduce the synchronous forces transmitted through the bearings. The capabilities and limitations of notch filter control are investigated. First, a rigid rotor is examined with some classical root locus techniques. Notch filter control is shown to result in conditional stability whenever complete synchronous attenuation is required. Next, a nondimensional parametric symmetric flexible three mass rotor model is constructed. An examination of this model for several test cases illustrates the limited attenuation possible with notch filters at and near the system critical speeds when the bearing damping is low. The notch filter's alteration of the feedback loop is shown to cause stability problems which limits performance. Poor transient response may also result. A high speed compressor is then examined as a candidate for notch filter control. A collocated 22 mass station model with lead-lag control is used. The analysis confirms the reduction in stability robustness that can occur with notch filter control. It is concluded that other methods of synchronous vibration control yield greater performance without compromising stability.

Enzyme-adenylate structure of a bacterial ATP-dependent DNA ligase with a minimized DNA-binding surface.

PubMed

Williamson, Adele; Rothweiler, Ulli; Leiros, Hanna Kirsti Schrøder

2014-11-01

DNA ligases are a structurally diverse class of enzymes which share a common catalytic core and seal breaks in the phosphodiester backbone of double-stranded DNA via an adenylated intermediate. Here, the structure and activity of a recombinantly produced ATP-dependent DNA ligase from the bacterium Psychromonas sp. strain SP041 is described. This minimal-type ligase, like its close homologues, is able to ligate singly nicked double-stranded DNA with high efficiency and to join cohesive-ended and blunt-ended substrates to a more limited extent. The 1.65 Å resolution crystal structure of the enzyme-adenylate complex reveals no unstructured loops or segments, and suggests that this enzyme binds the DNA without requiring full encirclement of the DNA duplex. This is in contrast to previously characterized minimal DNA ligases from viruses, which use flexible loop regions for DNA interaction. The Psychromonas sp. enzyme is the first structure available for the minimal type of bacterial DNA ligases and is the smallest DNA ligase to be crystallized to date.

Novel sensor for color control in solid state lighting applications

NASA Astrophysics Data System (ADS)

Gourevitch, Alex; Thurston, Thomas; Singh, Rajiv; Banachowicz, Bartosz; Korobov, Vladimir; Drowley, Cliff

2010-02-01

LED wavelength and luminosity shifts due to temperature, dimming, aging, and binning uncertainty can cause large color errors in open-loop light-mixing illuminators. Multispectral color light sensors combined with feedback circuits can compensate for these LED shifts. Typical color light sensor design variables include the choice of light-sensing material, filter configuration, and read-out circuitry. Cypress Semiconductor has designed and prototyped a color sensor chip that consists of photodiode arrays connected to a I/F (Current to Frequency) converter. This architecture has been chosen to achieve high dynamic range (~100dB) and provide flexibility for tailoring sensor response. Several different optical filter configurations were evaluated in this prototype. The color-sensor chip was incorporated into an RGB light color mixing system with closed-loop optical feedback. Color mixing accuracy was determined by calculating the difference between (u',v') set point values and CIE coordinates measured with a reference colorimeter. A typical color precision ▵u'v' less than 0.0055 has been demonstrated over a wide range of colors, a temperature range of 50C, and light dimming up to 80%.

Organic memory capacitor device fabricated with Ag nanoparticles.

PubMed

Kim, Yo-Han; Jung, Sung Mok; Hu, Quanli; Kim, Yong-Sang; Yoon, Tae-Sik; Lee, Hyun Ho

2011-07-01

In this study, it is demonstrated that an organic memory structure using pentacene and citrate-stabilized silver nanoparticles (Ag NPs) as charge storage elements on dielectric SiO2 layer and silicon substrate. The Ag NPs were synthesized by thermal reduction method of silver trifluoroacetate with oleic acid. The synthesized Ag NPs were analyzed with high resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) for their crystalline structure. The capacitance versus voltage (C-V) curves obtained for the Ag NPs embedded capacitor exhibited flat-band voltage shifts, which demonstrated the presence of charge storages. The citrate-capping of the Ag NPs was confirmed by ultraviolet-visible (UV-VIS) and Fourier transformed infrared (FTIR) spectroscopy. With voltage sweeping of +/-7 V, a hysteresis loop having flatband voltage shift of 7.1 V was obtained. The hysteresis loop showed a counter-clockwise direction. In addition, electrical performance test for charge storage showed more than 10,000 second charge retention time. The device with Ag NPs can be applied to an organic memory device for flexible electronics.

Evolution of the Generic Lock System at Jefferson Lab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brian Bevins; Yves Roblin

2003-10-13

The Generic Lock system is a software framework that allows highly flexible feedback control of large distributed systems. It allows system operators to implement new feedback loops between arbitrary process variables quickly and with no disturbance to the underlying control system. Several different types of feedback loops are provided and more are being added. This paper describes the further evolution of the system since it was first presented at ICALEPCS 2001 and reports on two years of successful use in accelerator operations. The framework has been enhanced in several key ways. Multiple-input, multiple-output (MIMO) lock types have been added formore » accelerator orbit and energy stabilization. The general purpose Proportional-Integral-Derivative (PID) locks can now be tuned automatically. The generic lock server now makes use of the Proxy IOC (PIOC) developed at Jefferson Lab to allow the locks to be monitored from any EPICS Channel Access aware client. (Previously clients had to be Cdev aware.) The dependency on the Qt XML parser has been replaced with the freely available Xerces DOM parser from the Apache project.« less

Neutron tomography of axially symmetric objects using 14 MeV neutrons from a portable neutron generator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, P., E-mail: peter.andersson@physics.uu.se; Andersson-Sunden, E.; Sjöstrand, H.

2014-08-01

In nuclear boiling water reactor cores, the distribution of water and steam (void) is essential for both safety and efficiency reasons. In order to enhance predictive capabilities, void distribution assessment is performed in two-phase test-loops under reactor-relevant conditions. This article proposes the novel technique of fast-neutron tomography using a portable deuterium-tritium neutron generator to determine the time-averaged void distribution in these loops. Fast neutrons have the advantage of high transmission through the metallic structures and pipes typically concealing a thermal-hydraulic test loop, while still being fairly sensitive to the water/void content. However, commercially available fast-neutron generators also have the disadvantagemore » of a relatively low yield and fast-neutron detection also suffers from relatively low detection efficiency. Fortunately, some loops are axially symmetric, a property which can be exploited to reduce the amount of data needed for tomographic measurement, thus limiting the interrogation time needed. In this article, three axially symmetric test objects depicting a thermal-hydraulic test loop have been examined; steel pipes with outer diameter 24 mm, thickness 1.5 mm, and with three different distributions of the plastic material POM inside the pipes. Data recorded with the FANTOM fast-neutron tomography instrument have been used to perform tomographic reconstructions to assess their radial material distribution. Here, a dedicated tomographic algorithm that exploits the symmetry of these objects has been applied, which is described in the paper. Results are demonstrated in 20 rixel (radial pixel) reconstructions of the interior constitution and 2D visualization of the pipe interior is demonstrated. The local POM attenuation coefficients in the rixels were measured with errors (RMS) of 0.025, 0.020, and 0.022 cm{sup −1}, solid POM attenuation coefficient. The accuracy and precision is high enough to provide a useful indication on the flow mode, and a visualization of the radial material distribution can be obtained. A benefit of this system is its potential to be mounted at any axial height of a two-phase test section without requirements for pre-fabricated entrances or windows. This could mean a significant increase in flexibility of the void distribution assessment capability at many existing two-phase test loops.« less

Neutron tomography of axially symmetric objects using 14 MeV neutrons from a portable neutron generator.

PubMed

Andersson, P; Andersson-Sunden, E; Sjöstrand, H; Jacobsson-Svärd, S

2014-08-01

In nuclear boiling water reactor cores, the distribution of water and steam (void) is essential for both safety and efficiency reasons. In order to enhance predictive capabilities, void distribution assessment is performed in two-phase test-loops under reactor-relevant conditions. This article proposes the novel technique of fast-neutron tomography using a portable deuterium-tritium neutron generator to determine the time-averaged void distribution in these loops. Fast neutrons have the advantage of high transmission through the metallic structures and pipes typically concealing a thermal-hydraulic test loop, while still being fairly sensitive to the water/void content. However, commercially available fast-neutron generators also have the disadvantage of a relatively low yield and fast-neutron detection also suffers from relatively low detection efficiency. Fortunately, some loops are axially symmetric, a property which can be exploited to reduce the amount of data needed for tomographic measurement, thus limiting the interrogation time needed. In this article, three axially symmetric test objects depicting a thermal-hydraulic test loop have been examined; steel pipes with outer diameter 24 mm, thickness 1.5 mm, and with three different distributions of the plastic material POM inside the pipes. Data recorded with the FANTOM fast-neutron tomography instrument have been used to perform tomographic reconstructions to assess their radial material distribution. Here, a dedicated tomographic algorithm that exploits the symmetry of these objects has been applied, which is described in the paper. Results are demonstrated in 20 rixel (radial pixel) reconstructions of the interior constitution and 2D visualization of the pipe interior is demonstrated. The local POM attenuation coefficients in the rixels were measured with errors (RMS) of 0.025, 0.020, and 0.022 cm(-1), solid POM attenuation coefficient. The accuracy and precision is high enough to provide a useful indication on the flow mode, and a visualization of the radial material distribution can be obtained. A benefit of this system is its potential to be mounted at any axial height of a two-phase test section without requirements for pre-fabricated entrances or windows. This could mean a significant increase in flexibility of the void distribution assessment capability at many existing two-phase test loops.

Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

PubMed

Beste, Christian; Ness, Vanessa; Lukas, Carsten; Hoffmann, Rainer; Stüwe, Sven; Falkenstein, Michael; Saft, Carsten

2012-08-01

Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict monitoring and flexible adaptation of actions. Copyright © 2012 Elsevier Inc. All rights reserved.

CAB-Align: A Flexible Protein Structure Alignment Method Based on the Residue-Residue Contact Area.

PubMed

Terashi, Genki; Takeda-Shitaka, Mayuko

2015-01-01

Proteins are flexible, and this flexibility has an essential functional role. Flexibility can be observed in loop regions, rearrangements between secondary structure elements, and conformational changes between entire domains. However, most protein structure alignment methods treat protein structures as rigid bodies. Thus, these methods fail to identify the equivalences of residue pairs in regions with flexibility. In this study, we considered that the evolutionary relationship between proteins corresponds directly to the residue-residue physical contacts rather than the three-dimensional (3D) coordinates of proteins. Thus, we developed a new protein structure alignment method, contact area-based alignment (CAB-align), which uses the residue-residue contact area to identify regions of similarity. The main purpose of CAB-align is to identify homologous relationships at the residue level between related protein structures. The CAB-align procedure comprises two main steps: First, a rigid-body alignment method based on local and global 3D structure superposition is employed to generate a sufficient number of initial alignments. Then, iterative dynamic programming is executed to find the optimal alignment. We evaluated the performance and advantages of CAB-align based on four main points: (1) agreement with the gold standard alignment, (2) alignment quality based on an evolutionary relationship without 3D coordinate superposition, (3) consistency of the multiple alignments, and (4) classification agreement with the gold standard classification. Comparisons of CAB-align with other state-of-the-art protein structure alignment methods (TM-align, FATCAT, and DaliLite) using our benchmark dataset showed that CAB-align performed robustly in obtaining high-quality alignments and generating consistent multiple alignments with high coverage and accuracy rates, and it performed extremely well when discriminating between homologous and nonhomologous pairs of proteins in both single and multi-domain comparisons. The CAB-align software is freely available to academic users as stand-alone software at http://www.pharm.kitasato-u.ac.jp/bmd/bmd/Publications.html.

Adaptive backstepping fault-tolerant control for flexible spacecraft with unknown bounded disturbances and actuator failures.

PubMed

Jiang, Ye; Hu, Qinglei; Ma, Guangfu

2010-01-01

In this paper, a robust adaptive fault-tolerant control approach to attitude tracking of flexible spacecraft is proposed for use in situations when there are reaction wheel/actuator failures, persistent bounded disturbances and unknown inertia parameter uncertainties. The controller is designed based on an adaptive backstepping sliding mode control scheme, and a sufficient condition under which this control law can render the system semi-globally input-to-state stable is also provided such that the closed-loop system is robust with respect to any disturbance within a quantifiable restriction on the amplitude, as well as the set of initial conditions, if the control gains are designed appropriately. Moreover, in the design, the control law does not need a fault detection and isolation mechanism even if the failure time instants, patterns and values on actuator failures are also unknown for the designers, as motivated from a practical spacecraft control application. In addition to detailed derivations of the new controller design and a rigorous sketch of all the associated stability and attitude error convergence proofs, illustrative simulation results of an application to flexible spacecraft show that high precise attitude control and vibration suppression are successfully achieved using various scenarios of controlling effective failures. 2009. Published by Elsevier Ltd.

Dynamic output feedback control of a flexible air-breathing hypersonic vehicle via T-S fuzzy approach

NASA Astrophysics Data System (ADS)

Hu, Xiaoxiang; Wu, Ligang; Hu, Changhua; Wang, Zhaoqiang; Gao, Huijun

2014-08-01

By utilising Takagi-Sugeno (T-S) fuzzy set approach, this paper addresses the robust H∞ dynamic output feedback control for the non-linear longitudinal model of flexible air-breathing hypersonic vehicles (FAHVs). The flight control of FAHVs is highly challenging due to the unique dynamic characteristics, and the intricate couplings between the engine and fight dynamics and external disturbance. Because of the dynamics' enormous complexity, currently, only the longitudinal dynamics models of FAHVs have been used for controller design. In this work, T-S fuzzy modelling technique is utilised to approach the non-linear dynamics of FAHVs, then a fuzzy model is developed for the output tracking problem of FAHVs. The fuzzy model contains parameter uncertainties and disturbance, which can approach the non-linear dynamics of FAHVs more exactly. The flexible models of FAHVs are difficult to measure because of the complex dynamics and the strong couplings, thus a full-order dynamic output feedback controller is designed for the fuzzy model. A robust H∞ controller is designed for the obtained closed-loop system. By utilising the Lyapunov functional approach, sufficient solvability conditions for such controllers are established in terms of linear matrix inequalities. Finally, the effectiveness of the proposed T-S fuzzy dynamic output feedback control method is demonstrated by numerical simulations.

Electrolyzers Enhancing Flexibility in Electric Grids

DOE PAGES

Mohanpurkar, Manish; Luo, Yusheng; Terlip, Danny; ...

2017-11-10

This paper presents a real-time simulation with a hardware-in-the-loop (HIL)-based approach for verifying the performance of electrolyzer systems in providing grid support. Hydrogen refueling stations may use electrolyzer systems to generate hydrogen and are proposed to have the potential of becoming smarter loads that can proactively provide grid services. On the basis of experimental findings, electrolyzer systems with balance of plant are observed to have a high level of controllability and hence can add flexibility to the grid from the demand side. A generic front end controller (FEC) is proposed, which enables an optimal operation of the load on themore » basis of market and grid conditions. This controller has been simulated and tested in a real-time environment with electrolyzer hardware for a performance assessment. It can optimize the operation of electrolyzer systems on the basis of the information collected by a communication module. Real-time simulation tests are performed to verify the performance of the FEC-driven electrolyzers to provide grid support that enables flexibility, greater economic revenue, and grid support for hydrogen producers under dynamic conditions. In conclusion, the FEC proposed in this paper is tested with electrolyzers, however, it is proposed as a generic control topology that is applicable to any load.« less

A translational platform for prototyping closed-loop neuromodulation systems

PubMed Central

Afshar, Pedram; Khambhati, Ankit; Stanslaski, Scott; Carlson, David; Jensen, Randy; Linde, Dave; Dani, Siddharth; Lazarewicz, Maciej; Cong, Peng; Giftakis, Jon; Stypulkowski, Paul; Denison, Tim

2013-01-01

While modulating neural activity through stimulation is an effective treatment for neurological diseases such as Parkinson's disease and essential tremor, an opportunity for improving neuromodulation therapy remains in automatically adjusting therapy to continuously optimize patient outcomes. Practical issues associated with achieving this include the paucity of human data related to disease states, poorly validated estimators of patient state, and unknown dynamic mappings of optimal stimulation parameters based on estimated states. To overcome these challenges, we present an investigational platform including: an implanted sensing and stimulation device to collect data and run automated closed-loop algorithms; an external tool to prototype classifier and control-policy algorithms; and real-time telemetry to update the implanted device firmware and monitor its state. The prototyping system was demonstrated in a chronic large animal model studying hippocampal dynamics. We used the platform to find biomarkers of the observed states and transfer functions of different stimulation amplitudes. Data showed that moderate levels of stimulation suppress hippocampal beta activity, while high levels of stimulation produce seizure-like after-discharge activity. The biomarker and transfer function observations were mapped into classifier and control-policy algorithms, which were downloaded to the implanted device to continuously titrate stimulation amplitude for the desired network effect. The platform is designed to be a flexible prototyping tool and could be used to develop improved mechanistic models and automated closed-loop systems for a variety of neurological disorders. PMID:23346048

Characteristics of Control Laws Tested on the Semi-Span Super-Sonic Transport (S4T) Wind-Tunnel Model

NASA Technical Reports Server (NTRS)

Christhilf, David M.; Moulin, Boris; Ritz, Erich; Chen, P. C.; Roughen, Kevin M.; Perry, Boyd

2012-01-01

The Semi-Span Supersonic Transport (S4T) is an aeroelastically scaled wind-tunnel model built to test active controls concepts for large flexible supersonic aircraft in the transonic flight regime. It is one of several models constructed in the 1990's as part of the High Speed Research (HSR) Program. Control laws were developed for the S4T by M4 Engineering, Inc. and by Zona Technologies, Inc. under NASA Research Announcement (NRA) contracts. The model was tested in the NASA-Langley Transonic Dynamics Tunnel (TDT) four times from 2007 to 2010. The first two tests were primarily for plant identification. The third entry was used for testing control laws for Ride Quality Enhancement, Gust Load Alleviation, and Flutter Suppression. Whereas the third entry only tested FS subcritically, the fourth test demonstrated closed-loop operation above the open-loop flutter boundary. The results of the third entry are reported elsewhere. This paper reports on flutter suppression results from the fourth wind-tunnel test. Flutter suppression is seen as a way to provide stability margins while flying at transonic flight conditions without penalizing the primary supersonic cruise design condition. An account is given for how Controller Performance Evaluation (CPE) singular value plots were interpreted with regard to progressing open- or closed-loop to higher dynamic pressures during testing.

A translational platform for prototyping closed-loop neuromodulation systems.

PubMed

Afshar, Pedram; Khambhati, Ankit; Stanslaski, Scott; Carlson, David; Jensen, Randy; Linde, Dave; Dani, Siddharth; Lazarewicz, Maciej; Cong, Peng; Giftakis, Jon; Stypulkowski, Paul; Denison, Tim

2012-01-01

While modulating neural activity through stimulation is an effective treatment for neurological diseases such as Parkinson's disease and essential tremor, an opportunity for improving neuromodulation therapy remains in automatically adjusting therapy to continuously optimize patient outcomes. Practical issues associated with achieving this include the paucity of human data related to disease states, poorly validated estimators of patient state, and unknown dynamic mappings of optimal stimulation parameters based on estimated states. To overcome these challenges, we present an investigational platform including: an implanted sensing and stimulation device to collect data and run automated closed-loop algorithms; an external tool to prototype classifier and control-policy algorithms; and real-time telemetry to update the implanted device firmware and monitor its state. The prototyping system was demonstrated in a chronic large animal model studying hippocampal dynamics. We used the platform to find biomarkers of the observed states and transfer functions of different stimulation amplitudes. Data showed that moderate levels of stimulation suppress hippocampal beta activity, while high levels of stimulation produce seizure-like after-discharge activity. The biomarker and transfer function observations were mapped into classifier and control-policy algorithms, which were downloaded to the implanted device to continuously titrate stimulation amplitude for the desired network effect. The platform is designed to be a flexible prototyping tool and could be used to develop improved mechanistic models and automated closed-loop systems for a variety of neurological disorders.

Crystal structure of the unactivated ribulose 1,5-bisphosphate carboxylase/oxygenase complexed with a transition state analog, 2-carboxy-D-arabinitol 1,5-bisphosphate.

PubMed Central

Zhang, K. Y.; Cascio, D.; Eisenberg, D.

1994-01-01

The crystal structure of unactivated ribulose 1,5-bisphosphate carboxylase/oxygenase from Nicotiana tabacum complexed with a transition state analog, 2-carboxy-D-arabinitol 1,5-bisphosphate, was determined to 2.7 A resolution by X-ray crystallography. The transition state analog binds at the active site in an extended conformation. As compared to the binding of the same analog in the activated enzyme, the analog binds in a reverse orientation. The active site Lys 201 is within hydrogen bonding distance of the carboxyl oxygen of the analog. Loop 6 (residues 330-339) remains open and flexible upon binding of the analog in the unactivated enzyme, in contrast to the closed and ordered loop 6 in the activated enzyme complex. The transition state analog is exposed to solvent due to the open conformation of loop 6. PMID:8142899

Modelling and experimental performance analysis of solar-assisted ground source heat pump system

NASA Astrophysics Data System (ADS)

Esen, Hikmet; Esen, Mehmet; Ozsolak, Onur

2017-01-01

In this study, slinky (the slinky-loop configuration is also known as the coiled loop or spiral loop of flexible plastic pipe)type ground heat exchanger (GHE) was established for a solar-assisted ground source heat pump system. System modelling is performed with the data obtained from the experiment. Artificial neural network (ANN) and adaptive neuro-fuzzy inference system (ANFIS) are used in modelling. The slinky pipes have been laid horizontally and vertically in a ditch. The system coefficient of performance (COPsys) and the heat pump coefficient of performance (COPhp) have been calculated as 2.88 and 3.55, respectively, at horizontal slinky-type GHE, while COPsys and COPhp were calculated as 2.34 and 2.91, respectively, at vertical slinky-type GHE. The obtained results showed that the ANFIS is more successful than that of ANN for forecasting performance of a solar ground source heat pump system.

Performance and operational considerations in the design of vehicle antennas for mobile satellite communications

NASA Technical Reports Server (NTRS)

Milne, R.

1995-01-01

This paper examines the vehicle antenna requirements for mobile satellite systems. The antenna parameters are discussed in the light of the requirements and the limitations in performance imposed by the physical constraints of antenna and by vehicle geometries. Measurements of diffraction and antenna noise temperature in an operational environment are examined, as well as their effects on system margins. Mechanical versus electronic designs are compared with regards to performance, cost, reliability, and design complexity. Comparisons between open-loop and close-loop tracking systems are made and the effects of bandwidth, sidelobe levels, operational constraints, vehicle angular velocity, and acceleration are discussed. Some consideration is given to the use of hybrid systems employing both open and closed-loop tracking. Changes to antenna/terminal specifications are recommended which will provide greater design flexibility and increase the likelihood of meeting the performance and operational requirements.

Advanced photonic filters based on cascaded Sagnac loop reflector resonators in silicon-on-insulator nanowires

NASA Astrophysics Data System (ADS)

Wu, Jiayang; Moein, Tania; Xu, Xingyuan; Moss, David J.

2018-04-01

We demonstrate advanced integrated photonic filters in silicon-on-insulator (SOI) nanowires implemented by cascaded Sagnac loop reflector (CSLR) resonators. We investigate mode splitting in these standing-wave (SW) resonators and demonstrate its use for engineering the spectral profile of on-chip photonic filters. By changing the reflectivity of the Sagnac loop reflectors (SLRs) and the phase shifts along the connecting waveguides, we tailor mode splitting in the CSLR resonators to achieve a wide range of filter shapes for diverse applications including enhanced light trapping, flat-top filtering, Q factor enhancement, and signal reshaping. We present the theoretical designs and compare the CSLR resonators with three, four, and eight SLRs fabricated in SOI. We achieve versatile filter shapes in the measured transmission spectra via diverse mode splitting that agree well with theory. This work confirms the effectiveness of using CSLR resonators as integrated multi-functional SW filters for flexible spectral engineering.

Coordination and Control of Flexible Building Loads for Renewable Integration; Demonstrations using VOLTTRON

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, He; Liu, Guopeng; Huang, Sen

Renewable energy resources such as wind and solar power have a high degree of uncertainty. Large-scale integration of these variable generation sources into the grid is a big challenge for power system operators. Buildings, in which we live and work, consume about 75% of the total electricity in the United States. They also have a large capacity of power flexibility due to their massive thermal capacitance. Therefore, they present a great opportunity to help the grid to manage power balance. In this report, we study coordination and control of flexible building loads for renewable integration. We first present the motivationmore » and background, and conduct a literature review on building-to-grid integration. We also compile a catalog of flexible building loads that have great potential for renewable integration, and discuss their characteristics. We next collect solar generation data from a photovoltaic panel on Pacific Northwest National Laboratory campus, and conduct data analysis to study their characteristics. We find that solar generation output has a strong uncertainty, and the uncertainty occurs at almost all time scales. Additional data from other sources are also used to verify our study. We propose two transactive coordination strategies to manage flexible building loads for renewable integration. We prove the theories that support the two transactive coordination strategies and discuss their pros and cons. In this report, we select three types of flexible building loads—air-handling unit, rooftop unit, and a population of WHs—for which we demonstrate control of the flexible load to track a dispatch signal (e.g., renewable generation fluctuation) using experiment, simulation, or hardware-in-the-loop study. More specifically, we present the system description, model identification, controller design, test bed setup, and experiment results for each demonstration. We show that coordination and control of flexible loads has a great potential to integrate variable generation sources. The flexible loads can successfully track a power dispatch signal from the coordinator, while having little impact on the quality of service to the end-users.« less

Kinetics of interior loop formation in semiflexible chains.

PubMed

Hyeon, Changbong; Thirumalai, D

2006-03-14

Loop formation between monomers in the interior of semiflexible chains describes elementary events in biomolecular folding and DNA bending. We calculate analytically the interior distance distribution function for semiflexible chains using a mean field approach. Using the potential of mean force derived from the distance distribution function we present a simple expression for the kinetics of interior looping by adopting Kramers theory. For the parameters, that are appropriate for DNA, the theoretical predictions in comparison with the case are in excellent agreement with explicit Brownian dynamics simulations of wormlike chain (WLC) model. The interior looping times (tauIC) can be greatly altered in the cases when the stiffness of the loop differs from that of the dangling ends. If the dangling end is stiffer than the loop then tauIC increases for the case of the WLC with uniform persistence length. In contrast, attachment of flexible dangling ends enhances rate of interior loop formation. The theory also shows that if the monomers are charged and interact via screened Coulomb potential then both the cyclization (tauc) and interior looping (tauIC) times greatly increase at low ionic concentration. Because both tauc and tauIC are determined essentially by the effective persistence length [lp(R)] we computed lp(R) by varying the range of the repulsive interaction between the monomers. For short range interactions lp(R) nearly coincides with the bare persistence length which is determined largely by the backbone chain connectivity. This finding rationalizes the efficacy of describing a number of experimental observations (response of biopolymers to force and cyclization kinetics) in biomolecules using WLC model with an effective persistence length.

The novel appearance of low rectal anastomosis on contrast enema following laparoscopic anterior resection: discriminating anastomotic leaks from "dog-ears" on water-soluble contrast enema and flexible sigmoidoscopy.

PubMed

Katory, Mark; McLean, Ross; Osman, Khalid; Ahmad, Mukhtar; Hughes, Tracey; Newby, Mike; Dennison, Christopher; O'Loughlin, Paul

2017-02-01

Interpretation of water-soluble contrast enema following laparoscopic low anterior resection can be very challenging for both radiologists and colorectal surgeons. Discriminating the radiological appearances secondary to anastomotic configuration from those caused by actual anastomotic dehiscence is a common problem and may be made worse with the advent of laparoscopic surgery. The aim of this study is to identify potential novel appearances of the water-soluble contrast enema (WSCE) images of rectal anastomosis following laparoscopic low anterior resection to radiologists and surgeons. We enrolled 45 patients who underwent laparoscopic low anterior resection with proximal de-functioning loop ileostomy within a specialized colorectal unit. The water-soluble contrast enema reports were reviewed. Two blinded colorectal radiologists independently reviewed the images of patients suspected of anastomotic leak. All of these patients also underwent a flexible sigmoidoscopy to confirm or exclude anastomotic leak before reversal of loop ileostomy. Inter-observer concordance was calculated. Seven out of eighteen patients (38.9%) were found to have true anastomotic leaks on flexible sigmoidoscopy (15% overall leak rate). In the remaining eleven patients the image appearances were attributed to the appearance of the anastomotic 'dog-ear effect', created by the anastomotic configuration due to multiple firing of the intra-corporeal laparoscopic stapling device. Radiologist inter-observer concordance was 83%. Sensitivity was 100%, specificity 71%, positive-predictive value (38.9%) and negative-predictive value (100%). The novel appearances of laparoscopic-stapled rectal anastomoses in WSCE can be mistaken for anastomotic leak. To avoid delay in reversal of ileostomy, a flexible sigmoidoscopy can be used to confirm or exclude a leak.

Advanced Ignition in Supersonic Airflow by Tunable Plasma System

NASA Astrophysics Data System (ADS)

Firsov, A. A.; Dolgov, E. V.; Leonov, S. B.; Yarantsev, D. A.

2017-10-01

The plasma-based technique was studied for ignition and flameholding in a supersonic airflow in different laboratories for a long time. It was shown that flameholding of gaseous and liquid hydrocarbon fuel is feasible by means of surface DC discharge without employing mechanical flameholders in a supersonic combustion chamber. However, a high power consumption may limit application of this method in a real apparatus. This experimental and computational work explores a distributed plasma system, which allows reducing the total energy consumption and extending the life cycle of the electrode system. Due to the circuit flexibility, this approach may be potentially enriched with feedbacks for design of a close loop control system.

Static Aeroelastic and Longitudinal Trim Model of Flexible Wing Aircraft Using Finite-Element Vortex-Lattice Coupled Solution

NASA Technical Reports Server (NTRS)

Ting, Eric; Nguyen, Nhan; Trinh, Khanh

2014-01-01

This paper presents a static aeroelastic model and longitudinal trim model for the analysis of a flexible wing transport aircraft. The static aeroelastic model is built using a structural model based on finite-element modeling and coupled to an aerodynamic model that uses vortex-lattice solution. An automatic geometry generation tool is used to close the loop between the structural and aerodynamic models. The aeroelastic model is extended for the development of a three degree-of-freedom longitudinal trim model for an aircraft with flexible wings. The resulting flexible aircraft longitudinal trim model is used to simultaneously compute the static aeroelastic shape for the aircraft model and the longitudinal state inputs to maintain an aircraft trim state. The framework is applied to an aircraft model based on the NASA Generic Transport Model (GTM) with wing structures allowed to flexibly deformed referred to as the Elastically Shaped Aircraft Concept (ESAC). The ESAC wing mass and stiffness properties are based on a baseline "stiff" values representative of current generation transport aircraft.

Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP.

PubMed

Cardone, A; Hassan, S A; Albers, R W; Sriram, R D; Pant, H C

2010-08-20

The crystal structure of the cdk5/p25 complex has provided information on possible molecular mechanisms of the ligand binding, specificity, and regulation of the kinase. Comparative molecular dynamics simulations are reported here for physiological conditions. This study provides new insight on the mechanisms that modulate such processes, which may be exploited to control pathological activation by p25. The structural changes observed in the kinase are stabilized by a network of interactions involving highly conserved residues within the cyclin-dependent kinase (cdk) family. Collective motions of the proteins (cdk5, p25, and CIP) and their complexes are identified by principal component analysis, revealing two conformational states of the activation loop upon p25 complexation, which are absent in the uncomplexed kinase and not apparent from the crystal. Simulations of the uncomplexed inhibitor CIP show structural rearrangements and increased flexibility of the interfacial loop containing the critical residue E240, which becomes fully hydrated and available for interactions with one of several positively charged residues in the kinase. These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5. Published by Elsevier Ltd.

Increasing the computational efficient of digital cross correlation by a vectorization method

NASA Astrophysics Data System (ADS)

Chang, Ching-Yuan; Ma, Chien-Ching

2017-08-01

This study presents a vectorization method for use in MATLAB programming aimed at increasing the computational efficiency of digital cross correlation in sound and images, resulting in a speedup of 6.387 and 36.044 times compared with performance values obtained from looped expression. This work bridges the gap between matrix operations and loop iteration, preserving flexibility and efficiency in program testing. This paper uses numerical simulation to verify the speedup of the proposed vectorization method as well as experiments to measure the quantitative transient displacement response subjected to dynamic impact loading. The experiment involved the use of a high speed camera as well as a fiber optic system to measure the transient displacement in a cantilever beam under impact from a steel ball. Experimental measurement data obtained from the two methods are in excellent agreement in both the time and frequency domain, with discrepancies of only 0.68%. Numerical and experiment results demonstrate the efficacy of the proposed vectorization method with regard to computational speed in signal processing and high precision in the correlation algorithm. We also present the source code with which to build MATLAB-executable functions on Windows as well as Linux platforms, and provide a series of examples to demonstrate the application of the proposed vectorization method.

A Flexible Hardware Test and Demonstration Platform for the Fractionated System Architecture YETE

NASA Astrophysics Data System (ADS)

Kempf, Florian; Haber, Roland; Tzschichholz, Tristan; Mikschl, Tobias; Hilgarth, Alexander; Montenegro, Sergio; Schilling, Klaus

2016-08-01

This paper introduces a hardware-in-the loop test and demonstration platform for the YETE system architecture for fractionated spacecraft. It is designed for rapid prototyping and testing of distributed control approaches for the YETE architecture subject to varying network topologies and transmission channel properties between the individual YETE hardware nodes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramanathan, Arvind; Agarwal, Pratul K

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function.more » Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.« less

Testing the Use of Implicit Solvent in the Molecular Dynamics Modelling of DNA Flexibility

NASA Astrophysics Data System (ADS)

Mitchell, J.; Harris, S.

DNA flexibility controls packaging, looping and in some cases sequence specific protein binding. Molecular dynamics simulations carried out with a computationally efficient implicit solvent model are potentially a powerful tool for studying larger DNA molecules than can be currently simulated when water and counterions are represented explicitly. In this work we compare DNA flexibility at the base pair step level modelled using an implicit solvent model to that previously determined from explicit solvent simulations and database analysis. Although much of the sequence dependent behaviour is preserved in implicit solvent, the DNA is considerably more flexible when the approximate model is used. In addition we test the ability of the implicit solvent to model stress induced DNA disruptions by simulating a series of DNA minicircle topoisomers which vary in size and superhelical density. When compared with previously run explicit solvent simulations, we find that while the levels of DNA denaturation are similar using both computational methodologies, the specific structural form of the disruptions is different.

Reducing model uncertainty effects in flexible manipulators through the addition of passive damping

NASA Technical Reports Server (NTRS)

Alberts, T. E.

1987-01-01

An important issue in the control of practical systems is the effect of model uncertainty on closed loop performance. This is of particular concern when flexible structures are to be controlled, due to the fact that states associated with higher frequency vibration modes are truncated in order to make the control problem tractable. Digital simulations of a single-link manipulator system are employed to demonstrate that passive damping added to the flexible member reduces adverse effects associated with model uncertainty. A controller was designed based on a model including only one flexible mode. This controller was applied to larger order systems to evaluate the effects of modal truncation. Simulations using a Linear Quadratic Regulator (LQR) design assuming full state feedback illustrate the effect of control spillover. Simulations of a system using output feedback illustrate the destabilizing effect of observation spillover. The simulations reveal that the system with passive damping is less susceptible to these effects than the untreated case.

Unified control/structure design and modeling research

NASA Technical Reports Server (NTRS)

Mingori, D. L.; Gibson, J. S.; Blelloch, P. A.; Adamian, A.

1986-01-01

To demonstrate the applicability of the control theory for distributed systems to large flexible space structures, research was focused on a model of a space antenna which consists of a rigid hub, flexible ribs, and a mesh reflecting surface. The space antenna model used is discussed along with the finite element approximation of the distributed model. The basic control problem is to design an optimal or near-optimal compensator to suppress the linear vibrations and rigid-body displacements of the structure. The application of an infinite dimensional Linear Quadratic Gaussian (LQG) control theory to flexible structure is discussed. Two basic approaches for robustness enhancement were investigated: loop transfer recovery and sensitivity optimization. A third approach synthesized from elements of these two basic approaches is currently under development. The control driven finite element approximation of flexible structures is discussed. Three sets of finite element basic vectors for computing functional control gains are compared. The possibility of constructing a finite element scheme to approximate the infinite dimensional Hamiltonian system directly, instead of indirectly is discussed.

Numerical characterization of a flexible circular coil for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Bautista, T.; Hernandez, R.; Solis-Najera, S. E.; Rodriguez, A. O.

2012-10-01

Numerical simulations of the magnetic field generated by a flexible surface coil were conducted to study its behavior for applications of animal models at 7 Tesla. This coil design is able to fully cover a volume of interest. The Finite Difference Method in Time Domain (FDTD) was used because of its ability to accurately model complex problems in electromagnetism. This particular coil design is best suited for regions of interests with a spherical shape, since B1 uniformity is not significantly attenuated as in the case of a circular-loop coil. It still remains to investigate the feasibility to actually construct a coil prototype.

Transform methods for precision continuum and control models of flexible space structures

NASA Technical Reports Server (NTRS)

Lupi, Victor D.; Turner, James D.; Chun, Hon M.

1991-01-01

An open loop optimal control algorithm is developed for general flexible structures, based on Laplace transform methods. A distributed parameter model of the structure is first presented, followed by a derivation of the optimal control algorithm. The control inputs are expressed in terms of their Fourier series expansions, so that a numerical solution can be easily obtained. The algorithm deals directly with the transcendental transfer functions from control inputs to outputs of interest, and structural deformation penalties, as well as penalties on control effort, are included in the formulation. The algorithm is applied to several structures of increasing complexity to show its generality.

Crystal structure of a polyhistidine-tagged recombinant catalytic subunit of cAMP-dependent protein kinase complexed with the peptide inhibitor PKI(5-24) and adenosine.

PubMed

Narayana, N; Cox, S; Shaltiel, S; Taylor, S S; Xuong, N

1997-04-15

The crystal structure of the hexahistidine-tagged mouse recombinant catalytic subunit (H6-rC) of cAMP-dependent protein kinase (cAPK), complexed with a 20-residue peptide inhibitor from the heat-stable protein kinase inhibitor PKI(5-24) and adenosine, was determined at 2.2 A resolution. Novel crystallization conditions were required to grow the ternary complex crystals. The structure was refined to a final crystallographic R-factor of 18.2% with good stereochemical parameters. The "active" enzyme adopts a "closed" conformation as found in rC:PKI(5-24) [Knighton et al. (1991a,b) Science 253, 407-414, 414-420] and packs in a similar manner with the peptide providing a major contact surface. This structure clearly defines the subsites of the unique nucleotide binding site found in the protein kinase family. The adenosine occupies a mostly hydrophobic pocket at the base of the cleft between the two lobes and is completely buried. The missing triphosphate moiety of ATP is filled with a water molecule (Wtr 415) which replaces the gamma-phosphate of ATP. The glycine-rich loop between beta1 and beta2 helps to anchor the phosphates while the ribose ring is buried beneath beta-strand 2. Another ordered water molecule (Wtr 375) is pentacoordinated with polar atoms from adenosine, Leu 49 in beta-strand 1, Glu 127 in the linker strand between the two lobes, Tyr 330, and a third water molecule, Wtr 359. The conserved nucleotide fold can be defined as a lid comprised of beta-strand 1, the glycine-rich loop, and beta-strand 2. The adenine ring is buried beneath beta-strand 1 and the linker strand (120-127) that joins the small and large lobes. The C-terminal tail containing Tyr 330, a segment that lies outside the conserved core, covers this fold and anchors it in a closed conformation. The main-chain atoms of the flexible glycine-rich loop (residues 50-55) in the ATP binding domain have a mean B-factor of 41.4 A2. This loop is quite mobile, in striking contrast to the other conserved loops that converge at the active site cleft. The catalytic loop (residues 166-171) and the Mg2+ positioning loop (residues 184-186) are a stable part of the large lobe and have low B-factors in all structures solved to date. The stability of the glycine-rich loop is highly dependent on the ligands that occupy the active site cleft with maximum stability achieved in the ternary complex containing Mg x ATP and the peptide inhibitor. In this ternary complex the gamma-phosphate is secured between both lobes by hydrogen bonds to the backbone amide of Ser 53 in the glycine-rich loop and the amino group of Lys 168 in the catalytic loop. In the adenosine ternary complex the water molecule replacing the gamma-phosphate hydrogen bonds between Lys 168 and Asp 166 and makes no contact with the small lobe. This glycine-rich loop is thus the most mobile component of the active site cleft, with the tip of the loop being highly sensitive to what occupies the gamma-subsite.

A Phased Array Coil for Human Cardiac Imaging

PubMed Central

Constantinides, Chris D.; Westgate, Charles R.; O'Dell, Walter G.; Zerhouni, Elias A.; McVeigh, Elliot R.

2007-01-01

A prototype cardiac phased array receiver coil was constructed that comprised a cylindrical array and a separate planar array. Both arrays had two coil loops with the same coil dimensions. Data acquisition with the cylindrical array placed on the human chest, and the planar array placed under the back, yielded an overall enhancement of the signal-to-noise ratio (SNR) over the entire heart by a factor of 1.1–2.85 over a commercially available flexible coil and a commercially available four-loop planar phased array coil. This improvement in SNR can be exploited in cardiac imaging to increase the spatial resolution and reduce the image acquisition time. PMID:7674903

Closed-Loop Neuromorphic Benchmarks

PubMed Central

Stewart, Terrence C.; DeWolf, Travis; Kleinhans, Ashley; Eliasmith, Chris

2015-01-01

Evaluating the effectiveness and performance of neuromorphic hardware is difficult. It is even more difficult when the task of interest is a closed-loop task; that is, a task where the output from the neuromorphic hardware affects some environment, which then in turn affects the hardware's future input. However, closed-loop situations are one of the primary potential uses of neuromorphic hardware. To address this, we present a methodology for generating closed-loop benchmarks that makes use of a hybrid of real physical embodiment and a type of “minimal” simulation. Minimal simulation has been shown to lead to robust real-world performance, while still maintaining the practical advantages of simulation, such as making it easy for the same benchmark to be used by many researchers. This method is flexible enough to allow researchers to explicitly modify the benchmarks to identify specific task domains where particular hardware excels. To demonstrate the method, we present a set of novel benchmarks that focus on motor control for an arbitrary system with unknown external forces. Using these benchmarks, we show that an error-driven learning rule can consistently improve motor control performance across a randomly generated family of closed-loop simulations, even when there are up to 15 interacting joints to be controlled. PMID:26696820

Structural basis for allosteric cross-talk between the asymmetric nucleotide binding sites of a heterodimeric ABC exporter.

PubMed

Hohl, Michael; Hürlimann, Lea M; Böhm, Simon; Schöppe, Jendrik; Grütter, Markus G; Bordignon, Enrica; Seeger, Markus A

2014-07-29

ATP binding cassette (ABC) transporters mediate vital transport processes in every living cell. ATP hydrolysis, which fuels transport, displays positive cooperativity in numerous ABC transporters. In particular, heterodimeric ABC exporters exhibit pronounced allosteric coupling between a catalytically impaired degenerate site, where nucleotides bind tightly, and a consensus site, at which ATP is hydrolyzed in every transport cycle. Whereas the functional phenomenon of cooperativity is well described, its structural basis remains poorly understood. Here, we present the apo structure of the heterodimeric ABC exporter TM287/288 and compare it to the previously solved structure with adenosine 5'-(β,γ-imido)triphosphate (AMP-PNP) bound at the degenerate site. In contrast to other ABC exporter structures, the nucleotide binding domains (NBDs) of TM287/288 remain in molecular contact even in the absence of nucleotides, and the arrangement of the transmembrane domains (TMDs) is not influenced by AMP-PNP binding, a notion confirmed by double electron-electron resonance (DEER) measurements. Nucleotide binding at the degenerate site results in structural rearrangements, which are transmitted to the consensus site via two D-loops located at the NBD interface. These loops owe their name from a highly conserved aspartate and are directly connected to the catalytically important Walker B motif. The D-loop at the degenerate site ties the NBDs together even in the absence of nucleotides and substitution of its aspartate by alanine is well-tolerated. By contrast, the D-loop of the consensus site is flexible and the aspartate to alanine mutation and conformational restriction by cross-linking strongly reduces ATP hydrolysis and substrate transport.

Optimization of a reusable, DNA pseudoknot-based electrochemical sensor for sequence-specific DNA detection in blood serum.

PubMed

Cash, Kevin J; Heeger, Alan J; Plaxco, Kevin W; Xiao, Yi

2009-01-15

We describe in detail a new electrochemical DNA (E-DNA) sensing platform based on target-induced conformation changes in an electrode-bound DNA pseudoknot. The pseudoknot, a DNA structure containing two stem-loops in which the first stem's loop forms part of the second stem, is modified with a methylene blue redox tag at its 3' terminus and covalently attached to a gold electrode via the 5' terminus. In the absence of a target, the structure of the pseudoknot probe minimizes collisions between the redox tag and the electrode, thus reducing faradaic current. Target binding disrupts the pseudoknot structure, liberating a flexible, single-stranded element that can strike the electrode and efficiently transfer electrons. In this article we report further characterization and optimization of this new E-DNA architecture. We find that optimal signaling is obtained at an intermediate probe density ( approximately 1.8 x 10(13) molecules/cm(2) apparent density), which presumably represents a balance between steric and electrostatic blocking at high probe densities and increased background currents arising from transfer from the pseudoknot probe at lower densities. We also find that optimal 3' stem length, which appears to be 7 base pairs, represents a balance between pseudoknot structural stability and target affinity. Finally, a 3' loop comprised of poly(A) exhibits better mismatch discrimination than the equivalent poly(T) loop, but at the cost of decreased gain. Optimization over this parameter space significantly improves the signaling of the pseudoknot-based E-DNA architecture, leading to the ability to sensitively and specifically detect DNA targets even when challenged in complex, multicomponent samples such as blood serum.

Optimization of a Reusable, DNA Pseudoknot-Based Electrochemical Sensor for Sequence-Specific DNA Detection in Blood Serum

PubMed Central

Cash, Kevin J.; Heeger, Alan J.; Plaxco, Kevin W.; Xiao, Yi

2010-01-01

We describe in detail a new electrochemical DNA (E-DNA) sensing platform based on target-induced conformation changes in an electrode-bound DNA pseudoknot. The pseudoknot, a DNA structure containing two stem-loops in which the first stem’s loop forms part of the second stem, is modified with a methylene blue redox tag at its 3′ terminus and covalently attached to a gold electrode via the 5′ terminus. In the absence of a target, the structure of the pseudoknot probe minimizes collisions between the redox tag and the electrode, thus reducing faradaic current. Target binding disrupts the pseudoknot structure, liberating a flexible, single-stranded element that can strike the electrode and efficiently transfer electrons. In this article we report further characterization and optimization of this new E-DNA architecture. We find that optimal signaling is obtained at an intermediate probe density (~1.8 × 1013 molecules/cm2 apparent density), which presumably represents a balance between steric and electrostatic blocking at high probe densities and increased background currents arising from transfer from the pseudoknot probe at lower densities. We also find that optimal 3′ stem length, which appears to be 7 base pairs, represents a balance between pseudoknot structural stability and target affinity. Finally, a 3′ loop comprised of poly(A) exhibits better mismatch discrimination than the equivalent poly(T) loop, but at the cost of decreased gain. Optimization over this parameter space significantly improves the signaling of the pseudoknot-based E-DNA architecture, leading to the ability to sensitively and specifically detect DNA targets even when challenged in complex, multicomponent samples such as blood serum. PMID:19093760

A Generic Inner-Loop Control Law Structure for Six-Degree-of-Freedom Conceptual Aircraft Design

NASA Technical Reports Server (NTRS)

Cox, Timothy H.; Cotting, M. Christopher

2005-01-01

A generic control system framework for both real-time and batch six-degree-of-freedom simulations is presented. This framework uses a simplified dynamic inversion technique to allow for stabilization and control of any type of aircraft at the pilot interface level. The simulation, designed primarily for the real-time simulation environment, also can be run in a batch mode through a simple guidance interface. Direct vehicle-state acceleration feedback is required with the simplified dynamic inversion technique. The estimation of surface effectiveness within real-time simulation timing constraints also is required. The generic framework provides easily modifiable control variables, allowing flexibility in the variables that the pilot commands. A direct control allocation scheme is used to command aircraft effectors. Primary uses for this system include conceptual and preliminary design of aircraft, when vehicle models are rapidly changing and knowledge of vehicle six-degree-of-freedom performance is required. A simulated airbreathing hypersonic vehicle and simulated high-performance fighter aircraft are used to demonstrate the flexibility and utility of the control system.

A Generic Inner-Loop Control Law Structure for Six-Degree-of-Freedom Conceptual Aircraft Design

NASA Technical Reports Server (NTRS)

Cox, Timothy H.; Cotting, Christopher

2005-01-01

A generic control system framework for both real-time and batch six-degree-of-freedom (6-DOF) simulations is presented. This framework uses a simplified dynamic inversion technique to allow for stabilization and control of any type of aircraft at the pilot interface level. The simulation, designed primarily for the real-time simulation environment, also can be run in a batch mode through a simple guidance interface. Direct vehicle-state acceleration feedback is required with the simplified dynamic inversion technique. The estimation of surface effectiveness within real-time simulation timing constraints also is required. The generic framework provides easily modifiable control variables, allowing flexibility in the variables that the pilot commands. A direct control allocation scheme is used to command aircraft effectors. Primary uses for this system include conceptual and preliminary design of aircraft, when vehicle models are rapidly changing and knowledge of vehicle 6-DOF performance is required. A simulated airbreathing hypersonic vehicle and simulated high-performance fighter aircraft are used to demonstrate the flexibility and utility of the control system.

Poly-Cross-Linked PEI Through Aromatically Conjugated Imine Linkages as a New Class of pH-Responsive Nucleic Acids Packing Cationic Polymers

PubMed Central

Chen, Shun; Jin, Tuo

2016-01-01

Cationic polyimines polymerized through aromatically conjugated bis-imine linkages and intra-molecular cross-linking were found to be a new class of effective transfection materials for their flexibility in structural optimization, responsiveness to intracellular environment, the ability to facilitate endosome escape and cytosol release of the nucleic acids, as well as self-metabolism. When three phthalaldehydes of different substitution positions were used to polymerize highly branched low-molecular weight polyethylenimine (PEI 1.8K), the product through ortho-phthalimines (named PPOP) showed significantly higher transfection activity than its two tere- and iso-analogs (named PPTP and PPIP). Physicochemical characterization confirmed the similarity of three polyimines in pH-responded degradability, buffer capacity, as well as the size and Zeta potential of the polyplexes formed from the polymers. A mechanistic speculation may be that the ortho-positioned bis-imine linkage of PPOP may only lead to the straight trans-configuration due to steric hindrance, resulting in larger loops of intra-polymer cross-linking and more flexible backbone. PMID:26869931

Coherent receiver design based on digital signal processing in optical high-speed intersatellite links with M-phase-shift keying

NASA Astrophysics Data System (ADS)

Schaefer, Semjon; Gregory, Mark; Rosenkranz, Werner

2016-11-01

We present simulative and experimental investigations of different coherent receiver designs for high-speed optical intersatellite links. We focus on frequency offset (FO) compensation in homodyne and intradyne detection systems. The considered laser communication terminal uses an optical phase-locked loop (OPLL), which ensures stable homodyne detection. However, the hardware complexity increases with the modulation order. Therefore, we show that software-based intradyne detection is an attractive alternative for OPLL-based homodyne systems. Our approach is based on digital FO and phase noise compensation, in order to achieve a more flexible coherent detection scheme. Analytic results will further show the theoretical impact of the different detection schemes on the receiver sensitivity. Finally, we compare the schemes in terms of bit error ratio measurements and optimal receiver design.

Coupled dual loop absorption heat pump

DOEpatents

Sarkisian, Paul H.; Reimann, Robert C.; Biermann, Wendell J.

1985-01-01

A coupled dual loop absorption system which utilizes two separate complete loops. Each individual loop operates at three temperatures and two pressures. This low temperature loop absorber and condenser are thermally coupled to the high temperature loop evaporator, and the high temperature loop condenser and absorber are thermally coupled to the low temperature generator.

Structural analysis of a highly glycosylated and unliganded gp120-based antigen using mass spectrometry†

PubMed Central

Wang, Liwen; Qin, Yali; Ilchenko, Serguei; Bohon, Jen; Shi, Wuxian; Cho, Michael W.; Takamoto, Keiji; Chance, Mark R.

2010-01-01

Structural characterization of the HIV envelope protein gp120 is very important to provide an understanding of the protein's immunogenicity and it's binding to cell receptors. So far, crystallographic structure determination of gp120 with an intact V3 loop (in the absence of CD4 co-receptor or antibody) has not been achieved. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for co-receptor binding and viral entry to T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated glycosylation occupancy of gp120-OD8; eleven sites from fifteen glycosylation motifs were determined as having high mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information on protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4/ gp120-OD8 crystal structure revealed a flexible V3 loop structure where the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure. PMID:20825246

Assessment of Adaptive Guidance for Responsive Launch Vehicles and Spacecraft

DTIC Science & Technology

2009-04-29

Figures 1 Earth centered inertial and launch plumbline coordinate systems . . . . . . . 7 2 Geodetic and geocentric latitude...Dramatically reduced reoccurring costs related to guidance. The same features of the closed-loop ascent guidance that provide operational flexibility...also result in greatly reduced need for human intervention. Thus the operational costs related to ascent guidance could be reduced to minimum

Digital controller design: Continuous and discrete describing function analysis of the IPS system

NASA Technical Reports Server (NTRS)

1977-01-01

The dynamic equations and the mathematical model of the continuous-data IPS control system are developed. The IPS model considered included one flexible body mode and was hardmounted to the Orbiter/Pallet. The model contains equations describing a torque feed-forward loop (using accelerometers as inputs) which will aid in reducing the pointing errors caused by Orbiter disturbances.

Delineating Substrate Diversity of Disparate Short-Chain Dehydrogenase Reductase from Debaryomyces hansenii.

PubMed

Ghatak, Arindam; Bharatham, Nagakumar; Shanbhag, Anirudh P; Datta, Santanu; Venkatraman, Janani

2017-01-01

Short-chain dehydrogenase reductases (SDRs) have been utilized for catalyzing the reduction of many aromatic/aliphatic prochiral ketones to their respective alcohols. However, there is a paucity of data that elucidates their innate biological role and diverse substrate space. In this study, we executed an in-depth biochemical characterization and substrate space mapping (with 278 prochiral ketones) of an unannotated SDR (DHK) from Debaryomyces hansenii and compared it with structurally and functionally characterized SDR Synechococcus elongatus. PCC 7942 FabG to delineate its industrial significance. It was observed that DHK was significantly more efficient than FabG, reducing a diverse set of ketones albeit at higher conversion rates. Comparison of the FabG structure with a homology model of DHK and a docking of substrate to both structures revealed the presence of additional flexible loops near the substrate binding site of DHK. The comparative elasticity of the cofactor and substrate binding site of FabG and DHK was experimentally substantiated using differential scanning fluorimetry. It is postulated that the loop flexibility may account for the superior catalytic efficiency of DHK although the positioning of the catalytic triad is conserved.

Delineating Substrate Diversity of Disparate Short-Chain Dehydrogenase Reductase from Debaryomyces hansenii

PubMed Central

Ghatak, Arindam; Bharatham, Nagakumar; Shanbhag, Anirudh P.; Datta, Santanu; Venkatraman, Janani

2017-01-01

Short-chain dehydrogenase reductases (SDRs) have been utilized for catalyzing the reduction of many aromatic/aliphatic prochiral ketones to their respective alcohols. However, there is a paucity of data that elucidates their innate biological role and diverse substrate space. In this study, we executed an in-depth biochemical characterization and substrate space mapping (with 278 prochiral ketones) of an unannotated SDR (DHK) from Debaryomyces hansenii and compared it with structurally and functionally characterized SDR Synechococcus elongatus. PCC 7942 FabG to delineate its industrial significance. It was observed that DHK was significantly more efficient than FabG, reducing a diverse set of ketones albeit at higher conversion rates. Comparison of the FabG structure with a homology model of DHK and a docking of substrate to both structures revealed the presence of additional flexible loops near the substrate binding site of DHK. The comparative elasticity of the cofactor and substrate binding site of FabG and DHK was experimentally substantiated using differential scanning fluorimetry. It is postulated that the loop flexibility may account for the superior catalytic efficiency of DHK although the positioning of the catalytic triad is conserved. PMID:28107498

Semi-globally input-to-state stable controller design for flexible spacecraft attitude stabilization under bounded disturbances

NASA Astrophysics Data System (ADS)

Hu, Qinglei

2010-02-01

Semi-globally input-to-state stable (ISS) control law is derived for flexible spacecraft attitude maneuvers in the presence of parameter uncertainties and external disturbances. The modified rodrigues parameters (MRP) are used as the kinematic variables since they are nonsingular for all possible rotations. This novel simple control is a proportional-plus-derivative (PD) type controller plus a sign function through a special Lyapunov function construction involving the sum of quadratic terms in the angular velocities, kinematic parameters, modal variables and the cross state weighting. A sufficient condition under which this nonlinear PD-type control law can render the system semi-globally input-to-state stable is provided such that the closed-loop system is robust with respect to any disturbance within a quantifiable restriction on the amplitude, as well as the set of initial conditions, if the control gains are designed appropriately. In addition to detailed derivations of the new controllers design and a rigorous sketch of all the associated stability and attitude convergence proofs, extensive simulation studies have been conducted to validate the design and the results are presented to highlight the ensuring closed-loop performance benefits when compared with the conventional control schemes.

The multiple-function multi-input/multi-output digital controller system for the AFW wind-tunnel model

NASA Technical Reports Server (NTRS)

Hoadley, Sherwood T.; Mcgraw, Sandra M.

1992-01-01

A real time multiple-function digital controller system was developed for the Active Flexible Wing (AFW) Program. The digital controller system (DCS) allowed simultaneous execution of two control laws: flutter suppression and either roll trim or a rolling maneuver load control. The DCS operated within, but independently of, a slower host operating system environment, at regulated speeds up to 200 Hz. It also coordinated the acquisition, storage, and transfer of data for near real time controller performance evaluation and both open- and closed-loop plant estimation. It synchronized the operation of four different processing units, allowing flexibility in the number, form, functionality, and order of control laws, and variability in the selection of the sensors and actuators employed. Most importantly, the DCS allowed for the successful demonstration of active flutter suppression to conditions approximately 26 percent (in dynamic pressure) above the open-loop boundary in cases when the model was fixed in roll and up to 23 percent when it was free to roll. Aggressive roll maneuvers with load control were achieved above the flutter boundary. The purpose here is to present the development, validation, and wind tunnel testing of this multiple-function digital controller system.

The OGO attitude control subsystem redesign as a result of OGO 3 experience. Volume 1: System analysis and design studies

NASA Technical Reports Server (NTRS)

Mckenna, K. J.

1967-01-01

An oscillation in the OGO-3 roll control channel, resulting from the EP-5 and EP-6 boom motion coupling into the control channel and causing loss of attitude control, is investigated. The study includes (1) an analysis of the OGO-3 and OGO-2 flight data to determine the nature and extent of the roll oscillation phenomena, (2) design analysis of the complete attitude control subsystem (ACS) to evolve changes which would prevent recurrences of the coupled ACS boom oscillation observed on OGO-3, and (3) analog simulations to verify the performance of the design changes selected. Portions of OGO-3 and OGO-2 flight data are illustrated and the major flexible body oscillation are identified. A model of the major flexible appendage dynamics is developed and is shown analytically and through analog simulations to reproduce the OGO-3 oscillation phenomena. The design changes which were found necessary are: a reversal delay logic for the roll reaction wheels, widening of the solar array dead zone from 0.5 to 1.0 deg, and modification of the OPEP control loop to include a filter and stabilizing feedback loops.

NASA Tech Briefs, June 2010

NASA Technical Reports Server (NTRS)

2010-01-01

Topics covered include: Situational Awareness from a Low-Cost Camera System; Data Acquisition System for Multi-Frequency Radar Flight Operations Preparation; Mercury Toolset for Spatiotemporal Metadata; Social Tagging of Mission Data; Integrating Radar Image Data with Google Maps; Demonstration of a Submillimeter-Wave HEMT Oscillator Module at 330 GHz; Flexible Peripheral Component Interconnect Input/Output Card; Interface Supports Lightweight Subsystem Routing for Flight Applications; MMIC Amplifiers and Wafer Probes for 350 to 500 GHz; Public Risk Assessment Program; Particle Swarm Optimization Toolbox; Telescience Support Center Data System Software; Update on PISCES; Ground and Space Radar Volume Matching and Comparison Software; Web-Based Interface for Command and Control of Network Sensors; Orbit Determination Toolbox; Distributed Observer Network; Computer-Automated Evolution of Spacecraft X-Band Antennas; Practical Loop-Shaping Design of Feedback Control Systems; Fully Printed High-Frequency Phased-Array Antenna on Flexible Substrate; Formula for the Removal and Remediation of Polychlorinated Biphenyls in Painted Structures; Integrated Solar Concentrator and Shielded Radiator; Water Membrane Evaporator; Modeling of Failure for Analysis of Triaxial Braided Carbon Fiber Composites; Catalyst for Carbon Monoxide Oxidation; Titanium Hydroxide - a Volatile Species at High Temperature; Selective Functionalization of Carbon Nanotubes: Part II; Steerable Hopping Six-Legged Robot; Launchable and Retrievable Tetherobot; Hybrid Heat Exchangers; Orbital Winch for High-Strength, Space-Survivable Tethers; Parameterized Linear Longitudinal Airship Model; and Physics of Life: A Model for Non-Newtonian Properties of Living Systems.

IGBT Switching Characteristic Curve Embedded Half-Bridge MMC Modelling and Real Time Simulation Realization

NASA Astrophysics Data System (ADS)

Zhengang, Lu; Hongyang, Yu; Xi, Yang

2017-05-01

The Modular Multilevel Converter (MMC) is one of the most attractive topologies in recent years for medium or high voltage industrial applications, such as high voltage dc transmission (HVDC) and medium voltage varying speed motor drive. The wide adoption of MMCs in industry is mainly due to its flexible expandability, transformer-less configuration, common dc bus, high reliability from redundancy, and so on. But, when the sub module number of MMC is more, the test of MMC controller will cost more time and effort. Hardware in the loop test based on real time simulator will save a lot of time and money caused by the MMC test. And due to the flexible of HIL, it becomes more and more popular in the industry area. The MMC modelling method remains an important issue for the MMC HIL test. Specifically, the VSC model should realistically reflect the nonlinear device switching characteristics, switching and conduction losses, tailing current, and diode reverse recovery behaviour of a realistic converter. In this paper, an IGBT switching characteristic curve embedded half-bridge MMC modelling method is proposed. This method is based on the switching curve referring and sample circuit calculation, and it is sample for implementation. Based on the proposed method, a FPGA real time simulation is carried out with 200ns sample time. The real time simulation results show the proposed method is correct.

Direct energy conversion using liquid metals

NASA Astrophysics Data System (ADS)

Onea, Alexandru; Diez de los Rios Ramos, Nerea; Hering, Wolfgang; Stieglitz, Robert; Moster, Peter

2014-12-01

Liquid metals have excellent properties to be used as heat transport fluids due to their high thermal conductivity and their wide applicable temperature range. The latter issue can be used to go beyond limitations of existing thermal solar energy systems. Furthermore, the direct energy converter Alkali Metal Thermo Electric Converter (AMTEC) can be used to make intangible areas of energy conversion suitable for a wide range of applications. One objective is to investigate AMTEC as a complementary cycle for the next generation of concentrating solar power (CSP) systems. The experimental research taking place in the Karlsruhe Institute of Technology (KIT) is focused on the construction of a flexible AMTEC test facility, development, test and improvement of liquid-anode and vapor-anode AMTEC devices as well as the coupling of the AMTEC cold side to the heat storage tank proposed for the CSP system. Within this project, the investigations foreseen will focus on the analyses of BASE-metal interface, electrode materials and deposition techniques, corrosion and erosion of materials brought in contact with high temperature sodium. This prototype demonstrator is planned to be integrated in the KArlsruhe SOdium LAboratory (KASOLA), a flexible closed mid-size sodium loop, completely in-house designed, presently under construction at the Institute for Neutron Physics and Reactor Technology (INR) within KIT.

Analysis and experiments for delay compensation in attitude control of flexible spacecraft

NASA Astrophysics Data System (ADS)

Sabatini, Marco; Palmerini, Giovanni B.; Leonangeli, Nazareno; Gasbarri, Paolo

2014-11-01

Space vehicles are often characterized by highly flexible appendages, with low natural frequencies which can generate coupling phenomena during orbital maneuvering. The stability and delay margins of the controlled system are deeply affected by the presence of bodies with different elastic properties, assembled to form a complex multibody system. As a consequence, unstable behavior can arise. In this paper the problem is first faced from a numerical point of view, developing accurate multibody mathematical models, as well as relevant navigation and control algorithms. One of the main causes of instability is identified with the unavoidable presence of time delays in the GNC loop. A strategy to compensate for these delays is elaborated and tested using the simulation tool, and finally validated by means of a free floating platform, replicating the flexible spacecraft attitude dynamics (single axis rotation). The platform is equipped with thrusters commanded according to the on-off modulation of the Linear Quadratic Regulator (LQR) control law. The LQR is based on the estimate of the full state vector, i.e. including both rigid - attitude - and elastic variables, that is possible thanks to the on line measurement of the flexible displacements, realized by processing the images acquired by a dedicated camera. The accurate mathematical model of the system and the rigid and elastic measurements enable a prediction of the state, so that the control is evaluated taking the predicted state relevant to a delayed time into account. Both the simulations and the experimental campaign demonstrate that by compensating in this way the time delay, the instability is eliminated, and the maneuver is performed accurately.

Compact, Highly Efficient, and Fully Flexible Circularly Polarized Antenna Enabled by Silver Nanowires for Wireless Body-Area Networks.

PubMed

Jiang, Zhi Hao; Cui, Zheng; Yue, Taiwei; Zhu, Yong; Werner, Douglas H

2017-08-01

A compact and flexible circularly polarized (CP) wearable antenna is introduced for wireless body-area network systems at the 2.4 GHz industrial, scientific, and medical (ISM) band, which is implemented by employing a low-loss composite of polydimethylsiloxane (PDMS) and silver nanowires (AgNWs). The circularly polarized radiation is enabled by placing a planar linearly polarized loop monopole above a finite anisotropic artificial ground plane. By truncating the anisotropic artificial ground plane to contain only 2 by 2 unit cells, an integrated antenna with a compact form factor of 0.41λ 0 × 0.41λ 0 × 0.045λ 0 is obtained, all while possessing an improved angular coverage of CP radiation. A flexible prototype was fabricated and characterized, experimentally achieving S 11 <- 15 dB, an axial ratio of less than 3 dB, a gain of around 5.2 dBi, and a wide CP angular coverage in the targeted ISM band. Furthermore, this antenna is compared to a conventional CP patch antenna of the same physical size, which is also comprised of the same PDMS and AgNW composite. The results of this comparison reveal that the proposed antenna has much more stable performance under bending and human body loading, as well as a lower specific absorption rate. In all, the demonstrated wearable antenna offers a compact, flexible, and robust solution which makes it a strong candidate for future integration into body-area networks that require efficient off-body communications.

Attitude and articulation control system testing for Project Galileo

NASA Technical Reports Server (NTRS)

Rasmussen, R. D.

1981-01-01

A type of facility required to integrate and test a complex autonomous spacecraft subsystem is presented, using the attitude and articulation control subsystem (AACS) of Project Galileo as an example. The equipment created for testing the AACS at both the subsystem and spacecraft system levels is described, including a description of the support equipment (SE) architecture in its two main configurations, closed loop simulation techniques, the user interface to the SE, and plans for the use of the facility beyond the test period. This system is capable of providing a flight-like functional environment through the use of accurate real-time models and carefully chosen points of interaction, and flexible control capability and high visibility to the test operator.

Bonsai: an event-based framework for processing and controlling data streams

PubMed Central

Lopes, Gonçalo; Bonacchi, Niccolò; Frazão, João; Neto, Joana P.; Atallah, Bassam V.; Soares, Sofia; Moreira, Luís; Matias, Sara; Itskov, Pavel M.; Correia, Patrícia A.; Medina, Roberto E.; Calcaterra, Lorenza; Dreosti, Elena; Paton, Joseph J.; Kampff, Adam R.

2015-01-01

The design of modern scientific experiments requires the control and monitoring of many different data streams. However, the serial execution of programming instructions in a computer makes it a challenge to develop software that can deal with the asynchronous, parallel nature of scientific data. Here we present Bonsai, a modular, high-performance, open-source visual programming framework for the acquisition and online processing of data streams. We describe Bonsai's core principles and architecture and demonstrate how it allows for the rapid and flexible prototyping of integrated experimental designs in neuroscience. We specifically highlight some applications that require the combination of many different hardware and software components, including video tracking of behavior, electrophysiology and closed-loop control of stimulation. PMID:25904861

AMP-Activated Protein Kinase β-Subunit Requires Internal Motion for Optimal Carbohydrate Binding

PubMed Central

Bieri, Michael; Mobbs, Jesse I.; Koay, Ann; Louey, Gavin; Mok, Yee-Foong; Hatters, Danny M.; Park, Jong-Tae; Park, Kwan-Hwa; Neumann, Dietbert; Stapleton, David; Gooley, Paul R.

2012-01-01

AMP-activated protein kinase interacts with oligosaccharides and glycogen through the carbohydrate-binding module (CBM) containing the β-subunit, for which there are two isoforms (β1 and β2). Muscle-specific β2-CBM, either as an isolated domain or in the intact enzyme, binds carbohydrates more tightly than the ubiquitous β1-CBM. Although residues that contact carbohydrate are strictly conserved, an additional threonine in a loop of β2-CBM is concurrent with an increase in flexibility in β2-CBM, which may account for the affinity differences between the two isoforms. In contrast to β1-CBM, unbound β2-CBM showed microsecond-to-millisecond motion at the base of a β-hairpin that contains residues that make critical contacts with carbohydrate. Upon binding to carbohydrate, similar microsecond-to-millisecond motion was observed in this β-hairpin and the loop that contains the threonine insertion. Deletion of the threonine from β2-CBM resulted in reduced carbohydrate affinity. Although motion was retained in the unbound state, a significant loss of motion was observed in the bound state of the β2-CBM mutant. Insertion of a threonine into the background of β1-CBM resulted in increased ligand affinity and flexibility in these loops when bound to carbohydrate. However, these mutations indicate that the additional threonine is not solely responsible for the differences in carbohydrate affinity and protein dynamics. Nevertheless, these results suggest that altered protein dynamics may contribute to differences in the ligand affinity of the two naturally occurring CBM isoforms. PMID:22339867

A photoaffinity scan maps regions of the p85 SH2 domain involved in phosphoprotein binding.

PubMed

Williams, K P; Shoelson, S E

1993-03-15

Src homology 2 (SH2) domains are modular phosphotyrosine binding pockets found within a wide variety of cytoplasmic signaling molecules. Here we develop a new approach to analyzing protein-protein interfaces termed photoaffinity scanning, and apply the method to map regions of the phosphatidylinositol 3-kinase p85 SH2 domain that participate in phospho-protein binding. Each residue except phosphotyrosine (pY) within a tightly binding, IRS-1-derived phosphopeptide (GNGDpYMPMSPKS) was substituted with the photoactive amino acid, benzoylphenylalanine (Bpa). Whereas most substitutions had little effect on binding affinity, Bpa substitution of either Met (+1 and +3 with respect to pY) reduced affinity 50-100-fold to confirm their importance in the pYMXM recognition motif. In three cases photolysis of SH2 domain/Bpa phosphopeptide complexes led to cross-linking of > 50% of the SH2 domain; cross-link positions were identified by microsequence, amino acid composition, and electrospray mass spectrometric analyses. Bpa-1 cross-links within alpha-helix I, whereas Bpa+1 and Bpa+4 cross-link the SH2 domain within the flexible loop C-terminal to alpha-helix II. Moreover, cross-linking at any position prevents SH2 domain cleavage at a trypsin-sensitive site within the flexible loop between beta-strands 1 and 2. Therefore, at least three distinct SH2 regions in addition to the beta-sheet participate in phosphoprotein binding; the loop cross-linked by phosphopeptide residues C-terminal to pY appears to confer specificity to the phosphoprotein/SH2 domain interaction.

Direct adaptive fuzzy control of a translating piezoelectric flexible manipulator driven by a pneumatic rodless cylinder

NASA Astrophysics Data System (ADS)

Qiu, Zhi-cheng; Wang, Bin; Zhang, Xian-min; Han, Jian-da

2013-04-01

This study presents a novel translating piezoelectric flexible manipulator driven by a rodless cylinder. Simultaneous positioning control and vibration suppression of the flexible manipulator is accomplished by using a hybrid driving scheme composed of the pneumatic cylinder and a piezoelectric actuator. Pulse code modulation (PCM) method is utilized for the cylinder. First, the system dynamics model is derived, and its standard multiple input multiple output (MIMO) state-space representation is provided. Second, a composite proportional derivative (PD) control algorithms and a direct adaptive fuzzy control method are designed for the MIMO system. Also, a time delay compensation algorithm, bandstop and low-pass filters are utilized, under consideration of the control hysteresis and the caused high-frequency modal vibration due to the long stroke of the cylinder, gas compression and nonlinear factors of the pneumatic system. The convergence of the closed loop system is analyzed. Finally, experimental apparatus is constructed and experiments are conducted. The effectiveness of the designed controllers and the hybrid driving scheme is verified through simulation and experimental comparison studies. The numerical simulation and experimental results demonstrate that the proposed system scheme of employing the pneumatic drive and piezoelectric actuator can suppress the vibration and achieve the desired positioning location simultaneously. Furthermore, the adopted adaptive fuzzy control algorithms can significantly enhance the control performance.

Single-Molecule Microscopy and Force Spectroscopy of Membrane Proteins

NASA Astrophysics Data System (ADS)

Engel, Andreas; Janovjak, Harald; Fotiadis, Dimtrios; Kedrov, Alexej; Cisneros, David; Müller, Daniel J.

Single-molecule atomic force microscopy (AFM) provides novel ways to characterize the structure-function relationship of native membrane proteins. High-resolution AFM topographs allow observing the structure of single proteins at sub-nanometer resolution as well as their conformational changes, oligomeric state, molecular dynamics and assembly. We will review these feasibilities illustrating examples of membrane proteins in native and reconstituted membranes. Classification of individual topographs of single proteins allows understanding the principles of motions of their extrinsic domains, to learn about their local structural flexibilities and to find the entropy minima of certain conformations. Combined with the visualization of functionally related conformational changes these insights allow understanding why certain flexibilities are required for the protein to function and how structurally flexible regions allow certain conformational changes. Complementary to AFM imaging, single-molecule force spectroscopy (SMFS) experiments detect molecular interactions established within and between membrane proteins. The sensitivity of this method makes it possible to measure interactions that stabilize secondary structures such as transmembrane α-helices, polypeptide loops and segments within. Changes in temperature or protein-protein assembly do not change the locations of stable structural segments, but influence their stability established by collective molecular interactions. Such changes alter the probability of proteins to choose a certain unfolding pathway. Recent examples have elucidated unfolding and refolding pathways of membrane proteins as well as their energy landscapes.

Finite element based model predictive control for active vibration suppression of a one-link flexible manipulator.

PubMed

Dubay, Rickey; Hassan, Marwan; Li, Chunying; Charest, Meaghan

2014-09-01

This paper presents a unique approach for active vibration control of a one-link flexible manipulator. The method combines a finite element model of the manipulator and an advanced model predictive controller to suppress vibration at its tip. This hybrid methodology improves significantly over the standard application of a predictive controller for vibration control. The finite element model used in place of standard modelling in the control algorithm provides a more accurate prediction of dynamic behavior, resulting in enhanced control. Closed loop control experiments were performed using the flexible manipulator, instrumented with strain gauges and piezoelectric actuators. In all instances, experimental and simulation results demonstrate that the finite element based predictive controller provides improved active vibration suppression in comparison with using a standard predictive control strategy. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Control of a flexible planar truss using proof mass actuators

NASA Technical Reports Server (NTRS)

Minas, Constantinos; Garcia, Ephrahim; Inman, Daniel J.

1989-01-01

A flexible structure was modeled and actively controlled by using a single space realizable linear proof mass actuator. The NASA/UVA/UB actuator was attached to a flexible planar truss structure at an optimal location and it was considered as both passive and active device. The placement of the actuator was specified by examining the eigenvalues of the modified model that included the actuator dynamics, and the frequency response functions of the modified system. The electronic stiffness of the actuator was specified, such that the proof mass actuator system was tuned to the fourth structural mode of the truss by using traditional vibration absorber design. The active control law was limited to velocity feedback by integrating of the signals of two accelerometers attached to the structure. The two lower modes of the closed-loop structure were placed further in the LHS of the complex plane. The theoretically predicted passive and active control law was experimentally verified.

Input preshaping with frequency domain information for flexible-link manipulator control

NASA Technical Reports Server (NTRS)

Tzes, Anthony; Englehart, Matthew J.; Yurkovich, Stephen

1989-01-01

The application of an input preshaping scheme to flexible manipulators is considered. The resulting control corresponds to a feedforward term that convolves in real-time the desired reference input with a sequence of impulses and produces a vibration free output. The robustness of the algorithm with respect to injected disturbances and modal frequency variations is not satisfactory and can be improved by convolving the input with a longer sequence of impulses. The incorporation of the preshaping scheme to a closed-loop plant, using acceleration feedback, offers satisfactory disturbance rejection due to feedback and cancellation of the flexible mode effects due to the preshaping. A frequency domain identification scheme is used to estimate the modal frequencies on-line and subsequently update the spacing between the impulses. The combined adaptive input preshaping scheme provides the fastest possible slew that results in a vibration free output.

FlexibleSUSY-A spectrum generator generator for supersymmetric models

NASA Astrophysics Data System (ADS)

Athron, Peter; Park, Jae-hyeon; Stöckinger, Dominik; Voigt, Alexander

2015-05-01

We introduce FlexibleSUSY, a Mathematica and C++ package, which generates a fast, precise C++ spectrum generator for any SUSY model specified by the user. The generated code is designed with both speed and modularity in mind, making it easy to adapt and extend with new features. The model is specified by supplying the superpotential, gauge structure and particle content in a SARAH model file; specific boundary conditions e.g. at the GUT, weak or intermediate scales are defined in a separate FlexibleSUSY model file. From these model files, FlexibleSUSY generates C++ code for self-energies, tadpole corrections, renormalization group equations (RGEs) and electroweak symmetry breaking (EWSB) conditions and combines them with numerical routines for solving the RGEs and EWSB conditions simultaneously. The resulting spectrum generator is then able to solve for the spectrum of the model, including loop-corrected pole masses, consistent with user specified boundary conditions. The modular structure of the generated code allows for individual components to be replaced with an alternative if available. FlexibleSUSY has been carefully designed to grow as alternative solvers and calculators are added. Predefined models include the MSSM, NMSSM, E6SSM, USSM, R-symmetric models and models with right-handed neutrinos.

A three-level support method for smooth switching of the micro-grid operation model

NASA Astrophysics Data System (ADS)

Zong, Yuanyang; Gong, Dongliang; Zhang, Jianzhou; Liu, Bin; Wang, Yun

2018-01-01

Smooth switching of micro-grid between the grid-connected operation mode and off-grid operation mode is one of the key technologies to ensure it runs flexible and efficiently. The basic control strategy and the switching principle of micro-grid are analyzed in this paper. The reasons for the fluctuations of the voltage and the frequency in the switching process are analyzed from views of power balance and control strategy, and the operation mode switching strategy has been improved targeted. From the three aspects of controller’s current inner loop reference signal, voltage outer loop control strategy optimization and micro-grid energy balance management, a three-level security strategy for smooth switching of micro-grid operation mode is proposed. From the three aspects of controller’s current inner loop reference signal tracking, voltage outer loop control strategy optimization and micro-grid energy balance management, a three-level strategy for smooth switching of micro-grid operation mode is proposed. At last, it is proved by simulation that the proposed control strategy can make the switching process smooth and stable, the fluctuation problem of the voltage and frequency has been effectively improved.

Run-time scheduling and execution of loops on message passing machines

NASA Technical Reports Server (NTRS)

Crowley, Kay; Saltz, Joel; Mirchandaney, Ravi; Berryman, Harry

1989-01-01

Sparse system solvers and general purpose codes for solving partial differential equations are examples of the many types of problems whose irregularity can result in poor performance on distributed memory machines. Often, the data structures used in these problems are very flexible. Crucial details concerning loop dependences are encoded in these structures rather than being explicitly represented in the program. Good methods for parallelizing and partitioning these types of problems require assignment of computations in rather arbitrary ways. Naive implementations of programs on distributed memory machines requiring general loop partitions can be extremely inefficient. Instead, the scheduling mechanism needs to capture the data reference patterns of the loops in order to partition the problem. First, the indices assigned to each processor must be locally numbered. Next, it is necessary to precompute what information is needed by each processor at various points in the computation. The precomputed information is then used to generate an execution template designed to carry out the computation, communication, and partitioning of data, in an optimized manner. The design is presented for a general preprocessor and schedule executer, the structures of which do not vary, even though the details of the computation and of the type of information are problem dependent.

Run-time scheduling and execution of loops on message passing machines

NASA Technical Reports Server (NTRS)

Saltz, Joel; Crowley, Kathleen; Mirchandaney, Ravi; Berryman, Harry

1990-01-01

Sparse system solvers and general purpose codes for solving partial differential equations are examples of the many types of problems whose irregularity can result in poor performance on distributed memory machines. Often, the data structures used in these problems are very flexible. Crucial details concerning loop dependences are encoded in these structures rather than being explicitly represented in the program. Good methods for parallelizing and partitioning these types of problems require assignment of computations in rather arbitrary ways. Naive implementations of programs on distributed memory machines requiring general loop partitions can be extremely inefficient. Instead, the scheduling mechanism needs to capture the data reference patterns of the loops in order to partition the problem. First, the indices assigned to each processor must be locally numbered. Next, it is necessary to precompute what information is needed by each processor at various points in the computation. The precomputed information is then used to generate an execution template designed to carry out the computation, communication, and partitioning of data, in an optimized manner. The design is presented for a general preprocessor and schedule executer, the structures of which do not vary, even though the details of the computation and of the type of information are problem dependent.

PLATSIM: A Simulation and Analysis Package for Large-Order Flexible Systems. Version 2.0

NASA Technical Reports Server (NTRS)

Maghami, Peiman G.; Kenny, Sean P.; Giesy, Daniel P.

1997-01-01

The software package PLATSIM provides efficient time and frequency domain analysis of large-order generic space platforms. PLATSIM can perform open-loop analysis or closed-loop analysis with linear or nonlinear control system models. PLATSIM exploits the particular form of sparsity of the plant matrices for very efficient linear and nonlinear time domain analysis, as well as frequency domain analysis. A new, original algorithm for the efficient computation of open-loop and closed-loop frequency response functions for large-order systems has been developed and is implemented within the package. Furthermore, a novel and efficient jitter analysis routine which determines jitter and stability values from time simulations in a very efficient manner has been developed and is incorporated in the PLATSIM package. In the time domain analysis, PLATSIM simulates the response of the space platform to disturbances and calculates the jitter and stability values from the response time histories. In the frequency domain analysis, PLATSIM calculates frequency response function matrices and provides the corresponding Bode plots. The PLATSIM software package is written in MATLAB script language. A graphical user interface is developed in the package to provide convenient access to its various features.

Thermodynamics of single polyethylene and polybutylene glycols with hydrogen-bonding ends: A transition from looped to open conformations

NASA Astrophysics Data System (ADS)

Lee, Eunsang; Paul, Wolfgang

2018-02-01

A variety of linear polymer precursors with hydrogen bonding motifs at both ends enable us to design supramolecular polymer systems with tailored macroscopic properties including self-healing. In this study, we investigate thermodynamic properties of single polyethylene and polybutylene glycols with hydrogen bonding motifs. In this context, we first build a coarse-grained model of building blocks of the supramolecular polymer system based on all-atom molecular structures. The density of states of the single precursor is obtained using the stochastic approximation Monte Carlo method. Constructing canonical partition functions from the density of states, we find the transition from looped to open conformations at transition temperatures which are non-monotonously changing with an increasing degree of polymerization due to the competition between chain stiffness and loop-forming entropy penalty. In the complete range of chain length under investigation, a coexistence of the looped and open morphologies at the transition temperature is shown regardless of whether the transition is first-order-like or continuous. Polyethylene and polybutylene glycols show similar behavior in all the thermodynamic properties but the transition temperature of the more flexible polybutylene glycol is shown to change more gradually.

A reconfigurable visual-programming library for real-time closed-loop cellular electrophysiology

PubMed Central

Biró, István; Giugliano, Michele

2015-01-01

Most of the software platforms for cellular electrophysiology are limited in terms of flexibility, hardware support, ease of use, or re-configuration and adaptation for non-expert users. Moreover, advanced experimental protocols requiring real-time closed-loop operation to investigate excitability, plasticity, dynamics, are largely inaccessible to users without moderate to substantial computer proficiency. Here we present an approach based on MATLAB/Simulink, exploiting the benefits of LEGO-like visual programming and configuration, combined to a small, but easily extendible library of functional software components. We provide and validate several examples, implementing conventional and more sophisticated experimental protocols such as dynamic-clamp or the combined use of intracellular and extracellular methods, involving closed-loop real-time control. The functionality of each of these examples is demonstrated with relevant experiments. These can be used as a starting point to create and support a larger variety of electrophysiological tools and methods, hopefully extending the range of default techniques and protocols currently employed in experimental labs across the world. PMID:26157385

A Novel Amyloid Designable Scaffold and Potential Inhibitor Inspired by GAIIG of Amyloid Beta and the HIV-1 V3 loop.

PubMed

Kokotidou, C; Jonnalagadda, S V R; Orr, A A; Seoane-Blanco, M; Apostolidou, C P; van Raaij, M J; Kotzabasaki, M; Chatzoudis, A; Jakubowski, J M; Mossou, E; Forsyth, V T; Mitchell, E P; Bowler, M W; Llamas-Saiz, A L; Tamamis, P; Mitraki, A

2018-05-17

The GAIIG sequence, common to the amyloid beta peptide (residues 29-33) and to the HIV gp 120 (residues 24-28 in a typical V3 loop) self-assembles into amyloid fibrils, as suggested by theory and the experiments presented here. The longer YATGAIIGNII sequence from the V3 loop also self-assembles into amyloid fibrils, of which the first three and the last two residues are outside the amyloid GAIIG core. We postulate that this sequence, with suitable selected replacements at the flexible positions, can serve as a designable scaffold for novel amyloid-based materials. Moreover, we report the single X-ray crystal structure of the beta-breaker peptide GAIPIG at 1.05 Å resolution. This structural information could serve as the basis for structure-based design of potential inhibitors of amyloid formation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain.

PubMed

Shi, Hang; Rojas, Raul; Bonifacino, Juan S; Hurley, James H

2006-06-01

The mammalian retromer complex consists of SNX1, SNX2, Vps26, Vps29 and Vps35, and retrieves lysosomal enzyme receptors from endosomes to the trans-Golgi network. The structure of human Vps26A at 2.1-A resolution reveals two curved beta-sandwich domains connected by a polar core and a flexible linker. Vps26 has an unpredicted structural relationship to arrestins. The Vps35-binding site on Vps26 maps to a mobile loop spanning residues 235-246, near the tip of the C-terminal domain. The loop is phylogenetically conserved and provides a mechanism for Vps26 integration into the complex that leaves the rest of the structure free for engagements with membranes and for conformational changes. Hydrophobic residues and a glycine in this loop are required for integration into the retromer complex and endosomal localization of human Vps26, and for the function of yeast Vps26 in carboxypeptidase Y sorting.

Structure Prediction of the Second Extracellular Loop in G-Protein-Coupled Receptors

PubMed Central

Kmiecik, Sebastian; Jamroz, Michal; Kolinski, Michal

2014-01-01

G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs. PMID:24896119

Crystallization of dienelactone hydrolase in two space groups: structural changes caused by crystal packing

PubMed Central

Porter, Joanne L.; Carr, Paul D.; Collyer, Charles A.; Ollis, David L.

2014-01-01

Dienelactone hydrolase (DLH) is a monomeric protein with a simple α/β-hydrolase fold structure. It readily crystallizes in space group P212121 from either a phosphate or ammonium sulfate precipitation buffer. Here, the structure of DLH at 1.85 Å resolution crystallized in space group C2 with two molecules in the asymmetric unit is reported. When crystallized in space group P212121 DLH has either phosphates or sulfates bound to the protein in crucial locations, one of which is located in the active site, preventing substrate/inhibitor binding. Another is located on the surface of the enzyme coordinated by side chains from two different molecules. Crystallization in space group C2 from a sodium citrate buffer results in new crystallographic protein–protein interfaces. The protein backbone is highly similar, but new crystal contacts cause changes in side-chain orientations and in loop positioning. In regions not involved in crystal contacts, there is little change in backbone or side-chain configuration. The flexibility of surface loops and the adaptability of side chains are important factors enabling DLH to adapt and form different crystal lattices. PMID:25005082

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Yao; Tan, Kemin; Chhor, Gekleng

The EsxB protein from Bacillus anthracis belongs to the WXG100 family, a group of proteins secreted by a specialized secretion system. We have determined the crystal structures of recombinant EsxB and discovered that the small protein (~10 kDa), comprised of a helix-loop-helix (HLH) hairpin, is capable of associating into two different helical bundles. The two basic quaternary assemblies of EsxB are an antiparallel (AP) dimer and a rarely observed bisecting U (BU) dimer. This structural duality of EsxB is believed to originate from the heptad repeat sequence diversity of the first helix of its HLH hairpin, which allows for twomore » alternative helix packing. The flexibility of EsxB and the ability to form alternative helical bundles underscore the possibility that this protein can serve as an adaptor in secretion and can form hetero-oligomeric helix bundle(s) with other secreted members of the WXG100 family, such as EsxW. The highly conserved WXG motif is located within the loop of the HLH hairpin and is mostly buried within the helix bundle suggesting that its role is mainly structural. The exact functions of the motif, including a proposed role as a secretion signal, remain unknown.« less

A linear parameter-varying multiobjective control law design based on youla parametrization for a flexible blended wing body aircraft

NASA Astrophysics Data System (ADS)

Demourant, F.; Ferreres, G.

2013-12-01

This article presents a methodology for a linear parameter-varying (LPV) multiobjective flight control law design for a blended wing body (BWB) aircraft and results. So, the method is a direct design of a parametrized control law (with respect to some measured flight parameters) through a multimodel convex design to optimize a set of specifications on the full-flight domain and different mass cases. The methodology is based on the Youla parameterization which is very useful since closed loop specifications are affine with respect to Youla parameter. The LPV multiobjective design method is detailed and applied to the BWB flexible aircraft example.

Choosing Sensor Configuration for a Flexible Structure Using Full Control Synthesis

NASA Technical Reports Server (NTRS)

Lind, Rick; Nalbantoglu, Volkan; Balas, Gary

1997-01-01

Optimal locations and types for feedback sensors which meet design constraints and control requirements are difficult to determine. This paper introduces an approach to choosing a sensor configuration based on Full Control synthesis. A globally optimal Full Control compensator is computed for each member of a set of sensor configurations which are feasible for the plant. The sensor configuration associated with the Full Control system achieving the best closed-loop performance is chosen for feedback measurements to an output feedback controller. A flexible structure is used as an example to demonstrate this procedure. Experimental results show sensor configurations chosen to optimize the Full Control performance are effective for output feedback controllers.

Primary tracheal papilloma disguised as asthma: A case report.

PubMed

Chen, Yan-Bin; Jiang, Jun-Hong; Guo, Ling-Chuan; Huang, Jian-An

2016-12-01

Tracheal papilloma presenting as asthma is a rare occurrence. We report a case of a 32-year-old male patient who presented with features of asthma. Flexible bronchoscopy demonstrated a large growth arising from the lower end of the trachea. Successful treatment using snare loop and argon plasma coagulation (APC) of the polyploidal growth was performed via flexible bronchoscope. The patient had immediate relief of airway obstruction and histopathological examination of the neoplasm demonstrated features of papilloma. Primary tracheal papilloma is mimicker of asthma, CT scan should be considered in patients with persistent chronic cough, or stridor. Endoscopic papillectomy is a safe and effective treatment and should be considered as first-line therapy for tracheal papilloma.

Site-Directed Spin Labeling Reveals Pentameric Ligand-Gated Ion Channel Gating Motions

PubMed Central

Dellisanti, Cosma D.; Ghosh, Borna; Hanson, Susan M.; Raspanti, James M.; Grant, Valerie A.; Diarra, Gaoussou M.; Schuh, Abby M.; Satyshur, Kenneth; Klug, Candice S.; Czajkowski, Cynthia

2013-01-01

Pentameric ligand-gated ion channels (pLGICs) are neurotransmitter-activated receptors that mediate fast synaptic transmission. In pLGICs, binding of agonist to the extracellular domain triggers a structural rearrangement that leads to the opening of an ion-conducting pore in the transmembrane domain and, in the continued presence of neurotransmitter, the channels desensitize (close). The flexible loops in each subunit that connect the extracellular binding domain (loops 2, 7, and 9) to the transmembrane channel domain (M2–M3 loop) are essential for coupling ligand binding to channel gating. Comparing the crystal structures of two bacterial pLGIC homologues, ELIC and the proton-activated GLIC, suggests channel gating is associated with rearrangements in these loops, but whether these motions accurately predict the motions in functional lipid-embedded pLGICs is unknown. Here, using site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and functional GLIC channels reconstituted into liposomes, we examined if, and how far, the loops at the ECD/TMD gating interface move during proton-dependent gating transitions from the resting to desensitized state. Loop 9 moves ∼9 Å inward toward the channel lumen in response to proton-induced desensitization. Loop 9 motions were not observed when GLIC was in detergent micelles, suggesting detergent solubilization traps the protein in a nonactivatable state and lipids are required for functional gating transitions. Proton-induced desensitization immobilizes loop 2 with little change in position. Proton-induced motion of the M2–M3 loop was not observed, suggesting its conformation is nearly identical in closed and desensitized states. Our experimentally derived distance measurements of spin-labeled GLIC suggest ELIC is not a good model for the functional resting state of GLIC, and that the crystal structure of GLIC does not correspond to a desensitized state. These findings advance our understanding of the molecular mechanisms underlying pLGIC gating. PMID:24260024

Hepatitis Delta Antigen Requires a Flexible Quasi-Double-Stranded RNA Structure To Bind and Condense Hepatitis Delta Virus RNA in a Ribonucleoprotein Complex

PubMed Central

Griffin, Brittany L.; Chasovskikh, Sergey; Dritschilo, Anatoly

2014-01-01

ABSTRACT The circular genome and antigenome RNAs of hepatitis delta virus (HDV) form characteristic unbranched, quasi-double-stranded RNA secondary structures in which short double-stranded helical segments are interspersed with internal loops and bulges. The ribonucleoprotein complexes (RNPs) formed by these RNAs with the virus-encoded protein hepatitis delta antigen (HDAg) perform essential roles in the viral life cycle, including viral replication and virion formation. Little is understood about the formation and structure of these complexes and how they function in these key processes. Here, the specific RNA features required for HDAg binding and the topology of the complexes formed were investigated. Selective 2′OH acylation analyzed by primer extension (SHAPE) applied to free and HDAg-bound HDV RNAs indicated that the characteristic secondary structure of the RNA is preserved when bound to HDAg. Notably, the analysis indicated that predicted unpaired positions in the RNA remained dynamic in the RNP. Analysis of the in vitro binding activity of RNAs in which internal loops and bulges were mutated and of synthetically designed RNAs demonstrated that the distinctive secondary structure, not the primary RNA sequence, is the major determinant of HDAg RNA binding specificity. Atomic force microscopy analysis of RNPs formed in vitro revealed complexes in which the HDV RNA is substantially condensed by bending or wrapping. Our results support a model in which the internal loops and bulges in HDV RNA contribute flexibility to the quasi-double-stranded structure that allows RNA bending and condensing by HDAg. IMPORTANCE RNA-protein complexes (RNPs) formed by the hepatitis delta virus RNAs and protein, HDAg, perform critical roles in virus replication. Neither the structures of these RNPs nor the RNA features required to form them have been characterized. HDV RNA is unusual in that it forms an unbranched quasi-double-stranded structure in which short base-paired segments are interspersed with internal loops and bulges. We analyzed the role of the HDV RNA sequence and secondary structure in the formation of a minimal RNP and visualized the structure of this RNP using atomic force microscopy. Our results indicate that HDAg does not recognize the primary sequence of the RNA; rather, the principle contribution of unpaired bases in HDV RNA to HDAg binding is to allow flexibility in the unbranched quasi-double-stranded RNA structure. Visualization of RNPs by atomic force microscopy indicated that the RNA is significantly bent or condensed in the complex. PMID:24741096

Redistribution of flexibility in stabilizing antibody fragment mutants follows Le Châtelier's principle.

PubMed

Li, Tong; Tracka, Malgorzata B; Uddin, Shahid; Casas-Finet, Jose; Jacobs, Donald J; Livesay, Dennis R

2014-01-01

Le Châtelier's principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier's principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect.

Redistribution of Flexibility in Stabilizing Antibody Fragment Mutants Follows Le Châtelier’s Principle

PubMed Central

Li, Tong; Tracka, Malgorzata B.; Uddin, Shahid; Casas-Finet, Jose; Jacobs, Donald J.; Livesay, Dennis R.

2014-01-01

Le Châtelier’s principle is the cornerstone of our understanding of chemical equilibria. When a system at equilibrium undergoes a change in concentration or thermodynamic state (i.e., temperature, pressure, etc.), La Châtelier’s principle states that an equilibrium shift will occur to offset the perturbation and a new equilibrium is established. We demonstrate that the effects of stabilizing mutations on the rigidity ⇔ flexibility equilibrium within the native state ensemble manifest themselves through enthalpy-entropy compensation as the protein structure adjusts to restore the global balance between the two. Specifically, we characterize the effects of mutation to single chain fragments of the anti-lymphotoxin-β receptor antibody using a computational Distance Constraint Model. Statistically significant changes in the distribution of both rigidity and flexibility within the molecular structure is typically observed, where the local perturbations often lead to distal shifts in flexibility and rigidity profiles. Nevertheless, the net gain or loss in flexibility of individual mutants can be skewed. Despite all mutants being exclusively stabilizing in this dataset, increased flexibility is slightly more common than increased rigidity. Mechanistically the redistribution of flexibility is largely controlled by changes in the H-bond network. For example, a stabilizing mutation can induce an increase in rigidity locally due to the formation of new H-bonds, and simultaneously break H-bonds elsewhere leading to increased flexibility distant from the mutation site via Le Châtelier. Increased flexibility within the VH β4/β5 loop is a noteworthy illustration of this long-range effect. PMID:24671209

Next-Generation NATO Reference Mobility Model (NG-NRMM)

DTIC Science & Technology

2016-05-11

facilitate comparisons between vehicle design candidates and to assess the mobility of existing vehicles under specific scenarios. Although NRMM has...of different deployed platforms in different areas of operation and routes  Improved flexibility as a design and procurement support tool through...Element Method DEM Digital Elevation Model DIL Driver in the Loop DP Drawbar Pull Force DOE Design of Experiments DTED Digital Terrain Elevation Data

Two AFC Loops For Low CNR And High Dynamics

NASA Technical Reports Server (NTRS)

Hinedi, Sami M.; Aguirre, Sergio

1992-01-01

Two alternative digital automatic-frequency-control (AFC) loops proposed to acquire (or reacquire) and track frequency of received carrier radio signal. Intended for use where carrier-to-noise ratios (CNR's) low and carrier frequency characterized by high Doppler shift and Doppler rate because of high relative speed and acceleration, respectively, between transmitter and receiver. Either AFC loops used in place of phase-locked loop. New loop concepts integrate ideas from classical spectrum-estimation, digital-phase-locked-loop, and Kalman-Filter theories.

Decorating fiber nanotip with single perovskite quantum dot and other luminescent nanocrystals synthesized in oil-phase

NASA Astrophysics Data System (ADS)

Qian, Yu; Xing, Xing; Xu, Ya; Lu, Zhenda; Zhang, Weihua

2017-11-01

We report a simple yet robust method for fabricating single perovskite quantum dot (QD) decorated fiber nanotips. In this method, a single QD is directly picked up and subsequently glued on the apex of a specially fabricated cantilever fiber tip with a high success rate (approx. 70%) without using expensive close-loop feedback systems. Thanks to the flexibility and robustness of the fiber tips, no damage of the tips was observed in the process. Moreover, nanocrystal (NC) dispersing technique was developed to avoid undesired aggregations of QDs, and it guarantees that only one QD is glued each time. Finally, we demonstrate that this technique can also be applied to other oil-phase synthesized NCs, including CdSe QDs and upconversion luminescent NCs. It leads to many important applications on probing the local environment using high performance luminescent nanoprobes.

Noncontact conductivity and dielectric measurement for high throughput roll-to-roll nanomanufacturing

NASA Astrophysics Data System (ADS)

Orloff, Nathan D.; Long, Christian J.; Obrzut, Jan; Maillaud, Laurent; Mirri, Francesca; Kole, Thomas P.; McMichael, Robert D.; Pasquali, Matteo; Stranick, Stephan J.; Alexander Liddle, J.

2015-11-01

Advances in roll-to-roll processing of graphene and carbon nanotubes have at last led to the continuous production of high-quality coatings and filaments, ushering in a wave of applications for flexible and wearable electronics, woven fabrics, and wires. These applications often require specific electrical properties, and hence precise control over material micro- and nanostructure. While such control can be achieved, in principle, by closed-loop processing methods, there are relatively few noncontact and nondestructive options for quantifying the electrical properties of materials on a moving web at the speed required in modern nanomanufacturing. Here, we demonstrate a noncontact microwave method for measuring the dielectric constant and conductivity (or geometry for samples of known dielectric properties) of materials in a millisecond. Such measurement times are compatible with current and future industrial needs, enabling real-time materials characterization and in-line control of processing variables without disrupting production.

Noncontact conductivity and dielectric measurement for high throughput roll-to-roll nanomanufacturing

PubMed Central

Orloff, Nathan D.; Long, Christian J.; Obrzut, Jan; Maillaud, Laurent; Mirri, Francesca; Kole, Thomas P.; McMichael, Robert D.; Pasquali, Matteo; Stranick, Stephan J.; Alexander Liddle, J.

2015-01-01

Advances in roll-to-roll processing of graphene and carbon nanotubes have at last led to the continuous production of high-quality coatings and filaments, ushering in a wave of applications for flexible and wearable electronics, woven fabrics, and wires. These applications often require specific electrical properties, and hence precise control over material micro- and nanostructure. While such control can be achieved, in principle, by closed-loop processing methods, there are relatively few noncontact and nondestructive options for quantifying the electrical properties of materials on a moving web at the speed required in modern nanomanufacturing. Here, we demonstrate a noncontact microwave method for measuring the dielectric constant and conductivity (or geometry for samples of known dielectric properties) of materials in a millisecond. Such measurement times are compatible with current and future industrial needs, enabling real-time materials characterization and in-line control of processing variables without disrupting production. PMID:26592441

Preliminary design for a Zero Gravity Test Facility (ZGTF). Volume 1: Technical

NASA Technical Reports Server (NTRS)

Germain, A.

1981-01-01

The functional requirements and best conceptual design of a test facility that simulates weightless operating conditions for a high gain antenna systems (HGAS), that will broadcast to the Tracking Data Relay Satellites were defined. The typical HGAS defined is mounted on a low Earth orbiting satellite, and consists of an antenna with a double gimbal pointing system mounted on a 13 foot long mast. Typically, the gimbals are driven by pulse modulated dc motors or stepper motors. These drivers produce torques on the mast, with jitter that excites the satellite and may cause disturbances to sensitive experiments. The dynamic properties of the antenna support structure (mast), including flexible mode characteristics were defined. The torque profile induced on the spacecraft by motion of the high gain antenna was estimated. Gain and phase margins of the servo control loop of the gimbal drive electronics was also verified.

High Resistivity Transparent/Conductive Coatings for Space Applications: Problems and Possible Improvements

NASA Technical Reports Server (NTRS)

Cashman, Thomas; Demko, Rikako; Uppala, Nischala; Vemulapalli, Jyothi; Welch, Bryan; Hambourger, Paul D.

2003-01-01

We have prepared transparent films with a sheet relativity of 10(exp 1) to 10(exp 12) ohm/square by co-depositing a transparent conducting oxide (TCO) with magnesium fluoride, using two independently controlled RF magnetron sputter guns to facilitate adjustment of the film composition, Co-deposited indium tin oxide (ITO) and MgF2 on quartz and flexible polymeric substrate exhibited reasonably stable sheet resistivity over several months' time, with substantially lower optical reflectance than that of pure ITO. However, exposure to low-intensity blue light reduces sheet resistivity by as much as two orders of magnitude. Our results suggest this photoconductivity effect may be present in all InO(x)-based materials. We find that sheet resistivity can by "tuned" by admitting a small amount of high-purity air during deposition offering the possibility of closed loop process control.

Advances in optical structure systems; Proceedings of the Meeting, Orlando, FL, Apr. 16-19, 1990

NASA Astrophysics Data System (ADS)

Breakwell, John; Genberg, Victor L.; Krumweide, Gary C.

Various papers on advances in optical structure systems are presented. Individual topics addressed include: beam pathlength optimization, thermal stress in glass/metal bond with PR 1578 adhesive, structural and optical properties for typical solid mirror shapes, parametric study of spinning polygon mirror deformations, simulation of small structures-optics-controls system, spatial PSDs of optical structures due to random vibration, mountings for a four-meter glass mirror, fast-steering mirrors in optical control systems, adaptive state estimation for control of flexible structures, surface control techniques for large segmented mirrors, two-time-scale control designs for large flexible structures, closed-loop dynamic shape control of a flexible beam. Also discussed are: inertially referenced pointing for body-fixed payloads, sensor blending line-of-sight stabilization, controls/optics/structures simulation development, transfer functions for piezoelectric control of a flexible beam, active control experiments for large-optics vibration alleviation, composite structures for a large-optical test bed, graphite/epoxy composite mirror for beam-steering applications, composite structures for optical-mirror applications, thin carbon-fiber prepregs for dimensionally critical structures.

Flexible manipulator control experiments and analysis

NASA Technical Reports Server (NTRS)

Yurkovich, S.; Ozguner, U.; Tzes, A.; Kotnik, P. T.

1987-01-01

Modeling and control design for flexible manipulators, both from an experimental and analytical viewpoint, are described. From the application perspective, an ongoing effort within the laboratory environment at the Ohio State University, where experimentation on a single link flexible arm is underway is described. Several unique features of this study are described here. First, the manipulator arm is slewed by a direct drive dc motor and has a rigid counterbalance appendage. Current experimentation is from two viewpoints: (1) rigid body slewing and vibration control via actuation with the hub motor, and (2) vibration suppression through the use of structure-mounted proof-mass actuation at the tip. Such an application to manipulator control is of interest particularly in design of space-based telerobotic control systems, but has received little attention to date. From an analytical viewpoint, parameter estimation techniques within the closed-loop for self-tuning adaptive control approaches are discussed. Also introduced is a control approach based on output feedback and frequency weighting to counteract effects of spillover in reduced-order model design. A model of the flexible manipulator based on experimental measurements is evaluated for such estimation and control approaches.

Decoupled and linear quadratic regulator control of a large, flexible space antenna with an observer in the control loop

NASA Technical Reports Server (NTRS)

Hamer, H. A.; Johnson, K. G.; Young, J. W.

1985-01-01

An analysis is performed to compare decoupled and linear quadratic regulator (LQR) procedures for the control of a large, flexible space antenna. Control objectives involve: (1) commanding changes in the rigid-body modes, (2) nulling initial disturbances in the rigid-body modes, or (3) nulling initial disturbances in the first three flexible modes. Control is achieved with two three-axis control-moment gyros located on the antenna column. Results are presented to illustrate various effects on control requirements for the two procedures. These effects include errors in the initial estimates of state variables, variations in the type, number, and location of sensors, and deletions of state-variable estimates for certain flexible modes after control activation. The advantages of incorporating a time lag in the control feedback are also illustrated. In addition, the effects of inoperative-control situations are analyzed with regard to control requirements and resultant modal responses. Comparisons are included which show the effects of perfect state feedback with no residual modes (ideal case). Time-history responses are presented to illustrate the various effects on the control procedures.

Posterior spinal osteosynthesis for cervical fracture/dislocation using a flexible multistrand cable system: technical note.

PubMed

Huhn, S L; Wolf, A L; Ecklund, J

1991-12-01

Cervical instability secondary to fracture/dislocation or traumatic subluxation involving the posterior elements may be treated by a variety of fusion techniques. The rigidity of the stainless steel wires used in posterior cervical fusions often leads to difficulty with insertion, adequate tension, and conformation of the graft construct. This report describes a technique of posterior cervical fusion employing a wire system using flexible stainless steel cables. The wire consists of a flexible, 49-strand, stainless steel cable connected on one end to a short, malleable, blunt leader with the opposite end connected to a small islet. The cable may be used in occipitocervical, atlantoaxial, facet-to-spinous process, and interspinous fusion techniques. The cable loop is secured by using a tension/crimper device that sets the desired tension in the cable. In addition to superior biomechanical strength, the flexibility of the cable allows greater ease of insertion and tension adjustment. In terms of direct operative instrumentation in posterior cervical arthrodesis, involving both the upper and lower cervical spine, the cable system appears to be a safe and efficient alternative to monofilament wires.

Large deflections and vibrations of a tip pulled beam with variable transversal section

NASA Astrophysics Data System (ADS)

Kurka, P.; Izuka, J.; Gonzalez, P.; Teixeira, L. H.

2016-10-01

The use of long flexible probes in outdoors exploration vehicles, as opposed to short and rigid arms, is a convenient way to grant easier access to regions of scientific interest such as terrain slopes and cliff sides. Longer and taller arms can also provide information from a wider exploration horizon. The drawback of employing long and flexible exploration probes is the fact that its vibration is not easily controlled in real time operation by means of a simple analytic linear dynamic model. The numerical model required to describe the dynamics of a very long and flexible structure is often very large and of slow computational convergence. The present work proposes a simplified numerical model of a long flexible beam with variable cross section, which is statically deflected by a pulling cable. The paper compares the proposed simplified model with experimental data regarding the static and dynamic characteristics of a beam with variable cross section. The simulations show the effectiveness of the simplified dynamic model employed in an active control loop to suppress tip vibrations of the beam.

An RNA internal loop acts as a hinge to facilitate ribozyme folding and catalysis.

PubMed Central

Szewczak, A A; Cech, T R

1997-01-01

RNA molecules commonly consist of helical regions separated by internal loops, and in many cases these internal loops have been found to assume stable structures. We have examined the function and dynamics of an internal loop, J5/5a, that joins the two halves of the P4-P6 domain of the Tetrahymena self-splicing group I intron. P4-P6 RNAs with mutations in the J5/5a region showed nondenaturing gel electrophoretic mobilities and levels of Fe(II)-EDTA cleavage protection intermediate between those of wild-type RNA and a mutant incapable of folding into the native P4-P6 tertiary structure. Mutants with the least structured J5/5a loops behaved the most like wild-type P4-P6, and required smaller amounts of Mg2+ to rescue folding. The activity of reconstituted introns containing mutant P4-P6 RNAs correlated similarly with the nature of the J5/5a mutation. Our results suggest that, in solution, the P4-P6 RNA is in a two-state equilibrium between folded and unfolded states. We conclude that this internal loop mainly acts as a flexible hinge, allowing the coaxially stacked helical regions on either side of it to interact via specific tertiary contacts. To a lesser extent, the specific bases within the loop contribute to folding. Furthermore, it is crucial that the junction remain unstructured in the unfolded state. These conclusions cannot be derived from a simple examination of the P4-P6 crystal structure (Cate JH et al., 1996, Science 273:1678-1685), showing once again that structure determination must be supplemented with mutational and thermodynamic analysis to provide a complete picture of a folded macromolecule. PMID:9257643

Closed Loop Experiment Manager (CLEM)-An Open and Inexpensive Solution for Multichannel Electrophysiological Recordings and Closed Loop Experiments.

PubMed

Hazan, Hananel; Ziv, Noam E

2017-01-01

There is growing need for multichannel electrophysiological systems that record from and interact with neuronal systems in near real-time. Such systems are needed, for example, for closed loop, multichannel electrophysiological/optogenetic experimentation in vivo and in a variety of other neuronal preparations, or for developing and testing neuro-prosthetic devices, to name a few. Furthermore, there is a need for such systems to be inexpensive, reliable, user friendly, easy to set-up, open and expandable, and possess long life cycles in face of rapidly changing computing environments. Finally, they should provide powerful, yet reasonably easy to implement facilities for developing closed-loop protocols for interacting with neuronal systems. Here, we survey commercial and open source systems that address these needs to varying degrees. We then present our own solution, which we refer to as Closed Loop Experiments Manager (CLEM). CLEM is an open source, soft real-time, Microsoft Windows desktop application that is based on a single generic personal computer (PC) and an inexpensive, general-purpose data acquisition board. CLEM provides a fully functional, user-friendly graphical interface, possesses facilities for recording, presenting and logging electrophysiological data from up to 64 analog channels, and facilities for controlling external devices, such as stimulators, through digital and analog interfaces. Importantly, it includes facilities for running closed-loop protocols written in any programming language that can generate dynamic link libraries (DLLs). We describe the application, its architecture and facilities. We then demonstrate, using networks of cortical neurons growing on multielectrode arrays (MEA) that despite its reliance on generic hardware, its performance is appropriate for flexible, closed-loop experimentation at the neuronal network level.

Closed Loop Experiment Manager (CLEM)—An Open and Inexpensive Solution for Multichannel Electrophysiological Recordings and Closed Loop Experiments

PubMed Central

Hazan, Hananel; Ziv, Noam E.

2017-01-01

There is growing need for multichannel electrophysiological systems that record from and interact with neuronal systems in near real-time. Such systems are needed, for example, for closed loop, multichannel electrophysiological/optogenetic experimentation in vivo and in a variety of other neuronal preparations, or for developing and testing neuro-prosthetic devices, to name a few. Furthermore, there is a need for such systems to be inexpensive, reliable, user friendly, easy to set-up, open and expandable, and possess long life cycles in face of rapidly changing computing environments. Finally, they should provide powerful, yet reasonably easy to implement facilities for developing closed-loop protocols for interacting with neuronal systems. Here, we survey commercial and open source systems that address these needs to varying degrees. We then present our own solution, which we refer to as Closed Loop Experiments Manager (CLEM). CLEM is an open source, soft real-time, Microsoft Windows desktop application that is based on a single generic personal computer (PC) and an inexpensive, general-purpose data acquisition board. CLEM provides a fully functional, user-friendly graphical interface, possesses facilities for recording, presenting and logging electrophysiological data from up to 64 analog channels, and facilities for controlling external devices, such as stimulators, through digital and analog interfaces. Importantly, it includes facilities for running closed-loop protocols written in any programming language that can generate dynamic link libraries (DLLs). We describe the application, its architecture and facilities. We then demonstrate, using networks of cortical neurons growing on multielectrode arrays (MEA) that despite its reliance on generic hardware, its performance is appropriate for flexible, closed-loop experimentation at the neuronal network level. PMID:29093659

Cation Coordination Alters the Conformation of a Thrombin-Binding G-Quadruplex DNA Aptamer That Affects Inhibition of Thrombin.

PubMed

Zavyalova, Elena; Tagiltsev, Grigory; Reshetnikov, Roman; Arutyunyan, Alexander; Kopylov, Alexey

2016-10-01

Thrombin-binding aptamers are promising anticoagulants. HD1 is a monomolecular antiparallel G-quadruplex with two G-quartets linked by three loops. Aptamer-thrombin interactions are mediated with two TT-loops that bind thrombin exosite I. Several cations were shown to be coordinated inside the G-quadruplex, including K + , Na + , NH 4 + , Ba 2+ , and Sr 2+ ; on the contrary, Mn 2+ was coordinated in the grooves, outside the G-quadruplex. K + or Na + coordination provides aptamer functional activity. The effect of other cations on aptamer functional activity has not yet been described, because of a lack of relevant tests. Interactions between aptamer HD1 and a series of cations were studied. A previously developed enzymatic method was applied to evaluate aptamer inhibitory activity. The structure-function correlation was studied using the characterization of G-quadruplex conformation by circular dichroism spectroscopy. K + coordination provided the well-known high inhibitory activity of the aptamer, whereas Na + coordination supported low activity. Although NH 4 + coordination yielded a typical antiparallel G-quadruplex, no inhibitory activity was shown; a similar effect was observed for Ba 2+ and Sr 2+ coordination. Mn 2+ coordination destabilized the G-quadruplex that drastically diminished aptamer inhibitory activity. Therefore, G-quadruplex existence per se is insufficient for aptamer inhibitory activity. To elicit the nature of these effects, we thoroughly analyzed nuclear magnetic resonance (NMR) and X-ray data on the structure of the HD1 G-quadruplex with various cations. The most reasonable explanation is that cation coordination changes the conformation of TT-loops, affecting thrombin binding and inhibition. HD1 counterparts, aptamers 31-TBA and NU172, behaved similarly with some distinctions. In 31-TBA, an additional duplex module stabilized antiparallel G-quadruplex conformation at high concentrations of divalent cations; whereas in NU172, a different sequence of loops in the G-quadruplex module provided an equilibrium of antiparallel and parallel G-quadruplexes that shifted with cation binding. In conclusion, structures of G-quadruplex aptamers are flexible enough and are fine-tuned with different cation coordination.

Activation of Latent Dihydroorotase from Aquifex aeolicus by Pressure*

PubMed Central

Hervé, Guy; Evans, Hedeel Guy; Fernado, Roshini; Patel, Chandni; Hachem, Fatme; Evans, David R.

2017-01-01

Elevated hydrostatic pressure was used to probe conformational changes of Aquifex aeolicus dihydroorotase (DHO), which catalyzes the third step in de novo pyrimidine biosynthesis. The isolated protein, a 45-kDa monomer, lacks catalytic activity but becomes active upon formation of a dodecameric complex with aspartate transcarbamoylase (ATC). X-ray crystallographic studies of the isolated DHO and of the complex showed that association induces several major conformational changes in the DHO structure. In the isolated DHO, a flexible loop occludes the active site blocking the access of substrates. The loop is mostly disordered but is tethered to the active site region by several electrostatic and hydrogen bonds. This loop becomes ordered and is displaced from the active site upon formation of DHO-ATC complex. The application of pressure to the complex causes its time-dependent dissociation and the loss of both DHO and ATC activities. Pressure induced irreversible dissociation of the obligate ATC trimer, and as a consequence the DHO is also inactivated. However, moderate hydrostatic pressure applied to the isolated DHO subunit mimics the complex formation and reversibly activates the isolated subunit in the absence of ATC, suggesting that the loop has been displaced from the active site. This effect of pressure is explained by the negative volume change associated with the disruption of ionic interactions and exposure of ionized amino acids to the solvent (electrostriction). The interpretation that the loop is relocated by pressure was validated by site-directed mutagenesis and by inhibition by small peptides that mimic the loop residues. PMID:27746403

Bio-Inspired Controller on an FPGA Applied to Closed-Loop Diaphragmatic Stimulation

PubMed Central

Zbrzeski, Adeline; Bornat, Yannick; Hillen, Brian; Siu, Ricardo; Abbas, James; Jung, Ranu; Renaud, Sylvie

2016-01-01

Cervical spinal cord injury can disrupt connections between the brain respiratory network and the respiratory muscles which can lead to partial or complete loss of ventilatory control and require ventilatory assistance. Unlike current open-loop technology, a closed-loop diaphragmatic pacing system could overcome the drawbacks of manual titration as well as respond to changing ventilation requirements. We present an original bio-inspired assistive technology for real-time ventilation assistance, implemented in a digital configurable Field Programmable Gate Array (FPGA). The bio-inspired controller, which is a spiking neural network (SNN) inspired by the medullary respiratory network, is as robust as a classic controller while having a flexible, low-power and low-cost hardware design. The system was simulated in MATLAB with FPGA-specific constraints and tested with a computational model of rat breathing; the model reproduced experimentally collected respiratory data in eupneic animals. The open-loop version of the bio-inspired controller was implemented on the FPGA. Electrical test bench characterizations confirmed the system functionality. Open and closed-loop paradigm simulations were simulated to test the FPGA system real-time behavior using the rat computational model. The closed-loop system monitors breathing and changes in respiratory demands to drive diaphragmatic stimulation. The simulated results inform future acute animal experiments and constitute the first step toward the development of a neuromorphic, adaptive, compact, low-power, implantable device. The bio-inspired hardware design optimizes the FPGA resource and time costs while harnessing the computational power of spike-based neuromorphic hardware. Its real-time feature makes it suitable for in vivo applications. PMID:27378844

Relationship of Catalysis and Active Site Loop Dynamics in the (βα)8-Barrel Enzyme Indole-3-glycerol Phosphate Synthase.

PubMed

Schlee, Sandra; Klein, Thomas; Schumacher, Magdalena; Nazet, Julian; Merkl, Rainer; Steinhoff, Heinz-Jürgen; Sterner, Reinhard

2018-03-08

It is important to understand how the catalytic activity of enzymes is related to their conformational flexibility. We have studied this activity-flexibility correlation using the example of indole-3-glycerol phosphate synthase from Sulfolobus solfataricus (ssIGPS), which catalyzes the fifth step in the biosynthesis of tryptophan. ssIGPS is a thermostable representative of enzymes with the frequently encountered and catalytically versatile (βα) 8 -barrel fold. Four variants of ssIGPS with increased catalytic turnover numbers were analyzed by transient kinetics at 25 °C, and wild-type ssIGPS was likewise analyzed both at 25 °C and at 60 °C. Global fitting with a minimal three-step model provided the individual rate constants for substrate binding, chemical transformation, and product release. The results showed that in both cases, namely, the application of activating mutations and temperature increase, the net increase in the catalytic turnover number is afforded by acceleration of the product release rate relative to the chemical transformation steps. Measurements of the solvent viscosity effect at 25 °C versus 60 °C confirmed this change in the rate-determining step with temperature, which is in accordance with a kink in the Arrhenius diagram of ssIGPS at ∼40 °C. When rotational diffusion rates of electron paramagnetic spin-labels attached to active site loop β1α1 are plotted in the form of an Arrhenius diagram, kinks are observed at the same temperature. These findings, together with molecular dynamics simulations, demonstrate that a different degree of loop mobility correlates with different rate-limiting steps in the catalytic mechanism of ssIGPS.

Identification of a Novel TGF-β-Binding Site in the Zona Pellucida C-terminal (ZP-C) Domain of TGF-β-Receptor-3 (TGFR-3)

PubMed Central

Diestel, Uschi; Resch, Marcus; Meinhardt, Kathrin; Weiler, Sigrid; Hellmann, Tina V.; Mueller, Thomas D.; Nickel, Joachim; Eichler, Jutta; Muller, Yves A.

2013-01-01

The zona pellucida (ZP) domain is present in extracellular proteins such as the zona pellucida proteins and tectorins and participates in the formation of polymeric protein networks. However, the ZP domain also occurs in the cytokine signaling co-receptor transforming growth factor β (TGF-β) receptor type 3 (TGFR-3, also known as betaglycan) where it contributes to cytokine ligand recognition. Currently it is unclear how the ZP domain architecture enables this dual functionality. Here, we identify a novel major TGF-β-binding site in the FG loop of the C-terminal subdomain of the murine TGFR-3 ZP domain (ZP-C) using protein crystallography, limited proteolysis experiments, surface plasmon resonance measurements and synthetic peptides. In the murine 2.7 Å crystal structure that we are presenting here, the FG-loop is disordered, however, well-ordered in a recently reported homologous rat ZP-C structure. Surprisingly, the adjacent external hydrophobic patch (EHP) segment is registered differently in the rat and murine structures suggesting that this segment only loosely associates with the remaining ZP-C fold. Such a flexible and temporarily-modulated association of the EHP segment with the ZP domain has been proposed to control the polymerization of ZP domain-containing proteins. Our findings suggest that this flexibility also extends to the ZP domain of TGFR-3 and might facilitate co-receptor ligand interaction and presentation via the adjacent FG-loop. This hints that a similar C-terminal region of the ZP domain architecture possibly regulates both the polymerization of extracellular matrix proteins and cytokine ligand recognition of TGFR-3. PMID:23826237

Crystal Structures of Trypanosoma cruzi UDP-Galactopyranose Mutase Implicate Flexibility of the Histidine Loop in Enzyme Activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle

2012-11-01

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitormore » design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3 {angstrom} movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10-50, primarily by decreasing k{sub cat}. Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens.« less

Crystal Structures of Trypanosoma cruzi UDP-Galactopyranose Mutase Implicate Flexibility of the Histidine Loop in Enzyme Activation

PubMed Central

Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle; Sobrado, Pablo; Tanner, John J.

2012-01-01

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3-Å movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45 % identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10–50, primarily by decreasing kcat. Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens. PMID:22646091

Crystal structures of Trypanosoma cruzi UDP-galactopyranose mutase implicate flexibility of the histidine loop in enzyme activation.

PubMed

Dhatwalia, Richa; Singh, Harkewal; Oppenheimer, Michelle; Sobrado, Pablo; Tanner, John J

2012-06-19

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Here we report crystal structures of the galactofuranose biosynthetic enzyme UDP-galactopyranose mutase (UGM) from T. cruzi, which are the first structures of this enzyme from a protozoan parasite. UGM is an attractive target for drug design because galactofuranose is absent in humans but is an essential component of key glycoproteins and glycolipids in trypanosomatids. Analysis of the enzyme-UDP noncovalent interactions and sequence alignments suggests that substrate recognition is exquisitely conserved among eukaryotic UGMs and distinct from that of bacterial UGMs. This observation has implications for inhibitor design. Activation of the enzyme via reduction of the FAD induces profound conformational changes, including a 2.3 Å movement of the histidine loop (Gly60-Gly61-His62), rotation and protonation of the imidazole of His62, and cooperative movement of residues located on the si face of the FAD. Interestingly, these changes are substantially different from those described for Aspergillus fumigatus UGM, which is 45% identical to T. cruzi UGM. The importance of Gly61 and His62 for enzymatic activity was studied with the site-directed mutant enzymes G61A, G61P, and H62A. These mutations lower the catalytic efficiency by factors of 10-50, primarily by decreasing k(cat). Considered together, the structural, kinetic, and sequence data suggest that the middle Gly of the histidine loop imparts flexibility that is essential for activation of eukaryotic UGMs. Our results provide new information about UGM biochemistry and suggest a unified strategy for designing inhibitors of UGMs from the eukaryotic pathogens.

Modulation of HIV Protease Flexibility by the T80N Mutation

PubMed Central

Zhou, Hao; Li, Shangyang; Badger, John; Nalivaika, Ellen; Cai, Yufeng; Foulkes-Murzycki, Jennifer; Schiffer, Celia; Makowski, Lee

2015-01-01

The flexibility of HIV protease plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80 which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle scattering (WAXS) data was measured for a series of HIV protease variants. Starting with a calculated WAXS pattern from a rigid atomic model, the modulations in the intensity distribution caused by structural fluctuations in the protein were predicted by simple analytic methods and compared to the experimental data. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. The effects of this single point mutation extend throughout the protein, so as to alter the mobility of amino acids in the enzymatic core. These results support the contentions that significant protein flexibility extends throughout HIV protease and is critical to catalytic function. PMID:25488402

Quasi-finite-time control for high-order nonlinear systems with mismatched disturbances via mapping filtered forwarding technique

NASA Astrophysics Data System (ADS)

Zhang, X.; Huang, X. L.; Lu, H. Q.

2017-02-01

In this study, a quasi-finite-time control method for designing stabilising control laws is developed for high-order strict-feedback nonlinear systems with mismatched disturbances. By using mapping filtered forwarding technique, a virtual control is designed to force the off-the-manifold coordinate to converge to zero in quasi-finite time at each step of the design; at the same time, the manifold is rendered insensitive to time-varying, bounded and unknown disturbances. In terms of standard forwarding methodology, the algorithm proposed here not only does not require the Lyapunov function for controller design, but also avoids to calculate the derivative of sign function. As far as the dynamic performance of closed-loop systems is concerned, we essentially obtain the finite-time performances, which is typically reflected in the following aspects: fast and accurate responses, high tracking precision, and robust disturbance rejection. Spring, mass, and damper system and flexible joints robot are tested to demonstrate the proposed controller performance.

Experimental evaluation of active-member control of precision structures

NASA Technical Reports Server (NTRS)

Fanson, James; Blackwood, Gary; Chu, Cheng-Chih

1989-01-01

The results of closed loop experiments that use piezoelectric active-members to control the flexible motion of a precision truss structure are described. These experiments are directed toward the development of high-performance structural systems as part of the Control/Structure Interaction (CSI) program at JPL. The focus of CSI activity at JPL is to develop the technology necessary to accurately control both the shape and vibration levels in the precision structures from which proposed large space-based observatories will be built. Structural error budgets for these types of structures will likely be in the sub-micron regime; optical tolerances will be even tighter. In order to achieve system level stability and local positioning at this level, it is generally expected that some form of active control will be required.

The crystal structure of choline kinase reveals a eukaryotic protein kinase fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peisach, D.; Gee, P.; Kent, K.

2010-03-08

Choline kinase catalyzes the ATP-dependent phosphorylation of choline, the first committed step in the CDP-choline pathway for the biosynthesis of phosphatidylcholine. The 2.0 {angstrom} crystal structure of a choline kinase from C. elegans (CKA-2) reveals that the enzyme is a homodimeric protein with each monomer organized into a two-domain fold. The structure is remarkably similar to those of protein kinases and aminoglycoside phosphotransferases, despite no significant similarity in amino acid sequence. Comparisons to the structures of other kinases suggest that ATP binds to CKA-2 in a pocket formed by highly conserved and catalytically important residues. In addition, a choline bindingmore » site is proposed to be near the ATP binding pocket and formed by several structurally flexible loops.« less

MOOSE: Manned On-Orbit Servicing Equipment

NASA Technical Reports Server (NTRS)

Budinoff, J. (Editor); Leontsinis, N. (Editor); Lane, J. (Editor); Singh, R. (Editor); Angelone, K.; Boswell, C.; Chamberlain, I.; Concha, M.; Corrodo, M.; Custodio, O.

1993-01-01

The ability to service satellites has thus far been limited to low earth orbit platforms within reach of the Space Shuttle. Other orbits, such as geosynchronous orbits containing high-value spacecraft have not been attainable by a servicing vehicle. The useful life of a satellite can be extended by replacing spent propellant and damaged orbital replacement units, forestalling the need for eventual replacement. This growing need for satellite on-orbits servicing can be met by the Manned On-Orbit Servicing Equipment (MOOSE). Missions requiring orbit transfer capability, precision manipulation and maneuvering, and man-in-the-loop control can be accomplished using MOOSE. MOOSE is a flexible, reusable, single operator, aerobraking spacecraft designed to refuel, repair, and service orbiting spacecraft. MOOSE will be deployed from Space Station Freedom, (SSF), where it will be stored, resupplied, and refurbished.

LabVIEW: a software system for data acquisition, data analysis, and instrument control.

PubMed

Kalkman, C J

1995-01-01

Computer-based data acquisition systems play an important role in clinical monitoring and in the development of new monitoring tools. LabVIEW (National Instruments, Austin, TX) is a data acquisition and programming environment that allows flexible acquisition and processing of analog and digital data. The main feature that distinguishes LabVIEW from other data acquisition programs is its highly modular graphical programming language, "G," and a large library of mathematical and statistical functions. The advantage of graphical programming is that the code is flexible, reusable, and self-documenting. Subroutines can be saved in a library and reused without modification in other programs. This dramatically reduces development time and enables researchers to develop or modify their own programs. LabVIEW uses a large amount of processing power and computer memory, thus requiring a powerful computer. A large-screen monitor is desirable when developing larger applications. LabVIEW is excellently suited for testing new monitoring paradigms, analysis algorithms, or user interfaces. The typical LabVIEW user is the researcher who wants to develop a new monitoring technique, a set of new (derived) variables by integrating signals from several existing patient monitors, closed-loop control of a physiological variable, or a physiological simulator.

Analysis on flexible manufacturing system layout using arena simulation software

NASA Astrophysics Data System (ADS)

Fadzly, M. K.; Saad, Mohd Sazli; Shayfull, Z.

2017-09-01

Flexible manufacturing system (FMS) was defined as highly automated group technology machine cell, consisting of a group of processing stations interconnected by an automated material handling and storage system, and controlled by an integrated computer system. FMS can produce parts or products are in the mid-volume, mid-variety production range. The layout system in FMS is an important criterion to design the FMS system to produce a part or product. This facility layout of an FMS involves the positioning of cells within given boundaries, so as to minimize the total projected travel time between cells. Defining the layout includes specifying the spatial coordinates of each cell, its orientation in either a horizontal or vertical position, and the location of its load or unloads point. There are many types of FMS layout such as In-line, loop ladder and robot centered cell layout. The research is concentrating on the design and optimization FMS layout. The final conclusion can be summarized that the objective to design and optimisation of FMS layout for this study is successful because the FMS In-line layout is the best layout based on effective time and cost using ARENA simulation software.

Distributed digital signal processors for multi-body flexible structures

NASA Technical Reports Server (NTRS)

Lee, Gordon K. F.

1992-01-01

Multi-body flexible structures, such as those currently under investigation in spacecraft design, are large scale (high-order) dimensional systems. Controlling and filtering such structures is a computationally complex problem. This is particularly important when many sensors and actuators are located along the structure and need to be processed in real time. This report summarizes research activity focused on solving the signal processing (that is, information processing) issues of multi-body structures. A distributed architecture is developed in which single loop processors are employed for local filtering and control. By implementing such a philosophy with an embedded controller configuration, a supervising controller may be used to process global data and make global decisions as the local devices are processing local information. A hardware testbed, a position controller system for a servo motor, is employed to illustrate the capabilities of the embedded controller structure. Several filtering and control structures which can be modeled as rational functions can be implemented on the system developed in this research effort. Thus the results of the study provide a support tool for many Control/Structure Interaction (CSI) NASA testbeds such as the Evolutionary model and the nine-bay truss structure.

Optimization of Closed Loop Eigenvalues: Maneuvering, Vibration Control, and Structure/Control Design Iteration for Flexible Spacecraft.

DTIC Science & Technology

1986-05-31

Nonlinear Feedback Control 8-16 for Spacecraft Attitude Maneuvers" 2. " Spacecraft Attitude Control Using 17-35... nonlinear state feedback control laws are developed for space- craft attitude control using the Euler parameters and conjugate angular momenta. Time... Nonlinear Feedback Control for Spacecraft Attitude Maneuvers," to appear in AIAA J. of Guidance, Control, and Dynamics, (AIAA Paper No. 83-2230-CP,

Closed-form recursive formula for an optimal tracker with terminal constraints

NASA Technical Reports Server (NTRS)

Juang, J. N.; Turner, J. D.; Chun, H. M.

1986-01-01

Feedback control laws are derived for a class of optimal finite time tracking problems with terminal constraints. Analytical solutions are obtained for the feedback gain and the closed-loop response trajectory. Such formulations are expressed in recursive forms so that a real-time computer implementation becomes feasible. An example involving the feedback slewing of a flexible spacecraft is given to illustrate the validity and usefulness of the formulations.

Embedded Meta-Material Antennas

DTIC Science & Technology

2009-01-31

influence of the overall capacitance . Based on the tunable SRRs, we designed a tunable loop antenna with SRRs and HPTs as tuning elements. In this case, we...are those of the authors) and should not be construed as an official Department of the Army position, policy or decision, unless so designated by...single aperture, which can provide significant miniaturization and flexibility to the entire system. To design such miniaturized antennas, new materials

Computer Simulations of Valveless Pumping using the Immersed Boundary Method

NASA Astrophysics Data System (ADS)

Jung, Eunok; Peskin, Charles

2000-03-01

Pumping blood in one direction is the main function of the heart, and the heart is equipped with valves that ensure unidirectional flow. Is it possible, though, to pump blood without valves? This report is intended to show by numerical simulation the possibility of a net flow which is generated by a valveless mechanism in a circulatory system. Simulations of valveless pumping are motivated by biomedical applications: cardiopulmonary resuscitation (CPR); and the human foetus before the development of the heart valves. The numerical method used in this work is immersed boundary method, which is applicable to problems involving an elastic structure interacting with a viscous incompressible fluid. This method has already been applied to blood flow in the heart, platelet aggregation during blood clotting, aquatic animal locomotion, and flow in collapsible tubes. The direction of flow inside a loop of tubing which consists of (almost) rigid and flexible parts is investigated when the boundary of one end of the flexible segment is forced periodically in time. Despite the absence of valves, net flow around the loop may appear in these simulations. Furthermore, we present the new, unexpected results that the direction of this flow is determined not only by the position of the periodic compression, but also by the frequency and amplitude of the driving force.

Docking, thermodynamics and molecular dynamics (MD) studies of a non-canonical protease inhibitor, MP-4, from Mucuna pruriens.

PubMed

Kumar, Ashish; Kaur, Harmeet; Jain, Abha; Nair, Deepak T; Salunke, Dinakar M

2018-01-12

Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens belongs to Kunitz-type protease inhibitor family. However, biochemical assays showed that this protein is a poor inhibitor of trypsin. To understand the basis of observed poor inhibition, thermodynamics and molecular dynamics (MD) simulation studies on binding of MP-4 to trypsin were carried out. Molecular dynamics simulations revealed that temperature influences the spectrum of conformations adopted by the loop regions in the MP-4 structure. At an optimal temperature, MP-4 achieves maximal binding while above and below the optimum temperature, its functional activity is hampered due to unfavourable flexibility and relative rigidity, respectively. The low activity at normal temperature is due to the widening of the conformational spectrum of the Reactive Site Loop (RSL) that reduces the probability of formation of stabilizing contacts with trypsin. The unique sequence of the RSL enhances flexibility at ambient temperature and thus reduces its ability to inhibit trypsin. This study shows that temperature influences the function of a protein through modulation in the structure of functional domain of the protein. Modulation of function through appearance of new sequences that are more sensitive to temperature may be a general strategy for evolution of new proteins.

A new design concept for knitted external vein-graft support mesh.

PubMed

Singh, Charanpreet; Wang, Xungai

2015-08-01

Autologous vein-graft failure significantly limits the long-term efficacy of coronary artery bypass procedures. The major cause behind this complication is biomechanical mismatch between the vein and coronary artery. The implanted vein experiences a sudden increase (10-12 fold) in luminal pressures. The resulting vein over-distension or 'ballooning' initiates wall thickening phenomenon and ultimate occlusion. Therefore, a primary goal in improving the longevity of a coronary bypass procedure is to inhibit vein over-distension using mechanical constriction. The idea of using an external vein-graft support mesh has demonstrated sustained benefits and wide acceptance in experimental studies. Nitinol based knitted structures have offered more promising mechanical features than other mesh designs owing to their unique loosely looped construction. However, the conventional plain knit construction still exhibits limitations (radial compliance, deployment ease, flexibility, and bending stresses) which limit this design from proving its real clinical advantage. The new knitted mesh design presented in this study is based on the concept of composite knitting utilising high modulus (nitinol and polyester) and low modulus (polyurethane) material components. The experimental comparison of the new design with a plain knit design demonstrated significant improvement in biomechanical (compliance, flexibility, extensibility, viscoelasticity) and procedural (deployment limit) parameters. The results are indicative of the promising role of new mesh in restoring the lost compliance and pulsatility of vein-graft at high arterial pressures. This way it can assist in controlled vein-graft remodelling and stepwise restoration of vein mechanical homoeostasis. Also, improvement in deployment limit parameter offers more flexibility for a surgeon to use a wide range of vein diameters, which may otherwise be rendered unusable for a plain knit mesh. Copyright © 2015 Elsevier Ltd. All rights reserved.

Minimum-Time and Vibration Avoidance Attitude Maneuver for Spacecraft with Torque and Momentum Limit Constraints in Redundant Reaction Wheel Configuration

NASA Technical Reports Server (NTRS)

Ha, Kong Q.; Femiano, Michael D.; Mosier, Gary E.

2004-01-01

In this paper, we present an optimal open-loop slew trajectory algorithm developed at GSFC for the so-called "Yardstick design" of the James Webb Space Telescope (JWST). JWST is an orbiting infrared observatory featuring a lightweight, segmented primary mirror approximately 6 meters in diameter and a sunshield approximately the size of a tennis court. This large, flexible structure will have significant number of lightly damped, dominant flexible modes. With very stringent requirements on pointing accuracy and image quality, it is important that slewing be done within the required time constraint and with minimal induced vibration in order to maximize observing efficiency. With reaction wheels as control actuators, initial wheel speeds as well as individual wheel torque and momentum limits become dominant constraints in slew performance. These constraints must be taken into account when performing slews to ensure that unexpected reaction wheel saturation does not occur, since such saturation leads to control failure in accurately tracking commanded motion and produces high frequency torque components capable of exciting structural modes. A minimum-time constraint is also included and coupled with reaction wheel limit constraints in the optimization to minimize both the effect of the control torque on the flexible body motion and the maneuver time. The optimization is on slew command parameters, such as maximum slew velocity and acceleration, for a given redundant reaction wheel configuration and is based on the dynamic interaction between the spacecraft and reaction wheel motion. Analytical development of the slew algorithm to generate desired slew position, rate, and acceleration profiles to command a feedback/feed forward control system is described. High-fidelity simulation and experimental results are presented to show that the developed slew law achieves the objectives.

Effect of input perturbation on the performance and wake dynamics of aquatic propulsion in heaving flexible foils

NASA Astrophysics Data System (ADS)

Lehn, Andrea M.; Thornycroft, Patrick J. M.; Lauder, George V.; Leftwich, Megan C.

2017-02-01

In this paper we consider the effects of adding high-frequency, low-amplitude perturbations to a smooth sinusoidal base input signal for a heaving panel in a closed loop flow tank. Specifically, 0.1 cm amplitude sinusoidal perturbation waves with frequency fp ranging from 0.5 to 13.0 Hz are added to 1 cm heave sinusoids with base frequencies, fb, ranging from 0.5 to 3.0 Hz. Two thin foils with different flexural stiffness are heaved with the combined input signals in addition to both the high-heave and low-heave signals independently. In all cases, the foils are heaved in a recirculating water channel with an incoming velocity of Vx=10 cm/s and a Reynolds number based on the chord length of Re=17 300 . Results demonstrate that perturbations increase the net axial force, in the streamwise direction, in most cases tested (with the exception of some poor performing flexible foil cases). Most significantly, for a base frequency of 1 Hz, perturbations at 9 Hz result in a 780.7% increase in net streamwise force production. Generally, the higher the perturbation frequency, fp the more axial force generated. However, for the stiffer foil, a clear peak in net force exists at fp=9 Hz , regardless of the base frequency. For the stiffer foil, swimming efficiency at a 1 Hz flapping frequency is increased dramatically with the addition of a perturbation, with reduced efficiency increases at higher flapping frequencies. Likewise, for the flexible foil, swimming efficiency gains are greatest at the lower flapping frequencies. Perturbations alter the wake structure by increasing the vorticity magnitude and increasing the vortex shedding frequency; i.e., more, stronger vortices are produced in each flapping cycle.

A distributed finite-element modeling and control approach for large flexible structures

NASA Technical Reports Server (NTRS)

Young, K. D.

1989-01-01

An unconventional framework is described for the design of decentralized controllers for large flexible structures. In contrast to conventional control system design practice which begins with a model of the open loop plant, the controlled plant is assembled from controlled components in which the modeling phase and the control design phase are integrated at the component level. The developed framework is called controlled component synthesis (CCS) to reflect that it is motivated by the well developed Component Mode Synthesis (CMS) methods which were demonstrated to be effective for solving large complex structural analysis problems for almost three decades. The design philosophy behind CCS is also closely related to that of the subsystem decomposition approach in decentralized control.

Reliability Assessment of a Robust Design Under Uncertainty for a 3-D Flexible Wing

NASA Technical Reports Server (NTRS)

Gumbert, Clyde R.; Hou, Gene J. -W.; Newman, Perry A.

2003-01-01

The paper presents reliability assessment results for the robust designs under uncertainty of a 3-D flexible wing previously reported by the authors. Reliability assessments (additional optimization problems) of the active constraints at the various probabilistic robust design points are obtained and compared with the constraint values or target constraint probabilities specified in the robust design. In addition, reliability-based sensitivity derivatives with respect to design variable mean values are also obtained and shown to agree with finite difference values. These derivatives allow one to perform reliability based design without having to obtain second-order sensitivity derivatives. However, an inner-loop optimization problem must be solved for each active constraint to find the most probable point on that constraint failure surface.

Adaptive integral dynamic surface control of a hypersonic flight vehicle

NASA Astrophysics Data System (ADS)

Aslam Butt, Waseem; Yan, Lin; Amezquita S., Kendrick

2015-07-01

In this article, non-linear adaptive dynamic surface air speed and flight path angle control designs are presented for the longitudinal dynamics of a flexible hypersonic flight vehicle. The tracking performance of the control design is enhanced by introducing a novel integral term that caters to avoiding a large initial control signal. To ensure feasibility, the design scheme incorporates magnitude and rate constraints on the actuator commands. The uncertain non-linear functions are approximated by an efficient use of the neural networks to reduce the computational load. A detailed stability analysis shows that all closed-loop signals are uniformly ultimately bounded and the ? tracking performance is guaranteed. The robustness of the design scheme is verified through numerical simulations of the flexible flight vehicle model.

Inverse dynamics of adaptive structures used as space cranes

NASA Technical Reports Server (NTRS)

Das, S. K.; Utku, S.; Wada, B. K.

1990-01-01

As a precursor to the real-time control of fast moving adaptive structures used as space cranes, a formulation is given for the flexibility induced motion relative to the nominal motion (i.e., the motion that assumes no flexibility) and for obtaining the open loop time varying driving forces. An algorithm is proposed for the computation of the relative motion and driving forces. The governing equations are given in matrix form with explicit functional dependencies. A simulator is developed to implement the algorithm on a digital computer. In the formulations, the distributed mass of the crane is lumped by two schemes, vz., 'trapezoidal' lumping and 'Simpson's rule' lumping. The effects of the mass lumping schemes are shown by simulator runs.

Boundary control for a constrained two-link rigid-flexible manipulator with prescribed performance

NASA Astrophysics Data System (ADS)

Cao, Fangfei; Liu, Jinkun

2018-05-01

In this paper, we consider a boundary control problem for a constrained two-link rigid-flexible manipulator. The nonlinear system is described by hybrid ordinary differential equation-partial differential equation (ODE-PDE) dynamic model. Based on the coupled ODE-PDE model, boundary control is proposed to regulate the joint positions and eliminate the elastic vibration simultaneously. With the help of prescribed performance functions, the tracking error can converge to an arbitrarily small residual set and the convergence rate is no less than a certain pre-specified value. Asymptotic stability of the closed-loop system is rigorously proved by the LaSalle's Invariance Principle extended to infinite-dimensional system. Numerical simulations are provided to demonstrate the effectiveness of the proposed controller.

Numerical investigation on pulsating heat pipes with nitrogen or hydrogen

NASA Astrophysics Data System (ADS)

Y Han, D.; Sun, X.; Gan, Z. H.; Y Luo, R.; Pfotenhauer, J. M.; Jiao, B.

2017-12-01

With flexible structure and excellent performance, pulsating heat pipes (PHP) are regarded as a great solution to distribute cooling power for cryocoolers. The experiments on PHPs with cryogenic fluids have been carried out, indicating their efficient performances in cryogenics. There are large differences in physical properties between the fluids at room and cryogenic temperature, resulting in their different heat transfer and oscillation characteristics. Up to now, the numerical investigations on cryogenic fluids have rarely been carried out. In this paper, the model of the closed-loop PHP with multiple liquid slugs and vapor plugs is performed with nitrogen and hydrogen as working fluids, respectively. The effects of heating wall temperature on the performance of close-looped PHPs are investigated and compared with that of water PHP.

Hardware-in-the-loop projector system for light detection and ranging sensor testing

NASA Astrophysics Data System (ADS)

Kim, Hajin J.; Naumann, Charles B.; Cornell, Michael C.

2012-08-01

Efforts in developing a synthetic environment for testing light detection and ranging (LADAR) sensors in a hardware-in-the-loop simulation are continuing at the Aviation and Missile Research, Engineering, and Development Center of the U.S. Army Research, Engineering and Development Command (RDECOM). Current activities have concentrated on evaluating the optical projection techniques for the LADAR synthetic environment. Schemes for generating the optical signals representing the individual pixels of the projection are of particular interest. Several approaches have been investigated and tested with emphasis on operating wavelength, intensity dynamic range and uniformity, and flexibility in pixel waveform generation. This paper will discuss some of the results from these current efforts at RDECOM's System Simulation and Development Directorate's Electro Optical Technology Development Laboratory.

Adaptive control of large space structures using recursive lattice filters

NASA Technical Reports Server (NTRS)

Sundararajan, N.; Goglia, G. L.

1985-01-01

The use of recursive lattice filters for identification and adaptive control of large space structures is studied. Lattice filters were used to identify the structural dynamics model of the flexible structures. This identification model is then used for adaptive control. Before the identified model and control laws are integrated, the identified model is passed through a series of validation procedures and only when the model passes these validation procedures is control engaged. This type of validation scheme prevents instability when the overall loop is closed. Another important area of research, namely that of robust controller synthesis, was investigated using frequency domain multivariable controller synthesis methods. The method uses the Linear Quadratic Guassian/Loop Transfer Recovery (LQG/LTR) approach to ensure stability against unmodeled higher frequency modes and achieves the desired performance.

NASA Tech Briefs, December 2013

NASA Technical Reports Server (NTRS)

2013-01-01

Topics include: Microwave Kinetic Inductance Detector With; Selective Polarization Coupling; Flexible Microstrip Circuits for; Superconducting Electronics; CFD Extraction Tool for TecPlot From DPLR Solutions; RECOVIR Software for Identifying Viruses; Enhanced Contact Graph Routing (ECGR) MACHETE Simulation Model; Orbital Debris Engineering Model (ORDEM) v.3; Scatter-Reducing Sounding Filtration Using a Genetic Algorithm and Mean Monthly Standard Deviation; Thermo-Mechanical Methodology for Stabilizing Shape Memory Alloy Response; Hermetic Seal Designs for Sample Return Sample Tubes; Silicon Alignment Pins: An Easy Way To Realize a Wafer-to-Wafer Alignment; Positive-Buoyancy Rover for Under Ice Mobility; Electric Machine With Boosted Inductance to Stabilize Current Control; International Space Station-Based Electromagnetic Launcher for Space Science Payloads; Advanced Hybrid Spacesuit Concept Featuring Integrated Open Loop and Closed Loop Ventilation Systems; Data Quality Screening Service.

Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction

PubMed Central

Becker, Matthias M. M.; Lapouge, Karine; Segnitz, Bernd; Wild, Klemens; Sinning, Irmgard

2017-01-01

Co-translational protein targeting and membrane protein insertion is a fundamental process and depends on the signal recognition particle (SRP). In mammals, SRP is composed of the SRP RNA crucial for SRP assembly and function and six proteins. The two largest proteins SRP68 and SRP72 form a heterodimer and bind to a regulatory site of the SRP RNA. Despite their essential roles in the SRP pathway, structural information has been available only for the SRP68 RNA-binding domain (RBD). Here we present the crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP. The SRP72-PBD is a tetratricopeptide repeat, which binds an extended linear motif of SRP68 with high affinity. The SRP72-RBD is a flexible peptide crawling along the 5e- and 5f-loops of SRP RNA. A conserved tryptophan inserts into the 5e-loop forming a novel type of RNA kink-turn stabilized by a potassium ion, which we define as K+-turn. In addition, SRP72-RBD remodels the 5f-loop involved in ribosome binding and visualizes SRP RNA plasticity. Docking of the S domain structure into cryo-electron microscopy density maps reveals multiple contact sites between SRP68/72 and the ribosome, and explains the role of SRP72 in the SRP pathway. PMID:27899666

Integrated active and passive control design methodology for the LaRC CSI evolutionary model

NASA Technical Reports Server (NTRS)

Voth, Christopher T.; Richards, Kenneth E., Jr.; Schmitz, Eric; Gehling, Russel N.; Morgenthaler, Daniel R.

1994-01-01

A general design methodology to integrate active control with passive damping was demonstrated on the NASA LaRC CSI Evolutionary Model (CEM), a ground testbed for future large, flexible spacecraft. Vibration suppression controllers designed for Line-of Sight (LOS) minimization were successfully implemented on the CEM. A frequency-shaped H2 methodology was developed, allowing the designer to specify the roll-off of the MIMO compensator. A closed loop bandwidth of 4 Hz, including the six rigid body modes and the first three dominant elastic modes of the CEM was achieved. Good agreement was demonstrated between experimental data and analytical predictions for the closed loop frequency response and random tests. Using the Modal Strain Energy (MSE) method, a passive damping treatment consisting of 60 viscoelastically damped struts was designed, fabricated and implemented on the CEM. Damping levels for the targeted modes were more than an order of magnitude larger than for the undamped structure. Using measured loss and stiffness data for the individual damped struts, analytical predictions of the damping levels were very close to the experimental values in the (1-10) Hz frequency range where the open loop model matched the experimental data. An integrated active/passive controller was successfully implemented on the CEM and was evaluated against an active-only controller. A two-fold increase in the effective control bandwidth and further reductions of 30 percent to 50 percent in the LOS RMS outputs were achieved compared to an active-only controller. Superior performance was also obtained compared to a High-Authority/Low-Authority (HAC/LAC) controller.

Study of Flexible Load Dispatch to Improve the Capacity of Wind Power Absorption

NASA Astrophysics Data System (ADS)

Yunlei, Yang; Shifeng, Zhang; Xiao, Chang; Da, Lei; Min, Zhang; Jinhao, Wang; Shengwen, Li; Huipeng, Li

2017-05-01

The dispatch method which track the trend of load demand by arranging the generation scheme of controllable hydro or thermal units faces great difficulties and challenges. With the increase of renewable energy sources such as wind power and photovoltaic power introduced to grid, system has to arrange much more spinning reserve units to compensate the unbalanced power. How to exploit the peak-shaving potential of flexible load which can be shifted with time or storage energy has become many scholars’ research direction. However, the modelling of different kinds of load and control strategy is considerably difficult, this paper choose the Air Conditioner with compressor which can storage energy in fact to study. The equivalent thermal parameters of Air Conditioner has been established. And with the use of “loop control” strategies, we can predict the regulated power of Air Conditioner. Then we established the Gen-Load optimal scheduling model including flexible load based on traditional optimal scheduling model. At last, an improved IEEE-30 case is used to verify. The result of simulation shows that flexible load can fast-track renewable power changes. More than that, with flexible load and reasonable incentive method to consumers, the operating cost of the system can be greatly cut down.

Movement Forms: A Graph-Dynamic Perspective

PubMed Central

Saltzman, Elliot; Holt, Ken

2014-01-01

The focus of this paper is on characterizing the physical movement forms (e.g., walk, crawl, roll, etc.) that can be used to actualize abstract, functionally-specified behavioral goals (e.g., locomotion). Emphasis is placed on how such forms are distinguished from one another, in part, by the set of topological patterns of physical contact between agent and environment (i.e., the set of physical graphs associated with each form) and the transitions among these patterns displayed over the course of performance (i.e., the form’s physical graph dynamics). Crucial in this regard is the creation and dissolution of loops in these graphs, which can be related to the distinction between open and closed kinematic chains. Formal similarities are described within the theoretical framework of task-dynamics between physically-closed kinematic chains (physical loops) that are created during various movement forms and functionally-closed kinematic chains (functional loops) that are associated with task-space control of end-effectors; it is argued that both types of loop must be flexibly incorporated into the coordinative structures that govern skilled action. Final speculation is focused on the role of graphs and their dynamics, not only in processes of coordination and control for individual agents, but also in processes of inter-agent coordination and the coupling of agents with (non-sentient) environmental objects. PMID:24910507

Movement Forms: A Graph-Dynamic Perspective.

PubMed

Saltzman, Elliot; Holt, Ken

2014-01-01

The focus of this paper is on characterizing the physical movement forms (e.g., walk, crawl, roll, etc.) that can be used to actualize abstract, functionally-specified behavioral goals (e.g., locomotion). Emphasis is placed on how such forms are distinguished from one another, in part, by the set of topological patterns of physical contact between agent and environment (i.e., the set of physical graphs associated with each form) and the transitions among these patterns displayed over the course of performance (i.e., the form's physical graph dynamics ). Crucial in this regard is the creation and dissolution of loops in these graphs, which can be related to the distinction between open and closed kinematic chains. Formal similarities are described within the theoretical framework of task-dynamics between physically-closed kinematic chains (physical loops) that are created during various movement forms and functionally-closed kinematic chains (functional loops) that are associated with task-space control of end-effectors; it is argued that both types of loop must be flexibly incorporated into the coordinative structures that govern skilled action. Final speculation is focused on the role of graphs and their dynamics, not only in processes of coordination and control for individual agents, but also in processes of inter-agent coordination and the coupling of agents with (non-sentient) environmental objects.

Programming of a flexible computer simulation to visualize pharmacokinetic-pharmacodynamic models.

PubMed

Lötsch, J; Kobal, G; Geisslinger, G

2004-01-01

Teaching pharmacokinetic-pharmacodynamic (PK/PD) models can be made more effective using computer simulations. We propose the programming of educational PK or PK/PD computer simulations as an alternative to the use of pre-built simulation software. This approach has the advantage of adaptability to non-standard or complicated PK or PK/PD models. Simplicity of the programming procedure was achieved by selecting the LabVIEW programming environment. An intuitive user interface to visualize the time courses of drug concentrations or effects can be obtained with pre-built elements. The environment uses a wiring analogy that resembles electrical circuit diagrams rather than abstract programming code. The goal of high interactivity of the simulation was attained by allowing the program to run in continuously repeating loops. This makes the program behave flexibly to the user input. The programming is described with the aid of a 2-compartment PK simulation. Examples of more sophisticated simulation programs are also given where the PK/PD simulation shows drug input, concentrations in plasma, and at effect site and the effects themselves as a function of time. A multi-compartmental model of morphine, including metabolite kinetics and effects is also included. The programs are available for download from the World Wide Web at http:// www. klinik.uni-frankfurt.de/zpharm/klin/ PKPDsimulation/content.html. For pharmacokineticists who only program occasionally, there is the possibility of building the computer simulation, together with the flexible interactive simulation algorithm for clinical pharmacological teaching in the field of PK/PD models.

Flexible Airspace Management (FAM) Research 2010 Human-in-the-Loop Simulation

NASA Technical Reports Server (NTRS)

Lee, Paul U.; Brasil, Connie; Homola, Jeffrey; Kessell, Angela; Prevot, Thomas; Smith, Nancy

2011-01-01

A human-in-the-Ioop (HITL) simulation was conducted to assess potential user and system benefits of Flexible Airspace Management (FAM) concept, as well as designing role definitions, procedures, and tools to support the FAM operations in the mid-term High Altitude Airspace (HAA) environment. The study evaluated the benefits and feasibility of flexible airspace reconfiguration in response to traffic overload caused by weather deviations, and compared them to those in a baseline condition without the airspace reconfiguration. The test airspace consisted of either four sectors in one Area of Specialization or seven sectors across two Areas. The test airspace was assumed to be at or above FL340 and fully equipped Vvith data communications (Data Comm). Other assumptions were consistent with those of the HAA concept. Overall, results showed that FAM operations with multiple Traffic Management Coordinators, Area Supervisors, and controllers worked remarkably well. The results showed both user and system benefits, some of which include the increased throughput, decreased flight distance, more manageable sector loads, and better utilized airspace. Also, the roles, procedures, airspace designs, and tools were all very well received. Airspace configuration options that resulted from a combination of algorithm-generated airspace configurations with manual modifications were well acceptec and posed little difficuIty and/or workload during airspace reconfiguration process. The results suggest a positive impact of FAM operations in HAA. Further investigation would be needed to evaluate if the benefits and feasibility would extend in either non-HAA or mixed equipage environment.

Low Speed and High Speed Correlation of SMART Active Flap Rotor Loads

NASA Technical Reports Server (NTRS)

Kottapalli, Sesi B. R.

2010-01-01

Measured, open loop and closed loop data from the SMART rotor test in the NASA Ames 40- by 80- Foot Wind Tunnel are compared with CAMRAD II calculations. One open loop high-speed case and four closed loop cases are considered. The closed loop cases include three high-speed cases and one low-speed case. Two of these high-speed cases include a 2 deg flap deflection at 5P case and a test maximum-airspeed case. This study follows a recent, open loop correlation effort that used a simple correction factor for the airfoil pitching moment Mach number. Compared to the earlier effort, the current open loop study considers more fundamental corrections based on advancing blade aerodynamic conditions. The airfoil tables themselves have been studied. Selected modifications to the HH-06 section flap airfoil pitching moment table are implemented. For the closed loop condition, the effect of the flap actuator is modeled by increased flap hinge stiffness. Overall, the open loop correlation is reasonable, thus confirming the basic correctness of the current semi-empirical modifications; the closed loop correlation is also reasonable considering that the current flap model is a first generation model. Detailed correlation results are given in the paper.

Orion Entry, Descent, and Landing Simulation

NASA Technical Reports Server (NTRS)

Hoelscher, Brian R.

2007-01-01

The Orion Entry, Descent, and Landing simulation was created over the past two years to serve as the primary Crew Exploration Vehicle guidance, navigation, and control (GN&C) design and analysis tool at the National Aeronautics and Space Administration (NASA). The Advanced NASA Technology Architecture for Exploration Studies (ANTARES) simulation is a six degree-of-freedom tool with a unique design architecture which has a high level of flexibility. This paper describes the decision history and motivations that guided the creation of this simulation tool. The capabilities of the models within ANTARES are presented in detail. Special attention is given to features of the highly flexible GN&C architecture and the details of the implemented GN&C algorithms. ANTARES provides a foundation simulation for the Orion Project that has already been successfully used for requirements analysis, system definition analysis, and preliminary GN&C design analysis. ANTARES will find useful application in engineering analysis, mission operations, crew training, avionics-in-the-loop testing, etc. This paper focuses on the entry simulation aspect of ANTARES, which is part of a bigger simulation package supporting the entire mission profile of the Orion vehicle. The unique aspects of entry GN&C design are covered, including how the simulation is being used for Monte Carlo dispersion analysis and for support of linear stability analysis. Sample simulation output from ANTARES is presented in an appendix.

pH-regulated metal-ligand switching in the HM loop of ATP7A: a new paradigm for metal transfer chemistry.

PubMed

Kline, Chelsey D; Gambill, Benjamin F; Mayfield, Mary; Lutsenko, Svetlana; Blackburn, Ninian J

2016-08-01

Cuproproteins such as PHM and DBM mature in late endosomal vesicles of the mammalian secretory pathway where changes in vesicle pH are employed for sorting and post-translational processing. Colocation with the P1B-type ATPase ATP7A suggests that the latter is the source of copper and supports a mechanism where selectivity in metal transfer is achieved by spatial colocation of partner proteins in their specific organelles or vesicles. In previous work we have suggested that a lumenal loop sequence located between trans-membrane helices TM1 and TM2 of the ATPase, and containing five histidines and four methionines, acts as an organelle-specific chaperone for metallation of the cuproproteins. The hypothesis posits that the pH of the vesicle regulates copper ligation and loop conformation via a mechanism which involves His to Met ligand switching induced by histidine protonation. Here we report the effect of pH on the HM loop copper coordination using X-ray absorption spectroscopy (XAS), and show via selenium substitution of the Met residues that the HM loop undergoes similar conformational switching to that found earlier for its partner PHM. We hypothesize that in the absence of specific chaperones, HM motifs provide a template for building a flexible, pH-sensitive transfer site whose structure and function can be regulated to accommodate the different active site structural elements and pH environments of its partner proteins.

Preconceptual design of a fluoride high temperature salt-cooled engineering demonstration reactor: Motivation and overview

DOE PAGES

Qualls, A. Louis; Betzler, Benjamin R.; Brown, Nicholas R.; ...

2016-12-21

Engineering demonstration reactors are nuclear reactors built to establish proof of concept for technology options that have never been built. Examples of engineering demonstration reactors include Peach Bottom 1 for high temperature gas-cooled reactors (HTGRs) and Experimental Breeder Reactor-II (EBR-II) for sodium-cooled fast reactors. Historically, engineering demonstrations have played a vital role in advancing the technology readiness level of reactor technologies. Our paper details a preconceptual design for a fluoride salt-cooled engineering demonstration reactor. The fluoride salt-cooled high-temperature reactor (FHR) demonstration reactor (DR) is a concept for a salt-cooled reactor with 100 megawatts of thermal output (MWt). It would usemore » tristructural-isotropic (TRISO) particle fuel within prismatic graphite blocks. FLiBe (2 7LiF-BeF2) is the reference primary coolant. The FHR DR is designed to be small, simple, and affordable. Development of the FHR DR is a necessary intermediate step to enable near-term commercial FHRs. The design philosophy of the FHR DR was focused on safety, near-term deployment, and flexibility. Lower risk technologies are purposely included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated as an engineering demonstration with minimal risk and cost. These technologies include TRISO particle fuel, replaceable core structures, and consistent structural material selection for core structures and the primary and intermediate loops, and tube-and-shell primary-to-intermediate heat exchangers. Important capabilities to be demonstrated by building and operating the FHR DR include fabrication and operation of high temperature reactors; heat exchanger performance (including passive decay heat removal); pump performance; and reactivity control; salt chemistry control to maximize vessel life; tritium management; core design methodologies; salt procurement, handling, maintenance and ultimate disposal. It is recognized that non-nuclear separate and integral test efforts (e.g., heated salt loops or loops using simulant fluids) are necessary to develop the technologies that will be demonstrated in the FHR DR.« less

Preconceptual design of a fluoride high temperature salt-cooled engineering demonstration reactor: Motivation and overview

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qualls, A. Louis; Betzler, Benjamin R.; Brown, Nicholas R.

Engineering demonstration reactors are nuclear reactors built to establish proof of concept for technology options that have never been built. Examples of engineering demonstration reactors include Peach Bottom 1 for high temperature gas-cooled reactors (HTGRs) and Experimental Breeder Reactor-II (EBR-II) for sodium-cooled fast reactors. Historically, engineering demonstrations have played a vital role in advancing the technology readiness level of reactor technologies. Our paper details a preconceptual design for a fluoride salt-cooled engineering demonstration reactor. The fluoride salt-cooled high-temperature reactor (FHR) demonstration reactor (DR) is a concept for a salt-cooled reactor with 100 megawatts of thermal output (MWt). It would usemore » tristructural-isotropic (TRISO) particle fuel within prismatic graphite blocks. FLiBe (2 7LiF-BeF2) is the reference primary coolant. The FHR DR is designed to be small, simple, and affordable. Development of the FHR DR is a necessary intermediate step to enable near-term commercial FHRs. The design philosophy of the FHR DR was focused on safety, near-term deployment, and flexibility. Lower risk technologies are purposely included in the initial FHR DR design to ensure that the reactor can be built, licensed, and operated as an engineering demonstration with minimal risk and cost. These technologies include TRISO particle fuel, replaceable core structures, and consistent structural material selection for core structures and the primary and intermediate loops, and tube-and-shell primary-to-intermediate heat exchangers. Important capabilities to be demonstrated by building and operating the FHR DR include fabrication and operation of high temperature reactors; heat exchanger performance (including passive decay heat removal); pump performance; and reactivity control; salt chemistry control to maximize vessel life; tritium management; core design methodologies; salt procurement, handling, maintenance and ultimate disposal. It is recognized that non-nuclear separate and integral test efforts (e.g., heated salt loops or loops using simulant fluids) are necessary to develop the technologies that will be demonstrated in the FHR DR.« less

Fiber photo-catheters for laser treatment of atrial fibrillation

PubMed Central

Peshko, Igor; Rubtsov, Vladimir; Vesselov, Leonid; Sigal, Gennady; Laks, Hillel

2009-01-01

A fiber photo-catheter has been developed for surgical treatment of atrial fibrillation with laser radiation. Atrial fibrillation (AF) is a heart rhythm abnormality that involves irregular and rapid heartbeats. Recent studies demonstrate the superiority of treating AF disease with optical radiation of the near infrared region. To produce long continuous transmural lesions, solid-state lasers and laser diodes, along with end-emitting fiber catheters, have been used experimentally. The absence of side-emitting flexible catheters with the ability to produce long continuous lesions limits the further development of this technology. In this research, a prototype of an optical catheter, consisting of a flexible 10-cm fiber diffuser has been used to make continuous photocoagulation lesions for effective maze procedure treatments. The system also includes: a flexible optical reflector; a series of openings for rapid self-attachment to the tissue; and an optional closed-loop irrigating chamber with circulating saline to cool the optical diffuser and irrigate the tissue. PMID:19587838

Entropic organization of interphase chromosomes

PubMed Central

Marenduzzo, Davide

2009-01-01

Chromosomes are not distributed randomly in nuclei. Appropriate positioning can activate (or repress) genes by bringing them closer to active (or inactive) compartments like euchromatin (or heterochromatin), and this is usually assumed to be driven by specific local forces (e.g., involving H bonds between nucleosomes or between nucleosomes and the lamina). Using Monte Carlo simulations, we demonstrate that nonspecific (entropic) forces acting alone are sufficient to position and shape self-avoiding polymers within a confining sphere in the ways seen in nuclei. We suggest that they can drive long flexible polymers (representing gene-rich chromosomes) to the interior, compact/thick ones (and heterochromatin) to the periphery, looped (but not linear) ones into appropriately shaped (ellipsoidal) territories, and polymers with large terminal beads (representing centromeric heterochromatin) into peripheral chromocenters. Flexible polymers tend to intermingle less than others, which is in accord with observations that gene-dense (and so flexible) chromosomes make poor translocation partners. Thus, entropic forces probably participate in the self-organization of chromosomes within nuclei. PMID:19752020

On the relationship between wave based control, absolute vibration suppression and input shaping

NASA Astrophysics Data System (ADS)

Peled, I.; O'Connor, W. J.; Halevi, Y.

2013-08-01

The modeling and control of continuous flexible structures is one of the most challenging problems in control theory. This topic gains more interest with the development of slender space structures, light weight aeronautical components or even traditional gears and drive shafts with flexible properties. Several control schemes are based on the traveling wave approach, rather than the more common modal methods. In this work we investigate the relationships between two of these methods. The Absolute Vibration Suppression (AVS) controller, which was developed for infinite dimension systems, is compared to Wave Based Control (WBC) which was designed primarily for lumped systems. The WBC was first adjusted to continuous systems and then the two controllers, whose algorithms seem different, are compared. The investigation shows that for the flexible shaft these two control laws are actually the same. Furthermore, when converted into an equivalent open loop controller they appear as an extension to continuous systems of the Input Shaping (IS) methodology.

Scheduling policies of intelligent sensors and sensor/actuators in flexible structures

NASA Astrophysics Data System (ADS)

Demetriou, Michael A.; Potami, Raffaele

2006-03-01

In this note, we revisit the problem of actuator/sensor placement in large civil infrastructures and flexible space structures within the context of spatial robustness. The positioning of these devices becomes more important in systems employing wireless sensor and actuator networks (WSAN) for improved control performance and for rapid failure detection. The ability of the sensing and actuating devices to possess the property of spatial robustness results in reduced control energy and therefore the spatial distribution of disturbances is integrated into the location optimization measures. In our studies, the structure under consideration is a flexible plate clamped at all sides. First, we consider the case of sensor placement and the optimization scheme attempts to produce those locations that minimize the effects of the spatial distribution of disturbances on the state estimation error; thus the sensor locations produce state estimators with minimized disturbance-to-error transfer function norms. A two-stage optimization procedure is employed whereby one first considers the open loop system and the spatial distribution of disturbances is found that produces the maximal effects on the entire open loop state. Once this "worst" spatial distribution of disturbances is found, the optimization scheme subsequently finds the locations that produce state estimators with minimum transfer function norms. In the second part, we consider the collocated actuator/sensor pairs and the optimization scheme produces those locations that result in compensators with the smallest norms of the disturbance-to-state transfer functions. Going a step further, an intelligent control scheme is presented which, at each time interval, activates a subset of the actuator/sensor pairs in order provide robustness against spatiotemporally moving disturbances and minimize power consumption by keeping some sensor/actuators in sleep mode.

Molecular dynamics simulations of the Bcl-2 protein to predict the structure of its unordered flexible loop domain.

PubMed

Raghav, Pawan Kumar; Verma, Yogesh Kumar; Gangenahalli, Gurudutta U

2012-05-01

B-cell lymphoma (Bcl-2) protein is an anti-apoptotic member of the Bcl-2 family. It is functionally demarcated into four Bcl-2 homology (BH) domains: BH1, BH2, BH3, BH4, one flexible loop domain (FLD), a transmembrane domain (TM), and an X domain. Bcl-2's BH domains have clearly been elucidated from a structural perspective, whereas the conformation of FLD has not yet been predicted, despite its important role in regulating apoptosis through its interactions with JNK-1, PKC, PP2A phosphatase, caspase 3, MAP kinase, ubiquitin, PS1, and FKBP38. Many important residues that regulate Bcl-2 anti-apoptotic activity are present in this domain, for example Asp34, Thr56, Thr69, Ser70, Thr74, and Ser87. The structural elucidation of the FLD would likely help in attempts to accurately predict the effect of mutating these residues on the overall structure of the protein and the interactions of other proteins in this domain. Therefore, we have generated an increased quality model of the Bcl-2 protein including the FLD through modeling. Further, molecular dynamics (MD) simulations were used for FLD optimization, to predict the flexibility, and to determine the stability of the folded FLD. In addition, essential dynamics (ED) was used to predict the collective motions and the essential subspace relevant to Bcl-2 protein function. The predicted average structure and ensemble of MD-simulated structures were submitted to the Protein Model Database (PMDB), and the Bcl-2 structures obtained exhibited enhanced quality. This study should help to elucidate the structural basis for Bcl-2 anti-apoptotic activity regulation through its binding to other proteins via the FLD.

Quasithermodynamic Contributions to the Fluctuations of a Protein Nanopore

PubMed Central

2015-01-01

Proteins undergo thermally activated conformational fluctuations among two or more substates, but a quantitative inquiry on their kinetics is persistently challenged by numerous factors, including the complexity and dynamics of various interactions, along with the inability to detect functional substates within a resolvable time scale. Here, we analyzed in detail the current fluctuations of a monomeric β-barrel protein nanopore of known high-resolution X-ray crystal structure. We demonstrated that targeted perturbations of the protein nanopore system, in the form of loop-deletion mutagenesis, accompanying alterations of electrostatic interactions between long extracellular loops, produced modest changes of the differential activation free energies calculated at 25 °C, ΔΔG⧧, in the range near the thermal energy but substantial and correlated modifications of the differential activation enthalpies, ΔΔH⧧, and entropies, ΔΔS⧧. This finding indicates that the local conformational reorganizations of the packing and flexibility of the fluctuating loops lining the central constriction of this protein nanopore were supplemented by changes in the single-channel kinetics. These changes were reflected in the enthalpy–entropy reconversions of the interactions between the loop partners with a compensating temperature, TC, of ∼300 K, and an activation free energy constant of ∼41 kJ/mol. We also determined that temperature has a much greater effect on the energetics of the equilibrium gating fluctuations of a protein nanopore than other environmental parameters, such as the ionic strength of the aqueous phase as well as the applied transmembrane potential, likely due to ample changes in the solvation activation enthalpies. There is no fundamental limitation for applying this approach to other complex, multistate membrane protein systems. Therefore, this methodology has major implications in the area of membrane protein design and dynamics, primarily by revealing a better quantitative assessment on the equilibrium transitions among multiple well-defined and functionally distinct substates of protein channels and pores. PMID:25479108

A unique serpin P1' glutamate and a conserved β-sheet C arginine are key residues for activity, protease recognition and stability of serpinA12 (vaspin).

PubMed

Ulbricht, David; Pippel, Jan; Schultz, Stephan; Meier, René; Sträter, Norbert; Heiker, John T

2015-09-15

SerpinA12 (vaspin) is thought to be mainly expressed in adipose tissue and has multiple beneficial effects on metabolic, inflammatory and atherogenic processes related to obesity. KLK7 (kallikrein 7) is the only known protease target of vaspin to date and is inhibited with a moderate inhibition rate. In the crystal structure, the cleavage site (P1-P1') of the vaspin reactive centre loop is fairly rigid compared with the flexible residues before P2, possibly supported by an ionic interaction of P1' glutamate (Glu(379)) with an arginine residue (Arg(302)) of the β-sheet C. A P1' glutamate seems highly unusual and unfavourable for the protease KLK7. We characterized vaspin mutants to investigate the roles of these two residues in protease inhibition and recognition by vaspin. Reactive centre loop mutations changing the P1' residue or altering the reactive centre loop conformation significantly increased inhibition parameters, whereas removal of the positive charge within β-sheet C impeded the serpin-protease interaction. Arg(302) is a crucial contact to enable vaspin recognition by KLK7 and it supports moderate inhibition of the serpin despite the presence of the detrimental P1' Glu(379), which clearly represents a major limiting factor for vaspin-inhibitory activity. We also show that the vaspin-inhibition rate for KLK7 can be modestly increased by heparin and demonstrate that vaspin is a heparin-binding serpin. Noteworthily, we observed vaspin as a remarkably thermostable serpin and found that Glu(379) and Arg(302) influence heat-induced polymerization. These structural and functional results reveal the mechanistic basis of how reactive centre loop sequence and exosite interaction in vaspin enable KLK7 recognition and regulate protease inhibition as well as stability of this adipose tissue-derived serpin. © 2015 Authors; published by Portland Press Limited.

Helical unwinding and side-chain unlocking unravel the outward open conformation of the melibiose transporter

NASA Astrophysics Data System (ADS)

Wang, Li-Ying; Ravi, Vidhya M.; Leblanc, Gérard; Padrós, Esteve; Cladera, Josep; Perálvarez-Marín, Alex

2016-09-01

Molecular dynamics simulations have been used to study the alternate access mechanism of the melibiose transporter from Escherichia coli. Starting from the outward-facing partially occluded form, 2 out of 12 simulations produced an outward full open form and one partially open, whereas the rest yielded fully or partially occluded forms. The shape of the outward-open form resembles other outward-open conformations of secondary transporters. During the transporter opening, conformational changes in some loops are followed by changes in the periplasm region of transmembrane helix 7. Helical curvature relaxation and unlocking of hydrophobic and ionic locks promote the outward opening of the transporter making accessible the substrate binding site. In particular, FRET studies on mutants of conserved aromatic residues of extracellular loop 4 showed lack of substrate binding, emphasizing the importance of this loop for making crucial interactions that control the opening of the periplasmic side. This study indicates that the alternate access mechanism for the melibiose transporter fits better into a flexible gating mechanism rather than the archetypical helical rigid-body rocker-switch mechanism.

Structure prediction of the second extracellular loop in G-protein-coupled receptors.

PubMed

Kmiecik, Sebastian; Jamroz, Michal; Kolinski, Michal

2014-06-03

G-protein-coupled receptors (GPCRs) play key roles in living organisms. Therefore, it is important to determine their functional structures. The second extracellular loop (ECL2) is a functionally important region of GPCRs, which poses significant challenge for computational structure prediction methods. In this work, we evaluated CABS, a well-established protein modeling tool for predicting ECL2 structure in 13 GPCRs. The ECL2s (with between 13 and 34 residues) are predicted in an environment of other extracellular loops being fully flexible and the transmembrane domain fixed in its x-ray conformation. The modeling procedure used theoretical predictions of ECL2 secondary structure and experimental constraints on disulfide bridges. Our approach yielded ensembles of low-energy conformers and the most populated conformers that contained models close to the available x-ray structures. The level of similarity between the predicted models and x-ray structures is comparable to that of other state-of-the-art computational methods. Our results extend other studies by including newly crystallized GPCRs. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Coupled Riccati equations for complex plane constraint

NASA Technical Reports Server (NTRS)

Strong, Kristin M.; Sesak, John R.

1991-01-01

A new Linear Quadratic Gaussian design method is presented which provides prescribed imaginary axis pole placement for optimal control and estimation systems. This procedure contributes another degree of design freedom to flexible spacecraft control. Current design methods which interject modal damping into the system tend to have little affect on modal frequencies, i.e., they predictably shift open plant poles horizontally in the complex plane to form the closed loop controller or estimator pole constellation, but make little provision for vertical (imaginary axis) pole shifts. Imaginary axis shifts which reduce the closed loop model frequencies (the bandwidths) are desirable since they reduce the sensitivity of the system to noise disturbances. The new method drives the closed loop modal frequencies to predictable (specified) levels, frequencies as low as zero rad/sec (real axis pole placement) can be achieved. The design procedure works through rotational and translational destabilizations of the plant, and a coupling of two independently solved algebraic Riccati equations through a structured state weighting matrix. Two new concepts, gain transference and Q equivalency, are introduced and their use shown.

Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torres, Rodrigo; Lan, Benson; Latif, Yama

2014-04-01

The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NOmore » levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully understand the function of the acyl-group binding pocket in substrate specificity.« less

Flexible and evolutionary optical access networks

NASA Astrophysics Data System (ADS)

Hsueh, Yu-Li

Passive optical networks (PONs) are promising solutions that will open the first-mile bottleneck. Current PONs employ time division multiplexing (TDM) to share bandwidth among users, leading to low cost but limited capacity. In the future, wavelength division multiplexing (WDM) technologies will be deployed to achieve high performance. This dissertation describes several advanced technologies to enhance PON systems. A spectral shaping line coding scheme is developed to allow a simple and cost-effective overlay of high data-rate services in existing PONs, leaving field-deployed fibers and existing services untouched. Spectral shapes of coded signals can be manipulated to adapt to different systems. For a specific tolerable interference level, the optimal line code can be found which maximizes the data throughput. Experiments are conducted to demonstrate and compare several optimized line codes. A novel PON employing dynamic wavelength allocation to provide bandwidth sharing across multiple physical PONs is designed and experimentally demonstrated. Tunable lasers, arrayed waveguide gratings, and coarse/fine filtering combine to create a flexible optical access solution. The network's excellent scalability can bridge the gap between conventional TDM PONs and WDM PONs. Scheduling algorithms with quality of service support are also investigated. Simulation results show that the proposed architecture exhibits significant performance gain over conventional PON systems. Streaming video transmission is demonstrated on the prototype experimental testbed. The powerful architecture is a promising candidate for next-generation optical access networks. A new CDR circuit for receiving the bursty traffic in PONs is designed and analyzed. It detects data transition edges upon arrival of the data burst and quickly selects the best clock phase by a control logic circuit. Then, an analog delay-locked loop (DLL) keeps track of data transitions and removes phase errors throughout the burst. The combination of the fast phase detection mechanism and a feedback loop based on DLL allows both fast response and manageable jitter performance in the burst-mode application. A new efficient numerical algorithm is developed to analyze holey optical fibers. The algorithm has been verified against experimental data, and is exploited to design holey optical fibers optimized for the discrete Raman amplification.

What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

PubMed

Filchtinski, Daniel; Sharabi, Oz; Rüppel, Alma; Vetter, Ingrid R; Herrmann, Christian; Shifman, Julia M

2010-06-11

Ras is a small GTP-binding protein that is an essential molecular switch for a wide variety of signaling pathways including the control of cell proliferation, cell cycle progression and apoptosis. In the GTP-bound state, Ras can interact with its effectors, triggering various signaling cascades in the cell. In the GDP-bound state, Ras looses its ability to bind to known effectors. The interaction of the GTP-bound Ras (Ras(GTP)) with its effectors has been studied intensively. However, very little is known about the much weaker interaction between the GDP-bound Ras (Ras(GDP)) and Ras effectors. We investigated the factors underlying the nucleotide-dependent differences in Ras interactions with one of its effectors, Raf kinase. Using computational protein design, we generated mutants of the Ras-binding domain of Raf kinase (Raf) that stabilize the complex with Ras(GDP). Most of our designed mutations narrow the gap between the affinity of Raf for Ras(GTP) and Ras(GDP), producing the desired shift in binding specificity towards Ras(GDP). A combination of our best designed mutation, N71R, with another mutation, A85K, yielded a Raf mutant with a 100-fold improvement in affinity towards Ras(GDP). The Raf A85K and Raf N71R/A85K mutants were used to obtain the first high-resolution structures of Ras(GDP) bound to its effector. Surprisingly, these structures reveal that the loop on Ras previously termed the switch I region in the Ras(GDP).Raf mutant complex is found in a conformation similar to that of Ras(GTP) and not Ras(GDP). Moreover, the structures indicate an increased mobility of the switch I region. This greater flexibility compared to the same loop in Ras(GTP) is likely to explain the natural low affinity of Raf and other Ras effectors to Ras(GDP). Our findings demonstrate that an accurate balance between a rigid, high-affinity conformation and conformational flexibility is required to create an efficient and stringent molecular switch. Copyright 2010 Elsevier Ltd. All rights reserved.

Loop Evolution Observed with AIA and Hi-C

NASA Technical Reports Server (NTRS)

Mulu-Moore, Fana; Winebarger, Amy R.; Cirtain, Jonathan W.; Kobayashi, Ken; Korreck, Kelly E.; Golub, Leon; Kuzin, Sergei; Walsh, Robert William; DeForest, Craig E.; De Pontieu, Bart;

In Vitro Characterization of Thermostable CAM Rubisco Activase Reveals a Rubisco Interacting Surface Loop.

PubMed

Shivhare, Devendra; Mueller-Cajar, Oliver

2017-07-01

To maintain metabolic flux through the Calvin-Benson-Bassham cycle in higher plants, dead-end inhibited complexes of Rubisco must constantly be engaged and remodeled by the molecular chaperone Rubisco activase (Rca). In C3 plants, the thermolability of Rca is responsible for the deactivation of Rubisco and reduction of photosynthesis at moderately elevated temperatures. We reasoned that crassulacean acid metabolism (CAM) plants must possess thermostable Rca to support Calvin-Benson-Bassham cycle flux during the day when stomata are closed. A comparative biochemical characterization of rice ( Oryza sativa ) and Agave tequilana Rca isoforms demonstrated that the CAM Rca isoforms are approximately10°C more thermostable than the C3 isoforms. Agave Rca also possessed a much higher in vitro biochemical activity, even at low assay temperatures. Mixtures of rice and agave Rca form functional hetero-oligomers in vitro, but only the rice isoforms denature at nonpermissive temperatures. The high thermostability and activity of agave Rca mapped to the N-terminal 244 residues. A Glu-217-Gln amino acid substitution was found to confer high Rca activity to rice Rca Further mutational analysis suggested that Glu-217 restricts the flexibility of the α4-β4 surface loop that interacts with Rubisco via Lys-216. CAM plants thus promise to be a source of highly functional, thermostable Rca candidates for thermal fortification of crop photosynthesis. Careful characterization of their properties will likely reveal further protein-protein interaction motifs to enrich our mechanistic model of Rca function. © 2017 American Society of Plant Biologists. All Rights Reserved.

In Vitro Characterization of Thermostable CAM Rubisco Activase Reveals a Rubisco Interacting Surface Loop1[OPEN

PubMed Central

Shivhare, Devendra

2017-01-01

To maintain metabolic flux through the Calvin-Benson-Bassham cycle in higher plants, dead-end inhibited complexes of Rubisco must constantly be engaged and remodeled by the molecular chaperone Rubisco activase (Rca). In C3 plants, the thermolability of Rca is responsible for the deactivation of Rubisco and reduction of photosynthesis at moderately elevated temperatures. We reasoned that crassulacean acid metabolism (CAM) plants must possess thermostable Rca to support Calvin-Benson-Bassham cycle flux during the day when stomata are closed. A comparative biochemical characterization of rice (Oryza sativa) and Agave tequilana Rca isoforms demonstrated that the CAM Rca isoforms are approximately10°C more thermostable than the C3 isoforms. Agave Rca also possessed a much higher in vitro biochemical activity, even at low assay temperatures. Mixtures of rice and agave Rca form functional hetero-oligomers in vitro, but only the rice isoforms denature at nonpermissive temperatures. The high thermostability and activity of agave Rca mapped to the N-terminal 244 residues. A Glu-217-Gln amino acid substitution was found to confer high Rca activity to rice Rca. Further mutational analysis suggested that Glu-217 restricts the flexibility of the α4-β4 surface loop that interacts with Rubisco via Lys-216. CAM plants thus promise to be a source of highly functional, thermostable Rca candidates for thermal fortification of crop photosynthesis. Careful characterization of their properties will likely reveal further protein-protein interaction motifs to enrich our mechanistic model of Rca function. PMID:28546437

Computational study of β-N-acetylhexosaminidase from Talaromyces flavus, a glycosidase with high substrate flexibility.

PubMed

Kulik, Natallia; Slámová, Kristýna; Ettrich, Rüdiger; Křen, Vladimír

2015-01-28

β-N-Acetylhexosaminidase (GH20) from the filamentous fungus Talaromyces flavus, previously identified as a prominent enzyme in the biosynthesis of modified glycosides, lacks a high resolution three-dimensional structure so far. Despite of high sequence identity to previously reported Aspergillus oryzae and Penicilluim oxalicum β-N-acetylhexosaminidases, this enzyme tolerates significantly better substrate modification. Understanding of key structural features, prediction of effective mutants and potential substrate characteristics prior to their synthesis are of general interest. Computational methods including homology modeling and molecular dynamics simulations were applied to shad light on the structure-activity relationship in the enzyme. Primary sequence analysis revealed some variable regions able to influence difference in substrate affinity of hexosaminidases. Moreover, docking in combination with consequent molecular dynamics simulations of C-6 modified glycosides enabled us to identify the structural features required for accommodation and processing of these bulky substrates in the active site of hexosaminidase from T. flavus. To access the reliability of predictions on basis of the reported model, all results were confronted with available experimental data that demonstrated the principal correctness of the predictions as well as the model. The main variable regions in β-N-acetylhexosaminidases determining difference in modified substrate affinity are located close to the active site entrance and engage two loops. Differences in primary sequence and the spatial arrangement of these loops and their interplay with active site amino acids, reflected by interaction energies and dynamics, account for the different catalytic activity and substrate specificity of the various fungal and bacterial β-N-acetylhexosaminidases.

Reconfigurable firmware-defined radios synthesized from standard digital logic cells

NASA Astrophysics Data System (ADS)

Faisal, Muhammad; Park, Youngmin; Wentzloff, David D.

2011-06-01

This paper presents recent work on reconfigurable all-digital radio architectures. We leverage the flexibility and scalability of synthesized digital cells to construct reconfigurable radio architectures that consume significantly less power than a software defined radio implementing similar architectures. We present two prototypes of such architectures that can receive and demodulate FM and FRS band signals. Moreover, a radio architecture based on a reconfigurable alldigital phase-locked loop for coherent demodulation is presented.

The Influence of Feedback on the Aeroelastic Behavior of Tilt Proprotor Aircraft Including the Effects of Fuselage Motion

NASA Technical Reports Server (NTRS)

Curtiss, H. C., Jr.; Komatsuzaki, T.; Traybar, J. J.

1979-01-01

The influence of single loop feedbacks to improve the stability of the system are considered. Reduced order dynamic models are employed where appropriate to promote physical insight. The influence of fuselage freedom on the aeroelastic stability, and the influence of the airframe flexibility on the low frequency modes of motion relevant to the stability and control characteristics of the vehicle were examined.

Hardware math for the 6502 microprocessor

NASA Technical Reports Server (NTRS)

Kissel, R.; Currie, J.

1985-01-01

A floating-point arithmetic unit is described which is being used in the Ground Facility of Large Space Structures Control Verification (GF/LSSCV). The experiment uses two complete inertial measurement units and a set of three gimbal torquers in a closed loop to control the structural vibrations in a flexible test article (beam). A 6502 (8-bit) microprocessor controls four AMD 9511A floating-point arithmetic units to do all the computation in 20 milliseconds.

Modeling and Control of Intelligent Flexible Structures

DTIC Science & Technology

1994-03-26

can be approximated as a simply supported beam in transverse vibration. Assuming that the Euler- Bernoulli beam assumptions hold, linear equations of...The assumptions made during the derivation are that the element can be modeled as an Euler- Bernoulli beam, that the cross-section is symmetric, and...parametes A,. and ,%. andc input maces 3,,. The closed loop system. ecuation (7), is stable when the 3.. 8 and output gain mantices H1., H., H. for

Development and testing of methodology for evaluating the performance of multi-input/multi-output digital control systems

NASA Technical Reports Server (NTRS)

Polotzky, Anthony S.; Wieseman, Carol; Hoadley, Sherwood Tiffany; Mukhopadhyay, Vivek

1990-01-01

The development of a controller performance evaluation (CPE) methodology for multiinput/multioutput digital control systems is described. The equations used to obtain the open-loop plant, controller transfer matrices, and return-difference matrices are given. Results of applying the CPE methodology to evaluate MIMO digital flutter suppression systems being tested on an active flexible wing wind-tunnel model are presented to demonstrate the CPE capability.

Efficient H2O2/CH3COOH oxidative desulfurization/denitrification of liquid fuels in sonochemical flow-reactors.

PubMed

Calcio Gaudino, Emanuela; Carnaroglio, Diego; Boffa, Luisa; Cravotto, Giancarlo; Moreira, Elizabeth M; Nunes, Matheus A G; Dressler, Valderi L; Flores, Erico M M

2014-01-01

The oxidative desulfurization/denitrification of liquid fuels has been widely investigated as an alternative or complement to common catalytic hydrorefining. In this process, all oxidation reactions occur in the heterogeneous phase (the oil and the polar phase containing the oxidant) and therefore the optimization of mass and heat transfer is of crucial importance to enhancing the oxidation rate. This goal can be achieved by performing the reaction in suitable ultrasound (US) reactors. In fact, flow and loop US reactors stand out above classic batch US reactors thanks to their greater efficiency and flexibility as well as lower energy consumption. This paper describes an efficient sonochemical oxidation with H2O2/CH3COOH at flow rates ranging from 60 to 800 ml/min of both a model compound, dibenzotiophene (DBT), and of a mild hydro-treated diesel feedstock. Four different commercially available US loop reactors (single and multi-probe) were tested, two of which were developed in the authors' laboratory. Full DBT oxidation and efficient diesel feedstock desulfurization/denitrification were observed after the separation of the polar oxidized S/N-containing compounds (S≤5 ppmw, N≤1 ppmw). Our studies confirm that high-throughput US applications benefit greatly from flow-reactors. Copyright © 2013 Elsevier B.V. All rights reserved.

Continuously wavelength-tunable passband-flattened fiber comb filter based on polarization-diversified loop structure.

PubMed

Jung, Jaehoon; Lee, Yong Wook

2017-08-16

Continuous wavelength tuning of optical comb filters, which is an essential functionality for flexible signal processing in reconfigurable optical systems, has been challenging in high order filter structures with two birefringent elements (BEs) or more due to cumbersomeness in finding a combination of waveplates and BEs and complexity in determining their individual azimuthal orientations. Here, we propose a continuously tunable polarization-independent passband-flattened fiber comb filter with two BEs using a polarization-diversified loop structure for the first time. The proposed filter consists of a polarization beam splitter and two groups of a half-wave plate, quarter-wave plate, and polarization-maintaining fiber (PMF). The azimuthal orientation of PMF in the second group is fixed as 22.5°. Orientation angle sets of the four waveplates, which can induce an arbitrary phase shift from 0 to 2π in the passband-flattened transmittance function, are found from the filter transmittance derived using Jones matrix formulation. From theoretical spectral analysis, it is confirmed that passband-flattened comb spectra can be continuously tuned. Theoretical prediction is verified by experimental demonstration. Moreover, the wavelength-dependent evolution of the output state of polarization (SOP) of each PMF is investigated on the Poincare sphere, and the relationship between wavelength tuning and SOP evolution is also discussed.

EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles

DOE PAGES

Fan, Yao; Tan, Kemin; Chhor, Gekleng; ...

2015-07-03

The EsxB protein from Bacillus anthracis belongs to the WXG100 family, a group of proteins secreted by a specialized secretion system. We have determined the crystal structures of recombinant EsxB and discovered that the small protein (~10 kDa), comprised of a helix-loop-helix (HLH) hairpin, is capable of associating into two different helical bundles. The two basic quaternary assemblies of EsxB are an antiparallel (AP) dimer and a rarely observed bisecting U (BU) dimer. This structural duality of EsxB is believed to originate from the heptad repeat sequence diversity of the first helix of its HLH hairpin, which allows for twomore » alternative helix packing. The flexibility of EsxB and the ability to form alternative helical bundles underscore the possibility that this protein can serve as an adaptor in secretion and can form hetero-oligomeric helix bundle(s) with other secreted members of the WXG100 family, such as EsxW. The highly conserved WXG motif is located within the loop of the HLH hairpin and is mostly buried within the helix bundle suggesting that its role is mainly structural. The exact functions of the motif, including a proposed role as a secretion signal, remain unknown.« less

Study of the dynamics of orbital assemblies including interactions with geometrical appendages

NASA Technical Reports Server (NTRS)

Ness, D. J.

1972-01-01

The complete equations for the Unified Flexible Spacecraft Simulation (UFSS) program developed for the NASA/MSFC are presented. This general purpose simulation program is based on an algorithm which utilizes the digital computer to synthesize the dynamic and kinematic equations for a topological tree configuration of N interconnected bodies (the interconnected system of bodies forms no closed loops), the terminal members of which may be flexible. Necessary input quantities to the dynamic subroutine include the mass and inertia properties of each body and the flexible characteristics of each terminal member in addition to the specification, for each body, of those bodies to which it connects. This latter description involves the specification of the number of rotational degrees of freedom at each interconnection along with the associated position vectors defining these connections relative to the mass centers of the bodies involved. These position vectors can be input as time-varying functions if desired, thus affording the capability of studying the effects of time-varying hinge locations. Springs and dampers are assumed to act at each interconnection and structural damping in the flexible terminal members is included in the form of equivalent viscous damping.

Multi-turn multi-gap transmission line resonators - Concept, design and first implementation at 4.7T and 7T.

PubMed

Frass-Kriegl, Roberta; Laistler, Elmar; Hosseinnezhadian, Sajad; Schmid, Albrecht Ingo; Moser, Ewald; Poirier-Quinot, Marie; Darrasse, Luc; Ginefri, Jean-Christophe

2016-12-01

A novel design scheme for monolithic transmission line resonators (TLRs) is presented - the multi-turn multi-gap TLR (MTMG-TLR) design. The MTMG-TLR design enables the construction of TLRs with multiple turns and multiple gaps. This presents an additional degree of freedom in tuning self-resonant TLRs, as their resonance frequency is fully determined by the coil geometry (e.g. diameter, number of turns, conductor width, etc.). The novel design is evaluated at 4.7T and 7T by simulations and experiments, where it is demonstrated that MTMG-TLRs can be used for MRI, and that the B 1 distribution of MTMG-TLRs strongly depends on the number and distribution of turns. A comparison to conventional loop coils revealed that the B 1 performance of MTMG-TLRs is comparable to a loop coil with the same mean diameter; however, lower 10g SAR values were found for MTMG-TLRs. The MTMG-TLR design is expected to bring most benefits at high static field, where it allows for independent size and frequency selection, which cannot be achieved with standard TLR design. However, it also enables more accurate geometric optimization at low static field. Thereby, the MTMG-TLR design preserves the intrinsic advantages of TLRs, i.e. mechanical flexibility, high SAR efficiency, mass production, and coil miniaturization. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Carbon Dioxide Control System for a Mars Space Suit Life Support System

NASA Technical Reports Server (NTRS)

Alptekin, Gokhan; Jayaraman, Ambalavanan; Copeland, Robert; Parker, amanda; Paul, Heather L.

2010-01-01

Carbon dioxide (CO2) control during Extravehicular Activities (EVAs) on Mars will be challenging. Lithium hydroxide (LiOH) canisters have impractical logistics penalties, and regenerable metal oxide (MetOx) canisters weigh too much. Cycling bed systems and permeable membranes that are regenerable in space vacuum cannot vent on Mars due to the high partial pressure of CO2 in the atmosphere. Although sweep gas regeneration is under investigation, the feasibility, logistics penalties, and failure modes associated with this technique have not been fully determined. TDA Research, Inc. is developing a durable, high-capacity regenerable adsorbent that can remove CO2 from the space suit ventilation loop. The system design allows sorbent regeneration at or above 6 torr, eliminating the potential for Martian atmosphere to leak into the regeneration bed and into the ventilation loop. Regeneration during EVA eliminates the consumable requirement related to the use of LiOH canisters and the mission duration limitations imposed by MetOx system. The concept minimizes the amount of consumable to be brought from Earth and makes the mission more affordable, while providing great operational flexibility during EVA. The feasibility of the concept has been demonstrated in a series of bench-scale experiments and a preliminary system analysis. Results indicate that sorbent regeneration can be accomplished by applying a 14 C temperature swing, while regenerating at 13 torr (well above the Martian atmospheric pressure), withstanding over 1,000 adsorption/regeneration cycles. This paper presents the latest results from these sorbent and system development efforts.

Reconfigurable HIL Testing of Earth Satellites

NASA Technical Reports Server (NTRS)

2008-01-01

In recent years, hardware-in-the-loop (HIL) testing has carved a strong niche in several industries, such as automotive, aerospace, telecomm, and consumer electronics. As desktop computers have realized gains in speed, memory size, and data storage capacity, hardware/software platforms have evolved into high performance, deterministic HIL platforms, capable of hosting the most demanding applications for testing components and subsystems. Using simulation software to emulate the digital and analog I/O signals of system components, engineers of all disciplines can now test new systems in realistic environments to evaluate their function and performance prior to field deployment. Within the Aerospace industry, space-borne satellite systems are arguably some of the most demanding in terms of their requirement for custom engineering and testing. Typically, spacecraft are built one or few at a time to fulfill a space science or defense mission. In contrast to other industries that can amortize the cost of HIL systems over thousands, even millions of units, spacecraft HIL systems have been built as one-of-a-kind solutions, expensive in terms of schedule, cost, and risk, to assure satellite and spacecraft systems reliability. The focus of this paper is to present a new approach to HIL testing for spacecraft systems that takes advantage of a highly flexible hardware/software architecture based on National Instruments PXI reconfigurable hardware and virtual instruments developed using LabVIEW. This new approach to HIL is based on a multistage/multimode spacecraft bus emulation development model called Reconfigurable Hardware In-the-Loop or RHIL.

Structural Insights into Antibody Sequestering and Neutralizing of Na+ Channel α-Type Modulator from Old World Scorpion Venom

PubMed Central

Fabrichny, Igor P.; Mondielli, Grégoire; Conrod, Sandrine; Martin-Eauclaire, Marie-France; Bourne, Yves; Marchot, Pascale

2012-01-01

The Old World scorpion Androctonus australis hector (Aah) produces one of the most lethal venoms for humans. Peptidic α-toxins AahI to AahIV are responsible for its potency, with AahII accounting for half of it. All four toxins are high affinity blockers of the fast inactivation phase of mammalian voltage-activated Na+ channels. However, the high antigenic polymorphism of α-toxins prevents production of a polyvalent neutralizing antiserum, whereas the determinants dictating their trapping by neutralizing antibodies remain elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab) with high affinity and selectivity for AahII and solved a 2.3 Å-resolution crystal structure of the complex. Sequestering of the C-terminal region of the bound toxin within a groove formed by the Fab combining loops is associated with a toxin orientation and main and side chain conformations that dictate the AahII antigenic specificity and efficient neutralization. From an anti-AahI mAb, we also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 Å-resolution structure solved revealed a Fab molecule devoid of a bound AahI and with combining loops involved in packing interactions, denoting expulsion of the bound antigen upon crystal formation. Comparative analysis of the groove-like combining site of the toxin-bound anti-AahII Fab and planar combining surface of the unbound anti-AahI Fab along with complementary data from a flexible docking approach suggests occurrence of distinctive trapping orientations for the two toxins relative to their respective Fab. This study provides complementary templates for designing new molecules aimed at capturing Aah α-toxins and suitable for immunotherapy. PMID:22371498

Observations with the GISMOS Airborne Radio Occultation System

NASA Astrophysics Data System (ADS)

Muradyan, Paytsar; Haase, Jennifer; Garrison, James; Lulich, Tyler; Xie, Feiqin

2010-05-01

The spatial sample density of temperature and moisture profiles derived from the current spaceborne GPS radio occultation (RO) constellation is limited by the number of occultation satellites in operation. With the current RO satellite configuration, only one RO profile per day is typically available in a 160,000 square kilometer area in the mid-latitude and tropics and slightly more in high latitudes. The airborne RO technique, which has the GPS receiver onboard an airplane, offers flexibility and much denser sampling for targeted observation within 400 km of the aircraft, and provides comparable high vertical resolution to that of the spaceborne case. With an airborne system, targeted measurements can be planned in an optimal geometry to study the accuracy of RO measurements in the lower troposphere where strong vertical gradients in moisture might lead to disruption of signal tracking. These dense measurements can also be used to test assimilation techniques of refractivity and lower tropospheric moisture derived from RO data. In February 2008, the GNSS Instrument System for Multistatic and Occultation Sensing (GISMOS), developed at Purdue University, was successfully deployed on the NSF HIAPER aircraft for series of research flights in the Gulf of Mexico coastal region to validate the airborne observing system. During this campaign, occultation observations were collected in conjunction with supplemental radiosonde and dropsonde soundings. RO signals were recorded using side-looking GPS antennas and dual frequency GPS receivers. However, these conventional phase-locked-loop GPS receivers cannot always track the signal in the lower troposphere, where there are rapid phase accelerations caused by highly variable moisture structures. To extend the observations deeper into the atmosphere, the raw signal from occulting satellites is recorded at 10MHz sampling interval by a GPS recording system (GRS). Open-loop (OL) tracking, which replaces the traditional GPS receiver feedback loop using an a priori estimate of Doppler frequency, was implemented in a software receiver and the data was post-processed after the flight. Such an extensive dataset can be of importance in studies aimed at improving signal processing performance for spaceborne as well as airborne RO measurements. We present data from the February 2008 campaign, and show several examples of occultations with clear atmospheric signals in the excess phase and Doppler. Many recordings that were made with conventional receivers descend below 5 km in the atmosphere. With an OL tracking procedure using the data recorded by the GRS, the measurements extended deeper into the atmosphere (~ 2km above surface). Raytracing was used to simulate the atmospheric excess phase profile from a nearby radiosonde sounding. The excess phase profiles acquired with both closed-loop and open-loop tracking show consistent patterns compared to the radiosonde observations.