Conformational analysis of oligosaccharides and polysaccharides using molecular dynamics simulations.

Science.gov (United States)

Frank, Martin

2015-01-01

Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).

Reliability modelling and simulation of switched linear system ...

African Journals Online (AJOL)

Reliability modelling and simulation of switched linear system control using temporal databases. ... design of fault-tolerant real-time switching systems control and modelling embedded micro-schedulers for complex systems maintenance.

Particle in cell simulation of peaking switch for breakdown evaluation

Energy Technology Data Exchange (ETDEWEB)

Umbarkar, Sachin B.; Bindu, S.; Mangalvedekar, H.A.; Saxena, A.; Singh, N.M., E-mail: sachin.b.umbarkar@gmail.com [Department of Electric Engineering, Veermata Jijabai Technological Institute, Mumbai (India); Sharma, Archana; Saroj, P.C.; Mittal, K.C. [Accelerator Pulse Power Division, Bhabha Atomic Research Centre, Mumbai (India)

2014-07-01

Marx generator connected to peaking capacitor and peaking switch can generate Ultra-Wideband (UWB) radiation. A new peaking switch is designed for converting the existing nanosecond Marx generator to a UWB source. The paper explains the particle in cell (PIC) simulation for this peaking switch, using MAGIC 3D software. This peaking switch electrode is made up of copper tungsten material and is fixed inside the hermitically sealed derlin material. The switch can withstand a gas pressure up to 13.5 kg/cm{sup 2}. The lower electrode of the switch is connected to the last stage of the Marx generator. Initially Marx generator (without peaking stage) in air; gives the output pulse with peak amplitude of 113.75 kV and pulse rise time of 25 ns. Thus, we design a new peaking switch to improve the rise time of output pulse and to pressurize this peaking switch separately (i.e. Marx and peaking switch is at different pressure). The PIC simulation gives the particle charge density, current density, E counter plot, emitted electron current, and particle energy along the axis of gap between electrodes. The charge injection and electric field dependence on ionic dissociation phenomenon are briefly analyzed using this simulation. The model is simulated with different gases (N{sub 2}, H{sub 2}, and Air) under different pressure (2 kg/cm{sup 2}, 5 kg/cm{sup 2}, 10 kg/cm{sup 2}). (author)

A Simulator of Periodically Switching Channels for Power Line Communications

Science.gov (United States)

Hayasaki, Taro; Umehara, Daisuke; Denno, Satoshi; Morikura, Masahiro

An indoor power line is one of the most attractive media for in-home networks. However, there are many technical problems for achieving in-home power line communication (PLC) with high rate and high reliability. One of such problem is the degradation in the performance of the in-home PLC caused by periodically time-varying channel responses, particularly when connecting the switching power supply equipment. We present a measurement method for power line channel responses and reveal the switching of the channel responses synchronized with power-frequency voltage when connecting switching power supply equipment in sending or receiving outlets. In this paper, we term them periodically switching channel responses. The performance of PLC adapters is seriously affected by the periodically switching channel responses. Therefore, we provide a modeling of the periodically switching channel responses by using finite impulse response (FIR) filters with a shared channel memory and construct a simulator for in-home power line channels including the periodically switching channel responses in order to evaluate the various communication systems through the power line. We present the validity of the proposed simulator through the performance evaluation of OFDM/64QAM over periodically switching channels with additive white Gaussian noise. Furthermore, we evaluate the influence of the periodically switching channel responses on the communication quality of a time-invariant modulation scheme by using the proposed simulator.

Fast simulation techniques for switching converters

Science.gov (United States)

King, Roger J.

1987-01-01

Techniques for simulating a switching converter are examined. The state equations for the equivalent circuits, which represent the switching converter, are presented and explained. The uses of the Newton-Raphson iteration, low ripple approximation, half-cycle symmetry, and discrete time equations to compute the interval durations are described. An example is presented in which these methods are illustrated by applying them to a parallel-loaded resonant inverter with three equivalent circuits for its continuous mode of operation.

Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches.

Directory of Open Access Journals (Sweden)

Tobias Sikosek

2016-06-01

Full Text Available Deciphering the effects of nonsynonymous mutations on protein structure is central to many areas of biomedical research and is of fundamental importance to the study of molecular evolution. Much of the investigation of protein evolution has focused on mutations that leave a protein's folded structure essentially unchanged. However, to evolve novel folds of proteins, mutations that lead to large conformational modifications have to be involved. Unraveling the basic biophysics of such mutations is a challenge to theory, especially when only one or two amino acid substitutions cause a large-scale conformational switch. Among the few such mutational switches identified experimentally, the one between the GA all-α and GB α+β folds is extensively characterized; but all-atom simulations using fully transferrable potentials have not been able to account for this striking switching behavior. Here we introduce an explicit-chain model that combines structure-based native biases for multiple alternative structures with a general physical atomic force field, and apply this construct to twelve mutants spanning the sequence variation between GA and GB. In agreement with experiment, we observe conformational switching from GA to GB upon a single L45Y substitution in the GA98 mutant. In line with the latent evolutionary potential concept, our model shows a gradual sequence-dependent change in fold preference in the mutants before this switch. Our analysis also indicates that a sharp GA/GB switch may arise from the orientation dependence of aromatic π-interactions. These findings provide physical insights toward rationalizing, predicting and designing evolutionary conformational switches.

A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms.

Science.gov (United States)

Gustafson, Chelsea L; Parsley, Nicole C; Asimgil, Hande; Lee, Hsiau-Wei; Ahlbach, Christopher; Michael, Alicia K; Xu, Haiyan; Williams, Owen L; Davis, Tara L; Liu, Andrew C; Partch, Carrie L

2017-05-18

The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping. Both cis and trans isomers interact with transcriptional regulators, suggesting that isomerization could serve a role in assembling regulatory complexes in vivo. Toward this end, we show that locking the switch into the trans isomer leads to shortened circadian periods. Furthermore, isomerization is regulated by the cyclophilin family of peptidyl-prolyl isomerases, highlighting the potential for regulation of BMAL1 protein dynamics in period determination. Copyright © 2017 Elsevier Inc. All rights reserved.

Asymmetric switching in a homodimeric ABC transporter: a simulation study.

Directory of Open Access Journals (Sweden)

Jussi Aittoniemi

2010-04-01

Full Text Available ABC transporters are a large family of membrane proteins involved in a variety of cellular processes, including multidrug and tumor resistance and ion channel regulation. Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two canonical nucleotide-binding sites (NBSs is co-operative and non-simultaneous. A conserved core architecture of bacterial and eukaryotic ABC exporters has been established, as exemplified by the crystal structure of the homodimeric multidrug exporter Sav1866. Currently, it is unclear how sequential ATP hydrolysis arises in a symmetric homodimeric transporter, since it implies at least transient asymmetry at the NBSs. We show by molecular dynamics simulation that the initially symmetric structure of Sav1866 readily undergoes asymmetric transitions at its NBSs in a pre-hydrolytic nucleotide configuration. MgATP-binding residues and a network of charged residues at the dimer interface are shown to form a sequence of putative molecular switches that allow ATP hydrolysis only at one NBS. We extend our findings to eukaryotic ABC exporters which often consist of two non-identical half-transporters, frequently with degeneracy substitutions at one of their two NBSs. Interestingly, many residues involved in asymmetric conformational switching in Sav1866 are substituted in degenerate eukaryotic NBS. This finding strengthens recent suggestions that the interplay of a consensus and a degenerate NBS in eukaroytic ABC proteins pre-determines the sequence of hydrolysis at the two NBSs.

ELECTROMAGNETIC AND THERMAL SIMULATIONS FOR THE SWITCH REGION OF A COMPACT PROTON ACCELERATOR

International Nuclear Information System (INIS)

Wang, L; Caporaso, G J; Sullivan, J S

2007-01-01

A compact proton accelerator for medical applications is being developed at Lawrence Livermore National Laboratory. The accelerator architecture is based on the dielectric wall accelerator (DWA) concept. One critical area to consider is the switch region. Electric field simulations and thermal calculations of the switch area were performed to help determine the operating limits of rmed SiC switches. Different geometries were considered for the field simulation including the shape of the thin Indium solder meniscus between the electrodes and SiC. Electric field simulations were also utilized to demonstrate how the field stress could be reduced. Both transient and steady steady-state thermal simulations were analyzed to find the average power capability of the switches

Selection of candidate wells and optimization of conformance treatment design in the Barrancas Field using a 3D conformance simulator

Energy Technology Data Exchange (ETDEWEB)

Crosta, Dante; Elitseche, Luis [Repsol YPF (Argentina); Gutierrez, Mauricio; Ansah, Joe; Everett, Don [Halliburton Argentina S.A., Buenos Aires (Argentina)

2004-07-01

Minimizing the amount of unwanted water production is an important goal at the Barrancas field. This paper describes a selection process for candidate injection wells that is part of a pilot conformance project aimed at improving vertical injection profiles, reducing water cut in producing wells, and improving ultimate oil recovery from this field. The well selection process is based on a review of limited reservoir information available for this field to determine inter-well communications. The methodology focuses on the best use of available information, such as production and injection history, well intervention files, open hole logs and injectivity surveys. After the candidate wells were selected and potential water injection channels were identified, conformance treatment design and future performance of wells in the selected pilot area were evaluated using a new 3 -D conformance simulator, developed specifically for optimization of the design and placement of unwanted fluid shut-off treatments. Thus, when acceptable history match ing of the pilot area production was obtained, the 3 -D simulator was used to: evaluate the required volume of selected conformance treatment fluid; review expected pressures and rates during placement;. model temperature behavior; evaluate placement techniques, and forecast water cut reduction and incremental oil recovery from the producers in this simulated section of the pilot area. This paper outlines a methodology for selecting candidate wells for conformance treatments. The method involves application of several engineering tools, an integral component of which is a user-friendly conformance simulator. The use of the simulator has minimized data preparation time and allows the running of sensitivity cases quickly to explore different possible scenarios that best represent the reservoir. The proposed methodology provides an efficient means of identifying conformance problems and designing optimized solutions for these individual

A lipid-mediated conformational switch modulates the thermosensing activity of DesK.

Science.gov (United States)

Inda, María Eugenia; Vandenbranden, Michel; Fernández, Ariel; de Mendoza, Diego; Ruysschaert, Jean-Marie; Cybulski, Larisa Estefanía

2014-03-04

The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially "buoy" to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a "linker region" (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.

Dynamic fluctuations provide the basis of a conformational switch mechanism in apo cyclic AMP receptor protein.

Directory of Open Access Journals (Sweden)

Burcu Aykaç Fas

Full Text Available Escherichia coli cyclic AMP Receptor Protein (CRP undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD simulations and Gaussian Network Model (GNM. The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra- and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.

Micromagnetic Simulation of Strain-Assisted Current-Induced Magnetization Switching

Directory of Open Access Journals (Sweden)

H. B. Huang

2016-01-01

Full Text Available We investigated the effect of substrate misfit strain on the current-induced magnetization switching in magnetic tunnel junctions by combining micromagnetic simulation with phase-field microelasticity theory. Our results indicate that the positive substrate misfit strain can decrease the critical current density of magnetization switching by pushing the magnetization from out-of-plane to in-plane directions, while the negative strain pushes the magnetization back to the out-of-plane directions. The magnetic domain evolution is obtained to demonstrate the strain-assisted current-induced magnetization switching.

Conformational elasticity can facilitate TALE-DNA recognition.

Science.gov (United States)

Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P; Segal, David J; Duan, Yong

2014-01-01

Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo and bound conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. © 2014 Elsevier Inc. All rights reserved.

A behavioral simulator for switched-capacitor sigma-delta modulator analog-to-digital converter

International Nuclear Information System (INIS)

San, H. Y.; Rezaul Hasan, S. M.

1998-01-01

In this paper, a PC-based simulator for state of the art oversampled switched-capacitor sigma-delta analog-to-digital converters is presented. The proposed simulator employs behavioral model of switched-capacitor integrator and non-linear quantizer to stimulate the system. The behavioral simulation of the integrator is also verified with SPICE. The simulator is fully integrated and standalone. It integrates an input netlist file interpreter, a behavioral simulator, a generic part library and a powerful post-processor to evaluate the SNR, SDR And TSNR. Both passive and active sensitivities can be investigated by the proposed simulator. The simulator is coded in C++, and is very fast

Assignment of Side-Chain Conformation Using Adiabatic Energy Mapping, Free Energy Perturbation, and Molecular Dynamic Simulations

DEFF Research Database (Denmark)

Frimurer, Thomas M.; Günther, Peter H.; Sørensen, Morten Dahl

1999-01-01

adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)......adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)...

Investigations and Simulations of All optical Switches in linear state Based on Photonic Crystal Directional Coupler

Directory of Open Access Journals (Sweden)

S. Maktoobi

2014-10-01

Full Text Available Switching is a principle process in digital computers and signal processing systems. The growth of optical signal processing systems, draws particular attention to design of ultra-fast optical switches. In this paper, All Optical Switches in linear state Based On photonic crystal Directional coupler is analyzed and simulated. Among different methods, the finite difference time domain method (FDTD is a preferable method and is used. We have studied the application of photonic crystal lattices, the physics of optical switching and photonic crystal Directional coupler. In this paper, Electric field intensity and the power output that are two factors to improve the switching performance and the device efficiency are investigated and simulated. All simulations are performed by COMSOL software.

Conformal fields in prostate radiotherapy: A comparison between measurement, calculation and simulation

Directory of Open Access Journals (Sweden)

Seied R Mahdavi

2012-01-01

Full Text Available Aims: The objective of this study is to evaluate the accuracy of a treatment planning system (TPS for calculating the dose distribution parameters in conformal fields (CF. Dosimetric parameters of CF′s were compared between measurement, Monte Carlo simulation (MCNP4C and TPS calculation. Materials and Methods: Field analyzer water phantom was used for obtaining percentage depth dose (PDD curves and beam profiles (BP of different conformal fields. MCNP4C was used to model conformal fields dose specification factors and head of linear accelerator varian model 2100C/D. Results: Results showed that the distance to agreement (DTA and dose difference (DD of our findings were well within the acceptance criteria of 3 mm and 3%, respectively. Conclusions: According to this study it can be revealed that TPS using equivalent tissue air ratio calculation method is still convenient for dose prediction in non small conformal fields normally used in prostate radiotherapy. It was also showed that, since there is a close correlation with Monte Carlo simulation, measurements and TPS, Monte Carlo can be further confirmed for implementation and calculation dose distribution in non standard and complex conformal irradiation field for treatment planning systems.

Simulation and test of the thermal behavior of pressure switch

Science.gov (United States)

Liu, Yifang; Chen, Daner; Zhang, Yao; Dai, Tingting

2018-04-01

Little, lightweight, low-power microelectromechanical system (MEMS) pressure switches offer a good development prospect for small, ultra-long, simple atmosphere environments. In order to realize MEMS pressure switch, it is necessary to solve one of the key technologies such as thermal robust optimization. The finite element simulation software is used to analyze the thermal behavior of the pressure switch and the deformation law of the pressure switch film under different temperature. The thermal stress releasing schemes are studied by changing the structure of fixed form and changing the thickness of the substrate, respectively. Finally, the design of the glass substrate thickness of 2.5 mm is used to ensure that the maximum equivalent stress is reduced to a quarter of the original value, only 154 MPa when the structure is in extreme temperature (80∘C). The test results show that after the pressure switch is thermally optimized, the upper and lower electrodes can be reliably contacted to accommodate different operating temperature environments.

Anthem simulation studies of the plasma opening switch

International Nuclear Information System (INIS)

Mason, R.J.

1993-01-01

For a deeper understanding of the physical processes governing the Plasma Opening Switch (POS) the authors use the ANTHEM 2D implicit simulation code to study: (1) ion dynamical effects on electrohydrodynamic (EHD) waves propagating along steep density interfaces in the switch plasmas. At radial interfaces where the density jumps toward the anode, these waves can drive a finger of magnetic field into the plasma toward the load. Ion dynamics can open the rear of such fingers into a wedge-like density gap. Then: (2) they examine ion effects in uniform switch plasmas. These first develop potential hill structures at the drive edge of the cathode from the competition between electron velocity advection and EHD magnetic exclusion waves. Magnetic pressure gradients at the hill periphery and EHD effects then establish a density gap propagating along the cathode with radial electron emission from its tip. Similar results are obtained under both multi-fluid and PIC modeling on the plasma components

A regenerated electrochemical biosensor for label-free detection of glucose and urea based on conformational switch of i-motif oligonucleotide probe

Energy Technology Data Exchange (ETDEWEB)

Gao, Zhong Feng; Chen, Dong Mei [Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Lei, Jing Lei [School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044 (China); Luo, Hong Qun, E-mail: luohq@swu.edu.cn [Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Li, Nian Bing, E-mail: linb@swu.edu.cn [Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

2015-10-15

Improving the reproducibility of electrochemical signal remains a great challenge over the past decades. In this work, i-motif oligonucleotide probe-based electrochemical DNA (E-DNA) sensor is introduced for the first time as a regenerated sensing platform, which enhances the reproducibility of electrochemical signal, for label-free detection of glucose and urea. The addition of glucose or urea is able to activate glucose oxidase-catalyzed or urease-catalyzed reaction, inducing or destroying the formation of i-motif oligonucleotide probe. The conformational switch of oligonucleotide probe can be recorded by electrochemical impedance spectroscopy. Thus, the difference of electron transfer resistance is utilized for the quantitative determination of glucose and urea. We further demonstrate that the E-DNA sensor exhibits high selectivity, excellent stability, and remarkable regenerated ability. The human serum analysis indicates that this simple and regenerated strategy holds promising potential in future biosensing applications. - Highlights: • Conformational switch of i-motif is used for the detection of glucose and urea. • The sensor can be regenerated. • The proposed method is successfully applied in real sample assay. • Our method is label-free and inexpensive.

Using simulation to interpret experimental data in terms of protein conformational ensembles.

Science.gov (United States)

Allison, Jane R

2017-04-01

In their biological environment, proteins are dynamic molecules, necessitating an ensemble structural description. Molecular dynamics simulations and solution-state experiments provide complimentary information in the form of atomically detailed coordinates and averaged or distributions of structural properties or related quantities. Recently, increases in the temporal and spatial scale of conformational sampling and comparison of the more diverse conformational ensembles thus generated have revealed the importance of sampling rare events. Excitingly, new methods based on maximum entropy and Bayesian inference are promising to provide a statistically sound mechanism for combining experimental data with molecular dynamics simulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quasi-Resonant Full-Wave Zero-Current Switching Buck Converter Design, Simulation and Application

OpenAIRE

Yanik, G.; Isen, E.

2015-01-01

—This paper presents a full wave quasi-resonant zerocurrent switching buck converter design, simulation and application. The converter control uses with zero-current switching (ZCS) technique to decrease the switching losses. Comparing to conventional buck converter, resonant buck converter includes a resonant tank equipped with resonant inductor and capacitor. The converter is analyzed in mathematical for each subintervals. Depending on the desired input and output electrical quantities, con...

Chiral Induction with Chiral Conformational Switches in the Limit of Low "Sergeants to Soldiers" Ratio

DEFF Research Database (Denmark)

Nuermaimaiti, Ajiguli; Bombis, Christian; Knudsen, Martin Markvard

2014-01-01

Molecular-level insights into chiral adsorption phenomena are highly relevant within the fields of asymmetric heterogeneous catalysis or chiral separation and may contribute to understand the origins of homochirality in nature. Here, we investigate chiral induction by the "sergeants and soldiers......" mechanism for an oligo(phenylene ethynylene) based chiral conformational switch by coadsorbing it with an intrinsically chiral seed on Au(111). Through statistical analysis of scanning tunneling microscopy (STM) data we demonstrate successful chiral induction with a very low concentration of seeding...... molecules down to 3%. The microscopic mechanism for the observed chiral induction is suggested to involve nucleation of the intrinsically chiral seeds, allowing for effective transfer and amplification of chirality to large numbers of soldier target molecules....

Exploring the relationship between the conformation and pK_a

DEFF Research Database (Denmark)

Olsen, Jacob Ingemar; Sauer, Stephan P. A.; Pedersen, Christian Marcus

2015-01-01

Four substituted cis and trans-4,5-dihydroxyhexahydropyridazines that were expected to undergo pH induced conformational switching were synthesized and carefully investigated by NMR analyses and calculations. For two of the compounds a large difference in pKa existed between the two possible chair...... conformers and for one compound this resulted in conformational switching as a result of pH change. For the first time it is shown that the pKa directly reflects the conformational equilibrium of conformers....

Unbiased simulations reveal the inward-facing conformation of the human serotonin transporter and Na+ ion release

DEFF Research Database (Denmark)

Koldsø, Heidi; Noer, Pernille Rimmer; Grouleff, Julie

2011-01-01

transporter has resulted in homology models of the monoamine transporters. Here we present extended molecular dynamics simulations of an experimentally supported homology model of hSERT with and without the natural substrate yielding a total of more than 1.5 µs of simulation of the protein dimer....... The simulations reveal a transition of hSERT from an outward-facing occluded conformation to an inward-facing conformation in a one-substrate-bound state. Simulations with a second substrate in the proposed symport effector site did not lead to conformational changes associated with translocation. The central...... substrate binding site becomes fully exposed to the cytoplasm leaving both the Na+-ion in the Na2-site and the substrate in direct contact with the cytoplasm through water interactions. The simulations reveal how sodium is released and show indications of early events of substrate transport. The notion...

EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

Science.gov (United States)

Weinelt, Martin; von Oppen, Felix

2012-10-01

In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

Design, simulation and fabrication of a novel contact-enhanced MEMS inertial switch with a movable contact point

International Nuclear Information System (INIS)

Cai Haogang; Ding Guifu; Yang Zhuoqing; Su Zhijuan; Zhou Jiansheng; Wang Hong

2008-01-01

A novel inertial switch based on a micro-electro-mechanical system (MEMS) was designed, which consists of three main parts: a proof mass as the movable electrode, a cross beam as the stationary electrode and a movable contact point to prolong the contact time. A MATLAB/Simulink model, which had been verified by comparison with ANSYS transient simulation, was built to simulate the dynamic response, based on which the contact-enhancing mechanism was confirmed and the dependence of threshold acceleration on the proof mass thickness was studied. The simulated dynamic responses under various accelerations exhibit satisfactory device behaviors: the switch-on time is prolonged under transient acceleration; the switch-on state is more continuous than the conventional design under long lasting acceleration. The inertial micro-switch was fabricated by multilayer electroplating technology and then tested by a drop hammer experiment. The test results indicate that the contact effect was improved significantly and a steady switch-on time of over 50 µs was observed under half-sine wave acceleration with 1 ms duration, in agreement with the dynamic simulation

Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

Energy Technology Data Exchange (ETDEWEB)

Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian, E-mail: jianzhou@scut.edu.cn

2016-07-30

Graphical abstract: Preferential adsorption of Vpr13-33 on graphene accompanied by early conformational change from α-helix to β-sheet structures was observed by molecular simulations. This work presents the molecular mechanism of graphene-induced peptide conformational alteration and sheds light on developing graphene-based materials to inhibit HIV. - Highlights: • Graphene induced early structural transition of Vpr13-33 is studied by MD simulations. • Both π-π stacking and hydrophobic interactions orchestrate the peptide adsorption. • Vpr has an increased propensity of β-sheet content on graphene surface. • To develop graphene-based materials to inhibit HIV is possible. - Abstract: The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of

Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

International Nuclear Information System (INIS)

Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

2016-01-01

Graphical abstract: Preferential adsorption of Vpr13-33 on graphene accompanied by early conformational change from α-helix to β-sheet structures was observed by molecular simulations. This work presents the molecular mechanism of graphene-induced peptide conformational alteration and sheds light on developing graphene-based materials to inhibit HIV. - Highlights: • Graphene induced early structural transition of Vpr13-33 is studied by MD simulations. • Both π-π stacking and hydrophobic interactions orchestrate the peptide adsorption. • Vpr has an increased propensity of β-sheet content on graphene surface. • To develop graphene-based materials to inhibit HIV is possible. - Abstract: The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of

Extracting Markov Models of Peptide Conformational Dynamics from Simulation Data.

Science.gov (United States)

Schultheis, Verena; Hirschberger, Thomas; Carstens, Heiko; Tavan, Paul

2005-07-01

A high-dimensional time series obtained by simulating a complex and stochastic dynamical system (like a peptide in solution) may code an underlying multiple-state Markov process. We present a computational approach to most plausibly identify and reconstruct this process from the simulated trajectory. Using a mixture of normal distributions we first construct a maximum likelihood estimate of the point density associated with this time series and thus obtain a density-oriented partition of the data space. This discretization allows us to estimate the transfer operator as a matrix of moderate dimension at sufficient statistics. A nonlinear dynamics involving that matrix and, alternatively, a deterministic coarse-graining procedure are employed to construct respective hierarchies of Markov models, from which the model most plausibly mapping the generating stochastic process is selected by consideration of certain observables. Within both procedures the data are classified in terms of prototypical points, the conformations, marking the various Markov states. As a typical example, the approach is applied to analyze the conformational dynamics of a tripeptide in solution. The corresponding high-dimensional time series has been obtained from an extended molecular dynamics simulation.

Simulated Switching Transients in the External Grid of Walney Offshore Wind Farm

DEFF Research Database (Denmark)

Arana Aristi, Iván; Johnsen, D. T.; Soerensen, T.

2011-01-01

. These switching operations were simulated using the EMT software PSCAD/EMTDC A number of parameters were varied in order to determine the most critical transients. Based on the results, it was concluded that the worst line-to-line transient overvoltage occurred in the DC05 and EF06 turbines, when a 25km cable......This paper presents the results of several simulations to assess the highest possible line-to-line overvoltage at the terminals of wind turbine converters after the switching operation of a cable or capacitor bank in the external grid of Walney 1, one of two phases of Walney Offshore Wind Farm...

The Role of Conserved Waters in Conformational Transitions of Q61H K-ras

Science.gov (United States)

Prakash, Priyanka; Sayyed-Ahmad, Abdallah; Gorfe, Alemayehu A.

2012-01-01

To investigate the stability and functional role of long-residence water molecules in the Q61H variant of the signaling protein K-ras, we analyzed all available Ras crystal structures and conformers derived from a series of independent explicit solvent molecular dynamics (MD) simulations totaling 1.76 µs. We show that the protein samples a different region of phase space in the presence and absence of several crystallographically conserved and buried water molecules. The dynamics of these waters is coupled with the local as well as the global motions of the protein, in contrast to less buried waters whose exchange with bulk is only loosely coupled with the motion of loops in their vicinity. Aided by two novel reaction coordinates involving the distance (d) between the Cα atoms of G60 at switch 2 and G10 at the P-loop and the N-Cα-C-O dihedral (ξ) of G60, we further show that three water molecules located in lobe1, at the interface between the lobes and at lobe2, are involved in the relative motion of residues at the two lobes of Q61H K-ras. Moreover, a d/ξ plot classifies the available Ras x-ray structures and MD-derived K-ras conformers into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free conformational states. The population of these states and the transition between them is modulated by water-mediated correlated motions involving the functionally critical switch 2, P-loop and helix 3. These results suggest that water molecules act as allosteric ligands to induce a population shift among distinct switch 2 conformations that differ in effector recognition. PMID:22359497

The Murid Herpesvirus-4 gL regulates an entry-associated conformation change in gH.

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Laurent Gillet

2008-07-01

Full Text Available The glycoprotein H (gH/gL heterodimer is crucial for herpesvirus membrane fusion. Yet how it functions is not well understood. The Murid Herpesvirus-4 gH, like that of other herpesviruses, adopts its normal virion conformation by associating with gL. However, gH switched back to a gL-independent conformation after virion endocytosis. This switch coincided with a conformation switch in gB and with capsid release. Virions lacking gL constitutively expressed the down-stream form of gH, prematurely switched gB to its down-stream form, and showed premature capsid release with poor infectivity. These data argue that gL plays a key role in regulating a gH and gB functional switch from cell binding to membrane fusion.

Reversible switching of ultrastrong light-molecule coupling

DEFF Research Database (Denmark)

Schwartz, T; Hutchison, J A; Genet, C

2011-01-01

We demonstrate that photochromic molecules enable switching from the weak- to ultrastrong-coupling regime reversibly, by using all-optical control. This switch is achieved by photochemically inducing conformational changes in the molecule. Remarkably, a Rabi splitting of 700 meV is measured at room...

Design of conformal cooling for plastic injection moulding by heat transfer simulation

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Sabrina Marques

2015-12-01

Full Text Available The cooling channels of a mold for plastic injection have to be as close as possible to the part geometry in order to ensure fast and homogeneous cooling. However, conventional methods to manufacture cooling channels (drilling can only produce linear holes. Selective laser melting (SLM is an additive manufacturing technique capable to manufacture complex cooling channels (known as conformal cooling. Nevertheless, because of the high costs of SLM the benefits of conformal collings are still not clear. The current work investigates two designs of conformal coolings: i parallel circuit; ii serial circuit. Both coolings are evaluated against to traditional cooling circuits (linear channels by CAE simulation to produce parts of polypropylene. The results show that if the conformal cooling is not properly designed it cannot provide reasonable results. The deformation of the product can be reduced significantly after injection but the cycle time reduced not more than 6%.

Antiferroelectric polarization switching and dynamic scaling of energy storage: A Monte Carlo simulation

Science.gov (United States)

Huang, B. Y.; Lu, Z. X.; Zhang, Y.; Xie, Y. L.; Zeng, M.; Yan, Z. B.; Liu, J.-M.

2016-05-01

The polarization-electric field hysteresis loops and the dynamics of polarization switching in a two-dimensional antiferroelectric (AFE) lattice submitted to a time-oscillating electric field E(t) of frequency f and amplitude E0, is investigated using Monte Carlo simulation based on the Landau-Devonshire phenomenological theory on antiferroelectrics. It is revealed that the AFE double-loop hysteresis area A, i.e., the energy loss in one cycle of polarization switching, exhibits the single-peak frequency dispersion A(f), suggesting the unique characteristic time for polarization switching, which is independent of E0 as long as E0 is larger than the quasi-static coercive field for the antiferroelectric-ferroelectric transitions. However, the dependence of recoverable stored energy W on amplitude E0 seems to be complicated depending on temperature T and frequency f. A dynamic scaling behavior of the energy loss dispersion A(f) over a wide range of E0 is obtained, confirming the unique characteristic time for polarization switching of an AFE lattice. The present simulation may shed light on the dynamics of energy storage and release in AFE thin films.

Simulated tempering distributed replica sampling: A practical guide to enhanced conformational sampling

Energy Technology Data Exchange (ETDEWEB)

Rauscher, Sarah; Pomes, Regis, E-mail: pomes@sickkids.ca

2010-11-01

Simulated tempering distributed replica sampling (STDR) is a generalized-ensemble method designed specifically for simulations of large molecular systems on shared and heterogeneous computing platforms [Rauscher, Neale and Pomes (2009) J. Chem. Theor. Comput. 5, 2640]. The STDR algorithm consists of an alternation of two steps: (1) a short molecular dynamics (MD) simulation; and (2) a stochastic temperature jump. Repeating these steps thousands of times results in a random walk in temperature, which allows the system to overcome energetic barriers, thereby enhancing conformational sampling. The aim of the present paper is to provide a practical guide to applying STDR to complex biomolecular systems. We discuss the details of our STDR implementation, which is a highly-parallel algorithm designed to maximize computational efficiency while simultaneously minimizing network communication and data storage requirements. Using a 35-residue disordered peptide in explicit water as a test system, we characterize the efficiency of the STDR algorithm with respect to both diffusion in temperature space and statistical convergence of structural properties. Importantly, we show that STDR provides a dramatic enhancement of conformational sampling compared to a canonical MD simulation.

Assessing methods for dealing with treatment switching in randomised controlled trials: a simulation study

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Latimer Nicholas

2011-01-01

Full Text Available Abstract Background We investigate methods used to analyse the results of clinical trials with survival outcomes in which some patients switch from their allocated treatment to another trial treatment. These included simple methods which are commonly used in medical literature and may be subject to selection bias if patients switching are not typical of the population as a whole. Methods which attempt to adjust the estimated treatment effect, either through adjustment to the hazard ratio or via accelerated failure time models, were also considered. A simulation study was conducted to assess the performance of each method in a number of different scenarios. Results 16 different scenarios were identified which differed by the proportion of patients switching, underlying prognosis of switchers and the size of true treatment effect. 1000 datasets were simulated for each of these and all methods applied. Selection bias was observed in simple methods when the difference in survival between switchers and non-switchers were large. A number of methods, particularly the AFT method of Branson and Whitehead were found to give less biased estimates of the true treatment effect in these situations. Conclusions Simple methods are often not appropriate to deal with treatment switching. Alternative approaches such as the Branson & Whitehead method to adjust for switching should be considered.

Micromagnetic simulation of energy consumption and excited eigenmodes in elliptical nanomagnetic switches

International Nuclear Information System (INIS)

Carlotti, G.; Madami, M.; Gubbiotti, G.; Tacchi, S.

2014-01-01

Sub-200 nm patterned magnetic dots are key elements for the design of magnetic switches, memory cells or elementary units of nanomagnetic logic circuits. In this paper, we analyse by micromagnetic simulations the magnetization reversal, the dissipated energy and the excited spin eigenmodes in bistable magnetic switches, consisting of elliptical nanodots with 100×60 nm lateral dimensions. Two different strategies for reversal are considered and the relative results compared: (i) the irreversible switching obtained by the application of an external field along the easy axis, in the direction opposite to the initial magnetization; (ii) the precessional switching accomplished by the application of a short magnetic field pulse, oriented perpendicular to the initial magnetization direction. The obtained results are discussed in terms of deviation from the macrospin behavior, energy dissipation and characteristics of the spectrum of spin eigenmodes excited during the magnetization reversal process

Simulation of a processor switching circuit with APLSV

International Nuclear Information System (INIS)

Dilcher, H.

1979-01-01

The report describes the simulation of a processor switching circuit with APL. Furthermore an APL function is represented to simulate a processor in an assembly like language. Both together serve as a tool for studying processor properties. By means of the programming function it is also possible to program other simulated processors. The processor is to be used in the processing of data in real time analysis that occur in high energy physics experiments. The data are already offered to the computer in digitalized form. A typical data rate is at 10 KB/ sec. The data are structured in blocks. The particular blocks are 1 KB wide and are independent from each other. Aprocessor has to decide, whether the block data belong to an event that is part of the backround noise and can therefore be forgotten, or whether the data should be saved for a later evaluation. (orig./WB) [de

A conformational switch high-throughput screening assay and allosteric inhibition of the flavivirus NS2B-NS3 protease.

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Matthew Brecher

2017-05-01

Full Text Available The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors. Binding of an active-site inhibitor to the protease resulted in a conformational change of NS2B and led to significant SLC enhancement. Mutagenesis of key residues at an allosteric site abolished this induced conformational change and SLC enhancement. We also performed a virtual screen of NCI library compounds to identify allosteric inhibitors, followed by in vitro biochemical screening of the resultant candidates. Only three of these compounds, NSC135618, 260594, and 146771, significantly inhibited the protease of Dengue virus 2 (DENV2 in vitro, with IC50 values of 1.8 μM, 11.4 μM, and 4.8 μM, respectively. Among the three compounds, only NSC135618 significantly suppressed the SLC enhancement triggered by binding of active-site inhibitor in a dose-dependent manner, indicating that it inhibits the conformational change of NS2B. Results from virus titer reduction assays revealed that NSC135618 is a broad spectrum flavivirus protease inhibitor, and can significantly reduce titers of DENV2, Zika virus (ZIKV, West Nile virus (WNV, and Yellow fever virus (YFV on A549 cells in vivo, with EC50 values in low micromolar range. In contrast, the cytotoxicity of NSC135618 is only moderate with CC50 of 48.8 μM on A549 cells. Moreover, NSC135618 inhibited ZIKV in human placental and neural progenitor cells relevant to ZIKV pathogenesis. Results from binding, kinetics, Western blot, mass spectrometry and

A parallel algorithm for switch-level timing simulation on a hypercube multiprocessor

Science.gov (United States)

Rao, Hariprasad Nannapaneni

1989-01-01

The parallel approach to speeding up simulation is studied, specifically the simulation of digital LSI MOS circuitry on the Intel iPSC/2 hypercube. The simulation algorithm is based on RSIM, an event driven switch-level simulator that incorporates a linear transistor model for simulating digital MOS circuits. Parallel processing techniques based on the concepts of Virtual Time and rollback are utilized so that portions of the circuit may be simulated on separate processors, in parallel for as large an increase in speed as possible. A partitioning algorithm is also developed in order to subdivide the circuit for parallel processing.

IGBT Switching Characteristic Curve Embedded Half-Bridge MMC Modelling and Real Time Simulation Realization

Science.gov (United States)

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.

Simulation of Novel NEMS Contact Switch Using MRTD with Alterable Steps

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Wen-Ge Yu

2010-01-01

Full Text Available In order to apply Radio Frequency Micro-nano-Electro-Mechanical System (MEMS/NEMS technologies to produce miniature, high isolation, low insertion loss, good linear characteristic, and low power consumption microwave switches, we present a novel NEMS switch with nanoscaling in this paper through the analysis of electrics and mechanics of the RF switch. The measured data show the pull-in voltage of 24.1 V and the good RF performance of the insertion loss of below −10 dB at 0 GHz on the “on” state, and the isolation of beyond –40 dB at 0–40 GHz on the “off” state, indicating that the witch is suitable for the 0–40 GHz applications. Our analysis shows that the NEMS switch not only can work in wide frequency bands, but also has better isolation performance in lower frequency, thus extending the application to the lower band. The Haar-wavelet-based multiresolution time domain (MRTD with compactly supported scaling function is used for modeling and analyzing the nanomachine switch for the first time. The major advantage of the MRTD algorithms is their capability to develop real-time time and space adaptive grids through the efficient thresholding of the wavelet coefficients. The error between the measured and computed results is below 5%, this indicated that the Haar-wavelet-based multiresolution time domain was suitable for simulating the nano-scaling contact switch.

DNA and RNA-controlled switching of protein kinase activity

NARCIS (Netherlands)

Röglin, L.; Altenbrunn, F.; Seitz, O.

2009-01-01

Protein switches use the binding energy gained upon recognition of ligands to modulate the conformation and binding properties of protein segments. We explored whether the programmable nucleic acid mediated recognition might be used to design or mimic constraints that limit the conformational

Simulation and optimization of a totally free flexible RF MEMS switch

International Nuclear Information System (INIS)

Lorphelin, N; Robin, R; Rollier, A S; Touati, S; Kanciurzewski, A; Millet, O; Segueni, K

2009-01-01

This paper presents the principle and the modeling of an innovative RF MEMS switch designed for low voltage applications, especially for mobile phones. This switch is based on a totally free flexible membrane, which is supported by pillars and actuated electrostatically by two pairs of electrodes, enabling two forced states. The main advantage of this structure is the use of a lever effect in order to provide high deflections above the transmission line even with a small gap, which explains why the actuation voltage is small compared to classical MEMS switches. The Euler–Bernoulli beam theory is applied to build an analytical 1D model with boundary conditions, which depend on the type of actuation and if pull-in is reached or not. This model is discretized and solved by the finite difference method. Then, a more accurate 3D finite element method is applied to add corrections to the first model. Once this modeling approach is validated, it is used to determine adequate geometrical parameters for the desired switch specifications. Mechanical characterizations on processed components show a pull-in voltage about 7.5 V, which is in good agreement with simulated values. RF measurements show excellent performances

A simulation method for lightning surge response of switching power

International Nuclear Information System (INIS)

Wei, Ming; Chen, Xiang

2013-01-01

In order to meet the need of protection design for lighting surge, a prediction method of lightning electromagnetic pulse (LEMP) response which is based on system identification is presented. Experiments of switching power's surge injection were conducted, and the input and output data were sampled, de-noised and de-trended. In addition, the model of energy coupling transfer function was obtained by system identification method. Simulation results show that the system identification method can predict the surge response of linear circuit well. The method proposed in the paper provided a convenient and effective technology for simulation of lightning effect.

Description and Simulation of a Fast Packet Switch Architecture for Communication Satellites

Science.gov (United States)

Quintana, Jorge A.; Lizanich, Paul J.

1995-01-01

The NASA Lewis Research Center has been developing the architecture for a multichannel communications signal processing satellite (MCSPS) as part of a flexible, low-cost meshed-VSAT (very small aperture terminal) network. The MCSPS architecture is based on a multifrequency, time-division-multiple-access (MF-TDMA) uplink and a time-division multiplex (TDM) downlink. There are eight uplink MF-TDMA beams, and eight downlink TDM beams, with eight downlink dwells per beam. The information-switching processor, which decodes, stores, and transmits each packet of user data to the appropriate downlink dwell onboard the satellite, has been fully described by using VHSIC (Very High Speed Integrated-Circuit) Hardware Description Language (VHDL). This VHDL code, which was developed in-house to simulate the information switching processor, showed that the architecture is both feasible and viable. This paper describes a shared-memory-per-beam architecture, its VHDL implementation, and the simulation efforts.

3D Pattern Synthesis of Time-Modulated Conformal Arrays with a Multiobjective Optimization Approach

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Wentao Li

2014-01-01

Full Text Available This paper addresses the synthesis of the three-dimensional (3D radiation patterns of the time-modulated conformal arrays. Due to the nature of periodic time modulation, harmonic radiation patterns are generated at the multiples of the modulation frequency in time-modulated arrays. Thus, the optimization goal of the time-modulated conformal array includes the optimization of the sidelobe level at the operating frequency and the sideband levels (SBLs at the harmonic frequency, and the design can be regarded as a multiobjective problem. The multiobjective particle swarm optimization (MOPSO is applied to optimize the switch-on instants and pulse durations of the time-modulated conformal array. To significantly reduce the optimization variables, the modified Bernstein polynomial is employed in the synthesis process. Furthermore, dual polarized patch antenna is designed as radiator to achieve low cross-polarization level during the beam scanning. A 12 × 13 (156-element conical conformal microstrip array is simulated to demonstrate the proposed synthesis mechanism, and good results reveal the promising ability of the proposed algorithm in solving the synthesis of the time-modulated conformal arrays problem.

Acoustic noise simulation for switched reluctance motors with audible output p

Energy Technology Data Exchange (ETDEWEB)

Rasmussen, P.O.; Blaabjerg, F.; Pedersen, J.K.; Kjaer, P.C. [Aalborg Univ., Inst. of Energy Technology (Denmark); Miller, T.J.E. [Univ. of Glasgow, SPEED Lab., Dep. of Electronics and Electrical Engineering (United Kingdom)

1999-07-01

Acoustic noise in switched reluctance motors is one of the last problems which have to be solved before a more widespread use will come. In order to design a low noise Switched Reluctance Motor drive, simulation tools are needed, and this paper describes a design programme where acoustic noise of electromagnetic origin can be estimated and even be heard by the motor-designer. The design program is based on a new, simple developed vibrational and acoustic model where the parameters can be calculated based on the geometry of the motor. The vibrational and acoustic model is verified in both time and frequency domain where vibrations and acoustic noise have been considered. (au)

A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

DEFF Research Database (Denmark)

Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

2007-01-01

Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

Conformational dynamics of ATP/Mg:ATP in motor proteins via data mining and molecular simulation

Science.gov (United States)

Bojovschi, A.; Liu, Ming S.; Sadus, Richard J.

2012-08-01

The conformational diversity of ATP/Mg:ATP in motor proteins was investigated using molecular dynamics and data mining. Adenosine triphosphate (ATP) conformations were found to be constrained mostly by inter cavity motifs in the motor proteins. It is demonstrated that ATP favors extended conformations in the tight pockets of motor proteins such as F1-ATPase and actin whereas compact structures are favored in motor proteins such as RNA polymerase and DNA helicase. The incorporation of Mg2+ leads to increased flexibility of ATP molecules. The differences in the conformational dynamics of ATP/Mg:ATP in various motor proteins was quantified by the radius of gyration. The relationship between the simulation results and those obtained by data mining of motor proteins available in the protein data bank is analyzed. The data mining analysis of motor proteins supports the conformational diversity of the phosphate group of ATP obtained computationally.

Thermal Simulation of Switching Pulses in an Insulated Gate Bipolar Transistor (IGBT) Power Module

Science.gov (United States)

2015-02-01

executed with SolidWorks Flow Simulation , a computational fluid-dynamics code. The graph in Fig. 2 shows the timing and amplitudes of power pulses...defined a convective flow of air perpendicular to the bottom surface of the mounting plate, with a velocity of 10 ft/s. The thermal simulations were...Thermal Simulation of Switching Pulses in an Insulated Gate Bipolar Transistor (IGBT) Power Module by Gregory K Ovrebo ARL-TR-7210

Molecular Dynamics Simulations of the STAS Domains of Rat Prestin and Human Pendrin Reveal Conformational Motions in Conserved Flexible Regions

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Alok K. Sharma

2014-02-01

Full Text Available Background: Molecular dynamics (MD simulations provide valuable information on the conformational changes that accompany time-dependent motions in proteins. The reported crystal structure of rat prestin (PDB 3LLO is remarkable for an α1-α2 inter-helical angle that differs substantially from those observed in bacterial STAS domains of SulP anion transporters and anti-sigma factor antagonists. However, NMR data on the rat prestin STAS domain in solution suggests dynamic features at or near the α1-α2 helical region (Pasqualetto et al JMB, 2010. We therefore performed a 100 ns 300K MD simulation study comparing the STAS domains of rat prestin and (modeled human pendrin, to explore possible conformational flexibility in the region of the α1 and α2 helices. Methods: The conformation of the loop missing in the crystal structure of rat prestin STAS (11 amino acids between helix α1 and strand β3 was built using Modeller. MD simulations were performed with GROMACSv4.6 using GROMOS96 53a6 all-atom force field. Results: A subset of secondary structured elements of the STAS domains exhibits significant conformational changes during the simulation time course. The conformationally perturbed segments include the majority of loop regions, as well as the α1 and α2 helices. A significant decrease in the α1-α2 inter-helical angle observed across the simulation trajectory leads to closer helical packing at their C-termini. The end-simulation conformations of the prestin and pendrin STAS domains, including their decreased α1-α2 inter-helical angles, resemble more closely the packing of corresponding helices in the STAS structures of bacterial SulP transporters Rv1739c and ychM, as well as those of the anti-sigma factor antagonists. Several structural segments of the modeled human pendrin STAS domain exhibit larger atomic motions and greater conformational deviations than the corresponding regions of rat prestin, predicting that the human pendrin STAS

Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

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Anastasios Papaioannou

Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

Effect of hydrophobic groups on the adsorption conformation of modified polycarboxylate superplasticizer investigated by molecular dynamics simulation

Energy Technology Data Exchange (ETDEWEB)

Zhao, Hongxia [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China); Wang, Yanwei, E-mail: wangyanwei@cnjsjk.cn [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China); Yang, Yong; Shu, Xin; Yan, Han [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China); Ran, Qianping, E-mail: qpran@cnjsjk.cn [State Key Laboratory of High Performance Civil Engineering Materials, Nanjing 210008, Jiangsu (China); Jiangsu Sobute New Materials Co. Ltd., Nanjing 211103, Jiangsu (China)

2017-06-15

Highlights: • Adsorption conformation of comb-like PCE was studied by all-atom MD simulations. • A comparison is made between vacuum-based and solution-based simulations. • Effects of hydrophobic modifications on adsorption properties are elucidated. - Abstract: All-atom molecular dynamics (MD) simulations were used to study the adsorption conformations of hydrophobically-modified comb-shaped polycarboxylate ether-based (PCE) superplasticizer molecules on a model surface of dicalcium silicate (C{sub 2}S) in vacuum and in an explicit solution, respectively. Three different hydrophobic modifying groups, namely, the ethyl group, the n-butyl group and the phenyl group, decorated to the backbone, were examined. Comparing the hydrophobically-modified PCEs to the unmodified one, differences were found in the binding energy, the adsorption conformation and the water density at the interface. The interaction between PCE molecules and C{sub 2}S was weakened in a solution with explicit solvents than that obtained from vacuum-based simulations. The presence of hydrophobic groups lowered the polymer-surface binding energy, decreased the radius of gyration (Rg) of the adsorbed polymer, increased the peak position in the heavy-atom density profiles in the direction perpendicular to the surface, and also caused the adsorbed conformations to be more globular in shape. The parallel and perpendicular components (relative to the surface plane) of the geometric sizes of the adsorbed polymers were calculated, and the results showed that the presence of hydrophobically modifying groups decreased the in-plane radius while increased the adsorption layer thickness compared to the unmodified control. The presence of PCEs perturbed the dense water layer above the C{sub 2}S surface and lowered the water density. Perturbations to the interfacial water density were found to correlate nicely with the adsorbed conformations of PCEs.

The effect of tensile stress on the conformational free energy landscape of disulfide bonds.

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Padmesh Anjukandi

Full Text Available Disulfide bridges are no longer considered to merely stabilize protein structure, but are increasingly recognized to play a functional role in many regulatory biomolecular processes. Recent studies have uncovered that the redox activity of native disulfides depends on their C-C-S-S dihedrals, χ2 and χ'2. Moreover, the interplay of chemical reactivity and mechanical stress of disulfide switches has been recently elucidated using force-clamp spectroscopy and computer simulation. The χ2 and χ'2 angles have been found to change from conformations that are open to nucleophilic attack to sterically hindered, so-called closed states upon exerting tensile stress. In view of the growing evidence of the importance of C-C-S-S dihedrals in tuning the reactivity of disulfides, here we present a systematic study of the conformational diversity of disulfides as a function of tensile stress. With the help of force-clamp metadynamics simulations, we show that tensile stress brings about a large stabilization of the closed conformers, thereby giving rise to drastic changes in the conformational free energy landscape of disulfides. Statistical analysis shows that native TDi, DO and interchain Ig protein disulfides prefer open conformations, whereas the intrachain disulfide bridges in Ig proteins favor closed conformations. Correlating mechanical stress with the distance between the two a-carbons of the disulfide moiety reveals that the strain of intrachain Ig protein disulfides corresponds to a mechanical activation of about 100 pN. Such mechanical activation leads to a severalfold increase of the rate of the elementary redox S(N2 reaction step. All these findings constitute a step forward towards achieving a full understanding of functional disulfides.

Synchronization Between Two Different Switched Chaotic Systems By Switching Control

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Du Li Ming

2016-01-01

Full Text Available This paper is concerned with the synchronization problem of two different switched chaotic systems, considering the general case that the master-slave switched chaotic systems have uncertainties. Two basic problems are considered: one is projective synchronization of switched chaotic systems under arbitrary switching; the other is projective synchronization of switched chaotic systems by design of switching when synchronization cannot achieved by using any subsystems alone. For the two problems, common Lyapunov function method and multiple Lyapunov function method are used respectively, an adaptive control scheme has been presented, some sufficient synchronization conditions are attainted, and the switching signal is designed. Finally, the numerical simulation is provide to show the effectiveness of our method.

Conformational Fluctuations in G-Protein-Coupled Receptors

Science.gov (United States)

Brown, Michael F.

2014-03-01

G-protein-coupled receptors (GPCRs) comprise almost 50% of pharmaceutical drug targets, where rhodopsin is an important prototype and occurs naturally in a lipid membrane. Rhodopsin photoactivation entails 11-cis to all-trans isomerization of the retinal cofactor, yielding an equilibrium between inactive Meta-I and active Meta-II states. Two important questions are: (1) Is rhodopsin is a simple two-state switch? Or (2) does isomerization of retinal unlock an activated conformational ensemble? For an ensemble-based activation mechanism (EAM) a role for conformational fluctuations is clearly indicated. Solid-state NMR data together with theoretical molecular dynamics (MD) simulations detect increased local mobility of retinal after light activation. Resultant changes in local dynamics of the cofactor initiate large-scale fluctuations of transmembrane helices that expose recognition sites for the signal-transducing G-protein. Time-resolved FTIR studies and electronic spectroscopy further show the conformational ensemble is strongly biased by the membrane lipid composition, as well as pH and osmotic pressure. A new flexible surface model (FSM) describes how the curvature stress field of the membrane governs the energetics of active rhodopsin, due to the spontaneous monolayer curvature of the lipids. Furthermore, influences of osmotic pressure dictate that a large number of bulk water molecules are implicated in rhodopsin activation. Around 60 bulk water molecules activate rhodopsin, which is much larger than the number of structural waters seen in X-ray crystallography, or inferred from studies of bulk hydrostatic pressure. Conformational selection and promoting vibrational motions of rhodopsin lead to activation of the G-protein (transducin). Our biophysical data give a paradigm shift in understanding GPCR activation. The new view is: dynamics and conformational fluctuations involve an ensemble of substates that activate the cognate G-protein in the amplified visual

Hierarchical Conformational Analysis of Native Lysozyme Based on Sub-Millisecond Molecular Dynamics Simulations.

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Kai Wang

Full Text Available Hierarchical organization of free energy landscape (FEL for native globular proteins has been widely accepted by the biophysics community. However, FEL of native proteins is usually projected onto one or a few dimensions. Here we generated collectively 0.2 milli-second molecular dynamics simulation trajectories in explicit solvent for hen egg white lysozyme (HEWL, and carried out detailed conformational analysis based on backbone torsional degrees of freedom (DOF. Our results demonstrated that at micro-second and coarser temporal resolutions, FEL of HEWL exhibits hub-like topology with crystal structures occupying the dominant structural ensemble that serves as the hub of conformational transitions. However, at 100 ns and finer temporal resolutions, conformational substates of HEWL exhibit network-like topology, crystal structures are associated with kinetic traps that are important but not dominant ensembles. Backbone torsional state transitions on time scales ranging from nanoseconds to beyond microseconds were found to be associated with various types of molecular interactions. Even at nanoseconds temporal resolution, the number of conformational substates that are of statistical significance is quite limited. These observations suggest that detailed analysis of conformational substates at multiple temporal resolutions is both important and feasible. Transition state ensembles among various conformational substates at microsecond temporal resolution were observed to be considerably disordered. Life times of these transition state ensembles are found to be nearly independent of the time scales of the participating torsional DOFs.

Low-Voltage Switched-Capacitor Circuits

DEFF Research Database (Denmark)

Bidari, E.; Keskin, M.; Maloberti, F.

1999-01-01

Switched-capacitor stages are described which can function with very low (typically 1 V) supply voltages, without using voltage boosting or switched op-amps. Simulations indicate that high performance may be achieved using these circuits in filter or data converter applications.......Switched-capacitor stages are described which can function with very low (typically 1 V) supply voltages, without using voltage boosting or switched op-amps. Simulations indicate that high performance may be achieved using these circuits in filter or data converter applications....

Rational Design and Tuning of Functional RNA Switch to Control an Allosteric Intermolecular Interaction.

Science.gov (United States)

Endoh, Tamaki; Sugimoto, Naoki

2015-08-04

Conformational transitions of biomolecules in response to specific stimuli control many biological processes. In natural functional RNA switches, often called riboswitches, a particular RNA structure that has a suppressive or facilitative effect on gene expression transitions to an alternative structure with the opposite effect upon binding of a specific metabolite to the aptamer region. Stability of RNA secondary structure (-ΔG°) can be predicted based on thermodynamic parameters and is easily tuned by changes in nucleobases. We envisioned that tuning of a functional RNA switch that causes an allosteric interaction between an RNA and a peptide would be possible based on a predicted switching energy (ΔΔG°) that corresponds to the energy difference between the RNA secondary structure before (-ΔG°before) and after (-ΔG°after) the RNA conformational transition. We first selected functional RNA switches responsive to neomycin with predicted ΔΔG° values ranging from 5.6 to 12.2 kcal mol(-1). We then demonstrated a simple strategy to rationally convert the functional RNA switch to switches responsive to natural metabolites thiamine pyrophosphate, S-adenosyl methionine, and adenine based on the predicted ΔΔG° values. The ΔΔG° values of the designed RNA switches proportionally correlated with interaction energy (ΔG°interaction) between the RNA and peptide, and we were able to tune the sensitivity of the RNA switches for the trigger molecule. The strategy demonstrated here will be generally applicable for construction of functional RNA switches and biosensors in which mechanisms are based on conformational transition of nucleic acids.

A Fourier analysis for a fast simulation algorithm. [for switching converters

Science.gov (United States)

King, Roger J.

1988-01-01

This paper presents a derivation of compact expressions for the Fourier series analysis of the steady-state solution of a typical switching converter. The modeling procedure for the simulation and the steady-state solution is described, and some desirable traits for its matrix exponential subroutine are discussed. The Fourier analysis algorithm was tested on a phase-controlled parallel-loaded resonant converter, providing an experimental confirmation.

Multiscale simulation of thermal disruption in resistance switching process in amorphous carbon

International Nuclear Information System (INIS)

Popov, A M; Nikishin, N G; Shumkin, G N

2015-01-01

The switching of material atomic structure and electric conductivity is used in novel technologies of making memory on the base of phase change. The possibility of making memory on the base of amorphous carbon is shown in experiment [1]. Present work is directed to simulation of experimentally observed effects. Ab initio quantum calculations were used for simulation of atomic structure changes in amorphous carbon [2]. These simulations showed that the resistance change is connected with thermally induced effects. The temperature was supposed to be the function of time. In present paper we propose a new multiscale, self-consistent model which combines three levels of simulation scales and takes into account the space and time dependencies of the temperature. On the first level of quantum molecular dynamic we provide the calculations of phase change in atomic structure with space and time dependence of the temperature. Nose-Hover thermostats are used for MD simulations to reproduce space dependency of the temperature. It is shown that atomic structure is localized near graphitic layers in conducting dot. Structure parameter is used then on the next levels of the modeling. Modified Ehrenfest Molecular Dynamics is used on the second level. Switching evolution of electronic subsystem is obtained. In macroscopic scale level the heat conductivity equation for continuous media is used for calculation space-time dependence of the temperature. Joule heat source depends on structure parameter and electric conductivity profiles obtained on previous levels of modeling. Iterative procedure is self-consistently repeated combining three levels of simulation. Space localization of Joule heat source leads to the thermal disruption. Obtained results allow us to explain S-form of the Volt-Ampere characteristic observed in experiment. Simulations were performed on IBM Blue Gene/P supercomputer at Moscow State University. (paper)

Large-scale conformational changes of Trypanosoma cruzi proline racemase predicted by accelerated molecular dynamics simulation.

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César Augusto F de Oliveira

2011-10-01

Full Text Available Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi, is a life-threatening illness affecting 11-18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery.

Conformational Ensemble of the Poliovirus 3CD Precursor Observed by MD Simulations and Confirmed by SAXS: A Strategy to Expand the Viral Proteome?

Science.gov (United States)

Moustafa, Ibrahim M; Gohara, David W; Uchida, Akira; Yennawar, Neela; Cameron, Craig E

2015-11-23

The genomes of RNA viruses are relatively small. To overcome the small-size limitation, RNA viruses assign distinct functions to the processed viral proteins and their precursors. This is exemplified by poliovirus 3CD protein. 3C protein is a protease and RNA-binding protein. 3D protein is an RNA-dependent RNA polymerase (RdRp). 3CD exhibits unique protease and RNA-binding activities relative to 3C and is devoid of RdRp activity. The origin of these differences is unclear, since crystal structure of 3CD revealed "beads-on-a-string" structure with no significant structural differences compared to the fully processed proteins. We performed molecular dynamics (MD) simulations on 3CD to investigate its conformational dynamics. A compact conformation of 3CD was observed that was substantially different from that shown crystallographically. This new conformation explained the unique properties of 3CD relative to the individual proteins. Interestingly, simulations of mutant 3CD showed altered interface. Additionally, accelerated MD simulations uncovered a conformational ensemble of 3CD. When we elucidated the 3CD conformations in solution using small-angle X-ray scattering (SAXS) experiments a range of conformations from extended to compact was revealed, validating the MD simulations. The existence of conformational ensemble of 3CD could be viewed as a way to expand the poliovirus proteome, an observation that may extend to other viruses.

The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength

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Diana Campelo

2017-10-01

Full Text Available NADPH-cytochrome P450 reductase (CPR is a redox partner of microsomal cytochromes P450 and is a prototype of the diflavin reductase family. CPR contains 3 distinct functional domains: a FMN-binding domain (acceptor reduction, a linker (hinge, and a connecting/FAD domain (NADPH oxidation. It has been demonstrated that the mechanism of CPR exhibits an important step in which it switches from a compact, closed conformation (locked state to an ensemble of open conformations (unlocked state, the latter enabling electron transfer to redox partners. The conformational equilibrium between the locked and unlocked states has been shown to be highly dependent on ionic strength, reinforcing the hypothesis of the presence of critical salt interactions at the interface between the FMN and connecting FAD domains. Here we show that specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. We constructed six single mutants and two double mutants of the human CPR, targeting residues G240, S243, I245 and R246 of the hinge segment, with the aim of modifying the flexibility or the potential ionic interactions of the hinge segment. We measured the reduction of cytochrome c at various salt concentrations of these 8 mutants, either in the soluble or membrane-bound form of human CPR. All mutants were found capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction were shifted to lower salt concentration. In particular, residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain. Interestingly, the effects of mutations, although similar, demonstrated specific differences when present in the soluble or membrane-bound context. Our results demonstrate that the electrostatic and flexibility properties of the hinge segment are critical for electron transfer from CPR to its redox partners.

Particle-in-cell simulations of plasma opening switch with external magnetic field

International Nuclear Information System (INIS)

Chen Yulan; Zeng Zhengzhong; Sun Fengju

2003-01-01

Fully electromagnetic particle-in-cell simulations are performed to study the effects of an external magnetic field on coaxial plasma opening switch (POS). The simulation results show that POS opening performance can be significantly improved only when external longitudinal magnetic field coils are placed at the cathode side, and an additional azimuthal magnetic field is effective whether the central electrode is of positive or negative polarity. Voltage multiplication coefficient K rises with the additional magnetic field increasing till the electron current is completely magnetically insulated during the opening of POS

The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop.

Science.gov (United States)

Zhang, Xu; Wu, Jiaxi; Du, Fenghe; Xu, Hui; Sun, Lijun; Chen, Zhe; Brautigam, Chad A; Zhang, Xuewu; Chen, Zhijian J

2014-02-13

The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop

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Xu Zhang

2014-02-01

Full Text Available The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP synthase (cGAS, which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.

Real-time observation of conformational switching in single conjugated polymer chains.

Science.gov (United States)

Tenopala-Carmona, Francisco; Fronk, Stephanie; Bazan, Guillermo C; Samuel, Ifor D W; Penedo, J Carlos

2018-02-01

Conjugated polymers (CPs) are an important class of organic semiconductors that combine novel optoelectronic properties with simple processing from organic solvents. It is important to study CP conformation in solution to understand the physics of these materials and because it affects the properties of solution-processed films. Single-molecule techniques are unique in their ability to extract information on a chain-to-chain basis; however, in the context of CPs, technical challenges have limited their general application to host matrices or semiliquid environments that constrain the conformational dynamics of the polymer. We introduce a conceptually different methodology that enables measurements in organic solvents using the single-end anchoring of polymer chains to avoid diffusion while preserving polymer flexibility. We explore the effect of organic solvents and show that, in addition to chain-to-chain conformational heterogeneity, collapsed and extended polymer segments can coexist within the same chain. The technique enables real-time solvent-exchange measurements, which show that anchored CP chains respond to sudden changes in solvent conditions on a subsecond time scale. Our results give an unprecedented glimpse into the mechanism of solvent-induced reorganization of CPs and can be expected to lead to a new range of techniques to investigate and conformationally manipulate CPs.

Conformational dynamics of dry lamellar crystals of sugar based lipids: an atomistic simulation study.

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Vijayan ManickamAchari

Full Text Available The rational design of a glycolipid application (e.g. drug delivery with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside and a C12C10 branched β-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (∼20% in the hydrophobic region of the lamellar crystal (LC phase. In contrast, the branched chain glycolipid in the fluid Lα phase has a high gauche population of up to ∼40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11-15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.

KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Lu, Jia; Harrison, Rane A.; Li, Lianbo; Zeng, Mei; Gondi, Sudershan; Scott, David; Gray, Nathanael S.; Engen, John R.; Westover, Kenneth D. (NEU); (DFCI); (UTSMC); (Harvard-Med)

2017-09-01

KRAS G12C, the most common RAS mutation found in non-small-cell lung cancer, has been the subject of multiple recent covalent small-molecule inhibitor campaigns including efforts directed at the guanine nucleotide pocket and separate work focused on an inducible pocket adjacent to the switch motifs. Multiple conformations of switch II have been observed, suggesting that switch II pocket (SIIP) binders may be capable of engaging a range of KRAS conformations. Here we report the use of hydrogen/deuterium-exchange mass spectrometry (HDX MS) to discriminate between conformations of switch II induced by two chemical classes of SIIP binders. We investigated the structural basis for differences in HDX MS using X-ray crystallography and discovered a new SIIP configuration in response to binding of a quinazoline chemotype. These results have implications for structure-guided drug design targeting the RAS SIIP.

Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

International Nuclear Information System (INIS)

Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

2014-01-01

Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

Generalized Multi-Cell Switched-Inductor and Switched-Capacitor Z-source Inverters

DEFF Research Database (Denmark)

Li, Ding; Chiang Loh, Poh; Zhu, Miao

2013-01-01

. Their boosting gains are, therefore, limited in practice. To overcome these shortcomings, the generalized switched-inductor and switched-capacitor Z-source inverters are proposed, whose extra boosting abilities and other advantages have already been verified in simulation and experiment....

Communication over the network of binary switches regulates the activation of A2A adenosine receptor.

Directory of Open Access Journals (Sweden)

Yoonji Lee

2015-02-01

Full Text Available Dynamics and functions of G-protein coupled receptors (GPCRs are accurately regulated by the type of ligands that bind to the orthosteric or allosteric binding sites. To glean the structural and dynamical origin of ligand-dependent modulation of GPCR activity, we performed total ~ 5 μsec molecular dynamics simulations of A2A adenosine receptor (A2AAR in its apo, antagonist-bound, and agonist-bound forms in an explicit water and membrane environment, and examined the corresponding dynamics and correlation between the 10 key structural motifs that serve as the allosteric hotspots in intramolecular signaling network. We dubbed these 10 structural motifs "binary switches" as they display molecular interactions that switch between two distinct states. By projecting the receptor dynamics on these binary switches that yield 2(10 microstates, we show that (i the receptors in apo, antagonist-bound, and agonist-bound states explore vastly different conformational space; (ii among the three receptor states the apo state explores the broadest range of microstates; (iii in the presence of the agonist, the active conformation is maintained through coherent couplings among the binary switches; and (iv to be most specific, our analysis shows that W246, located deep inside the binding cleft, can serve as both an agonist sensor and actuator of ensuing intramolecular signaling for the receptor activation. Finally, our analysis of multiple trajectories generated by inserting an agonist to the apo state underscores that the transition of the receptor from inactive to active form requires the disruption of ionic-lock in the DRY motif.

Protein Conformational Plasticity: the 'off-on' Switching Movement in Cdk5

International Nuclear Information System (INIS)

Cavalli, Andrea; Recanatini, Maurizio; Berteotti, Anna; Branduardi, Davide; Gervasio, Francesco L.; Parrinello, Michele

2007-01-01

Cyclin-dependent kinases (CDKs) are mostly known for their role in the cell cycle regulation. The activation mechanism of all CDKs involves the association with a regulatory protein, generally a cyclin, that binds to the kinase unit and stabilizes a catalytically active conformation. Active and inactive conformations of CDKs are characterized by the different spatial localization of two typical elements, namely the activation loop and an □-helix, whose amino-acid composition varies throughout the family

Investigation of resistance switching in SiO x RRAM cells using a 3D multi-scale kinetic Monte Carlo simulator

Science.gov (United States)

Sadi, Toufik; Mehonic, Adnan; Montesi, Luca; Buckwell, Mark; Kenyon, Anthony; Asenov, Asen

2018-02-01

We employ an advanced three-dimensional (3D) electro-thermal simulator to explore the physics and potential of oxide-based resistive random-access memory (RRAM) cells. The physical simulation model has been developed recently, and couples a kinetic Monte Carlo study of electron and ionic transport to the self-heating phenomenon while accounting carefully for the physics of vacancy generation and recombination, and trapping mechanisms. The simulation framework successfully captures resistance switching, including the electroforming, set and reset processes, by modeling the dynamics of conductive filaments in the 3D space. This work focuses on the promising yet less studied RRAM structures based on silicon-rich silica (SiO x ) RRAMs. We explain the intrinsic nature of resistance switching of the SiO x layer, analyze the effect of self-heating on device performance, highlight the role of the initial vacancy distributions acting as precursors for switching, and also stress the importance of using 3D physics-based models to capture accurately the switching processes. The simulation work is backed by experimental studies. The simulator is useful for improving our understanding of the little-known physics of SiO x resistive memory devices, as well as other oxide-based RRAM systems (e.g. transition metal oxide RRAMs), offering design and optimization capabilities with regard to the reliability and variability of memory cells.

Investigation of resistance switching in SiO x RRAM cells using a 3D multi-scale kinetic Monte Carlo simulator.

Science.gov (United States)

Sadi, Toufik; Mehonic, Adnan; Montesi, Luca; Buckwell, Mark; Kenyon, Anthony; Asenov, Asen

2018-02-28

We employ an advanced three-dimensional (3D) electro-thermal simulator to explore the physics and potential of oxide-based resistive random-access memory (RRAM) cells. The physical simulation model has been developed recently, and couples a kinetic Monte Carlo study of electron and ionic transport to the self-heating phenomenon while accounting carefully for the physics of vacancy generation and recombination, and trapping mechanisms. The simulation framework successfully captures resistance switching, including the electroforming, set and reset processes, by modeling the dynamics of conductive filaments in the 3D space. This work focuses on the promising yet less studied RRAM structures based on silicon-rich silica (SiO x ) RRAMs. We explain the intrinsic nature of resistance switching of the SiO x layer, analyze the effect of self-heating on device performance, highlight the role of the initial vacancy distributions acting as precursors for switching, and also stress the importance of using 3D physics-based models to capture accurately the switching processes. The simulation work is backed by experimental studies. The simulator is useful for improving our understanding of the little-known physics of SiO x resistive memory devices, as well as other oxide-based RRAM systems (e.g. transition metal oxide RRAMs), offering design and optimization capabilities with regard to the reliability and variability of memory cells.

Unbiased simulations reveal the inward-facing conformation of the human serotonin transporter and Na(+ ion release.

Directory of Open Access Journals (Sweden)

Heidi Koldsø

2011-10-01

Full Text Available Monoamine transporters are responsible for termination of synaptic signaling and are involved in depression, control of appetite, and anxiety amongst other neurological processes. Despite extensive efforts, the structures of the monoamine transporters and the transport mechanism of ions and substrates are still largely unknown. Structural knowledge of the human serotonin transporter (hSERT is much awaited for understanding the mechanistic details of substrate translocation and binding of antidepressants and drugs of abuse. The publication of the crystal structure of the homologous leucine transporter has resulted in homology models of the monoamine transporters. Here we present extended molecular dynamics simulations of an experimentally supported homology model of hSERT with and without the natural substrate yielding a total of more than 1.5 µs of simulation of the protein dimer. The simulations reveal a transition of hSERT from an outward-facing occluded conformation to an inward-facing conformation in a one-substrate-bound state. Simulations with a second substrate in the proposed symport effector site did not lead to conformational changes associated with translocation. The central substrate binding site becomes fully exposed to the cytoplasm leaving both the Na(+-ion in the Na2-site and the substrate in direct contact with the cytoplasm through water interactions. The simulations reveal how sodium is released and show indications of early events of substrate transport. The notion that ion dissociation from the Na2-site drives translocation is supported by experimental studies of a Na2-site mutant. Transmembrane helices (TMs 1 and 6 are identified as the helices involved in the largest movements during transport.

Optimizing switching frequency of the soliton transistor by numerical simulation

Energy Technology Data Exchange (ETDEWEB)

Izadyar, S., E-mail: S_izadyar@yahoo.co [Department of Electronics, Khaje Nasir Toosi University of Technology, Shariati Ave., Tehran (Iran, Islamic Republic of); Niazzadeh, M.; Raissi, F. [Department of Electronics, Khaje Nasir Toosi University of Technology, Shariati Ave., Tehran (Iran, Islamic Republic of)

2009-10-15

In this paper, by numerical simulations we have examined different ways to increase the soliton transistor's switching frequency. Speed of the solitons in a soliton transistor depends on various parameters such as the loss of the junction, the applied bias current, and the transmission line characteristics. Three different ways have been examined; (i) decreasing the size of the transistor without losing transistor effect. (ii) Decreasing the amount of loss of the junction to increase the soliton speed. (iii) Optimizing the bias current to obtain maximum possible speed. We have obtained the shortest possible length to have at least one working soliton inside the transistor. The dimension of the soliton can be decreased by changing the inductance of the transmission line, causing a further decrease in the size of the transistor, however, a trade off between the size and the inductance is needed to obtain the optimum switching speed. Decreasing the amount of loss can be accomplished by increasing the characteristic tunneling resistance of the device, however, a trade off is again needed to make soliton and antisoliton annihilation possible. By increasing the bias current, the forces acting the solitons increases and so does their speed. Due to nonuniform application of bias current a self induced magnetic field is created which can result in creation of unwanted solitons. Optimum bias current application can result in larger bias currents and larger soliton speed. Simulations have provided us with such an arrangement of bias current paths.

Optimizing switching frequency of the soliton transistor by numerical simulation

International Nuclear Information System (INIS)

Izadyar, S.; Niazzadeh, M.; Raissi, F.

2009-01-01

In this paper, by numerical simulations we have examined different ways to increase the soliton transistor's switching frequency. Speed of the solitons in a soliton transistor depends on various parameters such as the loss of the junction, the applied bias current, and the transmission line characteristics. Three different ways have been examined; (i) decreasing the size of the transistor without losing transistor effect. (ii) Decreasing the amount of loss of the junction to increase the soliton speed. (iii) Optimizing the bias current to obtain maximum possible speed. We have obtained the shortest possible length to have at least one working soliton inside the transistor. The dimension of the soliton can be decreased by changing the inductance of the transmission line, causing a further decrease in the size of the transistor, however, a trade off between the size and the inductance is needed to obtain the optimum switching speed. Decreasing the amount of loss can be accomplished by increasing the characteristic tunneling resistance of the device, however, a trade off is again needed to make soliton and antisoliton annihilation possible. By increasing the bias current, the forces acting the solitons increases and so does their speed. Due to nonuniform application of bias current a self induced magnetic field is created which can result in creation of unwanted solitons. Optimum bias current application can result in larger bias currents and larger soliton speed. Simulations have provided us with such an arrangement of bias current paths.

Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

Science.gov (United States)

Sullivan, David C; Lim, Carmay

2006-08-24

Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

Ab initio investigation of the switching behavior of the dithiole-benzene nano-molecular wire

International Nuclear Information System (INIS)

Darvish Ganji, M.; Rungger, I.

2008-01-01

We report a first-principle study of electrical transport and switching behavior in a single molecular conductor consisting of a dithiole-benzene sandwiched between two Au( 100) electrodes. Ab initio total energy calculations reveal dithiole-benzene molecules on a gold surface, contacted by a monoatomic gold scanning tunneling microscope tip to have two classes of low energy conformations with differing symmetries. Lateral motion of the tip or excitation of the molecule cause it 10 change from one conformation class to the other and to switch between a strongly and a weakly conducting state. Thus, surprisingly. despite their apparent simplicity, these Au-dithiole-benzene -Au nano wires are shown to be electrically bi-stable switches, the smallest two-terminal molecular switches to date. The projected density of states and transmission coefficients are analyzed, and it suggests that the variation of the coupling between the molecule and the electrodes with external bias leads to switching behavior

A multiscale approach to simulating the conformational properties of unbound multi-C₂H₂ zinc finger proteins.

Science.gov (United States)

Liu, Lei; Wade, Rebecca C; Heermann, Dieter W

2015-09-01

The conformational properties of unbound multi-Cys2 His2 (mC2H2) zinc finger proteins, in which zinc finger domains are connected by flexible linkers, are studied by a multiscale approach. Three methods on different length scales are utilized. First, atomic detail molecular dynamics simulations of one zinc finger and its adjacent flexible linker confirmed that the zinc finger is more rigid than the flexible linker. Second, the end-to-end distance distributions of mC2H2 zinc finger proteins are computed using an efficient atomistic pivoting algorithm, which only takes excluded volume interactions into consideration. The end-to-end distance distribution gradually changes its profile, from left-tailed to right-tailed, as the number of zinc fingers increases. This is explained by using a worm-like chain model. For proteins of a few zinc fingers, an effective bending constraint favors an extended conformation. Only for proteins containing more than nine zinc fingers, is a somewhat compacted conformation preferred. Third, a mesoscale model is modified to study both the local and the global conformational properties of multi-C2H2 zinc finger proteins. Simulations of the CCCTC-binding factor (CTCF), an important mC2H2 zinc finger protein for genome spatial organization, are presented. © 2015 Wiley Periodicals, Inc.

Ligand binding turns moth pheromone-binding protein into a pH sensor: effect on the Antheraea polyphemus PBP1 conformation.

Science.gov (United States)

Katre, Uma V; Mazumder, Suman; Prusti, Rabi K; Mohanty, Smita

2009-11-13

In moths, pheromone-binding proteins (PBPs) are responsible for the transport of the hydrophobic pheromones to the membrane-bound receptors across the aqueous sensillar lymph. We report here that recombinant Antheraea polyphemus PBP1 (ApolPBP1) picks up hydrophobic molecule(s) endogenous to the Escherichia coli expression host that keeps the protein in the "open" (bound) conformation at high pH but switches to the "closed" (free) conformation at low pH. This finding has bearing on the solution structures of undelipidated lepidopteran moth PBPs determined thus far. Picking up a hydrophobic molecule from the host expression system could be a common feature for lipid-binding proteins. Thus, delipidation is critical for bacterially expressed lipid-binding proteins. We have shown for the first time that the delipidated ApolPBP1 exists primarily in the closed form at all pH levels. Thus, current views on the pH-induced conformational switch of PBPs hold true only for the ligand-bound open conformation of the protein. Binding of various ligands to delipidated ApolPBP1 studied by solution NMR revealed that the protein in the closed conformation switches to the open conformation only at or above pH 6.0 with a protein to ligand stoichiometry of approximately 1:1. Mutation of His(70) and His(95) to alanine drives the equilibrium toward the open conformation even at low pH for the ligand-bound protein by eliminating the histidine-dependent pH-induced conformational switch. Thus, the delipidated double mutant can bind ligand even at low pH in contrast to the wild type protein as revealed by fluorescence competitive displacement assay using 1-aminoanthracene and solution NMR.

Conformational preludes to the latency transition in PAI-1 as determined by atomistic computer simulations and hydrogen/deuterium-exchange mass spectrometry

DEFF Research Database (Denmark)

Petersen, Michael; Madsen, Jeppe B; Jørgensen, Thomas J D

2017-01-01

activator inhibitor 1 (PAI-1). We report the first multi-microsecond atomistic molecular dynamics simulations of PAI-1 and compare the data with experimental hydrogen/deuterium-exchange data (HDXMS). The simulations reveal notable conformational flexibility of helices D, E and F and major fluctuations...... are observed in the W86-loop which occasionally leads to progressive detachment of β-strand 2 A from β-strand 3 A. An interesting correlation between Cα-RMSD values from simulations and experimental HDXMS data is observed. Helices D, E and F are known to be important for the overall stability of active PAI-1......Both function and dysfunction of serine protease inhibitors (serpins) involve massive conformational change in their tertiary structure but the dynamics facilitating these events remain poorly understood. We have studied the dynamic preludes to conformational change in the serpin plasminogen...

Conformational switching of ethano-bridged Cu,H2-bis-porphyrin induced by aromatic amines.

Science.gov (United States)

Bettini, Simona; Maglie, Emanuela; Pagano, Rosanna; Borovkov, Victor; Inoue, Yoshihisa; Valli, Ludovico; Giancane, Gabriele

2015-01-01

Cu,H2-bis-porphyrin (Cu,H2-Por2), in which copper porphyrin and free-base porphyrin are linked together by an ethano-bridge, was dissolved in chloroform and spread at the air/liquid subphase interface of a Langmuir trough. The bis-porphyrin derivative, floating film was characterized by reflection spectroscopy and the surface pressure of the floating film was studied as a function of the mean area per molecule. When aromatic amines are dissolved in the subphase, an evident interaction between the bis-porphyrin host and the aromatic amine guest is observed. A clear-cut variation of the profile of surface pressure vs area per molecule curve is observed. Reflection spectroscopy highlights that the aromatic amines dissolved in the subphase are able to induce the syn-to-anti conformational switching in the bis-porphyrin derivative. The Langmuir-Schaefer technique has been used to transfer the floating bis-porphyrin film (when using pure water as a subphase) to a surface plasmon resonance (SPR) substrate and the resulting device was able to detect the presence of aniline at concentrations as low as 1 nM in aqueous solution. The high selectivity of the SPR sensing device has been verified by checking the spectral response of the active layer towards other analytes dissolved in the aqueous solutions.

Conformational switching of ethano-bridged Cu,H2-bis-porphyrin induced by aromatic amines

Directory of Open Access Journals (Sweden)

Simona Bettini

2015-11-01

Full Text Available Cu,H2-bis-porphyrin (Cu,H2-Por2, in which copper porphyrin and free-base porphyrin are linked together by an ethano-bridge, was dissolved in chloroform and spread at the air/liquid subphase interface of a Langmuir trough. The bis-porphyrin derivative, floating film was characterized by reflection spectroscopy and the surface pressure of the floating film was studied as a function of the mean area per molecule. When aromatic amines are dissolved in the subphase, an evident interaction between the bis-porphyrin host and the aromatic amine guest is observed. A clear-cut variation of the profile of surface pressure vs area per molecule curve is observed. Reflection spectroscopy highlights that the aromatic amines dissolved in the subphase are able to induce the syn-to-anti conformational switching in the bis-porphyrin derivative. The Langmuir–Schaefer technique has been used to transfer the floating bis-porphyrin film (when using pure water as a subphase to a surface plasmon resonance (SPR substrate and the resulting device was able to detect the presence of aniline at concentrations as low as 1 nM in aqueous solution. The high selectivity of the SPR sensing device has been verified by checking the spectral response of the active layer towards other analytes dissolved in the aqueous solutions.

A computer-controlled conformal radiotherapy system. III: graphical simulation and monitoring of treatment delivery

International Nuclear Information System (INIS)

Kessler, Marc L.; McShan, Daniel L.; Fraass, Benedick A.

1995-01-01

Purpose: Safe and efficient delivery of radiotherapy using computer-controlled machines requires new procedures to design and verify the actual delivery of these treatments. Graphical simulation and monitoring techniques for treatment delivery have been developed for this purpose. Methods and Materials: A graphics-based simulator of the treatment machine and a set of procedures for creating and manipulating treatment delivery scripts are used to simulate machine motions, detect collisions, and monitor machine positions during treatment. The treatment delivery simulator is composed of four components: a three-dimensional dynamic model of the treatment machine; a motion simulation and collision detection algorithm, user-interface widgets that mimic the treatment machine's control and readout devices; and an icon-based interface for creating and manipulating treatment delivery scripts. These components are used in a stand-alone fashion for interactive treatment delivery planning and integrated with a machine control system for treatment implementation and monitoring. Results: A graphics-based treatment delivery simulator and a set of procedures for planning and monitoring computer-controlled treatment delivery have been developed and implemented as part of a comprehensive computer-controlled conformal radiotherapy system. To date, these techniques have been used to design and help monitor computer-controlled treatments on a radiotherapy machine for more than 200 patients. Examples using these techniques for treatment delivery planning and on-line monitoring of machine motions during therapy are described. Conclusion: A system that provides interactive graphics-based tools for defining the sequence of machine motions, simulating treatment delivery including collision detection, and presenting the therapists with continual visual feedback from the treatment machine has been successfully implemented for routine clinical use as part of an overall system for computer

Comparison of Chain Conformation of Poly(vinyl alcohol) in Solutions and Melts from Quantum Chemistry Based Molecular Dynamics Simulations

Science.gov (United States)

Jaffe, Richard; Han, Jie; Matsuda, Tsunetoshi; Yoon, Do; Langhoff, Stephen R. (Technical Monitor)

1997-01-01

Confirmations of 2,4-dihydroxypentane (DHP), a model molecule for poly(vinyl alcohol), have been studied by quantum chemistry (QC) calculations and molecular dynamics (MD) simulations. QC calculations at the 6-311G MP2 level show the meso tt conformer to be lowest in energy followed by the racemic tg, due to intramolecular hydrogen bond between the hydroxy groups. The Dreiding force field has been modified to reproduce the QC conformer energies for DHP. MD simulations using this force field have been carried out for DHP molecules in the gas phase, melt, and CHCl3 and water solutions. Extensive intramolecular hydrogen bonding is observed for the gas phase and CHCl3 solution, but not for the melt or aqueous solution, Such a condensed phase effect due to intermolecular interactions results in a drastic change in chain conformations, in agreement with experiments.

Characterizing protein conformations by correlation analysis of coarse-grained contact matrices

Science.gov (United States)

Lindsay, Richard J.; Siess, Jan; Lohry, David P.; McGee, Trevor S.; Ritchie, Jordan S.; Johnson, Quentin R.; Shen, Tongye

2018-01-01

We have developed a method to capture the essential conformational dynamics of folded biopolymers using statistical analysis of coarse-grained segment-segment contacts. Previously, the residue-residue contact analysis of simulation trajectories was successfully applied to the detection of conformational switching motions in biomolecular complexes. However, the application to large protein systems (larger than 1000 amino acid residues) is challenging using the description of residue contacts. Also, the residue-based method cannot be used to compare proteins with different sequences. To expand the scope of the method, we have tested several coarse-graining schemes that group a collection of consecutive residues into a segment. The definition of these segments may be derived from structural and sequence information, while the interaction strength of the coarse-grained segment-segment contacts is a function of the residue-residue contacts. We then perform covariance calculations on these coarse-grained contact matrices. We monitored how well the principal components of the contact matrices is preserved using various rendering functions. The new method was demonstrated to assist the reduction of the degrees of freedom for describing the conformation space, and it potentially allows for the analysis of a system that is approximately tenfold larger compared with the corresponding residue contact-based method. This method can also render a family of similar proteins into the same conformational space, and thus can be used to compare the structures of proteins with different sequences.

Nucleotide-induced conformational dynamics in ABC transporters from structure-based coarse grained modelling.

Science.gov (United States)

Flechsig, Holger

2016-02-01

ATP-binding cassette (ABC) transporters are integral membrane proteins which mediate the exchange of diverse substrates across membranes powered by ATP molecules. Our understanding of their activity is still hampered since the conformational dynamics underlying the operation of such proteins cannot yet be resolved in detailed molecular dynamics studies. Here a coarse grained model which allows to mimic binding of nucleotides and follow subsequent conformational motions of full-length transporter structures in computer simulations is proposed and implemented. To justify its explanatory quality, the model is first applied to the maltose transporter system for which multiple conformations are known and we find that the model predictions agree remarkably well with the experimental data. For the MalK subunit the switching from open to the closed dimer configuration upon ATP binding is reproduced and, moreover, for the full-length maltose transporter, progression from inward-facing to the outward-facing state is correctly obtained. For the heme transporter HmuUV, for which only the free structure could yet be determined, the model was then applied to predict nucleotide-induced conformational motions. Upon binding of ATP-mimicking ligands the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact, while, at the same time, a pronounced rotation of the transmembrane domains was observed. This finding is supported by normal mode analysis, and, comparison with structural data of the homologous vitamin B12 transporter BtuCD suggests that the observed rotation mechanism may contribute a common functional aspect for this class of ABC transporters. Although in HmuuV noticeable rearrangement of essential transmembrane helices was detected, there are no indications from our simulations that ATP binding alone may facilitate propagation of substrate molecules in this transporter

A dynamic view of molecular switch behavior at serotonin receptors: implications for functional selectivity.

Directory of Open Access Journals (Sweden)

Maria Martí-Solano

Full Text Available Functional selectivity is a property of G protein-coupled receptors that allows them to preferentially couple to particular signaling partners upon binding of biased agonists. Publication of the X-ray crystal structure of serotonergic 5-HT1B and 5-HT2B receptors in complex with ergotamine, a drug capable of activating G protein coupling and β-arrestin signaling at the 5-HT1B receptor but clearly favoring β-arrestin over G protein coupling at the 5-HT2B subtype, has recently provided structural insight into this phenomenon. In particular, these structures highlight the importance of specific residues, also called micro-switches, for differential receptor activation. In our work, we apply classical molecular dynamics simulations and enhanced sampling approaches to analyze the behavior of these micro-switches and their impact on the stabilization of particular receptor conformational states. Our analysis shows that differences in the conformational freedom of helix 6 between both receptors could explain their different G protein-coupling capacity. In particular, as compared to the 5-HT1B receptor, helix 6 movement in the 5-HT2B receptor can be constrained by two different mechanisms. On the one hand, an anchoring effect of ergotamine, which shows an increased capacity to interact with the extracellular part of helices 5 and 6 and stabilize them, hinders activation of a hydrophobic connector region at the center of the receptor. On the other hand, this connector region in an inactive conformation is further stabilized by unconserved contacts extending to the intracellular part of the 5-HT2B receptor, which hamper opening of the G protein binding site. This work highlights the importance of considering receptor capacity to adopt different conformational states from a dynamic perspective in order to underpin the structural basis of functional selectivity.

Increasing the sampling efficiency of protein conformational transition using velocity-scaling optimized hybrid explicit/implicit solvent REMD simulation

Energy Technology Data Exchange (ETDEWEB)

Yu, Yuqi; Wang, Jinan; Shao, Qiang, E-mail: qshao@mail.shcnc.ac.cn, E-mail: Jiye.Shi@ucb.com, E-mail: wlzhu@mail.shcnc.ac.cn; Zhu, Weiliang, E-mail: qshao@mail.shcnc.ac.cn, E-mail: Jiye.Shi@ucb.com, E-mail: wlzhu@mail.shcnc.ac.cn [ACS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203 (China); Shi, Jiye, E-mail: qshao@mail.shcnc.ac.cn, E-mail: Jiye.Shi@ucb.com, E-mail: wlzhu@mail.shcnc.ac.cn [UCB Pharma, 216 Bath Road, Slough SL1 4EN (United Kingdom)

2015-03-28

The application of temperature replica exchange molecular dynamics (REMD) simulation on protein motion is limited by its huge requirement of computational resource, particularly when explicit solvent model is implemented. In the previous study, we developed a velocity-scaling optimized hybrid explicit/implicit solvent REMD method with the hope to reduce the temperature (replica) number on the premise of maintaining high sampling efficiency. In this study, we utilized this method to characterize and energetically identify the conformational transition pathway of a protein model, the N-terminal domain of calmodulin. In comparison to the standard explicit solvent REMD simulation, the hybrid REMD is much less computationally expensive but, meanwhile, gives accurate evaluation of the structural and thermodynamic properties of the conformational transition which are in well agreement with the standard REMD simulation. Therefore, the hybrid REMD could highly increase the computational efficiency and thus expand the application of REMD simulation to larger-size protein systems.

OpenFlow Switching Performance using Network Simulator - 3

OpenAIRE

Sriram Prashanth, Naguru

2016-01-01

Context. In the present network inventive world, there is a quick expansion of switches and protocols, which are used to cope up with the increase in customer requirement in the networking. With increasing demand for higher bandwidths and lower latency and to meet these requirements new network paths are introduced. To reduce network load in present switching network, development of new innovative switching is required. These required results can be achieved by Software Define Network or Trad...

Conformational Control of Energy Transfer: A Mechanism for Biocompatible Nanocrystal-Based Sensors

OpenAIRE

Kay, Euan R.; Lee, Jungmin; Nocera, Daniel; Bawendi, Moungi G.

2012-01-01

Fold-up fluorophore: A new paradigm for designing self-referencing fluorescent nanosensors is demonstrated by interfacing a pH-triggered molecular conformational switch with quantum dots. Analytedependent, large-amplitude conformational motion controls the distance between the nanocrystal energy donor and an organic FRET acceptor. The result is a fluorescence signal capable of reporting pH values from individual endosomes in living cells.

Uniform stable conformal convolutional perfectly matched layer for enlarged cell technique conformal finite-difference time-domain method

International Nuclear Information System (INIS)

Wang Yue; Wang Jian-Guo; Chen Zai-Gao

2015-01-01

Based on conformal construction of physical model in a three-dimensional Cartesian grid, an integral-based conformal convolutional perfectly matched layer (CPML) is given for solving the truncation problem of the open port when the enlarged cell technique conformal finite-difference time-domain (ECT-CFDTD) method is used to simulate the wave propagation inside a perfect electric conductor (PEC) waveguide. The algorithm has the same numerical stability as the ECT-CFDTD method. For the long-time propagation problems of an evanescent wave in a waveguide, several numerical simulations are performed to analyze the reflection error by sweeping the constitutive parameters of the integral-based conformal CPML. Our numerical results show that the integral-based conformal CPML can be used to efficiently truncate the open port of the waveguide. (paper)

Isomerization of Orthogonal Molecular Switches Encapsulated within Micelles Solubilizing Carbon Nanotubes

DEFF Research Database (Denmark)

Kreft, Stefanie K.; Petersen, Michael Åxman; Nielsen, Mogens Brøndsted

2015-01-01

We study the effects of the proximity of the orthogonal dipole-switching moiety dihydroazulene/vinylheptafulvene (DHA/VHF) to carbon nanotubes (CNTs). The switches are introduced into a micelle surrounding the CNTs, thereby achieving very close proximity between the molecules and the CNTs...... of the CNTs and the resulting reversible redshift of the nanotubes' emission by the change of the molecules' conformation....

Switching behavior of double-decker single molecule magnets on a metal surface

Energy Technology Data Exchange (ETDEWEB)

Fu, Yingshuang; Schwoebel, Joerg; Hoffmann, Germar; Brede, Jens; Wiesendanger, Roland [University of Hamburg, Hamburg (Germany); Dillulo, Andrew [Ohio University, Athens (United States); Klyatskaya, Svetlana [Karlsruhe Institute of Technology, Karlsruhe (Germany); Ruben, Mario [Karlsruhe Institute of Technology, Karlsruhe (Germany); Universite de Strasbourg, Strasbourg (France)

2011-07-01

Single molecule magnets (SMM) are most promising materials for spin based molecular electronics. Due to their large magnetic anisotropy stabilized by inside chemical bonds, SMM can potentially be used for information storage at the single molecule level. For applications, it is of importance to adsorb the SMM onto surfaces and to study their subsequent conformational, electronic and magnetic properties. We have investigated the adsorption behavior of Tb and Dy based double-decker SMM on an Ir(111) surface with low temperature scanning tunneling microscopy and spectroscopy. It is found that Tb double-decker molecules bind tightly to the Ir(111) surface. By resonantly injecting tunneling electrons into its LUMO or HOMO state, the Tb double-decker molecule can be switched from a four-lobed structure to an eight-lobed structure. After switching, energy positions of the HOMO and LUMO states both shift closer to the Fermi level. Dy double-decker molecules also exhibit the same switching properties on the Ir(111) surface. The switching behavior of the molecules is tentatively attributed to a conformational change of the double-decker molecular frame.

Monte Carlo simulations of an Ising-like model for photoinduced spin-state switching in nanoparticles of transition metal complexes

International Nuclear Information System (INIS)

Kawamoto, Tohru; Abe, Shuji

2005-01-01

We investigated the switching behavior of small particles of an Ising-like model under constant excitation by means of Monte Carlo simulations to study photoinduced spinstate switching in nanoparticles of transition metal complexes. The threshold intensity required for that switching becomes drastically small in small particles with diameter of less than 10 pseudospins. This lower intensity results enhancement of the pseudospin fluctuation at the surface in the small particles. Our result might originate the increase of the photoinduced magnetization in nanoparticles of a Mo-Cu cyanide

Modeling and analysis of the Rimfire gas switch

International Nuclear Information System (INIS)

Gahl, John M.; Kemp, Mark A.; Struve, Kenneth William; Curry, Randy D.; McDonald, Ken F.

2005-01-01

Many accelerators at Sandia National Laboratories utilize the Rimfire gas switch for high-voltage, high-power switching. Future accelerators will have increased performance requirements for switching elements. When designing improved versions of the Rimfire switch, there is a need for quick and accurate simulation of the electrical effects of geometry changes. This paper presents an advanced circuit model of the Rimfire switch that can be used for these simulations. The development of the model is shown along with comparisons to past models and experimental results.

Demonstration of Ultra-Fast Switching in Nano metallic Resistive Switching Memory Devices

International Nuclear Information System (INIS)

Yang, Y.

2016-01-01

Interdependency of switching voltage and time creates a dilemma/obstacle for most resistive switching memories, which indicates low switching voltage and ultra-fast switching time cannot be simultaneously achieved. In this paper, an ultra-fast (sub-100 ns) yet low switching voltage resistive switching memory device (“nano metallic ReRAM”) was demonstrated. Experimental switching voltage is found independent of pulse width (intrinsic device property) when the pulse is long but shows abrupt time dependence (“cliff”) as pulse width approaches characteristic RC time of memory device (extrinsic device property). Both experiment and simulation show that the onset of cliff behavior is dependent on physical device size and parasitic resistance, which is expected to diminish as technology nodes shrink down. We believe this study provides solid evidence that nano metallic resistive switching memory can be reliably operated at low voltage and ultra-fast regime, thus beneficial to future memory technology.

Conformable liquid metal printed epidermal electronics for smart physiological monitoring and simulation treatment

Science.gov (United States)

Wang, Xuelin; Zhang, Yuxin; Guo, Rui; Wang, Hongzhang; Yuan, Bo; Liu, Jing

2018-03-01

Conformable epidermal printed electronics enabled from gallium-based liquid metals (LMs), highly conductive and low-melting-point alloys, are proposed as the core to achieving immediate contact between skin surface and electrodes, which can avoid the skin deformation often caused by conventional rigid electrodes. When measuring signals, LMs can eliminate resonance problems with shorter time to reach steady state than Pt and gelled Pt electrodes. By comparing the contact resistance under different working conditions, it is demonstrated that both ex vivo and in vivo LM electrode-skin models have the virtues of direct and immediate contact with skin surface without the deformation encountered with conventional rigid electrodes. In addition, electrocardio electrodes composed of conformable LM printed epidermal electronics are adopted as smart devices to monitor electrocardiogram signals of rabbits. Furthermore, simulation treatment for smart defibrillation offers a feasible way to demonstrate the effect of liquid metal electrodes (LMEs) on the human body with less energy loss. The remarkable features of soft epidermal LMEs such as high conformability, good conductivity, better signal stability, and fine biocompatibility represent a critical step towards accurate medical monitoring and future smart treatments.

Molecular dynamics studies of the conformation of sorbitol

Science.gov (United States)

Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

2009-01-01

Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

Probing the Mechanism of pH-Induced Large-Scale Conformational Changes in Dengue Virus Envelope Protein Using Atomistic Simulations

Science.gov (United States)

Prakash, Meher K.; Barducci, Alessandro; Parrinello, Michele

2010-01-01

Abstract One of the key steps in the infection of the cell by dengue virus is a pH-induced conformational change of the viral envelope proteins. These envelope proteins undergo a rearrangement from a dimer to a trimer, with large conformational changes in the monomeric unit. In this article, metadynamics simulations were used to enable us to understand the mechanism of these large-scale changes in the monomer. By using all-atom, explicit solvent simulations of the monomers, the stability of the protein structure is studied under low and high pH conditions. Free energy profiles obtained along appropriate collective coordinates demonstrate that pH affects the domain interface in both the conformations of E monomer, stabilizing one and destabilizing the other. These simulations suggest a mechanism with an intermediate detached state between the two monomeric structures. Using further analysis, we comment on the key residue interactions responsible for the instability and the pH-sensing role of a histidine that could not otherwise be studied experimentally. The insights gained from this study and methodology can be extended for studying similar mechanisms in the E proteins of the other members of class II flavivirus family. PMID:20643078

Efficient CT simulation of the four-field technique for conformal radiotherapy of prostate carcinoma

International Nuclear Information System (INIS)

Valicenti, Richard K.; Waterman, Frank M.; Croce, Raymond J.; Corn, Benjamin; Suntharalingam, Nagalingam; Curran, Walter J.

1997-01-01

Purpose: Conformal radiotherapy of prostate carcinoma relies on contouring of individual CT slices for target and normal tissue localization. This process can be very time consuming. In the present report, we describe a method to more efficiently localize pelvic anatomy directly from digital reconstructed radiographs (DRRs). Materials and Methods: Ten patients with prostate carcinoma underwent CT simulation (the spiral mode at 3 mm separation) for conformal four-field 'box' radiotherapy. The bulbous urethra and bladder were opacified with iodinated contrast media. On lateral and anteroposterior DRRs, the volume of interest (VOI) was restricted to 1.0-1.5 cm tissue thickness to optimize digital radiograph reconstruction of the prostate and seminal vesicles. By removing unessential voxel elements, this method provided direct visualization of those structures. For comparison, the targets of each patient were also obtained by contouring CT axial slices. Results: The method was successfully performed if the target structures were readily visualized and geometrically corresponded to those generated by contouring axial images. The targets in 9 of 10 patients were reliable representations of the CT-contoured volumes. One patient had 18 mm variation due to the lack of bladder opacification. Using VOIs to generate thin tissue DRRs, the time required for target and normal tissue localization was on the average less than 5 min. Conclusion: In CT simulation of the four-field irradiation technique for prostate carcinoma, thin-tissue DRRs allowed for efficient and accurate target localization without requiring individual axial image contouring. This method may facilitate positioning of the beam isocenter and provide reliable conformal radiotherapy

Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin.

Directory of Open Access Journals (Sweden)

Ayse Ozlem Aykut

Full Text Available We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca(2+-CaM. We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca(2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca(2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca(2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength.

Modeling, Simulation, and Experiment of Switched Reluctance Ocean Current Generator System

Directory of Open Access Journals (Sweden)

Hao Chen

2013-01-01

Full Text Available This paper presents nonlinear simulation model of switched reluctance (SR ocean current generator system on MATLAB/SIMULINK with describing the structure of generator system. The developed model is made up of main model, rotor position calculation module, controller module, gate module, power converter module, phase windings module, flux-linkage module, torque module, and power calculation module. The magnetization curves obtained by two-dimensional finite-element electromagnetic field calculation and the conjugated magnetic energy graphics obtained from the three-dimensional graphics of flux linkage are stored in the “Lookup Table” modules on MATLAB/SIMULINK. The hardware of the developed three-phase 12/8 structure SR ocean current generator system prototype with the experimental platform is presented. The simulation of the prototype is performed by the developed models, and the experiments have been carried out under the same condition with different output power, turn-off angle, and rotor speed. The simulated phase current waveforms agree well with the tested phase current waveforms experimentally. The simulated output voltage curves agree well with the tested output voltage curves experimentally. It is shown that the developed nonlinear simulation model of the three-phase 12/8 structure SR ocean current generator system is valid.

Molecular Dynamics Simulations and Classical Multidimensional Scaling Unveil New Metastable States in the Conformational Landscape of CDK2.

Directory of Open Access Journals (Sweden)

Pasquale Pisani

Full Text Available Protein kinases are key regulatory nodes in cellular networks and their function has been shown to be intimately coupled with their structural flexibility. However, understanding the key structural mechanisms of large conformational transitions remains a difficult task. CDK2 is a crucial regulator of cell cycle. Its activity is finely tuned by Cyclin E/A and the catalytic segment phosphorylation, whereas its deregulation occurs in many types of cancer. ATP competitive inhibitors have failed to be approved for clinical use due to toxicity issues raised by a lack of selectivity. However, in the last few years type III allosteric inhibitors have emerged as an alternative strategy to selectively modulate CDK2 activity. In this study we have investigated the conformational variability of CDK2. A low dimensional conformational landscape of CDK2 was modeled using classical multidimensional scaling on a set of 255 crystal structures. Microsecond-scale plain and accelerated MD simulations were used to populate this landscape by using an out-of-sample extension of multidimensional scaling. CDK2 was simulated in the apo-form and in complex with the allosteric inhibitor 8-anilino-1-napthalenesulfonic acid (ANS. The apo-CDK2 landscape analysis showed a conformational equilibrium between an Src-like inactive conformation and an active-like form. These two states are separated by different metastable states that share hybrid structural features with both forms of the kinase. In contrast, the CDK2/ANS complex landscape is compatible with a conformational selection picture where the binding of ANS in proximity of the αC helix causes a population shift toward the inactive conformation. Interestingly, the new metastable states could enlarge the pool of candidate structures for the development of selective allosteric CDK2 inhibitors. The method here presented should not be limited to the CDK2 case but could be used to systematically unmask similar mechanisms

Action of Molecular Switches in GPCRs - Theoretical and Experimental Studies

Science.gov (United States)

Trzaskowski, B; Latek, D; Yuan, S; Ghoshdastider, U; Debinski, A; Filipek, S

2012-01-01

G protein coupled receptors (GPCRs), also called 7TM receptors, form a huge superfamily of membrane proteins that, upon activation by extracellular agonists, pass the signal to the cell interior. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. Biochemical and crystallographic methods together with molecular dynamics simulations and other theoretical techniques provided models of the receptor activation based on the action of so-called “molecular switches” buried in the receptor structure. They are changed by agonists but also by inverse agonists evoking an ensemble of activation states leading toward different activation pathways. Switches discovered so far include the ionic lock switch, the 3-7 lock switch, the tyrosine toggle switch linked with the nPxxy motif in TM7, and the transmission switch. The latter one was proposed instead of the tryptophan rotamer toggle switch because no change of the rotamer was observed in structures of activated receptors. The global toggle switch suggested earlier consisting of a vertical rigid motion of TM6, seems also to be implausible based on the recent crystal structures of GPCRs with agonists. Theoretical and experimental methods (crystallography, NMR, specific spectroscopic methods like FRET/BRET but also single-molecule-force-spectroscopy) are currently used to study the effect of ligands on the receptor structure, location of stable structural segments/domains of GPCRs, and to answer the still open question on how ligands are binding: either via ensemble of conformational receptor states or rather via induced fit mechanisms. On the other hand the structural investigations of homo- and heterodimers and higher oligomers revealed the mechanism of allosteric signal transmission and receptor

Switching overvoltages in offshore wind power grids

DEFF Research Database (Denmark)

Arana Aristi, Ivan

and cables are presented. In Chapter 4 results from time domain measurements and simulations of switching operations in offshore wind power grids are described. Specifically, switching operations on a single wind turbine, the collection grid, the export system and the external grid measured in several real...... offshore wind farms are shown together with simulation results. Switching operations in offshore wind power grids can be simulated with different electromagnetic transient programs. Different programs were used in the project and compared results are included in Chapter 4. Also in Chapter 4 different......Switching transients in wind turbines, the collection grid, the export system and the external grid in offshore wind farms, during normal or abnormal operation, are the most important phenomena when conducting insulation coordination studies. However, the recommended models and methods from...

Molecular Dynamics Simulations of the Human Glucose Transporter GLUT1.

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Min-Sun Park

Full Text Available Glucose transporters (GLUTs provide a pathway for glucose transport across membranes. Human GLUTs are implicated in devastating diseases such as heart disease, hyper- and hypo-glycemia, type 2 diabetes and cancer. The human GLUT1 has been recently crystalized in the inward-facing open conformation. However, there is no other structural information for other conformations. The X-ray structures of E. coli Xylose permease (XylE, a glucose transporter homolog, are available in multiple conformations with and without the substrates D-xylose and D-glucose. XylE has high sequence homology to human GLUT1 and key residues in the sugar-binding pocket are conserved. Here we construct a homology model for human GLUT1 based on the available XylE crystal structure in the partially occluded outward-facing conformation. A long unbiased all atom molecular dynamics simulation starting from the model can capture a new fully opened outward-facing conformation. Our investigation of molecular interactions at the interface between the transmembrane (TM domains and the intracellular helices (ICH domain in the outward- and inward-facing conformation supports that the ICH domain likely stabilizes the outward-facing conformation in GLUT1. Furthermore, inducing a conformational transition, our simulations manifest a global asymmetric rocker switch motion and detailed molecular interactions between the substrate and residues through the water-filled selective pore along a pathway from the extracellular to the intracellular side. The results presented here are consistent with previously published biochemical, mutagenesis and functional studies. Together, this study shed light on the structure and functional relationships of GLUT1 in multiple conformational states.

Torsional Arming of Thiomannosyl Donors & Conformational Control of Hexahydropyridazines via pH

DEFF Research Database (Denmark)

Olsen, Jacob Ingemar

The overall objective of the research presented in this PhD thesis was to investigate torsional arming of thiogalacto- and thiomannosyl donors (part 1) and to investigate the possible synthesis and attachment of a pH regulated conformational switch to an α-cyclodextrin (part 2). Part 1: It is well...... demonstrated their ability to change conformation under different conditions. These conformational changes are connected to various intramolecular interactions and can to some extent, be controlled by pH (Chapter 3). Fusing these conformationally labile compounds to the rim of a cyclodextrin would create...... compounds that could release molecules at a specified change in pH conditions. To investigate this, four hexahydropyridazines were synthesized and investigated for their pH induced conformational change (Chapter 4). Out of the four compounds, one revealed to flip between two conformations depending on pH...

New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

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Hugo de Almeida

Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

A numerical simulation model of valence-change-based resistive switching

OpenAIRE

Marchewka, Astrid

2017-01-01

Due to their superior scalability and performance, nanoscale resistive switches based on the valence-change mechanism are considered promising candidates for future nonvolatile memory and logic applications. These devices are metal-oxide-metal structures that can be reversibly switched between different resistance states by electrical signals. Typically, they contain one Schottky-like and one ohmic-like metal-oxide contact and exhibit bipolar switching. The switching mechanism and the initial...

NUMERICAL SIMULATION OF Q-SWITCHED Nd: YAG LASER WITH UNSTABLE RESONATOR AND OUTPUT VARIABLE REFLECTIVITY MIRROR

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I. N. Dubinkin

2017-05-01

Full Text Available The article deals with a method of numerical simulation of laser oscillation in the radially symmetric unstable resonator with an output variable reflectivity mirror (VRM. Research results of the VRM parameters influence on the spatial and energy properties of the laser radiation are obtained. Numerical simulation of laser oscillation in active and passive Q-switching and comparative analysis of the spatial and energy radiation characteristics is done for these modes.

Enhanced conformational sampling using enveloping distribution sampling.

Science.gov (United States)

Lin, Zhixiong; van Gunsteren, Wilfred F

2013-10-14

To lessen the problem of insufficient conformational sampling in biomolecular simulations is still a major challenge in computational biochemistry. In this article, an application of the method of enveloping distribution sampling (EDS) is proposed that addresses this challenge and its sampling efficiency is demonstrated in simulations of a hexa-β-peptide whose conformational equilibrium encompasses two different helical folds, i.e., a right-handed 2.7(10∕12)-helix and a left-handed 3(14)-helix, separated by a high energy barrier. Standard MD simulations of this peptide using the GROMOS 53A6 force field did not reach convergence of the free enthalpy difference between the two helices even after 500 ns of simulation time. The use of soft-core non-bonded interactions in the centre of the peptide did enhance the number of transitions between the helices, but at the same time led to neglect of relevant helical configurations. In the simulations of a two-state EDS reference Hamiltonian that envelops both the physical peptide and the soft-core peptide, sampling of the conformational space of the physical peptide ensures that physically relevant conformations can be visited, and sampling of the conformational space of the soft-core peptide helps to enhance the transitions between the two helices. The EDS simulations sampled many more transitions between the two helices and showed much faster convergence of the relative free enthalpy of the two helices compared with the standard MD simulations with only a slightly larger computational effort to determine optimized EDS parameters. Combined with various methods to smoothen the potential energy surface, the proposed EDS application will be a powerful technique to enhance the sampling efficiency in biomolecular simulations.

Fluid simulation of the conduction phase of the plasma erosion opening switch

International Nuclear Information System (INIS)

Grossmann, J.M.; Mosher, D.; Ottinger, P.F.

1987-01-01

The conduction phase of the plasma erosion openings switch (PEOS) is studied using a 1 1/2-D electromagnetic two-fluid code. The focus of this work is on understanding how two effects, a current-limiting model of electron emission, and the magnetic insulation of electrons at the cathode, determine current conduction in the plasma. Simulations are performed in the parameter regimes of the Gamble I, POP, and PBFA II pulsed power generators, and previous low-density, short-rise time simulations of the PEOS. Fluid code results are compared to a 1-D analytic theory and to the Gamble I and POP experiments. Good agreement between theory and simulation, but mixed agreement between simulation and experiment is found. Experimental Β-field measurements on POP show weaker j x Β compression than the simulation. Current penetration and plasma current channels qualitatively similar to experimental observation are found in the Gamble I regime. However, magnetic insulation of electrons emitted from the cathode bunches the electron flow into narrower current channels than observed experimentally. In several cases, the presence of an electron-scattering or energy-loss mechanism near the cathode must be invoked to overcome magnetic insulation and widen the current channels

Adjusting for treatment switching in randomised controlled trials - A simulation study and a simplified two-stage method.

Science.gov (United States)

Latimer, Nicholas R; Abrams, K R; Lambert, P C; Crowther, M J; Wailoo, A J; Morden, J P; Akehurst, R L; Campbell, M J

2017-04-01

Estimates of the overall survival benefit of new cancer treatments are often confounded by treatment switching in randomised controlled trials (RCTs) - whereby patients randomised to the control group are permitted to switch onto the experimental treatment upon disease progression. In health technology assessment, estimates of the unconfounded overall survival benefit associated with the new treatment are needed. Several switching adjustment methods have been advocated in the literature, some of which have been used in health technology assessment. However, it is unclear which methods are likely to produce least bias in realistic RCT-based scenarios. We simulated RCTs in which switching, associated with patient prognosis, was permitted. Treatment effect size and time dependency, switching proportions and disease severity were varied across scenarios. We assessed the performance of alternative adjustment methods based upon bias, coverage and mean squared error, related to the estimation of true restricted mean survival in the absence of switching in the control group. We found that when the treatment effect was not time-dependent, rank preserving structural failure time models (RPSFTM) and iterative parameter estimation methods produced low levels of bias. However, in the presence of a time-dependent treatment effect, these methods produced higher levels of bias, similar to those produced by an inverse probability of censoring weights method. The inverse probability of censoring weights and structural nested models produced high levels of bias when switching proportions exceeded 85%. A simplified two-stage Weibull method produced low bias across all scenarios and provided the treatment switching mechanism is suitable, represents an appropriate adjustment method.

Using MEMS Capacitive Switches in Tunable RF Amplifiers

OpenAIRE

Danson John; Plett Calvin; Tait Niall

2006-01-01

A MEMS capacitive switch suitable for use in tunable RF amplifiers is described. A MEMS switch is designed, fabricated, and characterized with physical and RF measurements for inclusion in simulations. Using the MEMS switch models, a dual-band low-noise amplifier (LNA) operating at GHz and GHz, and a tunable power amplifier (PA) at GHz are simulated in m CMOS. MEMS switches allow the LNA to operate with 11 dB of isolation between the two bands while maintaining dB of gain and sub- dB no...

Low pull-in voltage electrostatic MEMS switch using liquid dielectric

KAUST Repository

Zidan, Mohammed A.

2014-08-01

In this paper, we present an electrostatic MEMS switch with liquids as dielectric to reduce the actuation voltage. The concept is verified by simulating a lateral dual gate switch, where the required pull-in voltage is reduced by more than 8 times after using water as a dielectric, to become as low as 5.36V. The proposed switch is simulated using COMSOL multiphysics using various liquid volumes to study their effect on the switching performance. Finally, we propose the usage of the lateral switch as a single switch XOR logic gate.

Polarization and Segregation through Conformity Pressure and Voluntary Migration: Simulation Analysis of Co-Evolutionary Dynamics

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Dai Zusai

2017-11-01

Full Text Available While conformity pressures people to assimilate in a community, an individual occasionally migrates among communities when the individual feels discomfort. These two factors cause segregation and cultural diversity within communities in the society. By embedding a migration dynamic into Kuran and Sandholm’s model (2008 of preference evolution, we build an agent-based model to see how the variance of preferences in the entire society quantitatively changes over time. We find from the Monte-Carlo simulations that, while preferences assimilate within a community, self-selected migrations enlarge the diversity of preferences over communities in the society. We further study how the arrival rate of migration opportunities and the degree of conformity pressures affect the variance of preferences.

Analytical Modeling and Simulation of Four-Switch Hybrid Power Filter Working with Sixfold Switching Symmetry

Czech Academy of Sciences Publication Activity Database

Tlustý, J.; Škramlík, Jiří; Švec, J.; Valouch, Viktor

2012-01-01

Roč. 2012, č. 292178 (2012), s. 1-17 ISSN 1024-123X Institutional support: RVO:61388998 Keywords : analytical modeling * four-switch hybrid power filter * sixfold switching symmetry Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.383, year: 2012 http://www.hindawi.com/journals/mpe/2012/292178/

Using MEMS Capacitive Switches in Tunable RF Amplifiers

Directory of Open Access Journals (Sweden)

Danson John

2006-01-01

Full Text Available A MEMS capacitive switch suitable for use in tunable RF amplifiers is described. A MEMS switch is designed, fabricated, and characterized with physical and RF measurements for inclusion in simulations. Using the MEMS switch models, a dual-band low-noise amplifier (LNA operating at GHz and GHz, and a tunable power amplifier (PA at GHz are simulated in m CMOS. MEMS switches allow the LNA to operate with 11 dB of isolation between the two bands while maintaining dB of gain and sub- dB noise figure. MEMS switches are used to implement a variable matching network that allows the PA to realize up to 37% PAE improvement at low input powers.

Microscopic insights into the NMR relaxation based protein conformational entropy meter

Science.gov (United States)

Kasinath, Vignesh; Sharp, Kim A.; Wand, A. Joshua

2013-01-01

Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven pro! teins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side-chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion - the NMR-derived generalized order parameters - as a proxy from which to derive changes in protein conformational entropy. PMID:24007504

Autoinhibition and signaling by the switch II motif in the G-protein chaperone of a radical B12 enzyme.

Science.gov (United States)

Lofgren, Michael; Koutmos, Markos; Banerjee, Ruma

2013-10-25

MeaB is an accessory GTPase protein involved in the assembly, protection, and reactivation of 5'-deoxyadenosyl cobalamin-dependent methylmalonyl-CoA mutase (MCM). Mutations in the human ortholog of MeaB result in methylmalonic aciduria, an inborn error of metabolism. G-proteins typically utilize conserved switch I and II motifs for signaling to effector proteins via conformational changes elicited by nucleotide binding and hydrolysis. Our recent discovery that MeaB utilizes an unusual switch III region for bidirectional signaling with MCM raised questions about the roles of the switch I and II motifs in MeaB. In this study, we addressed the functions of conserved switch II residues by performing alanine-scanning mutagenesis. Our results demonstrate that the GTPase activity of MeaB is autoinhibited by switch II and that this loop is important for coupling nucleotide-sensitive conformational changes in switch III to elicit the multiple chaperone functions of MeaB. Furthermore, we report the structure of MeaB·GDP crystallized in the presence of AlFx(-) to form the putative transition state analog, GDP·AlF4(-). The resulting crystal structure and its comparison with related G-proteins support the conclusion that the catalytic site of MeaB is incomplete in the absence of the GTPase-activating protein MCM and therefore unable to stabilize the transition state analog. Favoring an inactive conformation in the absence of the client MCM protein might represent a strategy for suppressing the intrinsic GTPase activity of MeaB in which the switch II loop plays an important role.

Slow sand filters effectively reduce Phytophthora after a pathogen switch from Fusarium and a simulated pump failure.

Science.gov (United States)

Lee, Eric; Oki, Lorence R

2013-09-15

Slow sand filtration has been shown to effectively reduce Phytophthora zoospores in irrigation water. This experiment tested the reduction of Phytophthora colony forming units (CFUs) by slow sand filtration systems after switching the pathogen contaminating plant leachate from Fusarium to Phytophthora and the resilience of the system to a short period without water, as might be caused by a pump failure. The slow sand filtration system greatly reduced Phytophthora CFUs and transmission after switching the pathogens. In addition, Phytophthora reduction by the slow sand filter was equally effective before and after the simulated pump failure. Reduction of Fusarium was not seen by the SSFs, before or after the simulated pump failure. The results suggest that slow sand filters are effective at reducing larger organisms, such as Phytophthora zoospores, even after a pump failure or a change in pathogens. Copyright © 2013 Elsevier Ltd. All rights reserved.

Combining SDM-Based Circuit Switching with Packet Switching in a Router for On-Chip Networks

Directory of Open Access Journals (Sweden)

Angelo Kuti Lusala

2012-01-01

Full Text Available A Hybrid router architecture for Networks-on-Chip “NoC” is presented, it combines Spatial Division Multiplexing “SDM” based circuit switching and packet switching in order to efficiently and separately handle both streaming and best-effort traffic generated in real-time applications. Furthermore the SDM technique is combined with Time Division Multiplexing “TDM” technique in the circuit switching part in order to increase path diversity, thus improving throughput while sharing communication resources among multiple connections. Combining these two techniques allows mitigating the poor resource usage inherent to circuit switching. In this way Quality of Service “QoS” is easily provided for the streaming traffic through the circuit-switched sub-router while the packet-switched sub-router handles best-effort traffic. The proposed hybrid router architectures were synthesized, placed and routed on an FPGA. Results show that a practicable Network-on-Chip “NoC” can be built using the proposed router architectures. 7 × 7 mesh NoCs were simulated in SystemC. Simulation results show that the probability of establishing paths through the NoC increases with the number of sub-channels and has its highest value when combining SDM with TDM, thereby significantly reducing contention in the NoC.

Two-dimensional single fluid MHD simulations of plasma opening switches

International Nuclear Information System (INIS)

Roderick, N.F.; Payne, S.S.; Peterkin, R.E. Jr.; Frese, M.H.; Hussey, T.W.

1989-01-01

Simulations of plasma opening switch have been made using two-dimensional, single fluid, magnetohydrodynamic codes HAM and MACH2. A variety of mechanisms for magnetic field penetration have been investigated. These include plasma convection, classical and microturbulent resistive diffusion, and Hall effect transport. We find that plasma microturbulent models are necessary to explain the broad current channels observed in experiments. Both heuristic and consistent microturbulent models are able to explain observed channel widths and penetration features. The best results are obtained for a consistent model that includes the Buneman, ion acoustic, and lower hybrid microturbulent collision frequencies and threshold conditions. Maximum microturbulent collision frequencies of 5 ω p , are typical. Field transport and current channel profiles are in excellent agreement with experimental observations for GAMBLE I, GAMBLE II, and SUPERMITE experiments. Dominant field penetration mechanisms and center of mass plasma motion are current and density dependent. Including the Hall effect enhanced field penetration. Center of mass motion is negligible for the GAMBLE I experiments but significant for the GAMBLE II conditions. Scaling of plasma opening time with switch length and density can be fit by linear representations for lengths from 0.03 m to 0.24 m and ion densities from 10 18 m -3 to 1.5 times 10 19 m -3 . 15 refs., 7 figs., 1 tab

Calcium-Responsive Liposomes via a Synthetic Lipid Switch.

Science.gov (United States)

Lou, Jinchao; Carr, Adam J; Watson, Alexa J; Mattern-Schain, Samuel I; Best, Michael D

2018-03-07

Liposomal drug delivery would benefit from enhanced control over content release. Here, we report a novel avenue for triggering release driven by chemical composition using liposomes sensitized to calcium-a target chosen due to its key roles in biology and disease. To demonstrate this principle, we synthesized calcium-responsive lipid switch 1, designed to undergo conformational changes upon calcium binding. The conformational change perturbs membrane integrity, thereby promoting cargo release. This was shown through fluorescence-based release assays via dose-dependent response depending on the percentage of 1 in liposomes, with minimal background leakage in controls. DLS experiments indicated dramatic changes in particle size upon treatment of liposomes containing 1 with calcium. In a comparison of ten naturally occurring metal cations, calcium provided the greatest release. Finally, STEM images showed significant changes in liposome morphology upon treatment of liposomes containing 1 with calcium. These results showcase lipid switches driven by molecular recognition principles as an exciting avenue for controlling membrane properties. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of force fields on the conformational and dynamic properties of amyloid β(1-40) dimer explored by replica exchange molecular dynamics simulations.

Science.gov (United States)

Watts, Charles R; Gregory, Andrew; Frisbie, Cole; Lovas, Sándor

2018-03-01

The conformational space and structural ensembles of amyloid beta (Aβ) peptides and their oligomers in solution are inherently disordered and proven to be challenging to study. Optimum force field selection for molecular dynamics (MD) simulations and the biophysical relevance of results are still unknown. We compared the conformational space of the Aβ(1-40) dimers by 300 ns replica exchange MD simulations at physiological temperature (310 K) using: the AMBER-ff99sb-ILDN, AMBER-ff99sb*-ILDN, AMBER-ff99sb-NMR, and CHARMM22* force fields. Statistical comparisons of simulation results to experimental data and previously published simulations utilizing the CHARMM22* and CHARMM36 force fields were performed. All force fields yield sampled ensembles of conformations with collision cross sectional areas for the dimer that are statistically significantly larger than experimental results. All force fields, with the exception of AMBER-ff99sb-ILDN (8.8 ± 6.4%) and CHARMM36 (2.7 ± 4.2%), tend to overestimate the α-helical content compared to experimental CD (5.3 ± 5.2%). Using the AMBER-ff99sb-NMR force field resulted in the greatest degree of variance (41.3 ± 12.9%). Except for the AMBER-ff99sb-NMR force field, the others tended to under estimate the expected amount of β-sheet and over estimate the amount of turn/bend/random coil conformations. All force fields, with the exception AMBER-ff99sb-NMR, reproduce a theoretically expected β-sheet-turn-β-sheet conformational motif, however, only the CHARMM22* and CHARMM36 force fields yield results compatible with collapse of the central and C-terminal hydrophobic cores from residues 17-21 and 30-36. Although analyses of essential subspace sampling showed only minor variations between force fields, secondary structures of lowest energy conformers are different. © 2017 Wiley Periodicals, Inc.

Molecular Dynamics Simulations Reveal the Conformational Flexibility of Lipid II and Its Loose Association with the Defensin Plectasin in the Staphylococcus aureus Membrane

DEFF Research Database (Denmark)

Witzke, Sarah; Petersen, Michael; Carpenter, Timothy S.

2016-01-01

dynamics simulation study of the conformational dynamics of Lipid II within a detailed model of the Staphylococcus aureus cell membrane. We show that Lipid II is able to adopt a range of conformations, even within the packed lipidic environment of the membrane. Our simulations also reveal dimerization...... the biosynthesis of the cell wall. Given the urgent need for development of novel antibiotics to counter the growing threat of bacterial infection resistance, it is imperative that a thorough molecular-level characterization of the molecules targeted by antibiotics be achieved. To this end, we present a molecular...... of Lipid II mediated by cations. In the presence of the defensin peptide plectasin, the conformational lability of Lipid II allows it to form loose complexes with the protein, via a number of different binding modes....

Optical switches based on surface plasmons

International Nuclear Information System (INIS)

Chen Cong; Wang Pei; Yuan Guanghui; Wang Xiaolei; Min Changjun; Deng Yan; Lu Yonghua; Ming Hai

2008-01-01

Great attention is being paid to surface plasmons (SPs) because of their potential applications in sensors, data storage and bio-photonics. Recently, more and more optical switches based on surface plasmon effects have been demonstrated either by simulation or experimentally. This article describes the principles, advantages and disadvantages of various types of optical switches based on SPs, in particular the all-optical switches. (authors)

Design and Simulation of an RF-MEMS Switch and analysis of its Electromagnetic aspect in realtion to stress

Directory of Open Access Journals (Sweden)

Amna Riaz

2018-01-01

Full Text Available Microelectromechanical Systems (MEMS are devices made up of several electrical and mechanical components. They consist of mechanical functions (sensing, thermal, inertial and electrical functions (switching, decision making on a single chip made by microfabrication methods. These chips exhibit combined properties of the two functions. The size of system has characteristic dimensions less than 1mm but more than 1μm. The configuration of these components determine the final deliverables of the switch. MEMS can be designed to meet user requirements on any level from microbiological application such as biomedical transducers or tissue engineering, to mechanical systems such as microfluidic diagnoses or chemical fuel cells. The low cost, small mass and minimal power consumption of the MEMS makes it possible to readily integrate to any kind of system in any environment. MEMS are faster, better and cheaper. They offer excellent electrical performances. MEMS working at Radio frequencies are RF MEMS. RF-MEMS switches find huge market in the modern telecommunication networks, biological, automobiles, satellites and defense systems because of their lower power consumptions at relatively higher frequencies and better electrical performances. But the reliability is the major hurdle in the fate of RF MEMS switches. Reliability mainly arises due to the presence of residual stresses, charging current, fatigue and creep and contact degradation. The presence of residual stresses in switches the S-Parameters of the switches are affected badly and the residual stress affects the final planarity of the fabricated structure. Design and simulation of an RF-MEMS switch is proposed considering the residual stresses in both on and off state. The operating frequency band is being optimized and the best possible feasible fabrication technique for the proposed switch design is being analyzed. S-Parameters are calculated and a comparison for the switches with stress and

Multimodal switching of conformation and solubility in homocysteine derived polypeptides

OpenAIRE

Kramer, JR; Deming, TJ

2014-01-01

We report the design and synthesis of poly(S-alkyl-l-homocysteine)s, which were found to be a new class of readily prepared, multiresponsive polymers that possess the unprecedented ability to respond in different ways to different stimuli, either through a change in chain conformation or in water solubility. The responsive properties of these materials are also effected under mild conditions and are completely reversible for all pathways. The key components of these polymers are the incorpora...

Study on the Application of the Combination of TMD Simulation and Umbrella Sampling in PMF Calculation for Molecular Conformational Transitions

Directory of Open Access Journals (Sweden)

Qing Wang

2016-05-01

Full Text Available Free energy calculations of the potential of mean force (PMF based on the combination of targeted molecular dynamics (TMD simulations and umbrella samplings as a function of physical coordinates have been applied to explore the detailed pathways and the corresponding free energy profiles for the conformational transition processes of the butane molecule and the 35-residue villin headpiece subdomain (HP35. The accurate PMF profiles for describing the dihedral rotation of butane under both coordinates of dihedral rotation and root mean square deviation (RMSD variation were obtained based on the different umbrella samplings from the same TMD simulations. The initial structures for the umbrella samplings can be conveniently selected from the TMD trajectories. For the application of this computational method in the unfolding process of the HP35 protein, the PMF calculation along with the coordinate of the radius of gyration (Rg presents the gradual increase of free energies by about 1 kcal/mol with the energy fluctuations. The feature of conformational transition for the unfolding process of the HP35 protein shows that the spherical structure extends and the middle α-helix unfolds firstly, followed by the unfolding of other α-helices. The computational method for the PMF calculations based on the combination of TMD simulations and umbrella samplings provided a valuable strategy in investigating detailed conformational transition pathways for other allosteric processes.

The Numerical Simulation of the Nanosecond Switching of a p-SOS Diode

Science.gov (United States)

Podolska, N. I.; Lyublinskiy, A. G.; Grekhov, I. V.

2017-12-01

Abrupt high-density reverse current interruption has been numerically simulated for switching from forward to reverse bias in a silicon p + P 0 n + structure ( p-SOS diode). It has been shown that the current interruption in this structure occurs as a result of the formation of two dynamic domains of a strong electric field in regions in which the free carrier concentration substantially exceeds the concentration of the doping impurity. The first domain is formed in the n + region at the n + P 0 junction, while the second domain is formed in the P 0 region at the interface with the p + layer. The second domain expands much faster, and this domain mainly determines the current interruption rate. Good agreement is achieved between the simulation results and the experimental data when the actual electric circuit determining the electron-hole plasma pumping in and out is accurately taken into account.

On The Snubber Influence To The Switching And Conduction Losses In A Converter Using Switched Capacitor

Directory of Open Access Journals (Sweden)

Viorel DUGAN

2002-12-01

Full Text Available The paper deals to design and to compute the snubber parameters influence on the switching and conduction losses of the transistors (IGBT used as bidirectional switches in a converter with switched capacitor. The converter was modelled with difference equations, and the transistors during turn-on and turn-off processes were simulated by dynamically varying resistance models. The energy loss per switching, commutation time, the variation of the transistor voltage etc. and the influence of snubber parameters in each of these cases are shown in the context of a converter used as a 50Hz reactive power controller unit

A Lithium-Ion Battery Simulator Based on a Diffusion and Switching Overpotential Hybrid Model for Dynamic Discharging Behavior and Runtime Predictions

Directory of Open Access Journals (Sweden)

Lan-Rong Dung

2016-01-01

Full Text Available A new battery simulator based on a hybrid model is proposed in this paper for dynamic discharging behavior and runtime predictions in existing electronic simulation environments, e.g., PSIM, so it can help power circuit designers to develop and optimize their battery-powered electronic systems. The hybrid battery model combines a diffusion model and a switching overpotential model, which automatically switches overpotential resistance mode or overpotential voltage mode to accurately describe the voltage difference between battery electro-motive force (EMF and terminal voltage. Therefore, this simulator can simply run in an electronic simulation software with less computational efforts and estimate battery performances by further considering nonlinear capacity effects. A linear extrapolation technique is adopted for extracting model parameters from constant current discharging tests, so the EMF hysteresis problem is avoided. For model validation, experiments and simulations in MATLAB and PSIM environments are conducted with six different profiles, including constant loads, an interrupted load, increasing and decreasing loads and a varying load. The results confirm the usefulness and accuracy of the proposed simulator. The behavior and runtime prediction errors can be as low as 3.1% and 1.2%, respectively.

Design, simulation and characterization of a MEMS inertia switch with flexible CNTs/Cu composite array layer between electrodes for prolonging contact time

International Nuclear Information System (INIS)

Wang, Yang; Yang, Zhuoqing; Xu, Qiu; Chen, Wenguo; Ding, Guifu; Zhao, Xiaolin

2015-01-01

This paper reports an inertia switch with a flexible carbon nanotubes/copper (CNTs/Cu) composite array layer between movable and fixed electrodes, which achieves a longer contact time compared to the traditional design using rigid-to-rigid impact between electrodes. The CNTs/Cu layer is fabricated using the composite electroplating method, and the whole device is completed by multi-layer metal electroplating based on the micro-electro-mechanical systems (MEMS) process. The dynamic responses of the designed inertia switch and the contact impact between a single CNT and a fixed electrode/another CNT have both been simulated by the ANSYS finite-element-method (FEM). It is shown that the contact time of the designed inertia switch is about 100 µs under the applied 80 g half-sine-shaped acceleration in the sensing direction. Finally, the fabricated MEMS inertia switch with the flexible CNTs/Cu composite array layer between electrodes has been evaluated by a dropping hammer system. The test contact time is about112 µs, which has a good agreement with the simulation and is much longer than that of the traditional design. (paper)

Optimization of multi-branch switched diversity systems

KAUST Repository

Nam, Haewoon

2009-10-01

A performance optimization based on the optimal switching threshold(s) for a multi-branch switched diversity system is discussed in this paper. For the conventional multi-branch switched diversity system with a single switching threshold, the optimal switching threshold is a function of both the average channel SNR and the number of diversity branches, where computing the optimal switching threshold is not a simple task when the number of diversity branches is high. The newly proposed multi-branch switched diversity system is based on a sequence of switching thresholds, instead of a single switching threshold, where a different diversity branch uses a different switching threshold for signal comparison. Thanks to the fact that each switching threshold in the sequence can be optimized only based on the number of the remaining diversity branches, the proposed system makes it easy to find these switching thresholds. Furthermore, some selected numerical and simulation results show that the proposed switched diversity system with the sequence of optimal switching thresholds outperforms the conventional system with the single optimal switching threshold. © 2009 IEEE.

Contribution of rivaroxaban to the international normalized ratio when switching to warfarin for anticoagulation as determined by simulation studies.

Science.gov (United States)

Siegmund, Hans-Ulrich; Burghaus, Rolf; Kubitza, Dagmar; Coboeken, Katrin

2015-06-01

This study evaluated the influence of rivaroxaban 20 mg once daily on international normalized ratio (INR) during the co-administration period when switching from rivaroxaban to warfarin. We developed a calibrated coagulation model that was qualified with phase I clinical data. Prothrombin time and INR values were simulated by use of phospholipid concentrations that matched Neoplastin Plus® and Innovin® reagents. To simulate the combined effects of rivaroxaban and warfarin on INR during switching, warfarin initiation was simulated by adjusting the magnitude of the warfarin effect to reach the desired target INRs over the course of 21 days. The warfarin effect values (obtained every 6 h) and the desired rivaroxaban plasma concentrations were used. Nomograms were generated from rivaroxaban induced increases in INR. The simulation had good prediction quality. Rivaroxaban induced increases in the total INR from the warfarin attributed INR were seen, which increased with rivaroxaban plasma concentration. When the warfarin only INR was 2.0-3.0, the INR contribution of rivaroxaban with Neoplastin Plus® was 0.5-1.2, decreasing to 0.3-0.6 with Innovin® at median trough rivaroxaban plasma concentrations (38 μg l(-1) ). The data indicate that measuring warfarin induced changes in INR are best performed at trough rivaroxaban concentrations (24 h after rivaroxaban dosing) during the co-administration period when switching from rivaroxaban to warfarin. Furthermore, Innovin® is preferable to Neoplastin Plus® because of its substantially lower sensitivity to rivaroxaban, thereby reducing the influence of rivaroxaban on the measured INR. © 2014 The British Pharmacological Society.

Switching Operation Simulations in a Large Offshore Wind Farm with Use of Parametric Variation and Frequency Domain Severity Factor

DEFF Research Database (Denmark)

Holdyk, Andrzej; Holbøll, Joachim; Arana, Ivan

2012-01-01

Transient voltages resulting from switching operations depend on an interaction between the breaker, the transformer, cables and a neighbourhood grid and imply a risk for the transformer and other components. In this paper the Frequency Domain Severity Factor (FDSF) is used to assess the severity...... of electrical stress imposed on wind turbine transformers by voltage waveforms produced during switching operations. The method is implemented in Matlab together with automatic and systematic variation of parameters. Simulations of a radial energization are performed on a 90MVA offshore wind farm model...

Generative Models of Conformational Dynamics

Science.gov (United States)

Langmead, Christopher James

2014-01-01

Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term ‘generative’ refers to a model of the joint probability distribution over the behaviors of the constituent atoms. In the context of molecular modeling, generative models reveal the correlation structure between the atoms, and may be used to predict how the system will respond to structural perturbations. We begin by discussing traditional methods, which produce multivariate Gaussian models. We then discuss GAMELAN (GrAphical Models of Energy LANdscapes), which produces generative models of complex, non-Gaussian conformational dynamics (e.g., allostery, binding, folding, etc) from long timescale simulation data. PMID:24446358

Design and advanced control of switched reluctance motor; Design og avanceret styring af switched reluctance motor

Energy Technology Data Exchange (ETDEWEB)

Blaabjerg, F.; Jensen, F.; Kierkegaard, P.; Pedersen, J.K.; Rasmussen, P.O.; Simonsen, L.

1999-03-01

The aim of the project is to design, construct and optimise the control of Switched Reluctance Motors with and without permanent magnets. The expectation was an increased efficiency and a decreased material consumption. The project included originally three types of SR-motors, two with a nominal number of revolutions of 3.000 rpm and one motor with a nominal number of revolutions of 50.000 rpm. The project was changed to focus on one motor with a nominal number of revolutions of 6.000 rpm, one with a nominal number of revolutions of 50.000 rpm and one two-phased low-voltage motor with a nominal number of revolutions of 2.000 rpm. The motors had different outputs of 2,7 kW, 0,9 kW and 3 kW, respectively. For this purpose an advanced simulation programme for Switched Reluctance Motors is developed. The programme differs from other programmes by being able to simulate multi-disciplinary such as vibrations and acoustic noise. It is even possible to play the sound. In this connection completely new models are developed. It is also possible to simulate different grid connected converters. Input to the simulation programme is finite element calculations, geometry of the motor and calculations or data from an advanced characterisation system for Switched Reluctance Motors. New methods to control the current in Switched Reluctance Motors are developed, which particularly make quick dynamics possible in a digitally controlled current without use of special noise filters. The method will soon have industrial use. Other new methods have emerged, which secure that the system all the time works with the maximum efficiency irrespective of load. In some cases an efficiency improvement of 10 % is obtained compared to a classic control of the Switched Reluctance Motor. (EHS) EFP-94; EFP-95; EFP-98. 16 refs.

Switching Phenomena

Science.gov (United States)

Stanley, H. E.; Buldyrev, S. V.; Franzese, G.; Havlin, S.; Mallamace, F.; Mazza, M. G.; Kumar, P.; Plerou, V.; Preis, T.; Stokely, K.; Xu, L.

One challenge of biology, medicine, and economics is that the systems treated by these serious scientific disciplines can suddenly "switch" from one behavior to another, even though they possess no perfect metronome in time. As if by magic, out of nothing but randomness one finds remarkably fine-tuned processes in time. The past century has, philosophically, been concerned with placing aside the human tendency to see the universe as a fine-tuned machine. Here we will address the challenge of uncovering how, through randomness (albeit, as we shall see, strongly correlated randomness), one can arrive at some of the many temporal patterns in physics, economics, and medicine and even begin to characterize the switching phenomena that enable a system to pass from one state to another. We discuss some applications of correlated randomness to understanding switching phenomena in various fields. Specifically, we present evidence from experiments and from computer simulations supporting the hypothesis that water's anomalies are related to a switching point (which is not unlike the "tipping point" immortalized by Malcolm Gladwell), and that the bubbles in economic phenomena that occur on all scales are not "outliers" (another Gladwell immortalization).

Pinning Synchronization of Switched Complex Dynamical Networks

Directory of Open Access Journals (Sweden)

Liming Du

2015-01-01

Full Text Available Network topology and node dynamics play a key role in forming synchronization of complex networks. Unfortunately there is no effective synchronization criterion for pinning synchronization of complex dynamical networks with switching topology. In this paper, pinning synchronization of complex dynamical networks with switching topology is studied. Two basic problems are considered: one is pinning synchronization of switched complex networks under arbitrary switching; the other is pinning synchronization of switched complex networks by design of switching when synchronization cannot achieved by using any individual connection topology alone. For the two problems, common Lyapunov function method and single Lyapunov function method are used respectively, some global synchronization criteria are proposed and the designed switching law is given. Finally, simulation results verify the validity of the results.

Adaptive switching of interaction potentials in the time domain: an extended Lagrangian approach tailored to transmute force field to QM/MM simulations and back.

Science.gov (United States)

Böckmann, Marcus; Doltsinis, Nikos L; Marx, Dominik

2015-06-09

An extended Lagrangian formalism that allows for a smooth transition between two different descriptions of interactions during a molecular dynamics simulation is presented. This time-adaptive method is particularly useful in the context of multiscale simulation as it provides a sound recipe to switch on demand between different hierarchical levels of theory, for instance between ab initio ("QM") and force field ("MM") descriptions of a given (sub)system in the course of a molecular dynamics simulation. The equations of motion can be integrated straightforwardly using the usual propagators, such as the Verlet algorithm. First test cases include a bath of harmonic oscillators, of which a subset is switched to a different force constant and/or equilibrium position, as well as an all-MM to QM/MM transition in a hydrogen-bonded water dimer. The method is then applied to a smectic 8AB8 liquid crystal and is shown to be able to switch dynamically a preselected 8AB8 molecule from an all-MM to a QM/MM description which involves partition boundaries through covalent bonds. These examples show that the extended Lagrangian approach is not only easy to implement into existing code but that it is also efficient and robust. The technique moreover provides easy access to a conserved energy quantity, also in cases when Nosé-Hoover chain thermostatting is used throughout dynamical switching. A simple quadratic driving potential proves to be sufficient to guarantee a smooth transition whose time scale can be easily tuned by varying the fictitious mass parameter associated with the auxiliary variable used to extend the Lagrangian. The method is general and can be applied to time-adaptive switching on demand between two different levels of theory within the framework of hybrid scale-bridging simulations.

Conformational study of bovine lactoferricin in membrane-micking conditions by molecular dynamics simulation and circular dichroism.

Science.gov (United States)

Daidone, Isabella; Magliano, Alessandro; Di Nola, Alfredo; Mignogna, Giuseppina; Clarkson, Matilda Manuela; Lizzi, Anna Rita; Oratore, Arduino; Mazza, Fernando

2011-04-01

Lactoferricins are potent antimicrobial peptides released by pepsin cleavage of Lactoferrins. Bovine Lactoferricin (LfcinB) has higher activity than the intact bovine Lactoferrin, and is the most active among the other Lactoferricins of human, murine and caprine origin. In the intact protein the fragment corresponding to LfcinB is in an helical conformation, while in water LfcinB adopts an amphipathic β-hairpin structure. However, whether any of these structural motifs is the antibacterial active conformation, i.e., the one interacting with bacterial membrane components, remains to be seen. Here we present Circular Dichroism (CD) spectra and Molecular Dynamics (MD) simulations indicating that in membrane-mimicking solvents the LfcinB adopts an amphipathic β-hairpin structure similar to that observed in water, but differing in the dynamic behavior of the side-chains of the two tryptophan residues. In the membrane-mimicking solvent these side-chains show a high propensity to point towards the hydrophobic environment, rather than being in the hydrophobic core as seen in water, while the backbone preserves the hairpin conformation as found in water. These results suggest that the tryptophans might act as anchors pulling the stable, solvent-invariant hairpin structure into the membrane.

Models of charge transport and transfer in molecular switch tunnel junctions of bistable catenanes and rotaxanes

International Nuclear Information System (INIS)

Flood, Amar H.; Wong, Eric W.; Stoddart, J. Fraser

2006-01-01

The processes by which charge transfer can occur play a foundational role in molecular electronics. Here we consider simplified models of the transfer processes that could be present in bistable molecular switch tunnel junction (MSTJ) devices during one complete cycle of the device from its low- to high- and back to low-conductance state. The bistable molecular switches, which are composed of a monolayer of either switchable catenanes or rotaxanes, exist in either a ground-state co-conformation or a metastable one in which the conduction properties of the two co-conformations, when measured at small biases (+0.1 V), are significantly different irrespective of whether transport is dominated by tunneling or hopping. The voltage-driven generation (±2 V) of molecule-based redox states, which are sufficiently long-lived to allow the relative mechanical movements necessary to switch between the two co-conformations, rely upon unequal charge transfer rates on to and/or off of the molecules. Surface-enhanced Raman spectroscopy has been used to image the ground state of the bistable rotaxane in MSTJ-like devices. Consideration of these models provide new ways of looking at molecular electronic devices that rely, not only on nanoscale charge-transport, but also upon the bustling world of molecular motion in mechanically interlocked bistable molecules

Study of simulations q-switching and mode-locking in Nd:YVO4 laser with Cr4+:YAG crystal

International Nuclear Information System (INIS)

Al-Sous, M. B.

2007-12-01

A numerical model of rate equations for a four-level solid-state laser with Cr 4+ :YAG saturable absorber including excited state absorption ESA is presented. The cavity is divided into a large number of disks and the model is solved for each disk and its local corresponding photon flux. The flux array is shifted for each recurrence simulating the movement of photons inside the cavity during the round trip. This simulator can describe the mode locking phenomenon and can be used to simulate the simultaneous mode locking and Q-switching with a saturable absorber.(author)

Thermodynamics of the GTP-GDP-operated conformational switch of selenocysteine-specific translation factor SelB.

Science.gov (United States)

Paleskava, Alena; Konevega, Andrey L; Rodnina, Marina V

2012-08-10

SelB is a specialized translation factor that binds GTP and GDP and delivers selenocysteyl-tRNA (Sec-tRNA(Sec)) to the ribosome. By analogy to elongation factor Tu (EF-Tu), SelB is expected to control the delivery and release of Sec-tRNA(Sec) to the ribosome by the structural switch between GTP- and GDP-bound conformations. However, crystal structures of SelB suggested a similar domain arrangement in the apo form and GDP- and GTP-bound forms of the factor, raising the question of how SelB can fulfill its delivery function. Here, we studied the thermodynamics of guanine nucleotide binding to SelB by isothermal titration calorimetry in the temperature range between 10 and 25 °C using GTP, GDP, and two nonhydrolyzable GTP analogs, guanosine 5'-O-(γ-thio)triphosphate (GTPγS) and guanosine 5'-(β,γ-imido)-triphosphate (GDPNP). The binding of SelB to either guanine nucleotide is characterized by a large heat capacity change (-621, -467, -235, and -275 cal × mol(-1) × K(-1), with GTP, GTPγS, GDPNP, and GDP, respectively), associated with compensatory changes in binding entropy and enthalpy. Changes in heat capacity indicate a large decrease of the solvent-accessible surface area in SelB, amounting to 43 or 32 amino acids buried upon binding of GTP or GTPγS, respectively, and 15-19 amino acids upon binding GDP or GDPNP. The similarity of the GTP and GDP forms in the crystal structures can be attributed to the use of GDPNP, which appears to induce a structure of SelB that is more similar to the GDP than to the GTP-bound form.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.

Science.gov (United States)

Ye, Qiaozhen; Rosenberg, Scott C; Moeller, Arne; Speir, Jeffrey A; Su, Tiffany Y; Corbett, Kevin D

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

Energy Technology Data Exchange (ETDEWEB)

Ye, Qiaozhen [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Rosenberg, Scott C. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Moeller, Arne [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Speir, Jeffrey A. [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Su, Tiffany Y. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Corbett, Kevin D. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

Multistage switching hardware and software implementations for student experiment purpose

Science.gov (United States)

Sani, A.; Suherman

2018-02-01

Current communication and internet networks are underpinned by the switching technologies that interconnect one network to the others. Students’ understanding on networks rely on how they conver the theories. However, understanding theories without touching the reality may exert spots in the overall knowledge. This paper reports the progress of the multistage switching design and implementation for student laboratory activities. The hardware and software designs are based on three stages clos switching architecture with modular 2x2 switches, controlled by an arduino microcontroller. The designed modules can also be extended for batcher and bayan switch, and working on circuit and packet switching systems. The circuit analysis and simulation show that the blocking probability for each switch combinations can be obtained by generating random or patterned traffics. The mathematic model and simulation analysis shows 16.4% blocking probability differences as the traffic generation is uniform. The circuits design components and interfacing solution have been identified to allow next step implementation.

Multilevel inverter switching controller using a field programmable ...

African Journals Online (AJOL)

Conducted simulation and measurement results verified and validated the switching controller design functionality and requirement. Keywords: multilevel inverter, switching controller; FPGA, general purpose processor (GPP);digital signal processing (DSP); IGBT; Verilog, power consumption; harmonic elimination (SHE).

Verifying different-modality properties for concepts produces switching costs.

Science.gov (United States)

Pecher, Diane; Zeelenberg, René; Barsalou, Lawrence W

2003-03-01

According to perceptual symbol systems, sensorimotor simulations underlie the representation of concepts. It follows that sensorimotor phenomena should arise in conceptual processing. Previous studies have shown that switching from one modality to another during perceptual processing incurs a processing cost. If perceptual simulation underlies conceptual processing, then verifying the properties of concepts should exhibit a switching cost as well. For example, verifying a property in the auditory modality (e.g., BLENDER-loud) should be slower after verifying a property in a different modality (e.g., CRANBERRIES-tart) than after verifying a property in the same modality (e.g., LEAVES-rustling). Only words were presented to subjects, and there were no instructions to use imagery. Nevertheless, switching modalities incurred a cost, analogous to the cost of switching modalities in perception. A second experiment showed that this effect was not due to associative priming between properties in the same modality. These results support the hypothesis that perceptual simulation underlies conceptual processing.

Selection of conformational states in self-assembled surface structures formed from an oligo(naphthylene-ethynylene) 3-bit binary switch

DEFF Research Database (Denmark)

Ning, Yanxiao; Cramer, Jacob Roland; Nuermaimaiti, Ajiguli

2015-01-01

). The conformations result from binary positions of n = 3 naphtalene units on a linear oligo(naphthylene-ethynylene) backbone. On Au(111), inter-molecular interactions involving carboxyl and bulky tert-butyl-phenyl functional groups induce the molecules to form two ordered phases with brick-wall and lamella structure...... conformational states. Together these observations imply selection and adaptation of conformational states upon molecular self-assembly. From DFT modeling and statistical analysis of the molecular conformations, the observed selection of conformational states is attributed to steric interaction between...

Non-fragile switched H∞ control for morphing aircraft with asynchronous switching

Directory of Open Access Journals (Sweden)

Haoyu CHENG

2017-06-01

Full Text Available This paper deals with the problem of non-fragile linear parameter-varying (LPV H∞ control for morphing aircraft with asynchronous switching. The switched LPV model of morphing aircraft is established by Jacobian linearization approach according to the nonlinear model. The data missing is taken into account in the link from sensors to controllers and the link from controllers to actuators, which satisfies Bernoulli distribution. The non-fragile switched LPV controllers are constructed with consideration of the uncertainties of controllers and asynchronous switching phenomenon. The parameter-dependent Lyapunov functional method and mode-dependent average dwell time (MDADT method are combined to guarantee the stability and prescribed performance of the system. The sufficient conditions on the solvability of the problem are derived in the form of linear matrix inequalities (LMI. In order to achieve higher efficiency of the designing process, an algorithm is applied to divide the whole set into subsets automatically. Simulation results are provided to verify the effectiveness and superiority of the method in the paper.

Effect of Chain Conformation on the Single-Molecule Melting Force in Polymer Single Crystals: Steered Molecular Dynamics Simulations Study.

Science.gov (United States)

Feng, Wei; Wang, Zhigang; Zhang, Wenke

2017-02-28

Understanding the relationship between polymer chain conformation as well as the chain composition within the single crystal and the mechanical properties of the corresponding single polymer chain will facilitate the rational design of high performance polymer materials. Here three model systems of polymer single crystals, namely poly(ethylene oxide) (PEO), polyethylene (PE), and nylon-66 (PA66) have been chosen to study the effects of chain conformation, helical (PEO) versus planar zigzag conformation (PE, PA66), and chain composition (PE versus PA66) on the mechanical properties of a single polymer chain. To do that, steered molecular dynamics simulations were performed on those polymer single crystals by pulling individual polymer chains out of the crystals. Our results show that the patterns of force-extension curve as well as the chain moving mode are closely related to the conformation of the polymer chain in the single crystal. In addition, hydrogen bonds can enhance greatly the force required to stretch the polymer chain out of the single crystal. The dynamic breaking and reformation of multivalent hydrogen bonds have been observed for the first time in PA66 at the single molecule level.

Synchronization in complex networks with switching topology

International Nuclear Information System (INIS)

Wang, Lei; Wang, Qing-guo

2011-01-01

This Letter investigates synchronization issues of complex dynamical networks with switching topology. By constructing a common Lyapunov function, we show that local and global synchronization for a linearly coupled network with switching topology can be evaluated by the time average of second smallest eigenvalues corresponding to the Laplacians of switching topology. This result is quite powerful and can be further used to explore various switching cases for complex dynamical networks. Numerical simulations illustrate the effectiveness of the obtained results in the end. -- Highlights: → Synchronization of complex networks with switching topology is investigated. → A common Lyapunov function is established for synchronization of switching network. → The common Lyapunov function is not necessary to monotonically decrease with time. → Synchronization is determined by the second smallest eigenvalue of its Laplacian. → Synchronization criterion can be used to investigate various switching cases.

Insight into the molecular switch mechanism of human Rab5a from molecular dynamics simulations

Energy Technology Data Exchange (ETDEWEB)

Wang, Jing-Fang, E-mail: jfwang@gordonlifescience.org [Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shanghai Center for Bioinformation Technology, 100 Qinzhou Road, Shanghai 200235 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States); Chou, Kuo-Chen [Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States)

2009-12-18

Rab5a is currently a most interesting target because it is responsible for regulating the early endosome fusion in endocytosis and possibly the budding process. We utilized longtime-scale molecular dynamics simulations to investigate the internal motion of the wild-type Rab5a and its A30P mutant. It was observed that, after binding with GTP, the global flexibility of the two proteins is increasing, while the local flexibility in their sensitive sites (P-loop, switch I and II regions) is decreasing. Also, the mutation of Ala30 to Pro30 can cause notable flexibility variations in the sensitive sites. However, this kind of variations is dramatically reduced after binding with GTP. Such a remarkable feature is mainly caused by the water network rearrangements in the sensitive sites. These findings might be of use for revealing the profound mechanism of the displacements of Rab5a switch regions, as well as the mechanism of the GDP dissociation and GTP association.

Generative Models of Conformational Dynamics

OpenAIRE

Langmead, Christopher James

2014-01-01

Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term ‘generative’ refers to a...

Conformal Nets II: Conformal Blocks

Science.gov (United States)

Bartels, Arthur; Douglas, Christopher L.; Henriques, André

2017-08-01

Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

Synthesis of Conformal Phased Antenna Arrays With A Novel Multiobjective Invasive Weed Optimization Algorithm

Science.gov (United States)

Li, Wen Tao; Hei, Yong Qiang; Shi, Xiao Wei

2018-04-01

By virtue of the excellent aerodynamic performances, conformal phased arrays have been attracting considerable attention. However, for the synthesis of patterns with low/ultra-low sidelobes of the conventional conformal arrays, the obtained dynamic range ratios of amplitude excitations could be quite high, which results in stringent requirements on various error tolerances for practical implementation. Time-modulated array (TMA) has the advantages of low sidelobe and reduced dynamic range ratio requirement of amplitude excitations. This paper takes full advantages of conformal antenna arrays and time-modulated arrays. The active-element-pattern, including element mutual coupling and platform effects, is employed in the whole design process. To optimize the pulse durations and the switch-on instants of the time-modulated elements, multiobjective invasive weed optimization (MOIWO) algorithm based on the nondominated sorting of the solutions is proposed. A S-band 8-element cylindrical conformal array is designed and a S-band 16-element cylindrical-parabolic conformal array is constructed and tested at two different steering angles.

Simulation of medical Q-switch flash-pumped Er:YAG laser

Energy Technology Data Exchange (ETDEWEB)

Wang Yanlin; Huang Chuyun; Yao Yucheng; Zou Xiaolin, E-mail: Wangyanlin0@126.com, E-mail: chuyunh@163.com, E-mail: yyuch@soho.com, E-mail: zouxiaol@126.com [Physics school, Hubei University of Technology, Wuhan, China 430068 (China)

2011-01-01

Er: YAG laser, the wavelength is 2940nm, can be absorbed strongly by water. The absorption coefficient is as high as 13000 cm{sup -1}. As the water strong absorption, Erbium laser can bring shallow penetration depth and smaller surrounding tissue injury in most soft tissue and hard tissue. At the same time, the interaction between 2940nm radiation and biological tissue saturated with water is equivalent to instantaneous heating within limited volume, thus resulting in the phenomenon of micro-explosion to removal organization. Different parameters can be set up to cut enamel, dentin, caries and soft tissue. For the development and optimization of laser system, it is a practical choice to use laser modeling to predict the influence of various parameters for laser performance. Aim at the status of low Erbium laser output power, flash-pumped Er: YAG laser performance was simulated to obtain optical output in theory. the rate equation model was obtained and used to predict the change of population densities in various manifolds and use the technology of Q-switch the simulate laser output for different design parameters and results showed that Er: YAG laser output energy can achieve the maximum average output power of 9.8W under the given parameters. The model can be used to find the potential laser systems that meet application requirements.

Manufacture of Radio Frequency Micromachined Switches with Annealing

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Cheng-Yang Lin

2014-01-01

Full Text Available The fabrication and characterization of a radio frequency (RF micromachined switch with annealing were presented. The structure of the RF switch consists of a membrane, coplanar waveguide (CPW lines, and eight springs. The RF switch is manufactured using the complementary metal oxide semiconductor (CMOS process. The switch requires a post-process to release the membrane and springs. The post-process uses a wet etching to remove the sacrificial silicon dioxide layer, and to obtain the suspended structures of the switch. In order to improve the residual stress of the switch, an annealing process is applied to the switch, and the membrane obtains an excellent flatness. The finite element method (FEM software CoventorWare is utilized to simulate the stress and displacement of the RF switch. Experimental results show that the RF switch has an insertion loss of 0.9 dB at 35 GHz and an isolation of 21 dB at 39 GHz. The actuation voltage of the switch is 14 V.

Manufacture of radio frequency micromachined switches with annealing.

Science.gov (United States)

Lin, Cheng-Yang; Dai, Ching-Liang

2014-01-17

The fabrication and characterization of a radio frequency (RF) micromachined switch with annealing were presented. The structure of the RF switch consists of a membrane, coplanar waveguide (CPW) lines, and eight springs. The RF switch is manufactured using the complementary metal oxide semiconductor (CMOS) process. The switch requires a post-process to release the membrane and springs. The post-process uses a wet etching to remove the sacrificial silicon dioxide layer, and to obtain the suspended structures of the switch. In order to improve the residual stress of the switch, an annealing process is applied to the switch, and the membrane obtains an excellent flatness. The finite element method (FEM) software CoventorWare is utilized to simulate the stress and displacement of the RF switch. Experimental results show that the RF switch has an insertion loss of 0.9 dB at 35 GHz and an isolation of 21 dB at 39 GHz. The actuation voltage of the switch is 14 V.

Dissecting the large-scale galactic conformity

Science.gov (United States)

Seo, Seongu

2018-01-01

Galactic conformity is an observed phenomenon that galaxies located in the same region have similar properties such as star formation rate, color, gas fraction, and so on. The conformity was first observed among galaxies within in the same halos (“one-halo conformity”). The one-halo conformity can be readily explained by mutual interactions among galaxies within a halo. Recent observations however further witnessed a puzzling connection among galaxies with no direct interaction. In particular, galaxies located within a sphere of ~5 Mpc radius tend to show similarities, even though the galaxies do not share common halos with each other ("two-halo conformity" or “large-scale conformity”). Using a cosmological hydrodynamic simulation, Illustris, we investigate the physical origin of the two-halo conformity and put forward two scenarios. First, back-splash galaxies are likely responsible for the large-scale conformity. They have evolved into red galaxies due to ram-pressure stripping in a given galaxy cluster and happen to reside now within a ~5 Mpc sphere. Second, galaxies in strong tidal field induced by large-scale structure also seem to give rise to the large-scale conformity. The strong tides suppress star formation in the galaxies. We discuss the importance of the large-scale conformity in the context of galaxy evolution.

Insight the C-site pocket conformational changes responsible for sirtuin 2 activity using molecular dynamics simulations.

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Sugunadevi Sakkiah

Full Text Available Sirtuin belongs to a family of typical histone deacetylase which regulates the fundamental cellular biological processes including gene expression, genome stability, mitosis, nutrient metabolism, aging, mitochondrial function, and cell motility. Michael et. al. reported that B-site mutation (Q167A and H187A decreased the SIRT2 activity but still the structural changes were not reported. Hence, we performed 5 ns molecular dynamics (MD simulation on SIRT2 Apo-form and complexes with substrate/NAD(+ and inhibitor of wild type (WT, Q167A, and H187A. The results revealed that the assembly and disassembly of C-site induced by presence of substrate/NAD(+ and inhibitor, respectively. This assembly and disassembly was mainly due to the interaction between the substrate/NAD(+ and inhibitor and F96 and the distance between F96 and H187 which are present at the neck of the C-site. MD simulations suggest that the conformational change of L3 plays a major role in assembly and disassembly of C-site. Our current results strongly suggest that the distinct conformational change of L3 as well as the assembly and disassembly of C-site plays an important role in SIRT2 deacetylation function. Our study unveiled the structural changes of SIRT2 in presence of NAD(+ and inhibitor which should be helpful to improve the inhibitory potency of SIRT2.

A Broadband Ultrathin Nonlinear Switching Metamaterial

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E. Zarnousheh Farahani

2017-05-01

Full Text Available In this paper, an ultrathin planar nonlinear metamaterial slab is designed and simulated. Nonlinearity is provided through placing diodes in each metamaterial unit cell. The diodes are auto-biased and activated by an incident wave. The proposed structure represents a broadband switching property between two transmission and reflection states depending on the intensity of the incident wave. High permittivity values are presented creating a near zero effective impedance at low power states, around the second resonant mode of the structure unit cell; as the result, the incident wave is reflected. Increasing the incident power to the level which can activate the loaded diodes in the structure results in elimination of the resonance and consequently a drop in the permittivity values near the permeability one as well as a switch to the transmission state. A full wave as well as a nonlinear simulations are performed. An optimization method based on weed colonization is applied to the unit cell of the metamaterial slab to achieve the maximum switching bandwidth. The structure represents a 24% switching bandwidth of a 10 dB reduction in the reflection coefficient.

Conformation analysis of trehalose. Molecular dynamics simulation and molecular mechanics

International Nuclear Information System (INIS)

Donnamaira, M.C.; Howard, E.I.; Grigera, J.R.

1992-09-01

Conformational analysis of the disaccharide trehalose is done by molecular dynamics and molecular mechanics. In spite of the different force fields used in each case, comparison between the molecular dynamics trajectories of the torsional angles of glycosidic linkage and energy conformational map shows a good agreement between both methods. By molecular dynamics it is observed a moderate mobility of the glycosidic linkage. The demands of computer time is comparable in both cases. (author). 6 refs, 4 figs

Increased conformity offers diminishing returns for reducing total knee replacement wear.

Science.gov (United States)

Fregly, Benjamin J; Marquez-Barrientos, Carlos; Banks, Scott A; DesJardins, John D

2010-02-01

Wear remains a significant problem limiting the lifespan of total knee replacements (TKRs). Though increased conformity between TKR components has the potential to decrease wear, the optimal amount and planes of conformity have not been investigated. Furthermore, differing conformities in the medial and lateral compartments may provide designers the opportunity to address both wear and kinematic design goals simultaneously. This study used a computational model of a Stanmore knee simulator machine and a previously validated wear model to investigate this issue for simulated gait. TKR geometries with different amounts and planes of conformity on the medial and lateral sides were created and tested in two phases. The first phase utilized a wide range of sagittal and coronal conformity combinations to blanket a physically realistic design space. The second phase performed a focused investigation of the conformity conditions from the first phase to which predicted wear volume was sensitive. For the first phase, sagittal but not coronal conformity was found to have a significant effect on predicted wear volume. For the second phase, increased sagittal conformity was found to decrease predicted wear volume in a nonlinear fashion, with reductions gradually diminishing as conformity increased. These results suggest that TKR geometric design efforts aimed at minimizing wear should focus on sagittal rather than coronal conformity and that at least moderate sagittal conformity is desirable in both compartments.

Analysis of Switched-Rigid Floating Oscillator

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Prabhakar R. Marur

2009-01-01

Full Text Available In explicit finite element simulations, a technique called deformable-to-rigid (D2R switching is used routinely to reduce the computation time. Using the D2R option, the deformable parts in the model can be switched to rigid and reverted back to deformable when needed during the analysis. The time of activation of D2R however influences the overall dynamics of the system being analyzed. In this paper, a theoretical basis for the selection of time of rigid switching based on system energy is established. A floating oscillator problem is investigated for this purpose and closed-form analytical expressions are derived for different phases in rigid switching. The analytical expressions are validated by comparing the theoretical results with numerical computations.

Conformal displays: human factor analysis of innovative landing aids

Science.gov (United States)

Schmerwitz, Sven; Lueken, Thomas; Doehler, Hans-Ullrich; Peinecke, Niklas; Ernst, Johannes M.; da Silva Rosa, David L.

2017-05-01

In the past couple of years, research on display content for helicopter operations headed in a new direction. The already reached goals could evolve into a paradigm change for information visualization. Technology advancements allow implementing three-dimensional and conformal content on a helmet-mounted see-through device. This superimposed imagery inherits the same optical flow as the environment. It is supposed to ease switching between display information and environmental cues. The concept is neither pathbreaking nor new, but it has not been successfully established in aviation yet. Nevertheless, there are certainly some advantages to expect-at least from perspective of a human-centered system design. Within the following pages, the next generation displays will be presented and discussed with a focus on human factors. Beginning with recalling some human factor related research facts, an experiment comparing the former two-dimensional research displays will be presented. Before introducing the DLR conformal symbol set and the three experiments about an innovative drift, indication related research activities toward conformal symbol sets will be addressed.

Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

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Joseph L Baker

2013-04-01

Full Text Available Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon

Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

Science.gov (United States)

Baker, Joseph L; Biais, Nicolas; Tama, Florence

2013-04-01

Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P) from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD) simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon stretching.

Wireless Chalcogenide Nanoionic-Based Radio-Frequency Switch

Science.gov (United States)

Nessel, James; Miranda, Felix

2013-01-01

A new nonvolatile nanoionic switch is powered and controlled through wireless radio-frequency (RF) transmission. A thin layer of chalcogenide glass doped with a metal ion, such as silver, comprises the operational portion of the switch. For the switch to function, an oxidizable electrode is made positive (anode) with respect to an opposing electrode (cathode) when sufficient bias, typically on the order of a few tenths of a volt or more, is applied. This action causes the metal ions to flow toward the cathode through a coordinated hopping mechanism. At the cathode, a reduction reaction occurs to form a metal deposit. This metal deposit creates a conductive path that bridges the gap between electrodes to turn the switch on. Once this conductive path is formed, no further power is required to maintain it. To reverse this process, the metal deposit is made positive with respect to the original oxidizable electrode, causing the dissolution of the metal bridge thereby turning the switch off. Once the metal deposit has been completely dissolved, the process self-terminates. This switching process features the following attributes. It requires very little to change states (i.e., on and off). Furthermore, no power is required to maintain the states; hence, the state of the switch is nonvolatile. Because of these attributes the integration of a rectenna to provide the necessary power and control is unique to this embodiment. A rectenna, or rectifying antenna, generates DC power from an incident RF signal. The low voltages and power required for the nanoionic switch control are easily generated from this system and provide the switch with a novel capability to be operated and powered from an external wireless device. In one realization, an RF signal of a specific frequency can be used to set the switch into an off state, while another frequency can be used to set the switch to an on state. The wireless, miniaturized, and nomoving- part features of this switch make it

Complete achromatic and robustness electro-optic switch between two integrated optical waveguides

Science.gov (United States)

Huang, Wei; Kyoseva, Elica

2018-01-01

In this paper, we present a novel design of electro-optic modulator and optical switching device, based on current integrated optics technique. The advantages of our optical switching device are broadband of input light wavelength, robustness against varying device length and operation voltages, with reference to previous design. Conforming to our results of previous paper [Huang et al, phys. lett. a, 90, 053837], the coupling of the waveguides has a hyperbolic-secant shape. while detuning has a sign flip at maximum coupling, we called it as with a sign flip of phase mismatch model. The a sign flip of phase mismatch model can produce complete robust population transfer. In this paper, we enhance this device to switch light intensity controllable, by tuning external electric field based on electro-optic effect.

On the Role of the SP1 Domain in HIV-1 Particle Assembly: a Molecular Switch?▿

Science.gov (United States)

Datta, Siddhartha A. K.; Temeselew, Lakew G.; Crist, Rachael M.; Soheilian, Ferri; Kamata, Anne; Mirro, Jane; Harvin, Demetria; Nagashima, Kunio; Cachau, Raul E.; Rein, Alan

2011-01-01

Expression of a retroviral protein, Gag, in mammalian cells is sufficient for assembly of immature virus-like particles (VLPs). VLP assembly is mediated largely by interactions between the capsid (CA) domains of Gag molecules but is facilitated by binding of the nucleocapsid (NC) domain to nucleic acid. We have investigated the role of SP1, a spacer between CA and NC in HIV-1 Gag, in VLP assembly. Mutational analysis showed that even subtle changes in the first 4 residues of SP1 destroy the ability of Gag to assemble correctly, frequently leading to formation of tubes or other misassembled structures rather than proper VLPs. We also studied the conformation of the CA-SP1 junction region in solution, using both molecular dynamics simulations and circular dichroism. Consonant with nuclear magnetic resonance (NMR) studies from other laboratories, we found that SP1 is nearly unstructured in aqueous solution but undergoes a concerted change to an α-helical conformation when the polarity of the environment is reduced by addition of dimethyl sulfoxide (DMSO), trifluoroethanol, or ethanol. Remarkably, such a coil-to-helix transition is also recapitulated in an aqueous medium at high peptide concentrations. The exquisite sensitivity of SP1 to mutational changes and its ability to undergo a concentration-dependent structural transition raise the possibility that SP1 could act as a molecular switch to prime HIV-1 Gag for VLP assembly. We suggest that changes in the local environment of SP1 when Gag oligomerizes on nucleic acid might trigger this switch. PMID:21325421

A reduced switch count UPF power conditioner for grid connected variable speed wind energy conversion system employing PM generators: a simulation study

Energy Technology Data Exchange (ETDEWEB)

Raju, A.B.; Fernandes, B.G.; Chatterjee, K. [Indian Institute of Technology, Mumbai (India). Dept. of Electrical Engineering

2004-07-01

In this paper, modelling and simulation of a grid connected variable speed wind energy conversion system (VSWECS) with reduced switch count power converter is presented. The system consists of a permanent magnet synchronous generator (PMSG), two-pulse width modulated B-4 power converters and a maximum power point tracker (MPPT). Mathematical models of each element of the system are developed separately and are then integrated to simulate the whole system for various wind velocities. The complete system is simulated using MATLAB/SIMULINK and simulation results are presented. (author)

A Novel Silicon-based Wideband RF Nano Switch Matrix Cell and the Fabrication of RF Nano Switch Structures

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Yi Xiu YANG

2011-12-01

Full Text Available This paper presents the concept of RF nano switch matrix cell and the fabrication of RF nano switch. The nano switch matrix cell can be implemented into complex switch matrix for signal routing. RF nano switch is the decision unit for the matrix cell; in this research, it is fabricated on a tri-layer high-resistivity-silicon substrate using surface micromachining approach. Electron beam lithography is introduced to define the pattern and IC compatible deposition process is used to construct the metal layers. Silicon-based nano switch fabricated by IC compatible process can lead to a high potential of system integration to perform a cost effective system-on-a-chip solution. In this paper, simulation results of the designed matrix cell are presented; followed by the details of the nano structure fabrication and fabrication challenges optimizations; finally, measurements of the fabricated nano structure along with analytical discussions are also discussed.

Computer simulation of the behaviour of Julia sets using switching processes

Energy Technology Data Exchange (ETDEWEB)

Negi, Ashish [Department of Computer Science and Engineering, G.B. Pant Engineering College, Pauri Garhwal 246001 (India)], E-mail: ashish_ne@yahoo.com; Rani, Mamta [Department of Computer Science, Galgotia College of Engineering and Technology, UP Technical University, Knowledge Park-II, Greater Noida, Gautam Buddha Nagar, UP (India)], E-mail: vedicmri@sancharnet.in; Mahanti, P.K. [Department of CSAS, University of New Brunswick, Saint Johhn, New Brunswick, E2L4L5 (Canada)], E-mail: pmahanti@unbsj.ca

2008-08-15

Inspired by the study of Julia sets using switched processes by Lakhtakia and generation of new fractals by composite functions by Shirriff, we study the effect of switched processes on superior Julia sets given by Rani and Kumar. Further, symmetry for such processes is also discussed in the paper.

Computer simulation of the behaviour of Julia sets using switching processes

International Nuclear Information System (INIS)

Negi, Ashish; Rani, Mamta; Mahanti, P.K.

2008-01-01

Inspired by the study of Julia sets using switched processes by Lakhtakia and generation of new fractals by composite functions by Shirriff, we study the effect of switched processes on superior Julia sets given by Rani and Kumar. Further, symmetry for such processes is also discussed in the paper

Two-Dimensional Simulation of Mass Transfer in Unitized Regenerative Fuel Cells under Operation Mode Switching

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Lulu Wang

2016-01-01

Full Text Available A two-dimensional, single-phase, isothermal, multicomponent, transient model is built to investigate the transport phenomena in unitized regenerative fuel cells (URFCs under the condition of switching from the fuel cell (FC mode to the water electrolysis (WE mode. The model is coupled with an electrochemical reaction. The proton exchange membrane (PEM is selected as the solid electrolyte of the URFC. The work is motivated by the need to elucidate the complex mass transfer and electrochemical process under operation mode switching in order to improve the performance of PEM URFC. A set of governing equations, including conservation of mass, momentum, species, and charge, are considered. These equations are solved by the finite element method. The simulation results indicate the distributions of hydrogen, oxygen, water mass fraction, and electrolyte potential response to the transient phenomena via saltation under operation mode switching. The hydrogen mass fraction gradients are smaller than the oxygen mass fraction gradients. The average mass fractions of the reactants (oxygen and hydrogen and product (water exhibit evident differences between each layer in the steady state of the FC mode. By contrast, the average mass fractions of the reactant (water and products (oxygen and hydrogen exhibit only slight differences between each layer in the steady state of the WE mode. Under either the FC mode or the WE mode, the duration of the transient state is only approximately 0.2 s.

Compact conformations of human protein disulfide isomerase.

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Shang Yang

Full Text Available Protein disulfide isomerase (PDI composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact.

Fluctuation Flooding Method (FFM) for accelerating conformational transitions of proteins

Science.gov (United States)

Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

2014-03-01

A powerful conformational sampling method for accelerating structural transitions of proteins, "Fluctuation Flooding Method (FFM)," is proposed. In FFM, cycles of the following steps enhance the transitions: (i) extractions of largely fluctuating snapshots along anisotropic modes obtained from trajectories of multiple independent molecular dynamics (MD) simulations and (ii) conformational re-sampling of the snapshots via re-generations of initial velocities when re-starting MD simulations. In an application to bacteriophage T4 lysozyme, FFM successfully accelerated the open-closed transition with the 6 ns simulation starting solely from the open state, although the 1-μs canonical MD simulation failed to sample such a rare event.

Research on the Inductance/Capacitance Switch Model for an LCC-HVDC Converter in an AC/DC Hybrid Grid

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Yangyang He

2018-03-01

Full Text Available In order to improve the simulation speed of the AC/DC hybrid grid, the inductance/capacitance (L/C switch model for line-commutated converter of high-voltage direct current (LCC-HVDC is presented in this study. The time domain modeling method is used to analyze the circuit of L/C switch model for the six-pulse system in LCC-HVDC in a switching period. A parameter setting method of L/C switch model is proposed considering the transient response, the steady state performance, switching losses and simulation error of the switch. The inductance/capacitance (L/C switch model for LCC-HVDC has the advantage of keeping the admittance matrix unchanged regardless of the change of switching state, which improves the simulation efficiency. Finally, the validity of the parameter setting method is verified. Compared with the test results of PSCAD/EMTDC, the accuracy of the proposed LCC-HVDC simulation model is proved. The model is suitable for real-time or offline simulation of AC/DC hybrid grid.

Delayed switching applied to memristor neural networks

Energy Technology Data Exchange (ETDEWEB)

Wang, Frank Z.; Yang Xiao; Lim Guan [Future Computing Group, School of Computing, University of Kent, Canterbury (United Kingdom); Helian Na [School of Computer Science, University of Hertfordshire, Hatfield (United Kingdom); Wu Sining [Xyratex, Havant (United Kingdom); Guo Yike [Department of Computing, Imperial College, London (United Kingdom); Rashid, Md Mamunur [CERN, Geneva (Switzerland)

2012-04-01

Magnetic flux and electric charge are linked in a memristor. We reported recently that a memristor has a peculiar effect in which the switching takes place with a time delay because a memristor possesses a certain inertia. This effect was named the ''delayed switching effect.'' In this work, we elaborate on the importance of delayed switching in a brain-like computer using memristor neural networks. The effect is used to control the switching of a memristor synapse between two neurons that fire together (the Hebbian rule). A theoretical formula is found, and the design is verified by a simulation. We have also built an experimental setup consisting of electronic memristive synapses and electronic neurons.

Delayed switching applied to memristor neural networks

International Nuclear Information System (INIS)

Wang, Frank Z.; Yang Xiao; Lim Guan; Helian Na; Wu Sining; Guo Yike; Rashid, Md Mamunur

2012-01-01

Magnetic flux and electric charge are linked in a memristor. We reported recently that a memristor has a peculiar effect in which the switching takes place with a time delay because a memristor possesses a certain inertia. This effect was named the ''delayed switching effect.'' In this work, we elaborate on the importance of delayed switching in a brain-like computer using memristor neural networks. The effect is used to control the switching of a memristor synapse between two neurons that fire together (the Hebbian rule). A theoretical formula is found, and the design is verified by a simulation. We have also built an experimental setup consisting of electronic memristive synapses and electronic neurons.

Average contraction and synchronization of complex switched networks

International Nuclear Information System (INIS)

Wang Lei; Wang Qingguo

2012-01-01

This paper introduces an average contraction analysis for nonlinear switched systems and applies it to investigating the synchronization of complex networks of coupled systems with switching topology. For a general nonlinear system with a time-dependent switching law, a basic convergence result is presented according to average contraction analysis, and a special case where trajectories of a distributed switched system converge to a linear subspace is then investigated. Synchronization is viewed as the special case with all trajectories approaching the synchronization manifold, and is thus studied for complex networks of coupled oscillators with switching topology. It is shown that the synchronization of a complex switched network can be evaluated by the dynamics of an isolated node, the coupling strength and the time average of the smallest eigenvalue associated with the Laplacians of switching topology and the coupling fashion. Finally, numerical simulations illustrate the effectiveness of the proposed methods. (paper)

Microcontroller based PWM controlled four switch three phase inverter fed induction motor drive

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Mohanty Kant Nalin

2010-01-01

Full Text Available This paper presents PIC microcontroller based PWM inverter controlled four switch three phase inverter (FSTPI fed Induction Motor drive. The advantage of this inverter that uses of 4 switches instead of conventional 6 switches is lesser switching losses, lower electromagnetic interference (EMI, less complexity of control algorithms and reduced interface circuits. Simulation and experimental work are carried out and results presented to demonstrate the feasibility of the proposed approach. Simulation is carried out using MATLAB SIMULINK and in the experimental work a prototype model is built to verify the simulation results. PIC microcontroller (PIC 16F877A is used to generate the PWM pulses for FSTPI to drive the 0.5 hp 3-phase Induction Motor.

The Topologies Research of a Soft Switching Bidirectional DC/DC Converter

DEFF Research Database (Denmark)

Zhang, Qi; Zhang, Yongping; Sun, Xiangdong

2017-01-01

A soft-switching solution implemented to the traditional bidirectional DC/DC converter is developed. The soft-switching cell, which composed of three auxiliary switches, one resonant capacitor and one resonant inductor, is equipped in the traditional bidirectional DC/DC converter to realize circuit...... circle. And the proposed topology of bidirectional soft-switching dc-dc converter(TASBC) performs ideal soft switching at boost operations. The characteristics of the proposed converter has been verified by MATLAB simulations and experimental results....

A method for determining the actual rate of orientation switching of DNA self-assembled monolayers using optical and electrochemical frequency response analysis.

Science.gov (United States)

Casanova-Moreno, J; Bizzotto, D

2015-02-17

Electrostatic control of the orientation of fluorophore-labeled DNA strands immobilized on an electrode surface has been shown to be an effective bioanalytical tool. Modulation techniques and later time-resolved measurements were used to evaluate the kinetics of the switching between lying and standing DNA conformations. These measurements, however, are the result of a convolution between the DNA "switching" response time and the other frequency limited responses in the measurement. In this work, a method for analyzing the response of a potential driven DNA sensor is presented by calculating the potential effectively dropped across the electrode interface (using electrochemical impedance spectroscopy) as opposed to the potential applied to the electrochemical cell. This effectively deconvolutes the effect of the charging time on the observed frequency response. The corrected response shows that DNA is able to switch conformation faster than previously reported using modulation techniques. This approach will ensure accurate measurements independent of the electrochemical system, removing the uncertainty in the analysis of the switching response, enabling comparison between samples and measurement systems.

Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

Energy Technology Data Exchange (ETDEWEB)

Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla (NCSU)

2012-08-31

Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the 'on' state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the 'ordered off' state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-{beta}. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

Conformal Radiotherapy: Physics, Treatment Planning and Verification. Proceedings book

Energy Technology Data Exchange (ETDEWEB)

De Wagter, C [ed.

1995-12-01

The goal of conformal radiotherapy is to establish radiation dose distributions that conform tightly to the target volume in view of limiting radiation to normal tissues. Conformal radiotherapy significantly improves both local control and palliation and thus contributes to increase survival and to improve the quality of life. The subjects covered by the symposium include : (1) conformal radiotherapy and multi-leaf collimation; (2) three dimensional imaging; (3) treatment simulation, planning and optimization; (4) quality assurance; and (5) dosimetry. The book of proceedings contains the abstracts of the invited lectures, papers and poster presentations as well as the full papers of these contributions.

Conformal Radiotherapy: Physics, Treatment Planning and Verification. Proceedings book

International Nuclear Information System (INIS)

De Wagter, C.

1995-12-01

The goal of conformal radiotherapy is to establish radiation dose distributions that conform tightly to the target volume in view of limiting radiation to normal tissues. Conformal radiotherapy significantly improves both local control and palliation and thus contributes to increase survival and to improve the quality of life. The subjects covered by the symposium include : (1) conformal radiotherapy and multi-leaf collimation; (2) three dimensional imaging; (3) treatment simulation, planning and optimization; (4) quality assurance; and (5) dosimetry. The book of proceedings contains the abstracts of the invited lectures, papers and poster presentations as well as the full papers of these contributions

Fully transparent conformal organic thin-film transistor array and its application as LED front driving.

Science.gov (United States)

Cui, Nan; Ren, Hang; Tang, Qingxin; Zhao, Xiaoli; Tong, Yanhong; Hu, Wenping; Liu, Yichun

2018-02-22

A fully transparent conformal organic thin-film field-effect transistor array is demonstrated based on a photolithography-compatible ultrathin metallic grid gate electrode and a solution-processed C 8 -BTBT film. The resulting organic field-effect transistor array exhibits a high optical transparency of >80% over the visible spectrum, mobility up to 2 cm 2 V -1 s -1 , on/off ratio of 10 5 -10 6 , switching current of >0.1 mA, and excellent light stability. The transparent conformal transistor array is demonstrated to adhere well to flat and curved LEDs as front driving. These results present promising applications of the solution-processed wide-bandgap organic semiconductor thin films in future large-scale transparent conformal active-matrix displays.

Conformational Dynamics of hSGLT1 during Na⁺/Glucose Cotransport

DEFF Research Database (Denmark)

Loo, D. D.; Hirayama, B. A.; Karakossian, M. H.

2006-01-01

at the expense of outward-facing conformations. The simulations predict, and we have observed experimentally, that presteady-state currents are blocked by saturating sugar, but not the changes in fluorescence. Thus we have isolated an electroneutral conformational change that has not been previously described......) was totally abolished, whereas Fmax was only reduced 50%. Phlorizin reduced both Qmax and Fmax (Ki 0.4 µM), with no changes in V0.5's or relaxation time constants. Simulations using an eight-state kinetic model indicate that external sugar increases the occupancy probability of inward-facing conformations...

The operational mechanism of ferroelectric-driven organic resistive switches

NARCIS (Netherlands)

Kemerink, M.; Asadi, K.; Blom, P.W.M.; Leeuw, D.M. de

2012-01-01

The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

The operational mechanism of ferroelectric-driven organic resistive switches

NARCIS (Netherlands)

Kemerink, M.; Asadi, K. (Kamal); Blom, P.W.M.; Leeuw, de D.M.

2012-01-01

The availability of a reliable memory element is crucial for the fabrication of ‘plastic’ logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

The operational mechanism of ferroelectric-driven organic resistive switches

NARCIS (Netherlands)

Kemerink, Martijn; Asadi, Kamal; Blom, Paul W. M.; de Leeuw, Dago M.

The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

New mode switching algorithm for the JPL 70-meter antenna servo controller

Science.gov (United States)

Nickerson, J. A.

1988-01-01

The design of control mode switching algorithms and logic for JPL's 70 m antenna servo controller are described. The old control mode switching logic was reviewed and perturbation problems were identified. Design approaches for mode switching are presented and the final design is described. Simulations used to compare old and new mode switching algorithms and logic show that the new mode switching techniques will significantly reduce perturbation problems.

Evaluating four-loop conformal Feynman integrals by D-dimensional differential equations

Science.gov (United States)

Eden, Burkhard; Smirnov, Vladimir A.

2016-10-01

We evaluate a four-loop conformal integral, i.e. an integral over four four-dimensional coordinates, by turning to its dimensionally regularized version and applying differential equations for the set of the corresponding 213 master integrals. To solve these linear differential equations we follow the strategy suggested by Henn and switch to a uniformly transcendental basis of master integrals. We find a solution to these equations up to weight eight in terms of multiple polylogarithms. Further, we present an analytical result for the given four-loop conformal integral considered in four-dimensional space-time in terms of single-valued harmonic polylogarithms. As a by-product, we obtain analytical results for all the other 212 master integrals within dimensional regularization, i.e. considered in D dimensions.

Evaluating four-loop conformal Feynman integrals by D-dimensional differential equations

Energy Technology Data Exchange (ETDEWEB)

Eden, Burkhard [Institut für Mathematik und Physik, Humboldt-Universität zu Berlin,Zum großen Windkanal 6, 12489 Berlin (Germany); Smirnov, Vladimir A. [Skobeltsyn Institute of Nuclear Physics, Moscow State University,119992 Moscow (Russian Federation)

2016-10-21

We evaluate a four-loop conformal integral, i.e. an integral over four four-dimensional coordinates, by turning to its dimensionally regularized version and applying differential equations for the set of the corresponding 213 master integrals. To solve these linear differential equations we follow the strategy suggested by Henn and switch to a uniformly transcendental basis of master integrals. We find a solution to these equations up to weight eight in terms of multiple polylogarithms. Further, we present an analytical result for the given four-loop conformal integral considered in four-dimensional space-time in terms of single-valued harmonic polylogarithms. As a by-product, we obtain analytical results for all the other 212 master integrals within dimensional regularization, i.e. considered in D dimensions.

Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation

Science.gov (United States)

Hudson, Brian D.; George, Ashley R.; Ford, Martyn G.; Livingstone, David J.

1992-04-01

Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.

Investigation on properties of ultrafast switching in a bulk gallium arsenide avalanche semiconductor switch

International Nuclear Information System (INIS)

Hu, Long; Su, Jiancang; Ding, Zhenjie; Hao, Qingsong; Yuan, Xuelin

2014-01-01

Properties of ultrafast switching in a bulk gallium arsenide (GaAs) avalanche semiconductor switch based on semi-insulating wafer, triggered by an optical pulse, were analyzed using physics-based numerical simulations. It has been demonstrated that when a voltage with amplitude of 5.2 kV is applied, after an exciting optical pulse with energy of 1 μJ arrival, the structure with thickness of 650 μm reaches a high conductivity state within 110 ps. Carriers are created due to photons absorption, and electrons and holes drift to anode and cathode terminals, respectively. Static ionizing domains appear both at anode and cathode terminals, and create impact-generated carriers which contribute to the formation of electron-hole plasma along entire channel. When the electric field in plasma region increases above the critical value (∼4 kV/cm) at which the electrons drift velocity peaks, a domain comes into being. An increase in carrier concentration due to avalanche multiplication in the domains reduces the domain width and results in the formation of an additional domain as soon as the field outside the domains increases above ∼4 kV/cm. The formation and evolution of multiple powerfully avalanching domains observed in the simulations are the physical reasons of ultrafast switching. The switch exhibits delayed breakdown with the characteristics affected by biased electric field, current density, and optical pulse energy. The dependence of threshold energy of the exciting optical pulse on the biased electric field is discussed

New open conformation of SMYD3 implicates conformational selection and allostery

Directory of Open Access Journals (Sweden)

Nicholas Spellmon

2016-12-01

Full Text Available SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD. The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation.

Revisiting imidazolium based ionic liquids: Effect of the conformation bias of the [NTf2] anion studied by molecular dynamics simulations

Science.gov (United States)

Neumann, Jan; Golub, Benjamin; Odebrecht, Lisa-Marie; Ludwig, Ralf; Paschek, Dietmar

2018-05-01

We study ionic liquids composed of 1-alkyl-3-methylimidazolium cations and bis(trifluoromethyl-sulfonyl)imide anions ([CnMIm][NTf2]) with varying chain-length n = 2, 4, 6, 8 by using molecular dynamics simulations. We show that a reparametrization of the dihedral potentials as well as charges of the [NTf2] anion leads to an improvement of the force field model introduced by Köddermann, Paschek, and Ludwig [ChemPhysChem 8, 2464 (2007)] (KPL-force field). A crucial advantage of the new parameter set is that the minimum energy conformations of the anion (trans and gauche), as deduced from ab initio calculations and Raman experiments, are now both well represented by our model. In addition, the results for [CnMIm][NTf2] show that this modification leads to an even better agreement between experiment and molecular dynamics simulation as demonstrated for densities, diffusion coefficients, vaporization enthalpies, reorientational correlation times, and viscosities. Even though we focused on a better representation of the anion conformation, also the alkyl chain-length dependence of the cation behaves closer to the experiment. We strongly encourage to use the new NGOLP (Neumann, Golub, Odebrecht, Ludwig, Paschek) force field for the [NTf2] anion instead of the earlier KPL parameter set for computer simulations aiming to describe the thermodynamics, dynamics, and also structure of imidazolium-based ionic liquids.

An Efficient Null Model for Conformational Fluctuations in Proteins

DEFF Research Database (Denmark)

Harder, Tim Philipp; Borg, Mikael; Bottaro, Sandro

2012-01-01

Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often...... limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide...... on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins....

Structure and conformational dynamics of the domain 5 RNA hairpin of a bacterial group II intron revealed by solution nuclear magnetic resonance and molecular dynamics simulations.

Science.gov (United States)

Pechlaner, Maria; Sigel, Roland K O; van Gunsteren, Wilfred F; Dolenc, Jožica

2013-10-08

Nuclear magnetic resonance (NMR) nuclear Overhauser enhancement (NOE) data obtained for a 35-nucleotide RNA segment of a bacterial group II intron indicate a helical hairpin structure in which three parts, a terminal pentaloop, a bulge, and a G-A mismatch, display no Watson-Crick base pairing. The 668 NOE upper distance bounds for atom pairs are insufficient to uniquely determine the conformation of these segments. Therefore, molecular dynamics simulations including time-averaged distance restraints have been used to obtain a conformational ensemble compatible with the observed NMR data. The ensemble shows alternating hydrogen bonding patterns for the mentioned segments. In particular, in the pentaloop and in the bulge, the hydrogen bonding networks correspond to distinct conformational clusters that could not be captured by using conventional single-structure refinement techniques. This implies that, to obtain a realistic picture of the conformational ensemble of such flexible biomolecules, it is necessary to properly account for the conformational variability in the structure refinement of RNA fragments.

A novel strategy for dual-channel detection of metallothioneins and mercury based on the conformational switching of functional chimera aptamer.

Science.gov (United States)

Tang, Xian; Wang, Yong-Sheng; Xue, Jin-Hua; Zhou, Bin; Cao, Jin-Xiu; Chen, Si-Han; Li, Ming-Hui; Wang, Xiao-Feng; Zhu, Yu-Feng; Huang, Yan-Qin

2015-03-25

A novel strategy for dual-channel detection of metallothioneins (MTs) and Hg(2+) has been proposed. In the absence of Hg(2+), the functional chimera aptamer (FCA) designed can form an intact G-quadruplex with flexibility, which was demonstrated to have peroxidase-like activities upon hemin binding. In the presence of Hg(2+), the formation of T-Hg(2+)-T complex results in the conformational switching of FCA, which lost the peroxidase-like activities and cannot catalyze the oxidation of ABTS by H2O2. Upon addition of MTs in this solution, MTs could interact with Hg(2+) to form a MTs-Hg(2+) complex, leading to the recovery of the G-quadruplex DNAzyme. The color and absorbance of the sensing system were also changed accordingly. In the optimizing condition, ΔA was directly proportional to the concentration ranging from 8.84 nM to 1.0 μM for Hg(2+), and 7.82 nM to 0.462 μM for MTs with the detection limits of 2.65 nM and 2.34 nM, respectively. The proposed dual-channel method avoids the label steps in common methods, and allows direct analysis of the samples without costly instruments, and is reliable, inexpensive and sensitive. Copyright © 2015 Elsevier B.V. All rights reserved.

A STUDY OF SOLID STATE LASER PASSIVE OPTICAL Q-SWITCHING OPERATION REGIME (Part 1

Directory of Open Access Journals (Sweden)

Ion LĂNCRĂNJAN

2009-09-01

Full Text Available This paper is the first of a four series treating, theoretically with experimental comparison, the issue of solid state laser passive optical Q-switching regime. In this first paper the technique of solid state lasers passive optical Q-switching is numerically investigated considering the case of longitudinally and transversally uniform photon, population inversion and absorption centres densities. The coupled differential equations defining photon, population inversion and absorption centres densities are numerically solved being the basis of passively optical Q-switched laser functional simulation. The numerical simulations are performed using the several software packages, mostly SCILAB programs. The developed SCILAB programs can be used for a large range of saturable absorption centre and active media parameters, mainly the initial (low signal optical transmittance of the passive optical Q-switch. The developed FORTRAN and SCILAB programs can be applied for passively Q-switched solid state lasers of several types emitting at several NIR wavelengths, in domain 1 ÷ 2 μm. For validating the numerical simulation results are compared with The results of the numerical simulation are compared with experimentally obtained ones, in the case of a LiF:F2- passively Q-switched Nd:YAG. A good agreement between the two kinds of results is observed.

Low pull-in voltage electrostatic MEMS switch using liquid dielectric

KAUST Repository

Zidan, Mohammed A.; Kosel, Jü rgen; Salama, Khaled N.

2014-01-01

In this paper, we present an electrostatic MEMS switch with liquids as dielectric to reduce the actuation voltage. The concept is verified by simulating a lateral dual gate switch, where the required pull-in voltage is reduced by more than 8 times

Conformal field theory in conformal space

International Nuclear Information System (INIS)

Preitschopf, C.R.; Vasiliev, M.A.

1999-01-01

We present a new framework for a Lagrangian description of conformal field theories in various dimensions based on a local version of d + 2-dimensional conformal space. The results include a true gauge theory of conformal gravity in d = (1, 3) and any standard matter coupled to it. An important feature is the automatic derivation of the conformal gravity constraints, which are necessary for the analysis of the matter systems

Conformational entropy changes upon lactose binding to the carbohydrate recognition domain of galectin-3

International Nuclear Information System (INIS)

Diehl, Carl; Genheden, Samuel; Modig, Kristofer; Ryde, Ulf; Akke, Mikael

2009-01-01

The conformational entropy of proteins can make significant contributions to the free energy of ligand binding. NMR spin relaxation enables site-specific investigation of conformational entropy, via order parameters that parameterize local reorientational fluctuations of rank-2 tensors. Here we have probed the conformational entropy of lactose binding to the carbohydrate recognition domain of galectin-3 (Gal3), a protein that plays an important role in cell growth, cell differentiation, cell cycle regulation, and apoptosis, making it a potential target for therapeutic intervention in inflammation and cancer. We used 15 N spin relaxation experiments and molecular dynamics simulations to monitor the backbone amides and secondary amines of the tryptophan and arginine side chains in the ligand-free and lactose-bound states of Gal3. Overall, we observe good agreement between the experimental and computed order parameters of the ligand-free and lactose-bound states. Thus, the 15 N spin relaxation data indicate that the molecular dynamics simulations provide reliable information on the conformational entropy of the binding process. The molecular dynamics simulations reveal a correlation between the simulated order parameters and residue-specific backbone entropy, re-emphasizing that order parameters provide useful estimates of local conformational entropy. The present results show that the protein backbone exhibits an increase in conformational entropy upon binding lactose, without any accompanying structural changes

Insight into microtubule destabilization mechanism of 3,4,5-trimethoxyphenyl indanone derivatives using molecular dynamics simulation and conformational modes analysis

Science.gov (United States)

Tripathi, Shubhandra; Srivastava, Gaurava; Singh, Aastha; Prakasham, A. P.; Negi, Arvind S.; Sharma, Ashok

2018-03-01

Colchicine site inhibitors are microtubule destabilizers having promising role in cancer therapeutics. In the current study, four such indanone derivatives (t1, t9, t14 and t17) with 3,4,5-trimethoxyphenyl fragment (ring A) and showing significant microtubule destabilization property have been explored. The interaction mechanism and conformational modes triggered by binding of these indanone derivatives and combretastatin at colchicine binding site (CBS) of αβ-tubulin dimer were studied using molecular dynamics (MD) simulation, principle component analysis and free energy landscape analysis. In the MD results, t1 showed binding similar to colchicine interacting in the deep hydrophobic core at the CBS. While t9, t14 and t17 showed binding conformation similar to combretastatin, with ring A superficially binding at the CBS. Results demonstrated that ring A played a vital role in binding via hydrophobic interactions and got anchored between the S8 and S9 sheets, H8 helix and T7 loop at the CBS. Conformational modes study revealed that twisting and bending conformational motions (as found in the apo system) were nearly absent in the ligand bound systems. Absence of twisting motion might causes loss of lateral contacts in microtubule, thus promoting microtubule destabilization. This study provides detailed account of microtubule destabilization mechanism by indanone ligands and combretastatin, and would be helpful for designing microtubule destabilizers with higher activity.

Conformational change of oil contaminants adhered onto crystalline alpha-alumina surface in aqueous solution

International Nuclear Information System (INIS)

Xie, Wenkun; Sun, Yazhou; Liu, Haitao; Fu, Hongya; Liang, Yingchun

2016-01-01

Graphical abstract: - Highlights: • Dynamic conformational change process of oil contaminations adhered onto Al-terminated α-Al_2O_3 surface in aqueous solution is given. • Effect of water penetration on the conformational change and even detachment of oil contaminants is considered. • Change of driving forces leading to the conformational change of oil contaminants is described. - Abstract: Microscopic conformational change of oil contaminants adhered onto perfect α-Al_2O_3 (0001) surface in the aqueous solution was simulated by means of detailed fully atomistic molecular dynamics simulations. The main driving forces of the conformation change process of the oil contaminants were explored. The simulation results indicate that with submerging of the contaminated α-Al_2O_3 (0001) surface into the aqueous solution, the oil contaminants undertake an evident conformational change process. The dynamic process can be divided into several stages, including early penetration of water molecules, formation and widening of water channel, and generation of molecularly adsorbed hydration layers. Moreover, the oil contaminants on the α-Al_2O_3 surface are not fully removed from solid surface after a 10 ns relaxation, while a relatively stable oil/water/solid three-phase interface is gradually formed. Further, the residual oil contaminants are finally divided into several new ordered molecular adsorption layers. In addition, by systemically analyzing the driving forces for the conformational change of the oil contaminants, the penetration of water molecules is found to be the most important driving force. With penetrating of the water molecules, the dominating interactions controlling the conformational change of the oil contaminants have been changing over the whole simulation.

Synchronization of Switched Interval Networks and Applications to Chaotic Neural Networks

Directory of Open Access Journals (Sweden)

Jinde Cao

2013-01-01

Full Text Available This paper investigates synchronization problem of switched delay networks with interval parameters uncertainty, based on the theories of the switched systems and drive-response technique, a mathematical model of the switched interval drive-response error system is established. Without constructing Lyapunov-Krasovskii functions, introducing matrix measure method for the first time to switched time-varying delay networks, combining Halanay inequality technique, synchronization criteria are derived for switched interval networks under the arbitrary switching rule, which are easy to verify in practice. Moreover, as an application, the proposed scheme is then applied to chaotic neural networks. Finally, numerical simulations are provided to illustrate the effectiveness of the theoretical results.

Activator Protein-1: redox switch controlling structure and DNA-binding.

Science.gov (United States)

Yin, Zhou; Machius, Mischa; Nestler, Eric J; Rudenko, Gabby

2017-11-02

The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a 'redox switch' centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the 'OFF' state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Exploration of conformational changes in lactose permease upon sugar binding and proton transfer through coarse-grained simulations.

Science.gov (United States)

Jewel, Yead; Dutta, Prashanta; Liu, Jin

2017-10-01

Escherichia coli lactose permease (LacY) actively transports lactose and other galactosides across cell membranes through lactose/H + symport process. Lactose/H + symport is a highly complex process that involves sugar translocation, H + transfer, and large-scale protein conformational changes. The complete picture of lactose/H + symport is largely unclear due to the complexity and multiscale nature of the process. In this work, we develop the force field for sugar molecules compatible with PACE, a hybrid and coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid. After validation, we implement the new force field to investigate the binding of a β-d-galactopyranosyl-1-thio- β-d-galactopyranoside (TDG) molecule to a wild-type LacY. Results show that the local interactions between TDG and LacY at the binding pocket are consistent with the X-ray experiment. Transitions from inward-facing to outward-facing conformations upon TDG binding and protonation of Glu269 have been achieved from ∼5.5 µs simulations. Both the opening of the periplasmic side and closure of the cytoplasmic side of LacY are consistent with double electron-electron resonance and thiol cross-linking experiments. Our analysis suggests that the conformational changes of LacY are a cumulative consequence of interdomain H-bonds breaking at the periplasmic side, interdomain salt-bridge formation at the cytoplasmic side, and the TDG orientational changes during the transition. © 2017 Wiley Periodicals, Inc.

Conformation Analysis of T1 Lipase on Alcohols Solvent using Molecular Dynamics Simulation

Science.gov (United States)

Putri, A. M.; Sumaryada, T.; Wahyudi, S. T.

2017-07-01

Biodiesel usually is produced commercially via a transesterification reaction of vegetable oil with alcohol and alkali catalyst. The alkali catalyst has some drawbacks, such as the soap formation during the reaction. T1 Lipase enzyme had been known as a thermostable biocatalyst which is able to produce biodiesel through a cleaner process. In this paper the performance of T1 lipase enzyme as catalyst for transesterification reaction in pure ethanol, methanol, and water solvents were studied using a Molecular Dynamics (MD) Simulation at temperature of 300 K for 10 nanoseconds. The results have shown that in general the conformation of T1 lipase enzyme in methanol is more dynamics as shown by the value of root mean square deviation (RMSD), root mean squared fluctuation (RMSF), and radius of gyration. The highest solvent accessible surface area (SASA) total was also found in methanol due to the contribution of non-polar amino acid in the interior of the protein. Analysis of MD simulation has also revealed that the enzyme structure tend to be more rigid in ethanol environment. The analysis of electrostatic interactions have shown that Glu359-Arg270 salt-bridge pair might hold the key of thermostability of T1 lipase enzyme as shown by its strong and stable binding in all three solvents.

Enrichment of Druggable Conformations from Apo Protein Structures Using Cosolvent-Accelerated Molecular Dynamics

Directory of Open Access Journals (Sweden)

Andrew Kalenkiewicz

2015-04-01

Full Text Available Here we describe the development of an improved workflow for utilizing experimental and simulated protein conformations in the structure-based design of inhibitors for anti-apoptotic Bcl-2 family proteins. Traditional structure-based approaches on similar targets are often constrained by the sparsity of available structures and difficulties in finding lead compounds that dock against flat, flexible protein-protein interaction surfaces. By employing computational docking of known small molecule inhibitors, we have demonstrated that structural ensembles derived from either accelerated MD (aMD or MD in the presence of an organic cosolvent generally give better scores than those assessed from analogous conventional MD. Furthermore, conformations obtained from combined cosolvent aMD simulations started with the apo-Bcl-xL structure yielded better average and minimum docking scores for known binders than an ensemble of 72 experimental apo- and ligand-bound Bcl-xL structures. A detailed analysis of the simulated conformations indicates that the aMD effectively enhanced conformational sampling of the flexible helices flanking the main Bcl-xL binding groove, permitting the cosolvent acting as small ligands to penetrate more deeply into the binding pocket and shape ligand-bound conformations not evident in conventional simulations. We believe this approach could be useful for identifying inhibitors against other protein-protein interaction systems involving highly flexible binding sites, particularly for targets with less accumulated structural data.

A 3D kinetic Monte Carlo simulation study of resistive switching processes in Ni/HfO2/Si-n+-based RRAMs

International Nuclear Information System (INIS)

Aldana, S; García-Fernández, P; Jiménez-Molinos, F; Gómez-Campos, F; Roldán, J B; Rodríguez-Fernández, Alberto; Romero-Zaliz, R; González, M B; Campabadal, F

2017-01-01

A new RRAM simulation tool based on a 3D kinetic Monte Carlo algorithm has been implemented. The redox reactions and migration of cations are developed taking into consideration the temperature and electric potential 3D distributions within the device dielectric at each simulation time step. The filamentary conduction has been described by obtaining the percolation paths formed by metallic atoms. Ni/HfO 2 /Si-n + unipolar devices have been fabricated and measured. The different experimental characteristics of the devices under study have been reproduced with accuracy by means of simulations. The main physical variables can be extracted at any simulation time to clarify the physics behind resistive switching; in particular, the final conductive filament shape can be studied in detail. (paper)

Silver ions-mediated conformational switch: facile design of structure-controllable nucleic acid probes.

Science.gov (United States)

Wang, Yongxiang; Li, Jishan; Wang, Hao; Jin, Jianyu; Liu, Jinhua; Wang, Kemin; Tan, Weihong; Yang, Ronghua

2010-08-01

Conformationally constraint nucleic acid probes were usually designed by forming an intramolecular duplex based on Watson-Crick hydrogen bonds. The disadvantages of these approaches are the inflexibility and instability in complex environment of the Watson-Crick-based duplex. We report that this hydrogen bonding pattern can be replaced by metal-ligation between specific metal ions and the natural bases. To demonstrate the feasibility of this principle, two linear oligonucleotides and silver ions were examined as models for DNA hybridization assay and adenosine triphosphate detection. The both nucleic acids contain target binding sequences in the middle and cytosine (C)-rich sequences at the lateral portions. The strong interaction between Ag(+) ions and cytosines forms stable C-Ag(+)-C structures, which promises the oligonucleotides to form conformationally constraint formations. In the presence of its target, interaction between the loop sequences and the target unfolds the C-Ag(+)-C structures, and the corresponding probes unfolding can be detected by a change in their fluorescence emission. We discuss the thermodynamic and kinetic opportunities that are provided by using Ag(+) ion complexes instead of traditional Watson-Crick-based duplex. In particular, the intrinsic feature of the metal-ligation motif facilitates the design of functional nucleic acids probes by independently varying the concentration of Ag(+) ions in the medium.

Twelve massless flavors and three colors below the conformal window

International Nuclear Information System (INIS)

Fodor, Zoltan; Holland, Kieran; Kuti, Julius; Nogradi, Daniel; Schroeder, Chris

2011-01-01

We report new results for a frequently discussed gauge theory with twelve fermion flavors in the fundamental representation of the SU(3) color gauge group. The model, controversial with respect to its conformality, is important in non-perturbative studies searching for a viable composite Higgs mechanism beyond the Standard Model (BSM). In comparison with earlier work, our new simulations apply larger volumes and probe deeper in fermion and pion masses toward the chiral limit. Investigating the controversy, we subject the model to opposite hypotheses with respect to the conformal window. In the first hypothesis, below the conformal window, we test chiral symmetry breaking (χSB) with its Goldstone spectrum, F π , the χSB condensate, and several composite hadron states as analytic functions of the fermion mass when varied in a limited range with our best effort to control finite volume effects. In the second test, for the alternate hypothesis inside the conformal window, we probe conformal behavior driven by a single anomalous mass dimension under the assumption of unbroken chiral symmetry at vanishing fermion mass. Our results at fixed gauge coupling, based on the assumptions of the two hypotheses we define, show low level of confidence in the conformal scenario with leading order scaling analysis. Relaxing the important assumption of leading mass-deformed conformality with its conformal finite size scaling would require added theoretical understanding of the scaling violation terms in the conformal analysis and a comprehensive test of its effects on the confidence level of the fits. Results for the running coupling, based on the force between static sources, and preliminary indications for the finite temperature transition are also presented. Staggered lattice fermions with stout-suppressed taste breaking are used throughout the simulations.

Design of adaptive switching control for hypersonic aircraft

Directory of Open Access Journals (Sweden)

Xin Jiao

2015-10-01

Full Text Available This article proposes a novel adaptive switching control of hypersonic aircraft based on type-2 Takagi–Sugeno–Kang fuzzy sliding mode control and focuses on the problem of stability and smoothness in the switching process. This method uses full-state feedback to linearize the nonlinear model of hypersonic aircraft. Combining the interval type-2 Takagi–Sugeno–Kang fuzzy approach with sliding mode control keeps the adaptive switching process stable and smooth. For rapid stabilization of the system, the adaptive laws use a direct constructive Lyapunov analysis together with an established type-2 Takagi–Sugeno–Kang fuzzy logic system. Simulation results indicate that the proposed control scheme can maintain the stability and smoothness of switching process for the hypersonic aircraft.

Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

Energy Technology Data Exchange (ETDEWEB)

Qiao, Qin, E-mail: qqiao@ust.hk; Zhang, Hou-Dao [Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Huang, Xuhui, E-mail: xuhuihuang@ust.hk [Department of Chemistry, Division of Biomedical Engineering, Center of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); The HKUST Shenzhen Research Institute, Shenzhen (China)

2016-04-21

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

Science.gov (United States)

Qiao, Qin; Zhang, Hou-Dao; Huang, Xuhui

2016-04-01

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

International Nuclear Information System (INIS)

Qiao, Qin; Zhang, Hou-Dao; Huang, Xuhui

2016-01-01

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

Conformal boundary state for the rectangular geometry

Energy Technology Data Exchange (ETDEWEB)

Bondesan, R., E-mail: roberto.bondesan@cea.fr [Institute de Physique Theorique, CEA Saclay, F-91191 Gif-sur-Yvette (France); LPTENS, Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris (France); Institut Henri Poincare, 11 rue Pierre et Marie Curie, 75231 Paris (France); Dubail, J. [Department of Physics, Yale University, P.O. Box 208120, New Haven, CT 06520-8120 (United States); Jacobsen, J.L. [LPTENS, Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris (France); Institut Henri Poincare, 11 rue Pierre et Marie Curie, 75231 Paris (France); Universite Pierre et Marie Curie, 4 place Jussieu, 75252 Paris (France); Saleur, H. [Institute de Physique Theorique, CEA Saclay, F-91191 Gif-sur-Yvette (France); Institut Henri Poincare, 11 rue Pierre et Marie Curie, 75231 Paris (France); Physics Department, USC, Los Angeles, CA 90089-0484 (United States)

2012-09-11

We discuss conformal field theories (CFTs) in rectangular geometries, and develop a formalism that involves a conformal boundary state for the 1+1d open system. We focus on the case of homogeneous boundary conditions (no insertion of a boundary condition changing operator), for which we derive an explicit expression of the associated boundary state, valid for any arbitrary CFT. We check the validity of our solution, comparing it with known results for partition functions, numerical simulations of lattice discretizations, and coherent state expressions for free theories.

Noise in Genetic Toggle Switch Models

Directory of Open Access Journals (Sweden)

Andrecut M.

2006-06-01

Full Text Available In this paper we study the intrinsic noise effect on the switching behavior of a simple genetic circuit corresponding to the genetic toggle switch model. The numerical results obtained from a noisy mean-field model are compared to those obtained from the stochastic Gillespie simulation of the corresponding system of chemical reactions. Our results show that by using a two step reaction approach for modeling the transcription and translation processes one can make the system to lock in one of the steady states for exponentially long times.

Ab initio theory for current-induced molecular switching: Melamine on Cu(001)

KAUST Repository

Ohto, Tatsuhiko

2013-05-28

Melamine on Cu(001) is mechanically unstable under the current of a scanning tunneling microscope tip and can switch among configurations. However, these are not equally accessible, and the switching critical current depends on the bias polarity. In order to explain such rich phenomenology, we have developed a scheme to evaluate the evolution of the reaction paths and activation barriers as a function of bias, which is rooted in the nonequilibrium Green\\'s function method implemented within density functional theory. This, combined with the calculation of the inelastic electron tunneling spectroscopy signal, allows us to identify the vibrational modes promoting the observed molecular conformational changes. Finally, once our ab initio results are used within a resonance model, we are able to explain the details of the switching behavior, such as its dependence on the bias polarity, and the noninteger power relation between the reaction rate constants and both the bias voltage and the electric current. © 2013 American Physical Society.

Ab initio theory for current-induced molecular switching: Melamine on Cu(001)

KAUST Repository

Ohto, Tatsuhiko; Rungger, Ivan; Yamashita, Koichi; Nakamura, Hisao; Sanvito, Stefano

2013-01-01

Melamine on Cu(001) is mechanically unstable under the current of a scanning tunneling microscope tip and can switch among configurations. However, these are not equally accessible, and the switching critical current depends on the bias polarity. In order to explain such rich phenomenology, we have developed a scheme to evaluate the evolution of the reaction paths and activation barriers as a function of bias, which is rooted in the nonequilibrium Green's function method implemented within density functional theory. This, combined with the calculation of the inelastic electron tunneling spectroscopy signal, allows us to identify the vibrational modes promoting the observed molecular conformational changes. Finally, once our ab initio results are used within a resonance model, we are able to explain the details of the switching behavior, such as its dependence on the bias polarity, and the noninteger power relation between the reaction rate constants and both the bias voltage and the electric current. © 2013 American Physical Society.

Novel, Four-Switch, Z-Source Three-Phase Inverter

DEFF Research Database (Denmark)

Antal, Robert; Muntean, Nicolae; Boldea, Ion

2010-01-01

This paper presents a new z-source three phase inverter topology. The proposed topology combines the advantages of a traditional four-switch three-phase inverter with the advantages of the z impedance network (one front-end diode, two inductors and two X connected capacitors). This new topology......, besides the self-boost property, has low switch count and it can operate as a buck-boost inverter. In contrast to standard four-switch three-phase inverter which operates at half dc input voltage the proposed four-switch z-source inverter, by self boosting, brings the output voltage at same (or higher......) value as in six switch standard three-phase inverter. The article presents the derivation of the equations describing the operation of the converter based on space vector analysis, validation through digital simulations in PSIM and preliminary experimental results on a laboratory setup with a dsPIC30F...

Modulation of calmodulin lobes by different targets: an allosteric model with hemiconcerted conformational transitions.

Directory of Open Access Journals (Sweden)

Massimo Lai

2015-01-01

Full Text Available Calmodulin is a calcium-binding protein ubiquitous in eukaryotic cells, involved in numerous calcium-regulated biological phenomena, such as synaptic plasticity, muscle contraction, cell cycle, and circadian rhythms. It exibits a characteristic dumbell shape, with two globular domains (N- and C-terminal lobe joined by a linker region. Each lobe can take alternative conformations, affected by the binding of calcium and target proteins. Calmodulin displays considerable functional flexibility due to its capability to bind different targets, often in a tissue-specific fashion. In various specific physiological environments (e.g. skeletal muscle, neuron dendritic spines several targets compete for the same calmodulin pool, regulating its availability and affinity for calcium. In this work, we sought to understand the general principles underlying calmodulin modulation by different target proteins, and to account for simultaneous effects of multiple competing targets, thus enabling a more realistic simulation of calmodulin-dependent pathways. We built a mechanistic allosteric model of calmodulin, based on an hemiconcerted framework: each calmodulin lobe can exist in two conformations in thermodynamic equilibrium, with different affinities for calcium and different affinities for each target. Each lobe was allowed to switch conformation on its own. The model was parameterised and validated against experimental data from the literature. In spite of its simplicity, a two-state allosteric model was able to satisfactorily represent several sets of experiments, in particular the binding of calcium on intact and truncated calmodulin and the effect of different skMLCK peptides on calmodulin's saturation curve. The model can also be readily extended to include multiple targets. We show that some targets stabilise the low calcium affinity T state while others stabilise the high affinity R state. Most of the effects produced by calmodulin targets can be

Method to optimize optical switch topology for photonic network-on-chip

Science.gov (United States)

Zhou, Ting; Jia, Hao

2018-04-01

In this paper, we propose a method to optimize the optical switch by substituting optical waveguide crossings for optical switching units and an optimizing algorithm to complete the optimization automatically. The functionality of the optical switch remains constant under optimization. With this method, we simplify the topology of optical switch, which means the insertion loss and power consumption of the whole optical switch can be effectively minimized. Simulation result shows that the number of switching units of the optical switch based on Spanke-Benes can be reduced by 16.7%, 20%, 20%, 19% and 17.9% for the scale from 4 × 4 to 8 × 8 respectively. As a proof of concept, the experimental demonstration of an optimized six-port optical switch based on Spanke-Benes structure by means of silicon photonics chip is reported.

Sex differences in confidence influence patterns of conformity.

Science.gov (United States)

Cross, Catharine P; Brown, Gillian R; Morgan, Thomas J H; Laland, Kevin N

2017-11-01

Lack of confidence in one's own ability can increase the likelihood of relying on social information. Sex differences in confidence have been extensively investigated in cognitive tasks, but implications for conformity have not been directly tested. Here, we tested the hypothesis that, in a task that shows sex differences in confidence, an indirect effect of sex on social information use will also be evident. Participants (N = 168) were administered a mental rotation (MR) task or a letter transformation (LT) task. After providing an answer, participants reported their confidence before seeing the responses of demonstrators and being allowed to change their initial answer. In the MR, but not the LT, task, women showed lower levels of confidence than men, and confidence mediated an indirect effect of sex on the likelihood of switching answers. These results provide novel, experimental evidence that confidence is a general explanatory mechanism underpinning susceptibility to social influences. Our results have implications for the interpretation of the wider literature on sex differences in conformity. © 2016 The British Psychological Society.

Buck Converter with Soft-Switching Cells for PV Panel Applications

Directory of Open Access Journals (Sweden)

Cheng-Tao Tsai

2016-03-01

Full Text Available In power conversion of photovoltaic (PV energy, a hard-switching buck converter always generates some disadvantages. For example, serious electromagnetic interference (EMI, high switching losses, and stresses on an active switch (metal-oxide-semiconductor-field-effect-transistor, MOSFET, and high reverse-recovery losses of a freewheeling diode result in low conversion efficiency. To release these disadvantages, a buck converter with soft-switching cells for PV panel applications is proposed. To create zero-voltage-switching (ZVS features of the active switches, a simple active soft-switching cell with an inductor, a capacitor, and a MOSFET is incorporated into the proposed buck converter. Therefore, the switching losses and stresses of the active switches and EMI can be reduced significantly. To reduce reverse-recovery losses of a freewheeling diode, a simple passive soft-switching cell with a capacitor and two diodes is implemented. To verify the performance and the feasibility of the proposed buck converter with soft-switching cells for PV panel applications, a prototype soft-switching buck converter is built and implemented by using a maximum-power-point-tracking (MPPT method. Simulated and experimental results are presented from a 100 W soft-switching buck converter for PV panel applications.

Ferroelectric switching of elastin

Science.gov (United States)

Liu, Yuanming; Cai, Hong-Ling; Zelisko, Matthew; Wang, Yunjie; Sun, Jinglan; Yan, Fei; Ma, Feiyue; Wang, Peiqi; Chen, Qian Nataly; Zheng, Hairong; Meng, Xiangjian; Sharma, Pradeep; Zhang, Yanhang; Li, Jiangyu

2014-01-01

Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of its switching. Nanoscale piezoresponse force microscopy and macroscopic pyroelectric measurements both show that elastin retains ferroelectricity at 473 K, with polarization on the order of 1 μC/cm2, whereas coarse-grained molecular dynamics simulations predict similar polarization with a Curie temperature of 580 K, which is higher than most synthetic molecular ferroelectrics. The polarization of elastin is found to be intrinsic in tropoelastin at the monomer level, analogous to the unit cell level polarization in classical perovskite ferroelectrics, and it switches via thermally activated cooperative rotation of dipoles. Our study sheds light onto a long-standing question on ferroelectric switching in biology and establishes ferroelectricity as an important biophysical property of proteins. This is a critical first step toward resolving its physiological significance and pathological implications. PMID:24958890

Modeling novel back-pressure mechanisms for a 100 Gb/s switch

DEFF Research Database (Denmark)

Fagertun, Anna Manolova; Ruepp, Sarah Renée

2012-01-01

In this work we evaluate the performance of novel back-pressure mechanisms in a Clos-based 100 Gb/s switch system via OPNET modeler simulations. The effectiveness of the mechanisms under different switch configurations, as well as under different traffic patterns, is presented. Our results indicate...... that the proposed back-pressure techniques can effectively reduce the requirements for buffer space in the different stages of the Clos switch....

Simulation and analysis of transient over voltages due to capacitor banks switching

International Nuclear Information System (INIS)

Jadid, Sh.; Yazdanpanah, D.

2002-01-01

The switching of any capacitor bank produces over voltages. Transient overvoltage will always occur in the switching device, the switching of shunt capacitor bank has become the most common source of transient voltage on power systems. Transient over voltages due to switching the capacitor bands hurt not only to the capacitor banks, but also to other equipment, such as circuit breakers and transformers. Several methods are available for reducing energising transients. These devices include pre-insertion resistors, pre-insertion inductors,synchronous closing, and MOV arresters. However, not all are practical or economical. The other important problem is existence of capacitor banks in presence of harmonics.Capacitors do not produce harmonics;however,the addition of capacitors to the electrical system will change the frequency response characteristics of the system will change the frequency response characteristics of the system, and in some cases can result in magnification of the voltage and current distortion in the system. In other word in presence of harmonic-producing loads,the capacitors used for power factor correction,may cause parallel resonance with the system inductance, so they increase the total harmonic distortion of voltage and current waveforms

Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

DEFF Research Database (Denmark)

Christensen, I T; Jørgensen, Flemming Steen

1997-01-01

. A series of methyl-substituted 1,3-dioxanes were investigated at 1000 K, and the number of chair-chair interconversions could be quantitatively correlated to the experimentally determined ring inversion barrier. Similarly, the distribution of sampled minimum-energy conformations correlated with the energy......-derived Boltzmann distribution. The macrocyclic ring system cyclododecane was subjected to an MD simulation at 1000 K and 71 different conformations could be sampled. These conformations were compared with the results of previously reported conformational analyses using stochastic search methods, and the MD method...

3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

Science.gov (United States)

Burtnyk, Mathieu; N'Djin, William Apoutou; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

2010-11-21

MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

Hybrid colored noise process with space-dependent switching rates

Science.gov (United States)

Bressloff, Paul C.; Lawley, Sean D.

2017-07-01

A fundamental issue in the theory of continuous stochastic process is the interpretation of multiplicative white noise, which is often referred to as the Itô-Stratonovich dilemma. From a physical perspective, this reflects the need to introduce additional constraints in order to specify the nature of the noise, whereas from a mathematical perspective it reflects an ambiguity in the formulation of stochastic differential equations (SDEs). Recently, we have identified a mechanism for obtaining an Itô SDE based on a form of temporal disorder. Motivated by switching processes in molecular biology, we considered a Brownian particle that randomly switches between two distinct conformational states with different diffusivities. In each state, the particle undergoes normal diffusion (additive noise) so there is no ambiguity in the interpretation of the noise. However, if the switching rates depend on position, then in the fast switching limit one obtains Brownian motion with a space-dependent diffusivity of the Itô form. In this paper, we extend our theory to include colored additive noise. We show that the nature of the effective multiplicative noise process obtained by taking both the white-noise limit (κ →0 ) and fast switching limit (ɛ →0 ) depends on the order the two limits are taken. If the white-noise limit is taken first, then we obtain Itô, and if the fast switching limit is taken first, then we obtain Stratonovich. Moreover, the form of the effective diffusion coefficient differs in the two cases. The latter result holds even in the case of space-independent transition rates, where one obtains additive noise processes with different diffusion coefficients. Finally, we show that yet another form of multiplicative noise is obtained in the simultaneous limit ɛ ,κ →0 with ɛ /κ2 fixed.

Switched diversity strategies for dual-hop relaying systems

KAUST Repository

Gaaloul, Fakhreddine

2011-04-29

This paper investigates the effect of different switched diversity configurations on the implementation complexity and achieved performance of dual-hop amplify-and-forward (AF) relaying networks. A low-complexity model of the relay station is adopted, wherein single-input single-output antenna configuration is employed. Each of the transmitter and the receiver however employs multiple antennas to improve the overall link performance. Single-phase and two-phase based receive switching strategies are investigated assuming optimum first hop signal-to-noise ratio (SNR). Moreover, the simple scheme in which the switched diversity is applied independently over the two hops is studied using tight upper bounds. Thorough performance comparisons and switching thresholds optimization for the aforementioned strategies are presented. Simulation results are also provided to validate the mathematical development and to verify the numerical computations.

Polymer Conformations in Ionic Microgels in the Presence of Salt: Theoretical and Mesoscale Simulation Results

Directory of Open Access Journals (Sweden)

Hideki Kobayashi

2017-01-01

Full Text Available We investigate the conformational properties of polymers in ionic microgels in the presence of salt ions by molecular dynamics simulations and analytical theory. A microgel particle consists of coarse-grained linear polymers, which are tetra-functionally crosslinked. Counterions and salt ions are taken into account explicitly, and charge-charge interactions are described by the Coulomb potential. By varying the charge interaction strength and salt concentration, we characterize the swelling of the polyelectrolytes and the charge distribution. In particular, we determine the amount of trapped mobile charges inside the microgel and the Debye screening length. Moreover, we analyze the polymer extension theoretically in terms of the tension blob model taking into account counterions and salt ions implicitly by the Debye–Hückel model. Our studies reveal a strong dependence of the amount of ions absorbed in the interior of the microgel on the electrostatic interaction strength, which is related to the degree of the gel swelling. This implies a dependence of the inverse Debye screening length κ on the ion concentration; we find a power-law increase of κ with the Coulomb interaction strength with the exponent 3 / 5 for a salt-free microgel and an exponent 1 / 2 for moderate salt concentrations. Additionally, the radial dependence of polymer conformations and ion distributions is addressed.

Covalent dye attachment influences the dynamics and conformational properties of flexible peptides.

Directory of Open Access Journals (Sweden)

Manuel P Luitz

Full Text Available Fluorescence spectroscopy techniques like Förster resonance energy transfer (FRET and fluorescence correlation spectroscopy (FCS have become important tools for the in vitro and in vivo investigation of conformational dynamics in biomolecules. These methods rely on the distance-dependent quenching of the fluorescence signal of a donor fluorophore either by a fluorescent acceptor fluorophore (FRET or a non-fluorescent quencher, as used in FCS with photoinduced electron transfer (PET. The attachment of fluorophores to the molecule of interest can potentially alter the molecular properties and may affect the relevant conformational states and dynamics especially of flexible biomolecules like intrinsically disordered proteins (IDP. Using the intrinsically disordered S-peptide as a model system, we investigate the impact of terminal fluorescence labeling on the molecular properties. We perform extensive molecular dynamics simulations on the labeled and unlabeled peptide and compare the results with in vitro PET-FCS measurements. Experimental and simulated timescales of end-to-end fluctuations were found in excellent agreement. Comparison between simulations with and without labels reveal that the π-stacking interaction between the fluorophore labels traps the conformation of S-peptide in a single dominant state, while the unlabeled peptide undergoes continuous conformational rearrangements. Furthermore, we find that the open to closed transition rate of S-peptide is decreased by at least one order of magnitude by the fluorophore attachment. Our approach combining experimental and in silico methods provides a benchmark for the simulations and reveals the significant effect that fluorescence labeling can have on the conformational dynamics of small biomolecules, at least for inherently flexible short peptides. The presented protocol is not only useful for comparing PET-FCS experiments with simulation results but provides a strategy to minimize the

Watching proteins function with picosecond X-ray crystallography and molecular dynamics simulations.

Science.gov (United States)

Anfinrud, Philip

2006-03-01

Time-resolved electron density maps of myoglobin, a ligand-binding heme protein, have been stitched together into movies that unveil with molecular dynamics (MD) calculations and picosecond time-resolved X-ray structures provides single-molecule insights into mechanisms of protein function. Ensemble-averaged MD simulations of the L29F mutant of myoglobin following ligand dissociation reproduce the direction, amplitude, and timescales of crystallographically-determined structural changes. This close agreement with experiments at comparable resolution in space and time validates the individual MD trajectories, which identify and structurally characterize a conformational switch that directs dissociated ligands to one of two nearby protein cavities. This unique combination of simulation and experiment unveils functional protein motions and illustrates at an atomic level relationships among protein structure, dynamics, and function. In collaboration with Friedrich Schotte and Gerhard Hummer, NIH.

Specific features of the switch-on gate current and different switch-on modes in silicon carbide thyristors

International Nuclear Information System (INIS)

Yurkov, S N; Mnatsakanov, T T; Levinshtein, M E; Cheng, L; Palmour, J W

2014-01-01

The specific features of the temperature and bias dependences of the switch-on gate current in SiC thyristors are examined analytically for two possible switching mechanisms. The so-called γ-mechanism, which is highly typical of the conventional Si thyristors, is characterized by very weak temperature and bias dependences. By contrast, the so-called α-mechanism, which is very characteristic of SiC thyristors, is highly sensitive to changes in temperature and bias. If the thyristor is switched on by the α-mechanism, the switch-on gate current density decreases very steeply with increasing temperature. As a result, the thyristor can lose its working capacity at elevated temperatures due to the instability against even very weak impacts. With decreasing the bias voltage U a , the gate switch-on current increases very steeply, which can make switching the thyristor on difficult. The unintentional shunting, which is apparently present in high-voltage SiC thyristors, causes the transition from the α- to the γ-mechanism at elevated temperatures and high biases. It can be supposed that introduction of a controllable technological shunting of the emitter–thin base junction allows stabilization of the temperature and bias parameters of SiC thyristors. The analytical results are confirmed by computer simulations performed in wide temperature and bias ranges for a 4H-SiC thyristor of the 18 kV class. (paper)

Orientation and conformation of a lipase at an interface studied by molecular dynamics simulations

DEFF Research Database (Denmark)

Jensen, Morten Østergaard; Jensen, T.R.; Kjær, Kristian

2002-01-01

Electron density profiles calculated from molecular dynamics trajectories are used to deduce the orientation and conformation of Thermomyces lanuginosa lipase and a mutant adsorbed at an air-water interface. It is demonstrated that the profiles display distinct fine structures, which uniquely...... characterize enzyme orientation and conformation. The density profiles are, on the nanosecond timescale, determined by the average enzyme conformation. We outline a Computational scheme that from a single molecular dynamics trajectory allows for extraction of electron density profiles referring to different...

Constructing large scale SCI-based processing systems by switch elements

International Nuclear Information System (INIS)

Wu, B.; Kristiansen, E.; Skaali, B.; Bogaerts, A.; Divia, R.; Mueller, H.

1993-05-01

The goal of this paper is to study some of the design criteria for the switch elements to form the interconnection of large scale SCI-based processing systems. The approved IEEE standard 1596 makes it possible to couple up to 64K nodes together. In order to connect thousands of nodes to construct large scale SCI-based processing systems, one has to interconnect these nodes by switch elements to form different topologies. A summary of the requirements and key points of interconnection networks and switches is presented. Two models of the SCI switch elements are proposed. The authors investigate several examples of systems constructed for 4-switches with simulations and the results are analyzed. Some issues and enhancements are discussed to provide the ideas behind the switch design that can improve performance and reduce latency. 29 refs., 11 figs., 3 tabs

Finite Volume Method for Pricing European Call Option with Regime-switching Volatility

Science.gov (United States)

Lista Tauryawati, Mey; Imron, Chairul; Putri, Endah RM

2018-03-01

In this paper, we present a finite volume method for pricing European call option using Black-Scholes equation with regime-switching volatility. In the first step, we formulate the Black-Scholes equations with regime-switching volatility. we use a finite volume method based on fitted finite volume with spatial discretization and an implicit time stepping technique for the case. We show that the regime-switching scheme can revert to the non-switching Black Scholes equation, both in theoretical evidence and numerical simulations.

Selection Criteria in Regime Switching Conditional Volatility Models

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Thomas Chuffart

2015-05-01

Full Text Available A large number of nonlinear conditional heteroskedastic models have been proposed in the literature. Model selection is crucial to any statistical data analysis. In this article, we investigate whether the most commonly used selection criteria lead to choice of the right specification in a regime switching framework. We focus on two types of models: the Logistic Smooth Transition GARCH and the Markov-Switching GARCH models. Simulation experiments reveal that information criteria and loss functions can lead to misspecification ; BIC sometimes indicates the wrong regime switching framework. Depending on the Data Generating Process used in the experiments, great care is needed when choosing a criterion.

Noise analysis of switched integrator preamplifiers

International Nuclear Information System (INIS)

Sun Hongbo; Li Yulan; Zhu Weibin

2004-01-01

The main noise sources of switched integrator preamplifiers are discussed, and their noise performance are given combined PSpice simulation and experiments on them. Then, some practical methods on how to reduce noise of preamplifiers in two different integrator modes are provided. (authors)

Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

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Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

2016-05-24

DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

Conformational transition paths harbor structures useful for aiding drug discovery and understanding enzymatic mechanisms in protein kinases.

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Wong, Chung F

2016-01-01

This short article examines the usefulness of fast simulations of conformational transition paths in elucidating enzymatic mechanisms and guiding drug discovery for protein kinases. It applies the transition path method in the MOIL software package to simulate the paths of conformational transitions between six pairs of structures from the Protein Data Bank. The structures along the transition paths were found to resemble experimental structures that mimic transient structures believed to form during enzymatic catalysis or conformational transitions, or structures that have drug candidates bound. These findings suggest that such simulations could provide quick initial insights into the enzymatic mechanisms or pathways of conformational transitions of proteins kinases, or could provide structures useful for aiding structure-based drug design. © 2015 The Protein Society.

Behavioral plasticity through the modulation of switch neurons.

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Vassiliades, Vassilis; Christodoulou, Chris

2016-02-01

A central question in artificial intelligence is how to design agents capable of switching between different behaviors in response to environmental changes. Taking inspiration from neuroscience, we address this problem by utilizing artificial neural networks (NNs) as agent controllers, and mechanisms such as neuromodulation and synaptic gating. The novel aspect of this work is the introduction of a type of artificial neuron we call "switch neuron". A switch neuron regulates the flow of information in NNs by selectively gating all but one of its incoming synaptic connections, effectively allowing only one signal to propagate forward. The allowed connection is determined by the switch neuron's level of modulatory activation which is affected by modulatory signals, such as signals that encode some information about the reward received by the agent. An important aspect of the switch neuron is that it can be used in appropriate "switch modules" in order to modulate other switch neurons. As we show, the introduction of the switch modules enables the creation of sequences of gating events. This is achieved through the design of a modulatory pathway capable of exploring in a principled manner all permutations of the connections arriving on the switch neurons. We test the model by presenting appropriate architectures in nonstationary binary association problems and T-maze tasks. The results show that for all tasks, the switch neuron architectures generate optimal adaptive behaviors, providing evidence that the switch neuron model could be a valuable tool in simulations where behavioral plasticity is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional Architecture of the Outer Arm Dynein Conformational Switch*

Science.gov (United States)

King, Stephen M.; Patel-King, Ramila S.

2012-01-01

Dynein light chain 1 (LC1/DNAL1) is one of the most highly conserved components of ciliary axonemal outer arm dyneins, and it associates with both a heavy chain motor unit and tubulin located within the A-tubule of the axonemal outer doublet microtubules. In a variety of model systems, lack of LC1 or expression of mutant forms leads to profound defects in ciliary motility, including the failure of the hydrodynamic coupling needed for ciliary metachronal synchrony, random stalling during the power/recovery stroke transition, an aberrant response to imposed viscous load, and in some cases partial failure of motor assembly. These phenotypes have led to the proposal that LC1 acts as part of a mechanical switch to control motor function in response to alterations in axonemal curvature. Here we have used NMR chemical shift mapping to define the regions perturbed by a series of mutations in the C-terminal domain that yield a range of phenotypic effects on motility. In addition, we have identified the subdomain of LC1 involved in binding microtubules and characterized the consequences of an Asn → Ser alteration within the terminal leucine-rich repeat that in humans causes primary ciliary dyskinesia. Together, these data define a series of functional subdomains within LC1 and allow us to propose a structural model for the organization of the dynein heavy chain-LC1-microtubule ternary complex that is required for the coordinated activity of dynein motors in cilia. PMID:22157010

Contribution to the electrothermal simulation in power electronics. Development of a simulation methodology applied to switching circuits under variable operating conditions; Contribution a la simulation electrothermique en electronique de puissance. Developpement d`une methode de simulation pour circuits de commutation soumis a des commandes variables

Energy Technology Data Exchange (ETDEWEB)

Vales, P.

1997-03-19

In modern hybrid or monolithic integrated power circuits, electrothermal effects can no longer be ignored. A methodology is proposed in order to simulate electrothermal effects in power circuits, with a significant reduction of the computation time while taking into account electrical and thermal time constants which are usually widely different. A supervising program, written in Fortran, uses system call sequences and manages an interactive dialog between a fast thermal simulator and a general electrical simulator. This explicit coupling process between two specific simulators requires a multi-task operating system. The developed software allows for the prediction of the electrothermal power dissipation drift in the active areas of components, and the prediction of thermally-induced coupling effects between adjacent components. An application to the study of hard switching circuits working under variable operating conditions is presented

Geometric decomposition of the conformation tensor in viscoelastic turbulence

Science.gov (United States)

Hameduddin, Ismail; Meneveau, Charles; Zaki, Tamer A.; Gayme, Dennice F.

2018-05-01

This work introduces a mathematical approach to analysing the polymer dynamics in turbulent viscoelastic flows that uses a new geometric decomposition of the conformation tensor, along with associated scalar measures of the polymer fluctuations. The approach circumvents an inherent difficulty in traditional Reynolds decompositions of the conformation tensor: the fluctuating tensor fields are not positive-definite and so do not retain the physical meaning of the tensor. The geometric decomposition of the conformation tensor yields both mean and fluctuating tensor fields that are positive-definite. The fluctuating tensor in the present decomposition has a clear physical interpretation as a polymer deformation relative to the mean configuration. Scalar measures of this fluctuating conformation tensor are developed based on the non-Euclidean geometry of the set of positive-definite tensors. Drag-reduced viscoelastic turbulent channel flow is then used an example case study. The conformation tensor field, obtained using direct numerical simulations, is analysed using the proposed framework.

Controlled perturbation-induced switching in pulse-coupled oscillator networks

International Nuclear Information System (INIS)

Schittler Neves, Fabio; Timme, Marc

2009-01-01

Pulse-coupled systems such as spiking neural networks exhibit nontrivial invariant sets in the form of attracting yet unstable saddle periodic orbits where units are synchronized into groups. Heteroclinic connections between such orbits may in principle support switching processes in these networks and enable novel kinds of neural computations. For small networks of coupled oscillators, we here investigate under which conditions and how system symmetry enforces or forbids certain switching transitions that may be induced by perturbations. For networks of five oscillators, we derive explicit transition rules that for two cluster symmetries deviate from those known from oscillators coupled continuously in time. A third symmetry yields heteroclinic networks that consist of sets of all unstable attractors with that symmetry and the connections between them. Our results indicate that pulse-coupled systems can reliably generate well-defined sets of complex spatiotemporal patterns that conform to specific transition rules. We briefly discuss possible implications for computation with spiking neural systems.

Controlled perturbation-induced switching in pulse-coupled oscillator networks

Energy Technology Data Exchange (ETDEWEB)

Schittler Neves, Fabio; Timme, Marc [Network Dynamics Group, Max Planck Institute for Dynamics and Self-Organization, Goettingen, D-37073 (Germany); Bernstein Center for Computational Neuroscience (BCCN), Goettingen (Germany)], E-mail: neves@nld.ds.mpg.de, E-mail: timme@nld.ds.mpg.de

2009-08-28

Pulse-coupled systems such as spiking neural networks exhibit nontrivial invariant sets in the form of attracting yet unstable saddle periodic orbits where units are synchronized into groups. Heteroclinic connections between such orbits may in principle support switching processes in these networks and enable novel kinds of neural computations. For small networks of coupled oscillators, we here investigate under which conditions and how system symmetry enforces or forbids certain switching transitions that may be induced by perturbations. For networks of five oscillators, we derive explicit transition rules that for two cluster symmetries deviate from those known from oscillators coupled continuously in time. A third symmetry yields heteroclinic networks that consist of sets of all unstable attractors with that symmetry and the connections between them. Our results indicate that pulse-coupled systems can reliably generate well-defined sets of complex spatiotemporal patterns that conform to specific transition rules. We briefly discuss possible implications for computation with spiking neural systems.

An Element of Determinism in a Stochastic Flagellar Motor Switch.

Science.gov (United States)

Xie, Li; Altindal, Tuba; Wu, Xiao-Lun

2015-01-01

Marine bacterium Vibrio alginolyticus uses a single polar flagellum to navigate in an aqueous environment. Similar to Escherichia coli cells, the polar flagellar motor has two states; when the motor is counter-clockwise, the cell swims forward and when the motor is clockwise, the cell swims backward. V. alginolyticus also incorporates a direction randomization step at the start of the forward swimming interval by flicking its flagellum. To gain an understanding on how the polar flagellar motor switch is regulated, distributions of the forward Δf and backward Δb intervals are investigated herein. We found that the steady-state probability density functions, P(Δf) and P(Δb), of freely swimming bacteria are strongly peaked at a finite time, suggesting that the motor switch is not Poissonian. The short-time inhibition is sufficiently strong and long lasting, i.e., several hundred milliseconds for both intervals, which is readily observed and characterized. Treating motor reversal dynamics as a first-passage problem, which results from conformation fluctuations of the motor switch, we calculated P(Δf) and P(Δb) and found good agreement with the measurements.

Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6

Science.gov (United States)

Dai, Yawei; Seeger, Markus; Weng, Jingwei; Song, Song; Wang, Wenning; Tan, Yan-Wen

2016-08-01

Cellular informational and metabolic processes are propagated with specific membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain neurons and plays a critical role in the membrane-trafficking process. Studies suggested that Ykt6 undergoes a conformational change at the interface between its longin domain and the SNARE core. In this work, we study the conformational state distributions and dynamics of rat Ykt6 by means of single-molecule Förster Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation Spectroscopy (FCCS). We observed that intramolecular conformational dynamics between longin domain and SNARE core occurred at the timescale ~200 μs. Furthermore, this dynamics can be regulated and even eliminated by the presence of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have shown that, the SNARE core exhibits a flexible structure while the longin domain retains relatively stable in apo state. Combining single molecule experiments and theoretical MD simulations, we are the first to provide a quantitative dynamics of Ykt6 and explain the functional conformational change from a qualitative point of view.

A Polymerization-Associated Structural Switch in FtsZ That Enables Treadmilling of Model Filaments

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James M. Wagstaff

2017-05-01

Full Text Available Bacterial cell division in many organisms involves a constricting cytokinetic ring that is orchestrated by the tubulin-like protein FtsZ. FtsZ forms dynamic filaments close to the membrane at the site of division that have recently been shown to treadmill around the division ring, guiding septal wall synthesis. Here, using X-ray crystallography of Staphylococcus aureus FtsZ (SaFtsZ, we reveal how an FtsZ can adopt two functionally distinct conformations, open and closed. The open form is found in SaFtsZ filaments formed in crystals and also in soluble filaments of Escherichia coli FtsZ as deduced by electron cryomicroscopy. The closed form is found within several crystal forms of two nonpolymerizing SaFtsZ mutants and corresponds to many previous FtsZ structures from other organisms. We argue that FtsZ’s conformational switch is polymerization-associated, driven by the formation of the longitudinal intersubunit interfaces along the filament. We show that such a switch provides explanations for both how treadmilling may occur within a single-stranded filament and why filament assembly is cooperative.

Fabrication of a Micromachined Capacitive Switch Using the CMOS-MEMS Technology

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Cheng-Yang Lin

2015-11-01

Full Text Available The study investigates the design and fabrication of a micromachined radio frequency (RF capacitive switch using the complementary metal oxide semiconductor-microelectromechanical system (CMOS-MEMS technology. The structure of the micromachined switch is composed of a membrane, eight springs, four inductors, and coplanar waveguide (CPW lines. In order to reduce the actuation voltage of the switch, the springs are designed as low stiffness. The finite element method (FEM software CoventorWare is used to simulate the actuation voltage and displacement of the switch. The micromachined switch needs a post-CMOS process to release the springs and membrane. A wet etching is employed to etch the sacrificial silicon dioxide layer, and to release the membrane and springs of the switch. Experiments show that the pull-in voltage of the switch is 12 V. The switch has an insertion loss of 0.8 dB at 36 GHz and an isolation of 19 dB at 36 GHz.

Allosteric substrate switching in a voltage-sensing lipid phosphatase.

Science.gov (United States)

Grimm, Sasha S; Isacoff, Ehud Y

2016-04-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis.

Allosteric substrate switching in a voltage sensing lipid phosphatase

Science.gov (United States)

Grimm, Sasha S.; Isacoff, Ehud Y.

2016-01-01

Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We find the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), to have not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage sensing domain (VSD). Using fast FRET reporters of PIPs to monitor enzyme activity and voltage clamp fluorometry to monitor conformational changes in the VSD, we find that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This novel 2-step allosteric control over a dual specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility and endo/exocytosis. PMID:26878552

Integrated Very High Frequency Switch Mode Power Supplies: Design Considerations

DEFF Research Database (Denmark)

Hertel, Jens Christian; Nour, Yasser; Knott, Arnold

2017-01-01

simulations. The required spiral inductors was modeled, and simulations show Q values of as high as 14 at a switching frequency of 250 MHz. Simulations of the converter show an efficiency of 55 % with a self oscillating gate drive. However the modeled inductor was not adequate for operating with the self...

Synchronization of switched system and application in communication

International Nuclear Information System (INIS)

Yu Wenwu; Cao Jinde; Yuan Kun

2008-01-01

In this Letter, synchronization of switched system is investigated based on Lyapunov method. A sufficient condition is derived to ensure the synchronization between two switched systems, and a new communication scheme is also proposed based on this. Furthermore, some secure analysis works, such as return map attack and moving average error attack, are also given to show the security of the proposed scheme. Finally, simulation examples are constructed to verify the theoretical analysis and its application for communication

Workers’ Conformism

Directory of Open Access Journals (Sweden)

Nikolay Ivantchev

2013-10-01

Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

Investigation on Capacitor Switching Transient Limiter with a Three phase Variable Resistance

DEFF Research Database (Denmark)

Naderi, Seyed Behzad; Jafari, Mehdi; Zandnia, Amir

2017-01-01

In this paper, a capacitor switching transient limiter based on a three phase variable resistance is proposed. The proposed structure eliminates the capacitor switching transient current and over-voltage by introducing a variable resistance to the current path with its special switching pattern...... transients on capacitor after bypassing. Analytic Analyses for this structure in transient cases are presented in details and simulations are performed by MATLAB software to prove its effectiveness....

Conformational control of the binding of the transactivation domain of the MLL protein and c-Myb to the KIX domain of CREB.

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Elif Nihal Korkmaz

Full Text Available The KIX domain of CBP is a transcriptional coactivator. Concomitant binding to the activation domain of proto-oncogene protein c-Myb and the transactivation domain of the trithorax group protein mixed lineage leukemia (MLL transcription factor lead to the biologically active ternary MLL∶KIX∶c-Myb complex which plays a role in Pol II-mediated transcription. The binding of the activation domain of MLL to KIX enhances c-Myb binding. Here we carried out molecular dynamics (MD simulations for the MLL∶KIX∶c-Myb ternary complex, its binary components and KIX with the goal of providing a mechanistic explanation for the experimental observations. The dynamic behavior revealed that the MLL binding site is allosterically coupled to the c-Myb binding site. MLL binding redistributes the conformational ensemble of KIX, leading to higher populations of states which favor c-Myb binding. The key element in the allosteric communication pathways is the KIX loop, which acts as a control mechanism to enhance subsequent binding events. We tested this conclusion by in silico mutations of loop residues in the KIX∶MLL complex and by comparing wild type and mutant dynamics through MD simulations. The loop assumed MLL binding conformation similar to that observed in the KIX∶c-Myb state which disfavors the allosteric network. The coupling with c-Myb binding site faded, abolishing the positive cooperativity observed in the presence of MLL. Our major conclusion is that by eliciting a loop-mediated allosteric switch between the different states following the binding events, transcriptional activation can be regulated. The KIX system presents an example how nature makes use of conformational control in higher level regulation of transcriptional activity and thus cellular events.

Trapping a Knot into Tight Conformations by Intra-Chain Repulsions

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Liang Dai

2017-02-01

Full Text Available Knots can occur in biopolymers such as DNA and peptides. In our previous study, we systematically investigated the effects of intra-chain interactions on knots and found that long-range repulsions can surprisingly tighten knots. Here, we use this knowledge to trap a knot into tight conformations in Langevin dynamics simulations. By trapping, we mean that the free energy landscape with respect to the knot size exhibits a potential well around a small knot size in the presence of long-range repulsions, and this potential can well lead to long-lived tight knots when its depth is comparable to or larger than thermal energy. We tune the strength of intra-chain repulsion such that a knot is weakly trapped. Driven by thermal fluctuations, the knot can escape from the trap and is then re-trapped. We find that the knot switches between tight and loose conformations—referred to as “knot breathing”. We use a Yukawa potential to model screened electrostatic interactions to explore the relevance of knot trapping and breathing in charged biopolymers. We determine the minimal screened length and the minimal strength of repulsion for knot trapping. We find that Coulomb-induced knot trapping is possible to occur in single-stranded DNA and peptides for normal ionic strengths.

Self Organizing Maps to efficiently cluster and functionally interpret protein conformational ensembles

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Fabio Stella

2013-09-01

Full Text Available An approach that combines Self-Organizing maps, hierarchical clustering and network components is presented, aimed at comparing protein conformational ensembles obtained from multiple Molecular Dynamic simulations. As a first result the original ensembles can be summarized by using only the representative conformations of the clusters obtained. In addition the network components analysis allows to discover and interpret the dynamic behavior of the conformations won by each neuron. The results showed the ability of this approach to efficiently derive a functional interpretation of the protein dynamics described by the original conformational ensemble, highlighting its potential as a support for protein engineering.

Soft switching PWM isolated boost converter for fuel cell application

Energy Technology Data Exchange (ETDEWEB)

Rezaei, M.; Adib, E. [Isfahan Univ. of Technology, Isfahan (Iran, Islamic Republic of)

2009-07-01

This presentation introduced a newly developed soft switching, isolated boost type converter for fuel cell applications. With a simple PWM control circuit, the converter achieves zero voltage switching the main switch. Since the auxiliary circuit is soft switched, the converter can operate at high powers which make it suitable for fuel cell applications. In particular, the converter is suitable for the interface of fuel cell and inverters because of its high voltage gain and isolation between input and output sources. In addition, the input current of the converter (current drained from the fuel cell) is almost constant since it is a boost type converter. The converter was analyzed and the simulation results validate the theoretical analysis.

A Novel Soft-Switching Synchronous Buck Converter for Portable Applications

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Anup Kumar Panda

2008-01-01

Full Text Available This paper proposes a zero-voltage-transition (ZVT pulse-width-modulated (PWM synchronous buck converter, which is designed to operate at low voltage and high efficiency typically required for portable systems. A new passive auxiliary circuit that allows the main switch to operate with zero-voltage switching has been incorporated in the conventional PWM synchronous buck converter. The operation principles and a detailed steady-state analysis of the ZVT-PWM synchronous converter implemented with the auxiliary circuit are presented. Besides, the main switch and all of the semiconductor devices operate under soft-switching conditions. Thus, the auxiliary circuit provides a larger overall efficiency. The feasibility of the auxiliary circuit is confirmed by simulation and experimental results.

Conformation radiotherapy and conformal radiotherapy

International Nuclear Information System (INIS)

Morita, Kozo

1999-01-01

In order to coincide the high dose region to the target volume, the 'Conformation Radiotherapy Technique' using the multileaf collimator and the device for 'hollow-out technique' was developed by Prof. S. Takahashi in 1960. This technique can be classified a type of 2D-dynamic conformal RT techniques. By the clinical application of this technique, the late complications of the lens, the intestine and the urinary bladder after radiotherapy for the maxillary cancer and the cervical cancer decreased. Since 1980's the exact position and shape of the tumor and the surrounding normal tissues can be easily obtained by the tremendous development of the CT/MRI imaging technique. As a result, various kinds of new conformal techniques such as the 3D-CRT, the dose intensity modulation, the tomotherapy have been developed since the beginning of 1990'. Several 'dose escalation study with 2D-/3D conformal RT' is now under way to improve the treatment results. (author)

A Tunable Cyclic Container: Guest-Induced Conformational Switching, Efficient Guest Exchange, and Selective Isolation of C70 from a Fullerene Mixture.

Science.gov (United States)

Mondal, Pritam; Rath, Sankar Prasad

2017-07-18

An adaptable cyclic porphyrin dimer with highly flexible linkers has been used as an artificial molecular container that can efficiently encapsulate various aromatic guests (TCNQ/C 60 /C 70 ) through strong π-π interactions by adjusting its cavity size and conformation. The planar aromatic guest (TCNQ) can be easily and selectively exchanged with larger aromatic guests (C 60 /C 70 ). During the guest-exchange process, the two porphyrin rings switch their relative orientation according to the size and shape of the guests. This behavior of the cyclic container has been thoroughly investigated by using UV/Vis spectroscopy, NMR spectroscopy, and X-ray crystal structure determination of the host-guest assemblies. The electrochemical and photophysical studies demonstrated the occurrence of photoinduced electron transfer from bisporphyrin to TCNQ/C 60 /C 70 in the respective host-guest assemblies. The cyclic host can form complexes with C 60 and C 70 with association constants of (2.8±0.2)×10 5 and (1.9±0.3)×10 8  m -1 , respectively; the latter value represents the highest binding affinity for C 70 reported so far for zinc(II) bisporphyrinic receptors. This high selectivity for the binding of C 70 versus C 60 allows the easy extraction and efficient isolation of C 70 from a C 60 /C 70 fullerene mixture. Experimental evidence was substantiated by DFT calculations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resistive switching in Pt/TiO{sub 2}/Pt

Energy Technology Data Exchange (ETDEWEB)

Jeong, Doo Seok

2008-08-15

Recently, the resistive switching behavior in TiO{sub 2} has drawn attention due to its application to resistive random access memory (RRAM) devices. TiO{sub 2} shows characteristic non-volatile resistive switching behavior, i.e. reversible switching between a high resistance state (HRS) and a low resistance state (LRS). Both unipolar resistive switching (URS) and bipolar resistive switching (BRS) are found to be observed in TiO{sub 2} depending on the compliance current for the electroforming. In this thesis the characteristic current-voltage (I-V) hysteresis in three different states of TiO{sub 2}, pristine, URS-activated, and BRS-activated states, was investigated and understood in terms of the migration of oxygen vacancies in TiO{sub 2}. The I-V hysteresis of pristine TiO{sub 2} was found to show volatile behavior. That is, the temporary variation of the resistance took place depending on the applied voltage. However, the I-V hysteresis of URS- and BRS-activated states showed non-volatile resistive switching behavior. Some evidences proving the evolution of oxygen gas during electroforming were obtained from time-of-flight secondary ion mass spectroscopy analysis and the variation of the morphology of switching cells induced by the electroforming. On the assumption that a large number of oxygen vacancies are introduced by the electroforming process, the I-V behavior in electroformed switching cells was simulated with varying the distribution of oxygen vacancies in electroformed TiO{sub x} (x simulated with taking into consideration oxygen formation/annihilation reactions at a Pt/TiO{sub x} interface. The oxygen-related reactions given as a function of the applied voltage affect the distribution of oxygen vacancies in TiO{sub x}, consequently, the Schottky barrier height at the cathode/TiO{sub x} interface is influenced by the oxygen vacancy distribution. Therefore, the BRS behavior including the

Killing tensors and conformal Killing tensors from conformal Killing vectors

International Nuclear Information System (INIS)

Rani, Raffaele; Edgar, S Brian; Barnes, Alan

2003-01-01

Koutras has proposed some methods to construct reducible proper conformal Killing tensors and Killing tensors (which are, in general, irreducible) when a pair of orthogonal conformal Killing vectors exist in a given space. We give the completely general result demonstrating that this severe restriction of orthogonality is unnecessary. In addition, we correct and extend some results concerning Killing tensors constructed from a single conformal Killing vector. A number of examples demonstrate that it is possible to construct a much larger class of reducible proper conformal Killing tensors and Killing tensors than permitted by the Koutras algorithms. In particular, by showing that all conformal Killing tensors are reducible in conformally flat spaces, we have a method of constructing all conformal Killing tensors, and hence all the Killing tensors (which will in general be irreducible) of conformally flat spaces using their conformal Killing vectors

Modeling of switching energy of magnetic tunnel junction devices with tilted magnetization

International Nuclear Information System (INIS)

Surawanitkun, C.; Kaewrawang, A.; Siritaratiwat, A.; Kruesubthaworn, A.; Sivaratana, R.; Jutong, N.; Mewes, C.K.A.; Mewes, T.

2015-01-01

For spin transfer torque (STT), the switching energy and thermal stability of magnetic tunnel junctions (MTJ) bits utilized in memory devices are important factors that have to be considered simultaneously. In this article, we examined the minimum energy for STT induced magnetization switching in MTJ devices for different in-plane angles of the magnetization in the free layer and the pinned layer with respect to the major axis of the elliptical cylinder of the cell. Simulations were performed by comparing the analytical solution with macrospin and full micromagnetic calculations. The results show good agreement of the switching energy calculated by using the three approaches for different initial angles of the magnetization of the free layer. Also, the low-energy location specifies the suitable value of both time and current in order to reduce the heat effect during the switching process. - Highlights: • Switching energy model was firstly examined with tiled magnetization in STT-RAM. • Simulation was performed by analytical solution, macrospin and micromagnetic models. • Low energy results from three models show agreement for tilt angle in free layer. • We also found an optimal tilt angle of the pinned layer. • Low-energy location specifies the suitable switching location to reduce heat effect

Current-driven thermo-magnetic switching in magnetic tunnel junctions

Science.gov (United States)

Kravets, A. F.; Polishchuk, D. M.; Pashchenko, V. A.; Tovstolytkin, A. I.; Korenivski, V.

2017-12-01

We investigate switching of magnetic tunnel junctions (MTJs) driven by the thermal effect of the transport current through the junctions. The switching occurs in a specially designed composite free layer, which acts as one of the MTJ electrodes, and is due to a current-driven ferro-to-paramagnetic Curie transition with the associated exchange decoupling within the free layer leading to magnetic reversal. We simulate the current and heat propagation through the device and show how heat focusing can be used to improve the power efficiency. The Curie-switch MTJ demonstrated in this work has the advantage of being highly tunable in terms of its operating temperature range, conveniently to or just above room temperature, which can be of technological significance and competitive with the known switching methods using spin-transfer torques.

Steered molecular dynamics simulations of a bacterial type IV pilus reveal characteristics of an experimentally-observed, force-induced conformational transition

Science.gov (United States)

Baker, Joseph; Biais, Nicolas; Tama, Florence

2011-10-01

Type IV pili (T4P) are long, filamentous structures that emanate from the cellular surface of many infectious bacteria. They are built from a 158 amino acid long subunit called pilin. T4P can grow to many micrometers in length, and can withstand large tension forces. During the infection process, pili attach themselves to host cells, and therefore naturally find themselves under tension. We investigated the response of a T4 pilus to a pulling force using the method of steered molecular dynamics (SMD) simulation. Our simulations expose to the external environment an amino acid sequence initially hidden in the native filament, in agreement with experimental data. Therefore, our simulations might be probing the initial stage of the transition to a force-induced conformation of the T4 pilus. Additional exposed amino acid sequences that might be useful targets for drugs designed to mitigate bacterial infection were also predicted.

A novel RF MEMS switch with novel mechanical structure modeling

International Nuclear Information System (INIS)

Chan, K Y; Ramer, R

2010-01-01

A novel RF MEMS contact-type switch for RF and microwave applications is presented. The switch is designed with special mechanical structures for stiffness enhancement. A method of using dimple lines to reduce the stress sensitivity of a beam is shown with complete mathematical modeling and finite element mechanical simulation. A complete mathematical model is developed for the proposed switch. Limited fabrication resolution and non-uniformities in layer thickness and stress were taken into consideration for this design, concomitantly with the preservation of device miniaturization and functionalities. The novel mechanical modeling of the switch leads to the estimation of the actuation voltage and shows simplification from previously published analysis. The measured actuation voltage and RF performance of the novel RF MEMS switch are also reported. The switch actuated at 20 V achieved better than 22 dB return loss and less than 0.7 dB insertion loss in on state from dc–40 GHz; it provided better than 30 dB isolation in off state

Research on IGBT solid state switch

CERN Document Server

Gan Kong Yin; Wang Xiao Feng; Wang Lang Ping; Wang Song Yan; Chu, P K; Wu Hong Chen

2002-01-01

The experiments on the IGBT solid state switch for induction accelerator was carried out with two series 1.2 kV, 75 A IGBT (GA75TS120U). The static and dynamic balancing modules were carried out with metal oxide varistors, capacities and diodes in order to suppress the over-voltage during IGBT on and off. Experimental results show that IGBT solid state switch works very stable under the different conditions. It can output peak voltage 1.8 kV, rise time 300 ns, fall time 1.64 mu s waveforms on the loads. The simulation data using OrCAD are in accord with experimental results except the rise time

Research on IGBT solid state switch

International Nuclear Information System (INIS)

Gan Kongyin; Tang Baoyin; Wang Xiaofeng; Wang Langping; Wang Songyan; Wu Hongchen

2002-01-01

The experiments on the IGBT solid state switch for induction accelerator was carried out with two series 1.2 kV, 75 A IGBT (GA75TS120U). The static and dynamic balancing modules were carried out with metal oxide varistors, capacities and diodes in order to suppress the over-voltage during IGBT on and off. Experimental results show that IGBT solid state switch works very stable under the different conditions. It can output peak voltage 1.8 kV, rise time 300 ns, fall time 1.64 μs waveforms on the loads. The simulation data using OrCAD are in accord with experimental results except the rise time

Role of non-equilibrium conformations on driven polymer translocation.

Science.gov (United States)

Katkar, H H; Muthukumar, M

2018-01-14

One of the major theoretical methods in understanding polymer translocation through a nanopore is the Fokker-Planck formalism based on the assumption of quasi-equilibrium of polymer conformations. The criterion for applicability of the quasi-equilibrium approximation for polymer translocation is that the average translocation time per Kuhn segment, ⟨τ⟩/N K , is longer than the relaxation time τ 0 of the polymer. Toward an understanding of conditions that would satisfy this criterion, we have performed coarse-grained three dimensional Langevin dynamics and multi-particle collision dynamics simulations. We have studied the role of initial conformations of a polyelectrolyte chain (which were artificially generated with a flow field) on the kinetics of its translocation across a nanopore under the action of an externally applied transmembrane voltage V (in the absence of the initial flow field). Stretched (out-of-equilibrium) polyelectrolyte chain conformations are deliberately and systematically generated and used as initial conformations in translocation simulations. Independent simulations are performed to study the relaxation behavior of these stretched chains, and a comparison is made between the relaxation time scale and the mean translocation time (⟨τ⟩). For such artificially stretched initial states, ⟨τ⟩/N K polymers including single stranded DNA (ssDNA), double stranded DNA (dsDNA), and synthetic polymers. Even when these data are rescaled assuming a constant effective velocity of translocation, it is found that for flexible (ssDNA and synthetic) polymers with N K Kuhn segments, the condition ⟨τ⟩/N K polymers such as ssDNA, a crossover from quasi-equilibrium to non-equilibrium behavior would occur at N K ∼ O(1000).

Electron induced conformational changes of an imine-based molecular switch on a Au(111) surface

Energy Technology Data Exchange (ETDEWEB)

Lotze, Christian; Henningsen, Nils; Franke, Katharina; Schulze, Gunnar; Pascual, Jose Ignacio [Inst. f. Experimentalphysik, Freie Universitaet Berlin (Germany); Luo, Ying; Haag, Rainer [Inst. f. Organische Chemie, Freie Universitaet Berlin (Germany)

2009-07-01

Azobenzene-based molecules exhibit a cis-trans configurational photoisomerisation in solution. Recently, the adsorption properties of azobenzene derivatives have been investigated on different metal surfaces in order to explore the possible changes in the film properties induced by external stimuli. In azobenzene, the diazo-bridge is a key group for the isomerization process. Its interaction with a metal surface is dominated through the N lone-pair electrons, which reduces the efficiency of the conformational change. In order to reduce the molecule-surface interaction, we explore an alternative molecular architecture by substituting the diazo-bridge (-N=N-) of azobenzene by an imine-group (-N=CH-). We have investigated the imine-based compound para-carboxyl-di-benzene-imine (PCI) adsorbed on a Au(111) surface. The carboxylic terminations mediates the formation of strongly bonded molecular dimers, which align in ordered rows preferentially following the fcc regions of the Au(111) herringbone reconstruction. Low temperature scanning tunneling microscopy was used to induce conformational changes between trans and cis state of individual molecules in a molecular monolayer.

Controlled lid-opening in Thermomyces lanuginosus lipase- An engineered switch for studying lipase function

DEFF Research Database (Denmark)

Skjold-Jørgensen, Jakob; Vind, Jesper; Moroz, Olga V.

2017-01-01

Here, we present a lipase mutant containing a biochemical switch allowing a controlled opening and closing of the lid independent of the environment. The closed form of the TlL mutant shows low binding to hydrophobic surfaces compared to the binding observed after activating the controlled switch...... inducing lid-opening. We directly show that lipid binding of this mutant is connected to an open lid conformation demonstrating the impact of the exposed amino acid residues and their participation in binding at the water-lipid interface. The switch was created by introducing two cysteine residues......-D measurements revealed a seven-fold increase in binding rate for the unlocked lipase. The TlL_locked mutant shows structural changes across the protein important for understanding the mechanism of lid-opening and closing. Our experimental results reveal sites of interest for future mutagenesis studies aimed...

IGBT Dynamic Loss Reduction through Device Level Soft Switching

Directory of Open Access Journals (Sweden)

Lan Ma

2018-05-01

Full Text Available Due to its low conduction loss, hence high current ratings, as well as low cost, Silicon Insulated Gate Bipolar Transistor (Si IGBT is widely used in high power applications. However, its switching frequency is generally low because of relatively large switching losses. Silicon carbide Metal-Oxide-Semiconductor Field-Effect Transistor (SiC MOSFET is much more superior due to their fast switching speed, which is determined by the internal parasitic capacitance instead of the stored charges, like the IGBT. By the combination of SiC MOSFET and Si IGBT, this paper presents a novel series hybrid switching method to achieve IGBT’s dynamic switching loss reduction by switching under Zero Voltage Hard Current (ZVHC turn-on and Zero Current Hard Voltage (ZCHV turn-off conditions. Both simulation and experimental results of IGBT are carried out, which shows that the soft switching of IGBT has been achieved both in turn-on and turn-off period. Thus 90% turn-on loss and 57% turn-off loss are reduced. Two different IGBTs’ test results are also provided to study the modulation parameter’s effect on the turn-off switching loss. Furthermore, with the consideration of voltage and current transient states, a new soft switching classification is proposed. At last, another improved modulation and Highly Efficient and Reliable Inverter Concept (HERIC inverter are given to validate the effectiveness of the device level hybrid soft switching method application.

Quadratic stabilisability of multi-agent systems under switching topologies

Science.gov (United States)

Guan, Yongqiang; Ji, Zhijian; Zhang, Lin; Wang, Long

2014-12-01

This paper addresses the stabilisability of multi-agent systems (MASs) under switching topologies. Necessary and/or sufficient conditions are presented in terms of graph topology. These conditions explicitly reveal how the intrinsic dynamics of the agents, the communication topology and the external control input affect stabilisability jointly. With the appropriate selection of some agents to which the external inputs are applied and the suitable design of neighbour-interaction rules via a switching topology, an MAS is proved to be stabilisable even if so is not for each of uncertain subsystem. In addition, a method is proposed to constructively design a switching rule for MASs with norm-bounded time-varying uncertainties. The switching rules designed via this method do not rely on uncertainties, and the switched MAS is quadratically stabilisable via decentralised external self-feedback for all uncertainties. With respect to applications of the stabilisability results, the formation control and the cooperative tracking control are addressed. Numerical simulations are presented to demonstrate the effectiveness of the proposed results.

Analyses of resource reservation schemes for optical burst switching networks

Science.gov (United States)

Solanska, Michaela; Scholtz, Lubomir; Ladanyi, Libor; Mullerova, Jarmila

2017-12-01

With growing demands of Internet Protocol services for transmission capacity and speed, the Optical Burst Switching presents the solution for future high-speed optical networks. Optical Burst Switching is a technology for transmitting large amounts of data bursts through a transparent optical switching network. To successfully transmit bursts over OBS network and reach the destination node, resource reservation schemes have to be implemented to allocate resources and configure optical switches for that burst at each node. The one-way resource reservation schemes and the performance evaluation of reservation schemes are presented. The OBS network model is performed using OMNeT++ simulation environment. During the reservation of network resources, the optical cross-connect based on semiconductor optical amplifier is used as the core node. Optical switches based on semiconductor optical amplifiers are a promising technology for high-speed optical communication networks.

Analytical and computational study of magnetization switching in kinetic Ising systems with demagnetizing fields

DEFF Research Database (Denmark)

Richards, H.L.; Rikvold, P.A.

1996-01-01

particularly promising as materials for high-density magnetic recording media. In this paper we use analytic arguments and Monte Carlo simulations to quantitatively study the effects of the demagnetizing field on the dynamics of magnetization switching in two-dimensional, single-domain, kinetic Ising systems....... For systems in the weak-field ''stochastic region,'' where magnetization switching is on average effected by the nucleation and growth of a single droplet, the simulation results can be explained by a simple model in which the free energy is a function only of magnetization. In the intermediate......-field ''multidroplet region,'' a generalization of Avrami's law involving a magnetization-dependent effective magnetic field gives good agreement with the simulations. The effects of the demagnetizing field do not qualitatively change the droplet-theoretical picture of magnetization switching in highly anisotropic...

Modelling of Moving Coil Actuators in Fast Switching Valves Suitable for Digital Hydraulic Machines

DEFF Research Database (Denmark)

Nørgård, Christian; Roemer, Daniel Beck; Bech, Michael Møller

2015-01-01

an estimation of the eddy currents generated in the actuator yoke upon current rise, as they may have significant influence on the coil current response. The analytical model facilitates fast simulation of the transient actuator response opposed to the transient electro-magnetic finite element model which......The efficiency of digital hydraulic machines is strongly dependent on the valve switching time. Recently, fast switching have been achieved by using a direct electromagnetic moving coil actuator as the force producing element in fast switching hydraulic valves suitable for digital hydraulic...... machines. Mathematical models of the valve switching, targeted for design optimisation of the moving coil actuator, are developed. A detailed analytical model is derived and presented and its accuracy is evaluated against transient electromagnetic finite element simulations. The model includes...

Modeling of Semiconductor Optical Amplifier Gain Characteristics for Amplification and Switching

Science.gov (United States)

Mahad, Farah Diana; Sahmah, Abu; Supa'at, M.; Idrus, Sevia Mahdaliza; Forsyth, David

2011-05-01

The Semiconductor Optical Amplifier (SOA) is presently commonly used as a booster or pre-amplifier in some communication networks. However, SOAs are also a strong candidate for utilization as multi-functional elements in future all-optical switching, regeneration and also wavelength conversion schemes. With this in mind, the purpose of this paper is to simulate the performance of the SOA for improved amplification and switching functions. The SOA is modeled and simulated using OptSim software. In order to verify the simulated results, a MATLAB mathematical model is also used to aid the design of the SOA. Using the model, the gain difference between simulated and mathematical results in the unsaturated region is <1dB. The mathematical analysis is in good agreement with the simulation result, with only a small offset due to inherent software limitations in matching the gain dynamics of the SOA.

Non-conforming finite-element formulation for cardiac electrophysiology: an effective approach to reduce the computation time of heart simulations without compromising accuracy

Science.gov (United States)

Hurtado, Daniel E.; Rojas, Guillermo

2018-04-01

Computer simulations constitute a powerful tool for studying the electrical activity of the human heart, but computational effort remains prohibitively high. In order to recover accurate conduction velocities and wavefront shapes, the mesh size in linear element (Q1) formulations cannot exceed 0.1 mm. Here we propose a novel non-conforming finite-element formulation for the non-linear cardiac electrophysiology problem that results in accurate wavefront shapes and lower mesh-dependance in the conduction velocity, while retaining the same number of global degrees of freedom as Q1 formulations. As a result, coarser discretizations of cardiac domains can be employed in simulations without significant loss of accuracy, thus reducing the overall computational effort. We demonstrate the applicability of our formulation in biventricular simulations using a coarse mesh size of ˜ 1 mm, and show that the activation wave pattern closely follows that obtained in fine-mesh simulations at a fraction of the computation time, thus improving the accuracy-efficiency trade-off of cardiac simulations.

Explicit mentalizing mechanisms and their adaptive role in memory conformity.

Science.gov (United States)

Wheeler, Rebecca; Allan, Kevin; Tsivilis, Dimitris; Martin, Douglas; Gabbert, Fiona

2013-01-01

Memory conformity occurs when an individual endorses what other individuals remember about past events. Research on memory conformity is currently dominated by a 'forensic' perspective, which views the phenomenon as inherently undesirable. This is because conformity not only distorts the accuracy of an individual's memory, but also produces false corroboration between individuals, effects that act to undermine criminal justice systems. There is growing awareness, however, that memory conformity may be interpreted more generally as an adaptive social behavior regulated by explicit mentalizing mechanisms. Here, we provide novel evidence in support of this emerging alternative theoretical perspective. We carried out a memory conformity experiment which revealed that explicit belief-simulation (i.e. using one's own beliefs to model what other people believe) systematically biases conformity towards like-minded individuals, even when there is no objective evidence that they have a more accurate memory than dissimilar individuals. We suggest that this bias is functional, i.e. adaptive, to the extent that it fosters trust, and hence cooperation, between in-group versus out-group individuals. We conclude that memory conformity is, in more fundamental terms, a highly desirable product of explicit mentalizing mechanisms that promote adaptive forms of social learning and cooperation.

Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

Directory of Open Access Journals (Sweden)

Stella Fabio

2011-05-01

Full Text Available Abstract Background Molecular dynamics (MD simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to

Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

Science.gov (United States)

2011-01-01

Background Molecular dynamics (MD) simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs) were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to conformational ensembles from

The Relationship between Self-Assembly and Conformal Mappings

Science.gov (United States)

Duque, Carlos; Santangelo, Christian

The isotropic growth of a thin sheet has been used as a way to generate programmed shapes through controlled buckling. We discuss how conformal mappings, which are transformations that locally preserve angles, provide a way to quantify the area growth needed to produce a particular shape. A discrete version of the conformal map can be constructed from circle packings, which are maps between packings of circles whose contact network is preserved. This provides a link to the self-assembly of particles on curved surfaces. We performed simulations of attractive particles on a curved surface using molecular dynamics. The resulting particle configurations were used to generate the corresponding discrete conformal map, allowing us to quantify the degree of area distortion required to produce a particular shape by finding particle configurations that minimize the area distortion.

Simulated Tempering Distributed Replica Sampling, Virtual Replica Exchange, and Other Generalized-Ensemble Methods for Conformational Sampling.

Science.gov (United States)

Rauscher, Sarah; Neale, Chris; Pomès, Régis

2009-10-13

Generalized-ensemble algorithms in temperature space have become popular tools to enhance conformational sampling in biomolecular simulations. A random walk in temperature leads to a corresponding random walk in potential energy, which can be used to cross over energetic barriers and overcome the problem of quasi-nonergodicity. In this paper, we introduce two novel methods: simulated tempering distributed replica sampling (STDR) and virtual replica exchange (VREX). These methods are designed to address the practical issues inherent in the replica exchange (RE), simulated tempering (ST), and serial replica exchange (SREM) algorithms. RE requires a large, dedicated, and homogeneous cluster of CPUs to function efficiently when applied to complex systems. ST and SREM both have the drawback of requiring extensive initial simulations, possibly adaptive, for the calculation of weight factors or potential energy distribution functions. STDR and VREX alleviate the need for lengthy initial simulations, and for synchronization and extensive communication between replicas. Both methods are therefore suitable for distributed or heterogeneous computing platforms. We perform an objective comparison of all five algorithms in terms of both implementation issues and sampling efficiency. We use disordered peptides in explicit water as test systems, for a total simulation time of over 42 μs. Efficiency is defined in terms of both structural convergence and temperature diffusion, and we show that these definitions of efficiency are in fact correlated. Importantly, we find that ST-based methods exhibit faster temperature diffusion and correspondingly faster convergence of structural properties compared to RE-based methods. Within the RE-based methods, VREX is superior to both SREM and RE. On the basis of our observations, we conclude that ST is ideal for simple systems, while STDR is well-suited for complex systems.

Replacement between conformity and counter-conformity in consumption decisions.

Science.gov (United States)

Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

2013-02-01

This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.

Study of switching behavior of exchange-coupled nanomagnets by transverse magnetization metrology

Science.gov (United States)

Dey, Himadri S.; Csaba, Gyorgy; Bernstein, Gary H.; Porod, Wolfgang

2017-05-01

We investigate the static switching modes of nanomagnets patterned from antiferromagnetically exchange-coupled magnetic multilayers, and compare them to nanomagnets having only dipole coupling between the ferromagnetic layers. Vibrating sample magnetometry experiments, supported by micromagnetic simulations, reveal two distinct switching mechanisms between the exchange-coupled and only dipole-coupled nanomagnets. The exchange-coupled nanomagnets exhibit gradual switching of the layers, dictated by the strong antiferromagnetic exchange coupling present between the layers. However, the layers of the only dipole-coupled nanomagnets show abrupt nucleation/growth type switching. A comprehensive understanding of the switching modes of such layered and patterned systems can add new insight into the reversal mechanisms of similar systems employed for spintronic and magneto-logic device applications.

Ribosome-induced changes in elongation factor Tu conformation control GTP hydrolysis

DEFF Research Database (Denmark)

Villa, Elizabeth; Sengupta, Jayati; Trabuco, Leonard G.

2009-01-01

In translation, elongation factor Tu (EF-Tu) molecules deliver aminoacyl-tRNAs to the mRNA-programmed ribosome. The GTPase activity of EF-Tu is triggered by ribosome-induced conformational changes of the factor that play a pivotal role in the selection of the cognate aminoacyl-tRNAs. We present a 6.......7-A cryo-electron microscopy map of the aminoacyl-tRNA x EF-Tu x GDP x kirromycin-bound Escherichia coli ribosome, together with an atomic model of the complex obtained through molecular dynamics flexible fitting. The model reveals the conformational changes in the conserved GTPase switch regions...... of EF-Tu that trigger hydrolysis of GTP, along with key interactions, including those between the sarcin-ricin loop and the P loop of EF-Tu, and between the effector loop of EF-Tu and a conserved region of the 16S rRNA. Our data suggest that GTP hydrolysis on EF-Tu is controlled through a hydrophobic...

Switching Investigations on a SiC MOSFET in a TO-247 Package

DEFF Research Database (Denmark)

Anthon, Alexander; Hernandez Botella, Juan Carlos; Zhang, Zhe

2014-01-01

This paper deals with the switching behavior of a SiC MOSFET in a TO-247 package. Based on simulations, critical parasitic inductances in the circuit layout are analyzed and their effect on the switching losses highlighted. Especially the common source inductance, a critical parameter in a TO-247...... package, has a major influence on the switching energy. Crucial design guidelines for an improved double pulse test circuit are introduced which are used for practical investigations on the switching behavior. Switching energies of a SiC MOSFET in a TO-247 package is measured depending on varying gate...... resistance and loop inductances. With total switching energy of 340.24 μJ, the SiC MOSFET has more than six times lower switching losses than a regular Si IGBT. Implementing the SiC switches in a 3 kW T-Type inverter topology, efficiency improvements of 0.8 % are achieved and maximum efficiency of 97...

An approach to evaluate switching overvoltages during power system restoration

Directory of Open Access Journals (Sweden)

Sadeghkhani Iman

2012-01-01

Full Text Available Transformer switching is one of the important stages during power system restoration. This switching can cause harmonic overvoltages that might damage some equipment and delay power system restoration. Core saturation on the energisation of a transformer with residual flux is a noticeable factor in harmonic overvoltages. This work uses artificial neural networks (ANN in order to estimate the temporary overvoltages (TOVs due to transformer energisation. In the proposed methodology, the Levenberg-Marquardt method is used to train the multilayer perceptron. The developed ANN is trained with the worst case of switching condition, and tested for typical cases. Simulated results for a partial 39-bus New England test system, show the proposed technique can accurately estimate the peak values and durations of switching overvoltages.

Activator Protein-1: redox switch controlling structure and DNA-binding

Energy Technology Data Exchange (ETDEWEB)

Yin, Zhou; Machius, Mischa; Nestler, Eric J.; Rudenko, Gabby (Texas-MED); (Icahn)

2017-09-07

The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a ‘redox switch’ centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the ‘OFF’ state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins.

Modular space-vector pulse-width modulation for nine-switch converters

DEFF Research Database (Denmark)

Dehghan, Seyed Mohammad; Amiri, Arash; Mohamadian, Mustafa

2013-01-01

Recently, nine-switch inverter (NSI) has been presented as a dual-output inverter with constant frequency (CF) or different frequency (DF) operation modes. However, the CF mode is more interesting because of its lower switching device rating. This study proposes a new space-vector modulation (SVM......) method for the NSI that supports both the CF and DF modes, whereas conventional SVM of NSI can be used only in the DF mode. The proposed SVM can be easily implemented based on the conventional six-switch inverter SVM modules. The performance of the proposed SVM is verified by the simulation...

High Performance Gigabit Ethernet Switches for DAQ Systems

CERN Document Server

Barczyk, Artur

2005-01-01

Commercially available high performance Gigabit Ethernet (GbE) switches are optimized mostly for Internet and standard LAN application traffic. DAQ systems on the other hand usually make use of very specific traffic patterns, with e.g. deterministic arrival times. Industry's accepted loss-less limit of 99.999% may be still unacceptably high for DAQ purposes, as e.g. in the case of the LHCb readout system. In addition, even switches passing this criteria under random traffic can show significantly higher loss rates if subject to our traffic pattern, mainly due to buffer memory limitations. We have evaluated the performance of several switches, ranging from "pizza-box" devices with 24 or 48 ports up to chassis based core switches in a test-bed capable to emulate realistic traffic patterns as expected in the readout system of our experiment. The results obtained in our tests have been used to refine and parametrize our packet level simulation of the complete LHCb readout network. In this paper we report on the...

Grazing incidence X-ray diffraction study of the tilted phases of Langmuir films: Determination of molecular conformations using simulated annealing

International Nuclear Information System (INIS)

Pignat, J.; Daillant, J.; Cantin, S.; Perrot, F.; Konovalov, O.

2007-01-01

We have analyzed grazing incidence X-ray diffraction (GIXD) data from condensed phases of Langmuir films of long-chain fatty acids at the air-water using a new method consisting in a careful extraction of the structure factors followed by fitting of molecular parameters using simulated annealing. We show that the information contained in GIXD spectra is enough to obtain near-atomic structural information. In particular, we directly determine the orientation of the chain backbone planes and of the carboxylic headgroups, and we evaluate chain conformation defects

Grazing incidence X-ray diffraction study of the tilted phases of Langmuir films: Determination of molecular conformations using simulated annealing

Energy Technology Data Exchange (ETDEWEB)

Pignat, J. [LIONS/Service de Chimie Moleculaire, CEA-Saclay bat. 125, F-91191 Gif-sur-Yvette Cedex (France); LPPI, universite de Cergy-Pontoise, 5 mail Gay-Lussac Neuville/Oise, 95031 Cergy-Pontoise Cedex (France); Daillant, J. [LIONS/Service de Chimie Moleculaire, CEA-Saclay bat. 125, F-91191 Gif-sur-Yvette Cedex (France)]. E-mail: jean.daillant@cea.fr; Cantin, S. [LPPI, universite de Cergy-Pontoise, 5 mail Gay-Lussac Neuville/Oise, 95031 Cergy-Pontoise Cedex (France); Perrot, F. [LPPI, universite de Cergy-Pontoise, 5 mail Gay-Lussac Neuville/Oise, 95031 Cergy-Pontoise Cedex (France); Konovalov, O. [ESRF, 6 rue Jules Horowitz, BP220, 38043 Grenoble Cedex (France)

2007-05-23

We have analyzed grazing incidence X-ray diffraction (GIXD) data from condensed phases of Langmuir films of long-chain fatty acids at the air-water using a new method consisting in a careful extraction of the structure factors followed by fitting of molecular parameters using simulated annealing. We show that the information contained in GIXD spectra is enough to obtain near-atomic structural information. In particular, we directly determine the orientation of the chain backbone planes and of the carboxylic headgroups, and we evaluate chain conformation defects.

Molecular dynamics of conformation-specific dopamine transporter-inhibitor complexes.

Science.gov (United States)

Jean, Bernandie; Surratt, Christopher K; Madura, Jeffry D

2017-09-01

The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation. The 3β-aryltropane cocaine analogs LX10 and LX11, however, differ only in stereochemistry and share a preference for the outward-facing DAT, yet are reported to vary widely in abuse potential in an animal model. In search of the molecular basis for DAT conformation preference, complexes of cocaine, benztropine, LX10 or LX11 bound to each DAT conformation were subjected to 100ns of all-atom molecular dynamics simulation. Results were consistent with previous findings from cysteine accessibility assays used to assess an inhibitor's DAT conformation preference. The respective 2β- and 2α-substituted phenyltropanes of LX10 and LX11 interacted with hydrophobic regions of the DAT S1 binding site that were inaccessible to cocaine. Solvent accessibility measurements also revealed subtle differences in inhibitor positioning within a given DAT conformation. This work serves to advance our understanding of the conformational selectivity of DAT inhibitors and suggests that MD may be useful in antipsychostimulant therapeutic design. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis and modeling of resistive switching mechanisms oriented to resistive random-access memory

International Nuclear Information System (INIS)

Huang Da; Wu Jun-Jie; Tang Yu-Hua

2013-01-01

With the progress of the semiconductor industry, the resistive random-access memory (RAM) has drawn increasing attention. The discovery of the memristor has brought much attention to this study. Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms. We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models. Finally, simulations are presented. We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms, which are applied to explain their resistive switchings

Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.

Directory of Open Access Journals (Sweden)

Zeynab Mohammad Hosseini Naveh

Full Text Available Despite the large number of studies available on nicotinic acetylcholine receptors, a complete account of the mechanistic aspects of their gating transition in response to ligand binding still remains elusive. As a first step toward dissecting the transition mechanism by accelerated sampling techniques, we study the ligand-induced conformational changes of the acetylcholine binding protein (AChBP, a widely accepted model for the full receptor extracellular domain. Using unbiased Molecular Dynamics (MD and Temperature Accelerated Molecular Dynamics (TAMD simulations we investigate the AChBP transition between the apo and the agonist-bound state. In long standard MD simulations, both conformations of the native protein are stable, while the agonist-bound structure evolves toward the apo one if the orientation of few key sidechains in the orthosteric cavity is modified. Conversely, TAMD simulations initiated from the native conformations are able to produce the spontaneous transition. With respect to the modified conformations, TAMD accelerates the transition by at least a factor 10. The analysis of some specific residue-residue interactions points out that the transition mechanism is based on the disruption/formation of few key hydrogen bonds. Finally, while early events of ligand dissociation are observed already in standard MD, TAMD accelerates the ligand detachment and, at the highest TAMD effective temperature, it is able to produce a complete dissociation path in one AChBP subunit.

Budget Impact Analysis of Switching to Digital Mammography in a Population-Based Breast Cancer Screening Program: A Discrete Event Simulation Model

Science.gov (United States)

Comas, Mercè; Arrospide, Arantzazu; Mar, Javier; Sala, Maria; Vilaprinyó, Ester; Hernández, Cristina; Cots, Francesc; Martínez, Juan; Castells, Xavier

2014-01-01

Objective To assess the budgetary impact of switching from screen-film mammography to full-field digital mammography in a population-based breast cancer screening program. Methods A discrete-event simulation model was built to reproduce the breast cancer screening process (biennial mammographic screening of women aged 50 to 69 years) combined with the natural history of breast cancer. The simulation started with 100,000 women and, during a 20-year simulation horizon, new women were dynamically entered according to the aging of the Spanish population. Data on screening were obtained from Spanish breast cancer screening programs. Data on the natural history of breast cancer were based on US data adapted to our population. A budget impact analysis comparing digital with screen-film screening mammography was performed in a sample of 2,000 simulation runs. A sensitivity analysis was performed for crucial screening-related parameters. Distinct scenarios for recall and detection rates were compared. Results Statistically significant savings were found for overall costs, treatment costs and the costs of additional tests in the long term. The overall cost saving was 1,115,857€ (95%CI from 932,147 to 1,299,567) in the 10th year and 2,866,124€ (95%CI from 2,492,610 to 3,239,638) in the 20th year, representing 4.5% and 8.1% of the overall cost associated with screen-film mammography. The sensitivity analysis showed net savings in the long term. Conclusions Switching to digital mammography in a population-based breast cancer screening program saves long-term budget expense, in addition to providing technical advantages. Our results were consistent across distinct scenarios representing the different results obtained in European breast cancer screening programs. PMID:24832200

Design of a bistable switch to control cellular uptake.

Science.gov (United States)

Oyarzún, Diego A; Chaves, Madalena

2015-12-06

Bistable switches are widely used in synthetic biology to trigger cellular functions in response to environmental signals. All bistable switches developed so far, however, control the expression of target genes without access to other layers of the cellular machinery. Here, we propose a bistable switch to control the rate at which cells take up a metabolite from the environment. An uptake switch provides a new interface to command metabolic activity from the extracellular space and has great potential as a building block in more complex circuits that coordinate pathway activity across cell cultures, allocate metabolic tasks among different strains or require cell-to-cell communication with metabolic signals. Inspired by uptake systems found in nature, we propose to couple metabolite import and utilization with a genetic circuit under feedback regulation. Using mathematical models and analysis, we determined the circuit architectures that produce bistability and obtained their design space for bistability in terms of experimentally tuneable parameters. We found an activation-repression architecture to be the most robust switch because it displays bistability for the largest range of design parameters and requires little fine-tuning of the promoters' response curves. Our analytic results are based on on-off approximations of promoter activity and are in excellent qualitative agreement with simulations of more realistic models. With further analysis and simulation, we established conditions to maximize the parameter design space and to produce bimodal phenotypes via hysteresis and cell-to-cell variability. Our results highlight how mathematical analysis can drive the discovery of new circuits for synthetic biology, as the proposed circuit has all the hallmarks of a toggle switch and stands as a promising design to control metabolic phenotypes across cell cultures. © 2015 The Author(s).

Software development for a switch-based data acquisition system

Energy Technology Data Exchange (ETDEWEB)

Booth, A. (Superconducting Super Collider Lab., Dallas, TX (United States)); Black, D.; Walsh, D. (Fermi National Accelerator Lab., Batavia, IL (United States))

1991-12-01

We report on the software aspects of the development of a switch-based data acquisition system at Fermilab. This paper describes how, with the goal of providing an integrated systems engineering'' environment, several powerful software tools were put in place to facilitate extensive exploration of all aspects of the design. These tools include a simulation package, graphics package and an Expert System shell which have been integrated to provide an environment which encourages the close interaction of hardware and software engineers. This paper includes a description of the simulation, user interface, embedded software, remote procedure calls, and diagnostic software which together have enabled us to provide real-time control and monitoring of a working prototype switch-based data acquisition (DAQ) system.

Monte Carlo conformal treatment planning as an independent assessment

International Nuclear Information System (INIS)

Rincon, M.; Leal, A.; Perucha, M.; Carrasco, E.; Sanchez-Doblado, F.; Hospital Univ. Virgen Macarena, Sevilla; Arrans, R.; Sanchez-Calzado, J.A.; Errazquin, L.; Medrano, J.C.

2001-01-01

The wide range of possibilities available in Radiotherapy with conformal fields cannot be covered experimentally. For this reason, dosimetrical and planning procedures are based on approximate algorithms or systematic measurements. Dose distribution calculations based on Monte Carlo (MC) simulations can be used to check results. In this work, two examples of conformal field treatments are shown: A prostate carcinoma and an ocular lymphoma. The dose distributions obtained with a conventional Planning System and with MC have been compared. Some significant differences have been found. (orig.)

Sate-of-the-art IP switching router architecture using SFQ technology

International Nuclear Information System (INIS)

Miyaho, N.; Miyahara, K.; Yamazaki, A.

2006-01-01

Taking the recent trend of rapid IP traffic increasing and QoS in the Internet into account, we propose an innovative IP router architecture from the viewpoint of minimum switching delay, switching capacity, QoS assurance for the next generation Internet services. We examined the IP router performance using superconductivity device simulator (WinS) assuming the future-generation Nb junction process and confirmed more than 300 GHz clock operation. For the evaluation of a novel IP switch architecture, we effectively apply the SFQ circuits using Josephson junctions to an extremely restricted function block in the switching node and a conventional semiconductor technology is also applied for the rest parts of the other function blocks inside it

Axis-switching of a micro-jet

Science.gov (United States)

Cabaleiro, Juan Martin; Aider, Jean-Luc

2014-03-01

In this study, it is shown that free microjets can undergo complex transitions similar to large-scale free jets despite relatively low Reynolds numbers. Using an original experimental method allowing for the 3D reconstruction of the instantaneous spatial organization of the microjet, the axis-switching of a micro-jet is observed for the first time. This is the first experimental evidence of such complex phenomena for free micro-jets. Combining these experimental results with Direct Numerical Simulations it is shown that the mechanism responsible for the axis-switching is the deformation of a micro-vortex ring due to induction by the corner vortices, as it occurs in large scale non-circular jets.

Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras

Energy Technology Data Exchange (ETDEWEB)

Xu, Shenyuan; Long, Brian N.; Boris, Gabriel H.; Chen, Anqi; Ni, Shuisong; Kennedy, Michael A.

2017-11-10

K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. The G12A mutation reduces intrinsic K-Ras GTP hydrolysis by an unexplained mechanism. Here, crystal structures of G12A K-Ras in complex with GDP, GTP, GTPγS and GppNHp, and of Q61A K-Ras in complex with GDP, are reported. In the G12A K-Ras–GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP γ-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants.

The Dynameomics Entropy Dictionary: A Large-Scale Assessment of Conformational Entropy across Protein Fold Space.

Science.gov (United States)

Towse, Clare-Louise; Akke, Mikael; Daggett, Valerie

2017-04-27

Molecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing data set of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identifies deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, α-helices have lower entropy on average than do β-sheets, and both are lower than coil regions.

Conformal house

DEFF Research Database (Denmark)

Ryttov, Thomas Aaby; Sannino, Francesco

2010-01-01

fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

KAUST Repository

Feng, Yitao

2016-10-13

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

KAUST Repository

Feng, Yitao; Zhang, Lu; Wu, Shaowen; Liu, Zhijun; Gao, Xin; Zhang, Xu; Liu, Maili; Liu, Jianwei; Huang, Xuhui; Wang, Wenning

2016-01-01

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Azobenzenes as light-controlled molecular electronic switches in nanoscale metal-molecule-metal junctions.

Science.gov (United States)

Mativetsky, Jeffrey M; Pace, Giuseppina; Elbing, Mark; Rampi, Maria A; Mayor, Marcel; Samorì, Paolo

2008-07-23

Conductance switching associated with the photoisomerization of azobenzene-based (Azo) molecules was observed in nanoscopic metal-molecule-metal junctions. The junctions were formed by using a conducting atomic force microscope (C-AFM) approach, where a metallic AFM tip was used to electrically contact a gold-supported Azo self-assembled monolayer. The measured 30-fold increase in conductance is consistent with the expected decrease in tunneling barrier length resulting from the conformational change of the Azo molecule.

Partial Finite-Time Synchronization of Switched Stochastic Chua's Circuits via Sliding-Mode Control

Directory of Open Access Journals (Sweden)

Zhang-Lin Wan

2011-01-01

Full Text Available This paper considers the problem of partial finite-time synchronization between switched stochastic Chua's circuits accompanied by a time-driven switching law. Based on the Ito formula and Lyapunov stability theory, a sliding-mode controller is developed to guarantee the synchronization of switched stochastic master-slave Chua's circuits and for the mean of error states to obtain the partial finite-time stability. Numerical simulations demonstrate the effectiveness of the proposed methods.

Perspectives on electrostatics and conformational motions in enzyme catalysis.

Science.gov (United States)

Hanoian, Philip; Liu, C Tony; Hammes-Schiffer, Sharon; Benkovic, Stephen

2015-02-17

CONSPECTUS: Enzymes are essential for all living organisms, and their effectiveness as chemical catalysts has driven more than a half century of research seeking to understand the enormous rate enhancements they provide. Nevertheless, a complete understanding of the factors that govern the rate enhancements and selectivities of enzymes remains elusive, due to the extraordinary complexity and cooperativity that are the hallmarks of these biomolecules. We have used a combination of site-directed mutagenesis, pre-steady-state kinetics, X-ray crystallography, nuclear magnetic resonance (NMR), vibrational and fluorescence spectroscopies, resonance energy transfer, and computer simulations to study the implications of conformational motions and electrostatic interactions on enzyme catalysis in the enzyme dihydrofolate reductase (DHFR). We have demonstrated that modest equilibrium conformational changes are functionally related to the hydride transfer reaction. Results obtained for mutant DHFRs illustrated that reductions in hydride transfer rates are correlated with altered conformational motions, and analysis of the evolutionary history of DHFR indicated that mutations appear to have occurred to preserve both the hydride transfer rate and the associated conformational changes. More recent results suggested that differences in local electrostatic environments contribute to finely tuning the substrate pKa in the initial protonation step. Using a combination of primary and solvent kinetic isotope effects, we demonstrated that the reaction mechanism is consistent across a broad pH range, and computer simulations suggested that deprotonation of the active site Tyr100 may play a crucial role in substrate protonation at high pH. Site-specific incorporation of vibrational thiocyanate probes into the ecDHFR active site provided an experimental tool for interrogating these microenvironments and for investigating changes in electrostatics along the DHFR catalytic cycle

Explicit mentalizing mechanisms and their adaptive role in memory conformity.

Directory of Open Access Journals (Sweden)

Rebecca Wheeler

Full Text Available Memory conformity occurs when an individual endorses what other individuals remember about past events. Research on memory conformity is currently dominated by a 'forensic' perspective, which views the phenomenon as inherently undesirable. This is because conformity not only distorts the accuracy of an individual's memory, but also produces false corroboration between individuals, effects that act to undermine criminal justice systems. There is growing awareness, however, that memory conformity may be interpreted more generally as an adaptive social behavior regulated by explicit mentalizing mechanisms. Here, we provide novel evidence in support of this emerging alternative theoretical perspective. We carried out a memory conformity experiment which revealed that explicit belief-simulation (i.e. using one's own beliefs to model what other people believe systematically biases conformity towards like-minded individuals, even when there is no objective evidence that they have a more accurate memory than dissimilar individuals. We suggest that this bias is functional, i.e. adaptive, to the extent that it fosters trust, and hence cooperation, between in-group versus out-group individuals. We conclude that memory conformity is, in more fundamental terms, a highly desirable product of explicit mentalizing mechanisms that promote adaptive forms of social learning and cooperation.

The place of conformal radiotherapy in the routine work: national investigation of SFRO members'opinion

International Nuclear Information System (INIS)

Lagrange, J.L.; Lipinski, F.

2001-01-01

National French investigation of the using of conformal radiotherapy in routine work, has been made in 2001, in 180 radiotherapeutic centers. Eighty responses have been obtained and analyzed. Conformal radiotherapy is used in 88% and virtual simulation in 60% of these centers. There is a heterogeneity in the equipment of these institutions, most of them have one or two machines. The accelerator equipment differs, and the availability of multi-leaf collimators and electronic portal imaging is limited. Actually only eleven centers have IMRT, eight have projects to install. Only six centers have CT-scans, used mainly for simulation. In 75% of centers conformal radiotherapy have been used in the treatment of CNS-tumors, head and neck cancers, prostate, and non-small cell lung carcinoma. If there are more equipment and human facilities to use conformal radiotherapy, this treatment can be proposed to patients with breast cancer, rectal and gynecological tumors. According 90% of responses, all prostatic cancers need conformal radiotherapy. The analysis of routine use of conformal radiotherapy in France shows an important heterogeneity but it seems that there is an agreement with objectives of this treatment. (authors)

Modulation of the Conformational Dynamics of Apo-Adenylate Kinase through a π-Cation Interaction.

Science.gov (United States)

Halder, Ritaban; Manna, Rabindra Nath; Chakraborty, Sandipan; Jana, Biman

2017-06-15

Large-scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in a way that closely resembles an open-to-closed conformational transition. Here, equilibrium simulations, free-energy simulations, and quantum mechanics/molecular mechanics (QM/MM) calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. In addition to its conventional open state, Escherichia coli apo-ADK adopts conformations that resemble a closed-like intermediate, the "half-open-half-closed" (HOHC) state, and a π-cation interaction can account for the stability of this HOHC state. Energetics and the electronic properties of this π-cation interaction have been explored using QM/MM calculations. Upon rescinding the π-cation interaction, the conformational landscape of the apo-ADK changes completely. The apo-ADK population is shifted completely toward the open state. This π-cation interaction is highly conserved in bacterial ADK; the cationic guanidinium moiety of a conserved ARG interacts with the delocalized π-electron cloud of either PHE or TYR. Interestingly, this study demonstrates the modulation of a principal protein dynamics by a conserved specific π-cation interaction across different organisms.

Energy reversible switching from amorphous metal based nanoelectromechanical switch

KAUST Repository

Mayet, Abdulilah M.; Smith, Casey; Hussain, Muhammad Mustafa

2013-01-01

We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young's modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young's modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

Energy reversible switching from amorphous metal based nanoelectromechanical switch

KAUST Repository

Mayet, Abdulilah M.

2013-08-01

We report observation of energy reversible switching from amorphous metal based nanoelectromechanical (NEM) switch. For ultra-low power electronics, NEM switches can be used as a complementary switching element in many nanoelectronic system applications. Its inherent zero power consumption because of mechanical detachment is an attractive feature. However, its operating voltage needs to be in the realm of 1 volt or lower. Appropriate design and lower Young\\'s modulus can contribute achieving lower operating voltage. Therefore, we have developed amorphous metal with low Young\\'s modulus and in this paper reporting the energy reversible switching from a laterally actuated double electrode NEM switch. © 2013 IEEE.

A soft switching with reduced voltage stress ZVT-PWM full-bridge converter

Science.gov (United States)

Sahin, Yakup; Ting, Naim Suleyman; Acar, Fatih

2018-04-01

This paper introduces a novel active snubber cell for soft switching pulse width modulation DC-DC converters. In the proposed converter, the main switch is turned on under zero voltage transition and turned off under zero voltage switching (ZVS). The auxiliary switch is turned on under zero current switching (ZCS) and turned off under zero current transition. The main diode is turned on under ZVS and turned off under ZCS. All of the other semiconductors in the converter are turned on and off with soft switching. There is no extra voltage stress on the semiconductor devices. Besides, the proposed converter has simple structure and ease of control due to common ground. The detailed theoretical analysis of the proposed converter is presented and also verified with both simulation and experimental study at 100 kHz switching frequency and 600 W output power. Furthermore, the efficiency of the proposed converter is 95.7% at nominal power.

Modeling of static characteristics of switched reluctance motor

International Nuclear Information System (INIS)

Asgharmemon, A.; Hussain, I.; Daudpoto, J.

2013-01-01

To investigate the running characteristics of a switched reluctance motor, the static characteristics and related input data tables are required. The static characteristics comprise of flux linkage, co-energy and static torque characteristics. The co-energy and static torque are calculated once data of magnetization characteristics is available. The data of co-energy is required for the calculation of static torque characteristics. The simulation model includes the data of static characteristics for prediction of the instantaneous and steady state performance of the motor. In this research a computer based procedure of experiments is carried out for measurement of the magnetization characteristics. For every set of measurements, the removal of eddy current is carefully addressed. The experiments are carried out on an existing 8/6 pole rotary switched reluctance motor. Additionally, the instantaneous phase current, instantaneous torque and flux waveforms are produced by using linear, which is by default and spline data interpolation separately. The information obtained from theses simulation results will help in an improved simulation model for predicting the performance of the machine. (author)

Modeling and Mitigation for High Frequency Switching Transients Due to Energization in Offshore Wind Farms

Directory of Open Access Journals (Sweden)

Yanli Xin

2016-12-01

Full Text Available This paper presents a comprehensive investigation on high frequency (HF switching transients due to energization of vacuum circuit breakers (VCBs in offshore wind farms (OWFs. This research not only concerns the modeling of main components in collector grids of an OWF for transient analysis (including VCBs, wind turbine transformers (WTTs, submarine cables, but also compares the effectiveness between several mainstream switching overvoltage (SOV protection methods and a new mitigation method called smart choke. In order to accurately reproduce such HF switching transients considering the current chopping, dielectric strength (DS recovery capability and HF quenching capability of VCBs, three models are developed, i.e., a user–defined VCB model, a HF transformer terminal model and a three-core (TC frequency dependent model of submarine cables, which are validated through simulations and compared with measurements. Based on the above models and a real OWF configuration, a simulation model is built and several typical switching transient cases are investigated to analyze the switching transient process and phenomena. Subsequently, according to the characteristics of overvoltages, appropriate parameters of SOV mitigation methods are determined to improve their effectiveness. Simulation results indicate that the user–defined VCB model can satisfactorily simulate prestrikes and the proposed component models display HF characteristics, which are consistent with onsite measurement behaviors. Moreover, the employed protection methods can suppress induced SOVs, which have a steep front, a high oscillation frequency and a high amplitude, among which the smart choke presents a preferable HF damping effect.

Optimization of the GBMV2 implicit solvent force field for accurate simulation of protein conformational equilibria.

Science.gov (United States)

Lee, Kuo Hao; Chen, Jianhan

2017-06-15

Accurate treatment of solvent environment is critical for reliable simulations of protein conformational equilibria. Implicit treatment of solvation, such as using the generalized Born (GB) class of models arguably provides an optimal balance between computational efficiency and physical accuracy. Yet, GB models are frequently plagued by a tendency to generate overly compact structures. The physical origins of this drawback are relatively well understood, and the key to a balanced implicit solvent protein force field is careful optimization of physical parameters to achieve a sufficient level of cancellation of errors. The latter has been hampered by the difficulty of generating converged conformational ensembles of non-trivial model proteins using the popular replica exchange sampling technique. Here, we leverage improved sampling efficiency of a newly developed multi-scale enhanced sampling technique to re-optimize the generalized-Born with molecular volume (GBMV2) implicit solvent model with the CHARMM36 protein force field. Recursive optimization of key GBMV2 parameters (such as input radii) and protein torsion profiles (via the CMAP torsion cross terms) has led to a more balanced GBMV2 protein force field that recapitulates the structures and stabilities of both helical and β-hairpin model peptides. Importantly, this force field appears to be free of the over-compaction bias, and can generate structural ensembles of several intrinsically disordered proteins of various lengths that seem highly consistent with available experimental data. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Constant Switching Frequency Self-Oscillating Controlled Class-D Amplifiers

DEFF Research Database (Denmark)

Nguyen-Duy, Khiem; Knott, Arnold; Andersen, Michael A. E.

2014-01-01

The self-oscillating control approach has been used extensively in class-D amplifiers. It has several advantages such as high bandwidth and high audio performance. However, one of the primary disadvantages in a self-oscillating controlled system is that the switching frequency of the amplifier...... varies with the ratio of the output voltage to the input rail voltage. In other words, the switching frequency varies with the duty cycle of the output. The drop in the frequency results in lower control bandwidth and higher output voltage ripple, which are undesirable. This paper proposes a new self-oscillating...... control scheme that maintains a constant switching frequency over the full range of output voltage. The frequency difference is processed by a compensator whose output adjusts the total loop gain of the control system. It has been proven by simulation that a con-stant switching frequency self-oscillating...

MD SIMULATION STUDIES TO INVESTIGATE ISO-ENERGETIC CONFORMATIONAL BEHAVIOUR OF MODIFIED NUCLEOSIDES M2G AND M22G PRESENT IN tRNA

Directory of Open Access Journals (Sweden)

Rohit S Bavi

2013-02-01

Full Text Available Modified nucleic acid bases are most commonly found in tRNA. These may contain modifications from simple methylation to addition of bulky groups. Methylation of the four canonical nucleotide bases at a wide variety of positions is particularly prominent among the known modification. Methylation of N2 group of guanine is a relatively common modification in tRNA and rRNA. N2-methylguanosine (m2G is the second most often encountered nucleoside in E. coli tRNAs. N2, N2-dimethylguanosine (m22G is found in the majority of eukaryotic tRNAs and involved in forming base pair interactions with adjacent bases. Hence, in order to understand the structural significance of these methylated nucleic acid bases we have carried out molecular dynamics simulation to see the salvation effect. The results obtained shows iso-energetic conformational behaviors for m2G and m22G. The simulation trajectory of m2G shows regular periodical fluctuations suggesting that m2G is equally stable as either s-cis or s-trans rotamers. The two rotamers of m2G may interact canonically or non-canonically with opposite base as s-trans m2G26:C/A/U44 and s-cis m2G26:A/U44. The free rotations around the C-N bond could be the possible reason for these iso-energetic conformations. Dimethylation of G has almost no influence on base pairing with either A or U. Thus, these results reveal that modified nucleosides m2G and m22G may play an important role to prevent tRNA from adopting the unusual mitochondrial like conformation.

A strategy to correct for intrafraction target translation in conformal prostate radiotherapy: Simulation results

International Nuclear Information System (INIS)

Keall, P. J.; Lauve, A. D.; Hagan, M. P.; Siebers, J. V.

2007-01-01

simulated internal motion shifts. Dose increases for adjacent organs at risk were rare. D 33 of the rectum and D 20 of the bladder were increased by more than 5% of the prescription dose in 9 and 1 instances of the 3600 sampled internal motion shifts, respectively. D mean of the right femoral head increased by more than 5% of the prescription dose in 651 (18%) internal motion shifts, predominantly due to the projection of the lateral beams through the femoral head for anterior prostate motion. However, D 2 was not increased by more than 5% for any of the internal motion shifts. These data demonstrate the robustness of the proposed dynamic compensation strategy for correction of internal motion in conformal prostate radiotherapy, with minimal deviation from the original treatment plans even for errors exceeding those commonly encountered in the clinic. The compensation strategy could be performed automatically with appropriate enhancements to available delivery software

Sensitivity of photoelectron diffraction to conformational changes of adsorbed molecules: Tetra-tert-butyl-azobenzene/Au(111

Directory of Open Access Journals (Sweden)

A. Schuler

2017-01-01

Full Text Available Electron diffraction is a standard tool to investigate the atomic structure of surfaces, interfaces, and adsorbate systems. In particular, photoelectron diffraction is a promising candidate for real-time studies of structural dynamics combining the ultimate time resolution of optical pulses and the high scattering cross-sections for electrons. In view of future time-resolved experiments from molecular layers, we studied the sensitivity of photoelectron diffraction to conformational changes of only a small fraction of molecules in a monolayer adsorbed on a metallic substrate. 3,3′,5,5′-tetra-tert-butyl-azobenzene served as test case. This molecule can be switched between two isomers, trans and cis, by absorption of ultraviolet light. X-ray photoelectron diffraction patterns were recorded from tetra-tert-butyl-azobenzene/Au(111 in thermal equilibrium at room temperature and compared to patterns taken in the photostationary state obtained by exposing the surface to radiation from a high-intensity helium discharge lamp. Difference patterns were simulated by means of multiple-scattering calculations, which allowed us to determine the fraction of molecules that underwent isomerization.

Advanced Macro-Model with Pulse-Width Dependent Switching Characteristic for Spin Transfer Torque Based Magnetic-Tunnel-Junction Elements

Science.gov (United States)

Sojeong Kim,; Seungjun Lee,; Hyungsoon Shin,

2010-04-01

In spin transfer torque (STT)-based magnetic tunnel junction (MTJ), the switching depends on the current pulse-width as well as the magnitude of the switching current. We present an advanced macro-model of an STT-MTJ for a circuit simulator such as HSPICE. The macro-model can simulate the dependence of switching behavior on current pulse-width in an STT-MTJ. An imaginary resistor-capacitor (RC) circuit is adopted to emulate complex timing behavior which cannot be described nicely by existing functions in HSPICE. Simulation results show the resistance-current (R-I) curve and timing behavior is in good agreement with the experimental data.

Simple and efficient methods for the accurate evaluation of patterning effects in ultrafast photonic switches

DEFF Research Database (Denmark)

Xu, Jing; Ding, Yunhong; Peucheret, Christophe

2011-01-01

Although patterning effects (PEs) are known to be a limiting factor of ultrafast photonic switches based on semiconductor optical amplifiers (SOAs), a simple approach for their evaluation in numerical simulations and experiments is missing. In this work, we experimentally investigate and verify...... as well as the operation bit rate. Furthermore, a simple and effective method for probing the maximum PEs is demonstrated, which may relieve the computational effort or the experimental difficulties associated with the use of long PRBSs for the simulation or characterization of SOA-based switches. Good...... agrement with conventional PRBS characterization is obtained. The method is suitable for quick and systematic estimation and optimization of the switching performance....

The interaction with gold suppresses fiber-like conformations of the amyloid β (16-22) peptide

Science.gov (United States)

Bellucci, Luca; Ardèvol, Albert; Parrinello, Michele; Lutz, Helmut; Lu, Hao; Weidner, Tobias; Corni, Stefano

2016-04-01

Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution.Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution. Electronic supplementary information (ESI

On the hydration and conformation of cocaine in solution

Science.gov (United States)

Gillams, Richard J.; Lorenz, Christian D.; McLain, Sylvia E.

2017-05-01

In order to develop theories relating to the mechanism through which cocaine can diffuse across the blood-brain barrier, it is important to understand the interplay between the hydration of the molecule and the adopted conformation. Here key differences in the hydration of cocaine hydrochloride (CHC) and freebase cocaine (CFB) are highlighted on the atomic scale in solution, through the use of molecular dynamics simulations. By adopting different conformations, CHC and CFB experience differing hydration environments. The interplay between these two factors may account for the vast difference in solubility of these two molecules.

Computer Simulation of Phase Shifted Series Resonant DC to DC Converter

Directory of Open Access Journals (Sweden)

P. PARVATHY

2016-01-01

Full Text Available This paper deals with digital simulation of phase shifted series resonant DC to DC converter using Matlab Simulink. The Simulink models for open loop and closed loop systems are developed and they are used for simulation studies. This converter is capable of producing ripple free DC output. Switching losses and switching stresses are reduced by using soft switching. This converter has advantages like high power density and low switching losses. Theoretical predictions are well supported by the simulation results.

Manipulation of Origin of Life Molecules: Recognizing Single-Molecule Conformations in β-Carotene and Chlorophyll-a/β-Carotene Clusters

Energy Technology Data Exchange (ETDEWEB)

Ngo, Anh T.; Skeini, Timur [Nanoscale; amp, Quantum Phenomena Institute and Physics & amp, Astronomy Department, Ohio University, Athens, Ohio 45701, United States; Iancu, Violeta [Nanoscale; amp, Quantum Phenomena Institute and Physics & amp, Astronomy Department, Ohio University, Athens, Ohio 45701, United States; Redfern, Paul C.; Curtiss, Larry A.; Hla, Saw Wai [Nanoscale; amp, Quantum Phenomena Institute and Physics & amp, Astronomy Department, Ohio University, Athens, Ohio 45701, United States

2018-01-11

Carotenoids and chlorophyll are essential parts of plant leaves and are involved in photosynthesis, a vital biological process responsible for the origin of life on Earth. Here, we investigate how beta-carotene and chlorophyll-a form mixed molecular phases On a Au(111) surface using low-temperature scanning tunneling microscopy and molecular manipulation at the single-molecule level supported by density functional theory calculations. By isolating individual molecules from nanoscale molecular clusters with a scanning tunneling microscope tip, we are able to identify five beta-carotene conformations including a structure exhibiting a three-dimensional conformation. Furthermore, molecular resolution images enable direct visualization of beta-carotene/chlorophyll-a clsuters, with intimate structural details highlighting how they pair: beta-carotene preferentially positions next to chlorophyll-a and induces switching of chlorophyll-a from straight to several bent tail conformations in the molecular clusters.

A complementary switching mechanism for organic memory devices to regulate the conductance of binary states

Science.gov (United States)

Vyas, Giriraj; Dagar, Parveen; Sahu, Satyajit

2016-06-01

We have fabricated an organic non-volatile memory device wherein the ON/OFF current ratio has been controlled by varying the concentration of a small organic molecule, 2,3-Dichloro-5,6-dicyano-p-benzoquinone (DDQ), in an insulating matrix of a polymer Poly(4-vinylphenol) (PVP). A maximum ON-OFF ratio of 106 is obtained when the concentration of DDQ is half or 10 wt. % of PVP. In this process, the switching direction for the devices has also been altered, indicating the disparity in conduction mechanism. Conduction due to metal filament formation through the active material and the voltage dependent conformational change of the organic molecule seem to be the motivation behind the gradual change in the switching direction.

Open and closed conformations of two SpoIIAA-like proteins (YP-749275.1 and YP-001095227.1) provide insights into membrane association and ligand binding

International Nuclear Information System (INIS)

Kumar, Abhinav; Lomize, Andrei; Jin, Kevin K.; Carlton, Dennis; Miller, Mitchell D.; Jaroszewski, Lukasz; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2009-01-01

The crystal structures of two orthologous proteins from different Shewanella species have uncovered a resemblance to CRAL-TRIO carrier proteins, which suggest that they function as transporters of small nonpolar molecules. One protein adopts an open conformation, while the other adopts a closed structure that may act as a conformational switch in the transport of ligands at the membrane surface. The crystal structures of the proteins encoded by the YP-749275.1 and YP-001095227.1 genes from Shewanella frigidimarina and S. loihica, respectively, have been determined at 1.8 and 2.25 Å resolution, respectively. These proteins are members of a novel family of bacterial proteins that adopt the α/β SpoIIAA-like fold found in STAS and CRAL-TRIO domains. Despite sharing 54% sequence identity, these two proteins adopt distinct conformations arising from different dispositions of their α2 and α3 helices. In the ‘open’ conformation (YP-001095227.1), these helices are 15 Å apart, leading to the creation of a deep nonpolar cavity. In the ‘closed’ structure (YP-749275.1), the helices partially unfold and rearrange, occluding the cavity and decreasing the solvent-exposed hydrophobic surface. These two complementary structures are reminiscent of the conformational switch in CRAL-TRIO carriers of hydrophobic compounds. It is suggested that both proteins may associate with the lipid bilayer in their ‘open’ monomeric state by inserting their amphiphilic helices, α2 and α3, into the lipid bilayer. These bacterial proteins may function as carriers of nonpolar substances or as interfacially activated enzymes

Magnonic interferometric switch for multi-valued logic circuits

Science.gov (United States)

Balynsky, Michael; Kozhevnikov, Alexander; Khivintsev, Yuri; Bhowmick, Tonmoy; Gutierrez, David; Chiang, Howard; Dudko, Galina; Filimonov, Yuri; Liu, Guanxiong; Jiang, Chenglong; Balandin, Alexander A.; Lake, Roger; Khitun, Alexander

2017-01-01

We investigated a possible use of the magnonic interferometric switches in multi-valued logic circuits. The switch is a three-terminal device consisting of two spin channels where input, control, and output signals are spin waves. Signal modulation is achieved via the interference between the source and gate spin waves. We report experimental data on a micrometer scale prototype based on the Y3Fe2(FeO4)3 structure. The output characteristics are measured at different angles of the bias magnetic field. The On/Off ratio of the prototype exceeds 13 dB at room temperature. Experimental data are complemented by the theoretical analysis and the results of micro magnetic simulations showing spin wave propagation in a micrometer size magnetic junction. We also present the results of numerical modeling illustrating the operation of a nanometer-size switch consisting of just 20 spins in the source-drain channel. The utilization of spin wave interference as a switching mechanism makes it possible to build nanometer-scale logic gates, and minimize energy per operation, which is limited only by the noise margin. The utilization of phase in addition to amplitude for information encoding offers an innovative route towards multi-state logic circuits. We describe possible implementation of the three-value logic circuits based on the magnonic interferometric switches. The advantages and shortcomings inherent in interferometric switches are also discussed.

Second-chance signal transduction explains cooperative flagellar switching.

Science.gov (United States)

Zot, Henry G; Hasbun, Javier E; Minh, Nguyen Van

2012-01-01

The reversal of flagellar motion (switching) results from the interaction between a switch complex of the flagellar rotor and a torque-generating stationary unit, or stator (motor unit). To explain the steeply cooperative ligand-induced switching, present models propose allosteric interactions between subunits of the rotor, but do not address the possibility of a reaction that stimulates a bidirectional motor unit to reverse direction of torque. During flagellar motion, the binding of a ligand-bound switch complex at the dwell site could excite a motor unit. The probability that another switch complex of the rotor, moving according to steady-state rotation, will reach the same dwell site before that motor unit returns to ground state will be determined by the independent decay rate of the excited-state motor unit. Here, we derive an analytical expression for the energy coupling between a switch complex and a motor unit of the stator complex of a flagellum, and demonstrate that this model accounts for the cooperative switching response without the need for allosteric interactions. The analytical result can be reproduced by simulation when (1) the motion of the rotor delivers a subsequent ligand-bound switch to the excited motor unit, thereby providing the excited motor unit with a second chance to remain excited, and (2) the outputs from multiple independent motor units are constrained to a single all-or-none event. In this proposed model, a motor unit and switch complex represent the components of a mathematically defined signal transduction mechanism in which energy coupling is driven by steady-state and is regulated by stochastic ligand binding. Mathematical derivation of the model shows the analytical function to be a general form of the Hill equation (Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40: iv-vii).

What makes Ras an efficient molecular switch: a computational, biophysical, and structural study of Ras-GDP interactions with mutants of Raf.

Science.gov (United States)

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

Fast and efficient STT switching in MTJ using additional transient pulse current

Science.gov (United States)

Pathak, Sachin; Cha, Jongin; Jo, Kangwook; Yoon, Hongil; Hong, Jongill

2017-06-01

We propose a profile of write pulse current-density to switch magnetization in a perpendicular magnetic tunnel junction to reduce switching time and write energy as well. Our simulated results show that an overshoot transient pulse current-density (current spike) imposed to conventional rectangular-shaped pulse current-density (main pulse) significantly improves switching speed that yields the reduction in write energy accordingly. For example, we could dramatically reduce the switching time by 80% and thereby reduce the write energy over 9% in comparison to the switching without current spike. The current spike affects the spin dynamics of the free layer and reduces the switching time mainly due to spin torque induced. On the other hand, the large Oersted field induced causes changes in spin texture. We believe our proposed write scheme can make a breakthrough in magnetic random access memory technology seeking both high speed operation and low energy consumption.

Pseudospark switches

International Nuclear Information System (INIS)

Billault, P.; Riege, H.; Gulik, M. van; Boggasch, E.; Frank, K.

1987-01-01

The pseudospark discharge is bound to a geometrical structure which is particularly well suited for switching high currents and voltages at high power levels. This type of discharge offers the potential for improvement in essentially all areas of switching operation: peak current and current density, current rise, stand-off voltage, reverse current capability, cathode life, and forward drop. The first pseudospark switch was built at CERN at 1981. Since then, the basic switching characteristics of pseudospark chambers have been studied in detail. The main feature of a pseudospark switch is the confinement of the discharge plasma to the device axis. The current transition to the hollow electrodes is spread over a rather large surface area. Another essential feature is the easy and precise triggering of the pseudospark switch from the interior of the hollow electrodes, relatively far from the main discharge gap. Nanosecond delay and jitter values can be achieved with trigger energies of less than 0.1 mJ, although cathode heating is not required. Pseudospark gaps may cover a wide range of high-voltage, high-current, and high-pulse-power switching at repetition rates of many kilohertz. This report reviews the basic researh on pseudospark switches which has been going on at CERN. So far, applications have been developed in the range of thyratron-like medium-power switches at typically 20 to 40 kV and 0.5 to 10 kA. High-current pseudospark switches have been built for a high-power 20 kJ pulse generator which is being used for long-term tests of plasma lenses developed for the future CERN Antiproton Collector (ACOL). The high-current switches have operated for several hundred thousand shots, with 20 to 50 ns jitter at 16 kV charging voltage and more than 100 kA peak current amplitude. (orig.)

Exciter switch

Science.gov (United States)

Mcpeak, W. L.

1975-01-01

A new exciter switch assembly has been installed at the three DSN 64-m deep space stations. This assembly provides for switching Block III and Block IV exciters to either the high-power or 20-kW transmitters in either dual-carrier or single-carrier mode. In the dual-carrier mode, it provides for balancing the two drive signals from a single control panel located in the transmitter local control and remote control consoles. In addition to the improved switching capabilities, extensive monitoring of both the exciter switch assembly and Transmitter Subsystem is provided by the exciter switch monitor and display assemblies.

A Switch Is Not a Switch: Syntactically-Driven Bilingual Language Control

Science.gov (United States)

Gollan, Tamar H.; Goldrick, Matthew

2018-01-01

The current study investigated the possibility that language switches could be relatively automatically triggered by context. "Single-word switches," in which bilinguals switched languages on a single word in midsentence and then immediately switched back, were contrasted with more complete "whole-language switches," in which…

Mismatch-shaping switching for two-capacitor DAC

DEFF Research Database (Denmark)

Steensgaard-Madsen, Jesper; Moon, U.; Temes, G.C.

1998-01-01

A mismatch-shaping scheme is proposed for a two-capacitor digital-to-analogue converter (DAC). It uses a delta-sigma loop for finding the optimal switching sequence for each input word. Simulations indicate that the scheme can be used for the realisation of DACs with 16 bit linearity and SNR...

Switching Phenomena in a System with No Switches

Science.gov (United States)

Preis, Tobias; Stanley, H. Eugene

2010-02-01

It is widely believed that switching phenomena require switches, but this is actually not true. For an intriguing variety of switching phenomena in nature, the underlying complex system abruptly changes from one state to another in a highly discontinuous fashion. For example, financial market fluctuations are characterized by many abrupt switchings creating increasing trends ("bubble formation") and decreasing trends ("financial collapse"). Such switching occurs on time scales ranging from macroscopic bubbles persisting for hundreds of days to microscopic bubbles persisting only for a few seconds. We analyze a database containing 13,991,275 German DAX Future transactions recorded with a time resolution of 10 msec. For comparison, a database providing 2,592,531 of all S&P500 daily closing prices is used. We ask whether these ubiquitous switching phenomena have quantifiable features independent of the time horizon studied. We find striking scale-free behavior of the volatility after each switching occurs. We interpret our findings as being consistent with time-dependent collective behavior of financial market participants. We test the possible universality of our result by performing a parallel analysis of fluctuations in transaction volume and time intervals between trades. We show that these financial market switching processes have properties similar to those of phase transitions. We suggest that the well-known catastrophic bubbles that occur on large time scales—such as the most recent financial crisis—are no outliers but single dramatic representatives caused by the switching between upward and downward trends on time scales varying over nine orders of magnitude from very large (≈102 days) down to very small (≈10 ms).

Practical computer analysis of switch mode power supplies

CERN Document Server

Bennett, Johnny C

2006-01-01

When designing switch-mode power supplies (SMPSs), engineers need much more than simple "recipes" for analysis. Such plug-and-go instructions are not at all helpful for simulating larger and more complex circuits and systems. Offering more than merely a "cookbook," Practical Computer Analysis of Switch Mode Power Supplies provides a thorough understanding of the essential requirements for analyzing SMPS performance characteristics. It demonstrates the power of the circuit averaging technique when used with powerful computer circuit simulation programs. The book begins with SMPS fundamentals and the basics of circuit averaging models, reviewing most basic topologies and explaining all of their various modes of operation and control. The author then discusses the general analysis requirements of power supplies and how to develop the general types of SMPS models, demonstrating the use of SPICE for analysis. He examines the basic first-order analyses generally associated with SMPS performance along with more pra...

Fixed switching frequency applied in single-phase boost AC to DC converter

International Nuclear Information System (INIS)

Chen, T.-C.; Ren, T.-J.; Ou, J.-C.

2009-01-01

The fixed switching frequency control for a single-phase boost AC to DC converter to achieve a sinusoidal line current and unity power factor is proposed in this paper. The relation between the line current error and the fixed switching frequency was developed. For a limit line current error, the minimum switching frequency for a boost AC to DC converter can be achieved. The proposed scheme was implemented using a 32-bit digital signal processor TMS320C32. Simulations and experimental results demonstrate the feasibility and fast dynamic response of the proposed control strategy.

HHM motif at the CuH-site of peptidylglycine monooxygenase is a pH-dependent conformational switch.

Science.gov (United States)

Kline, Chelsey D; Mayfield, Mary; Blackburn, Ninian J

2013-04-16

utility for the HHM motif as a copper- and pH-dependent conformational switch.

Interrupter and hybrid-switch testing for fusion devices

International Nuclear Information System (INIS)

Parsons, W.M.; Warren, R.W.; Honig, E.M.; Lindsay, J.D.G.; Bellamo, P.; Cassel, R.L.

1979-01-01

This paper discusses recent and ongoing switch testing for fusion devices. The first part describes testing for the TFTR ohmic-heating circuit. In this set of tests, which simulated the stresses produced during a plasma initiation pulse, circuit breakers were required to interrupt a current of 24 kA with an associated recovery voltage of 25 kV. Two interrupter systems were tested for over 1000 operations each, and both appear to satisfy TFTR requirements. The second part discusses hybrid-switch development for superconducting coil protection. These switching systems must be capable of carrying large currents on a continuous basis as well as performing interruption duties. The third part presents preliminary results on an early-counterpulse technique applied to vacuum interrupters. Implementation of this technique has resulted in large increases in interruptible current as well as a marked reduction in contact erosion

Effects of doping concentration ratio on electrical characterization in pseudomorphic HEMT-based MMIC switches for ICT system

Science.gov (United States)

Mun, Jae-Kyoung; Oh, Jung-Hun; Sung, Ho-Kun; Wang, Cong

2015-12-01

The effects of the doping concentration ratios between upper and lower silicon planar-doping layers on the DC and RF characteristics of the double planar doped pseudomorphic high electron mobility transistors (pHEMTs) are investigated. From the device simulation, an increase of maximum extrinsic transconductance and a decrease of total on- and off-state capacitances are observed, as well as an increase of the upper to lower planar-doping concentration ratios (UTLPDR), which give rise to an enhancement of the switching speed and isolation characteristics. On the basis of simulation results, two types of pHEMTs are fabricated with two different UTLPDRs of 4:1 and 1:2. After applying these two types' pHEMTs, single-pole-double-throw (SPDT) transmitter/receiver monolithic microwave integrated circuit (MMIC) switches are also designed and fabricated. The SPDT MMIC switch with a 4:1 UTLPDR shows an insertion loss of 0.58 dB, isolation of 40.2 dB, and switching speed of 100 ns, respectively, which correspondingly indicate a 0.23 dB lower insertion loss, 2.90 dB higher isolation and 2.5 times faster switching speed than those of 1:2 UTLPDR at frequency range of 2-6 GHz. From the simulation results and comparative studies, we propose that the UTLPDR must be greater than 4:1 for the best switching performance. With the abovementioned excellent performances, the proposed switch would be quite promising in the application of information and communications technology system.

Dependence of the Spin Transfer Torque Switching Current Density on the Exchange Stiffness Constant

OpenAIRE

You, Chun-Yeol

2012-01-01

We investigate the dependence of the switching current density on the exchange stiffness constant in the spin transfer torque magnetic tunneling junction structure with micromagnetic simulations. Since the widely accepted analytic expression of the switching current density is based on the macro-spin model, there is no dependence of the exchange stiffness constant. When the switching is occurred, however, the spin configuration forms C-, S-type, or complicated domain structures. Since the spi...

On non-conformal limit of the AGT relations

International Nuclear Information System (INIS)

Marshakov, A.; Mironov, A.; Morozov, A.

2009-01-01

The Seiberg-Witten prepotentials for N=2 SUSY gauge theories with N f c fundamental multiplets are obtained from conformal N f =2N c theory by decoupling 2N c -N f multiplets of heavy matter. This procedure can be lifted to the level of Nekrasov functions with arbitrary background parameters ε 1 and ε 2 . The AGT relations imply that similar limit exists for conformal blocks (or, for generic N c >2, for the blocks in conformal theories with W N c chiral algebra). We consider the limit of the four-point function explicitly in the Virasoro case of N c =2, by bringing the dimensions of external states to infinity. The calculation is performed entirely in terms of representation theory for the Virasoro algebra and reproduces the answers conjectured in [D. Gaiotto, (arXiv:0908.0307)] with the help of the brane-compactification analysis and computer simulations. In this limit, the conformal block involving four external primaries, corresponding to the theory with vanishing beta-function, turns either into a 2-point or 3-point function, with certain coherent rather than primary external states.

Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations.

Science.gov (United States)

Paul, Fabian; Noé, Frank; Weikl, Thomas R

2018-03-27

Unstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25-109 Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering.

DOA Estimation of Cylindrical Conformal Array Based on Geometric Algebra

Directory of Open Access Journals (Sweden)

Minjie Wu

2016-01-01

Full Text Available Due to the variable curvature of the conformal carrier, the pattern of each element has a different direction. The traditional method of analyzing the conformal array is to use the Euler rotation angle and its matrix representation. However, it is computationally demanding especially for irregular array structures. In this paper, we present a novel algorithm by combining the geometric algebra with Multiple Signal Classification (MUSIC, termed as GA-MUSIC, to solve the direction of arrival (DOA for cylindrical conformal array. And on this basis, we derive the pattern and array manifold. Compared with the existing algorithms, our proposed one avoids the cumbersome matrix transformations and largely decreases the computational complexity. The simulation results verify the effectiveness of the proposed method.

Switching dynamics in InP photonic-crystal nanocavity

DEFF Research Database (Denmark)

Yu, Yi; Palushani, Evarist; Heuck, Mikkel

2016-01-01

In this paper, we presented switching dynamic investigations on an InP photonic-crystal (PhC) nanocavity structure using homodyne pump-probe measurements. The measurements were compared with simulations based on temporal nonlinear coupled mode theory and carrier rate equations for the dynamics of...

Context Switching with Multiple Register Windows: A RISC Performance Study

Science.gov (United States)

Konsek, Marion B.; Reed, Daniel A.; Watcharawittayakul, Wittaya

1987-01-01

Although previous studies have shown that a large file of overlapping register windows can greatly reduce procedure call/return overhead, the effects of register windows in a multiprogramming environment are poorly understood. This paper investigates the performance of multiprogrammed, reduced instruction set computers (RISCs) as a function of window management strategy. Using an analytic model that reflects context switch and procedure call overheads, we analyze the performance of simple, linearly self-recursive programs. For more complex programs, we present the results of a simulation study. These studies show that a simple strategy that saves all windows prior to a context switch, but restores only a single window following a context switch, performs near optimally.

The Strategy of Inverter Seamless Mode Switching in Master-Slave Independent Micro-grid

Directory of Open Access Journals (Sweden)

Jiang Hanhong

2018-01-01

Full Text Available In order to realize the uninterruptible power supply in the master-slave independent micro-grid system, the micro-grid inverter needs to realize the mode switching of the grid-connection/grid-disconnection. How to reduce the transient oscillation during switching, so as to effectively achieve seamless mode switching is a key issue to be solved. In this paper, a typical master-slave control independent micro-grid is used as an example, the strategy of mode switching is improved in two aspects. On the one hand, the state-following algorithm is adopted to improve the switching strategy of the outer loop. On the other hand, the current inner loop is taken by the H∞ robust controller to improve the robustness of the controller. Compared with the traditional PI control mode switching, this paper illustrates the feasibility of the proposed strategy through the simulation and experiment verification. The improvement strategy in this paper can effectively reduce the voltage and current oscillation during mode switching.

Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

Directory of Open Access Journals (Sweden)

Anastasios Papaioannou

2017-09-01

Full Text Available Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1 hyperinsulinemia may be due to the drastically reduced activity (and binding affinity of the mutant insulins. 2 Y26BS and Y26BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

Quantum Conformal Algebras and Closed Conformal Field Theory

CERN Document Server

Anselmi, D

1999-01-01

We investigate the quantum conformal algebras of N=2 and N=1 supersymmetric gauge theories. Phenomena occurring at strong coupling are analysed using the Nachtmann theorem and very general, model-independent, arguments. The results lead us to introduce a novel class of conformal field theories, identified by a closed quantum conformal algebra. We conjecture that they are the exact solution to the strongly coupled large-N_c limit of the open conformal field theories. We study the basic properties of closed conformal field theory and work out the operator product expansion of the conserved current multiplet T. The OPE structure is uniquely determined by two central charges, c and a. The multiplet T does not contain just the stress-tensor, but also R-currents and finite mass operators. For this reason, the ratio c/a is different from 1. On the other hand, an open algebra contains an infinite tower of non-conserved currents, organized in pairs and singlets with respect to renormalization mixing. T mixes with a se...

C-metric solution for conformal gravity with a conformally coupled scalar field

Energy Technology Data Exchange (ETDEWEB)

Meng, Kun, E-mail: mengkun@tjpu.edu.cn [School of Science, Tianjin Polytechnic University, Tianjin 300387 (China); Zhao, Liu, E-mail: lzhao@nankai.edu.cn [School of Physics, Nankai University, Tianjin 300071 (China)

2017-02-15

The C-metric solution of conformal gravity with a conformally coupled scalar field is presented. The solution belongs to the class of Petrov type D spacetimes and is conformal to the standard AdS C-metric appeared in vacuum Einstein gravity. For all parameter ranges, we identify some of the physically interesting static regions and the corresponding coordinate ranges. The solution may contain a black hole event horizon, an acceleration horizon, either of which may be cut by the conformal infinity or be hidden behind the conformal infinity. Since the model is conformally invariant, we also discussed the possible effects of the conformal gauge choices on the structure of the spacetime.

Energy efficiency benefits of introducing optical switching in Data Center Networks

DEFF Research Database (Denmark)

Pilimon, Artur; Zeimpeki, Alexandra; Fagertun, Anna Manolova

2017-01-01

layers of the network topology. The analysis is based on network-level simulations using a transport network planning tool applied to small-scale setups of the considered DCNs. The obtained results show that introducing all-optical switching within the DCN leads to reduced power consumption in all......In this paper we analyze the impact of WDM-enhanced optical circuit switching on the power consumption of multiple Data Center Network (DCN) architectures. Traditional three-tier Tree, Fat-Tree and a ring-based structure are evaluated and optical switching is selectively introduced on different...... an optically switched core benefits most the ring-based network. For the latter, the core ring nodes need fewer long-reach transponders at the trunk interfaces and benefit from more efficient traffic grooming in the access part....

Power quality improvement in highly varying loads using thyristor-switched capacitor

Energy Technology Data Exchange (ETDEWEB)

Poshtan, M. [Petroleum Inst., Abu Dhabi (United Arab Emirates). Dept. of Electrical Engineering; Mokhtari, H.; Esmaeili, A. [Sharif Univ. of Technology, Tehran (Iran, Islamic Republic of). Dept. of Electrical Engineering

2007-07-01

Ordinary contactor-based-capacitor (CBC) banks may not be able to response quickly enough in highly varying electrical loads such as welding machines or arc furnace loads. Thyristor-switched capacitor (TSC) banks are therefore used to compensate for reactive power of highly varying loads. In this paper, the performance of a TSC was compared to CBC banks. The 2 systems, were also compared in terms of energy saving in transmission systems. Simulations carried out using PSCAD/EMTDC software showed that there was a considerable difference in the performance of the 2 systems. The shortcomings of existing CBC systems include slow response of mechanical switching systems; problem of switching more than one bank into the system; and, voltage/current transients during on-off switching. 3 refs., 6 tabs., 14 figs.

Studies of ZVS soft switching of dual-active-bridge isolated bidirectional DC-DC converters

Science.gov (United States)

Xu, Fei; Zhao, Feng; Shi, Qibiao; Wen, Xuhui

2018-05-01

To operate dual-active-bridge isolated bidirectional dc- dc converter (DAB) at high efficiency, the two bridge switches must operate with Zero-Voltage-Switching (ZVS) over as wide an operating range as possible. This paper proposes a new perspective on realizing ZVS in dead-time. An exact theoretical analysis and mathematical mode is built to explain the process of ZVS switching in dead-time under Single Phase Shift (SPS) control strategy. In order to assure the two bridge switches operate on soft switching, every SPS switching point is analyzed. Generally, dead-time will be determined when the power electronic devices is selected. The key factor to realizing ZVS is the size of the end time of resonance comparing to dead-time. Through detailed analysis, it can obtain the conditions of all switches achieving ZVS turn-on and turn-off. Finally, simulation validates the theoretical analysis and some advice are given to realize the ZVS soft switching.

Exciplex and excimer molecular probes: detection of conformational flip in a myo-inositol chair.

Science.gov (United States)

Kadirvel, Manikandan; Arsic, Biljana; Freeman, Sally; Bichenkova, Elena V

2008-06-07

2-O-tert-Butyldimethylsilyl-4,6-bis-O-pyrenoyl-myo-inositol-1,3,5-orthoformate (6) and 2-O-tert-butyldimethylsilyl-4-O-[4-(dimethylamino)benzoyl]-6-O-pyrenoyl-myo-inositol-1,3,5-orthoacetate (10) adopt conformationally restricted unstable chairs with five axial substituents. In the symmetrical diester 6, the two pi-stacked pyrenoyl groups are electron acceptor-donor partners, giving a strong intramolecular excimer emission. In the mixed ester 10, the pyrenoyl group is the electron acceptor and the 4-(dimethylamino)benzoyl ester is the electron donor, giving a strong intramolecular exciplex emission. The conformation of the mixed ester 10 was assessed using 1H NMR spectroscopy (1H-NOESY) and computational studies. which showed the minimum inter-centroid distance between the two aromatic systems to be approximately 3.9 A. Upon addition of acid, the orthoformate/orthoacetate trigger in 6 and 10 was cleaved, which caused a switch of the conformation of the myo-inositol ring to the more stable penta-equatorial chair, leading to separation of the aromatic ester groups and loss of excimer and exciplex fluorescence, respectively. This study provides proof of principle for the development of novel fluorescent molecular probes.

Modeling of Dynamic Fluid Forces in Fast Switching Valves

DEFF Research Database (Denmark)

Roemer, Daniel Beck; Johansen, Per; Pedersen, Henrik Clemmensen

2015-01-01

Switching valves experience opposing fluid forces due to movement of the moving member itself, as the surrounding fluid volume must move to accommodate the movement. This movement-induced fluid force may be divided into three main components; the added mass term, the viscous term and the socalled...... history term. For general valve geometries there are no simple solution to either of these terms. During development and design of such switching valves, it is therefore, common practice to use simple models to describe the opposing fluid forces, neglecting all but the viscous term which is determined...... based on shearing areas and venting channels. For fast acting valves the opposing fluid force may retard the valve performance significantly, if appropriate measures are not taken during the valve design. Unsteady Computational Fluid Dynamics (CFD) simulations are available to simulate the total fluid...

Switch Panel wear loading - a parametric study regarding governing train operational factors

Science.gov (United States)

Hiensch, E. J. M.; Burgelman, N.

2017-09-01

The acting forces and resulting material degradation at the running surfaces of wheels and rail are determined by vehicle, track, interface and operational characteristics. To effectively manage the experienced wear, plastic deformation and crack development at wheels and rail, the interaction between vehicle and track demands a system approach both in maintenance and in design. This requires insight into the impact of train operational parameters on rail- and wheel degradation, in particular at switches and crossings due to the complex dynamic behaviour of a railway vehicle at a turnout. A parametric study was carried out by means of vehicle-track simulations within the VAMPIRE® multibody simulation software, performing a sensitivity analysis regarding operational factors and their impact on expected switch panel wear loading. Additionally, theoretical concepts were cross-checked with operational practices by means of a case study in response to a dramatic change in lateral rail wear development at specific switches in Dutch track. Data from train operation, track maintenance and track inspection were analysed, providing further insight into the operational dependencies. From the simulations performed in this study, it was found that switch rail lateral wear loading at the diverging route of a 1:9 type turnout is significantly influenced by the level of wheel-rail friction and to a lesser extent by the direction of travel (facing or trailing). The influence of other investigated parameters, being vehicle speed, traction, gauge widening and track layout is found to be small. Findings from the case study further confirm the simulation outcome. This research clearly demonstrates the contribution flange lubrication can have in preventing abnormal lateral wear at locations where the wheel-rail interface is heavily loaded.

A nonlinear HP-type complementary resistive switch

Directory of Open Access Journals (Sweden)

Paul K. Radtke

2016-05-01

Full Text Available Resistive Switching (RS is the change in resistance of a dielectric under the influence of an external current or electric field. This change is non-volatile, and the basis of both the memristor and resistive random access memory. In the latter, high integration densities favor the anti-serial combination of two RS-elements to a single cell, termed the complementary resistive switch (CRS. Motivated by the irregular shape of the filament protruding into the device, we suggest a nonlinearity in the resistance-interpolation function, characterized by a single parameter p. Thereby the original HP-memristor is expanded upon. We numerically simulate and analytically solve this model. Further, the nonlinearity allows for its application to the CRS.

A nonlinear HP-type complementary resistive switch

Science.gov (United States)

Radtke, Paul K.; Schimansky-Geier, Lutz

2016-05-01

Resistive Switching (RS) is the change in resistance of a dielectric under the influence of an external current or electric field. This change is non-volatile, and the basis of both the memristor and resistive random access memory. In the latter, high integration densities favor the anti-serial combination of two RS-elements to a single cell, termed the complementary resistive switch (CRS). Motivated by the irregular shape of the filament protruding into the device, we suggest a nonlinearity in the resistance-interpolation function, characterized by a single parameter p. Thereby the original HP-memristor is expanded upon. We numerically simulate and analytically solve this model. Further, the nonlinearity allows for its application to the CRS.

Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

Directory of Open Access Journals (Sweden)

Tino Wolter

Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

Exploring modality switching effects in negated sentences: Further evidence for grounded representations

Directory of Open Access Journals (Sweden)

Lea eHald

2013-02-01

Full Text Available Theories of embodied cognition (e.g., Perceptual Symbol Systems Theory; Barsalou, 1999, 2009 suggest that modality-specific simulations underlie the representation of concepts. Supporting evidence comes from modality switch costs: Participants are slower to verify a property in one modality (e.g., auditory, BLENDER-loud after verifying a property in a different modality (e.g., gustatory, CRANBERRIES-tart compared to the same modality (e.g., LEAVES-rustling, Pecher, Zeelenberg, & Barsalou, 2003. Similarly, modality switching costs lead to a modulation of the N400 effect in event related potentials (ERPs (Collins, Pecher, Zeelenberg, & Coulson, 2011; Hald, Marshall, Janssen, & Garnham, 2011. This effect of modality switching has also been shown to interact with the veracity of the sentence (Hald, et al., 2011. The current event-related potentials study (ERPs further explores the role of modality match/mismatch on the processing of veracity as well as negation (sentences containing not. Our results indicate a modulation in the ERP based on modality and veracity, plus an interaction. The evidence supports the idea that modality-specific simulations occur during language processing, and furthermore suggest that these simulations alter the processing of negation.

Non-conformable, partial and conformable transposition

DEFF Research Database (Denmark)

König, Thomas; Mäder, Lars Kai

2013-01-01

and the Commission regarding a directive’s outcome, play a much more strategic role than has to date acknowledged in the transposition literature. Whereas disagreement of a member state delays conformable transposition, it speeds up non-conformable transposition. Disagreement of the Commission only prolongs...... the transposition process. We therefore conclude that a stronger focus on an effective sanctioning mechanism is warranted for safeguarding compliance with directives....

Conformal Einstein spaces

International Nuclear Information System (INIS)

Kozameh, C.N.; Newman, E.T.; Tod, K.P.

1985-01-01

Conformal transformations in four-dimensional. In particular, a new set of two necessary and sufficient conditions for a space to be conformal to an Einstein space is presented. The first condition defines the class of spaces conformal to C spaces, whereas the last one (the vanishing of the Bach tensor) gives the particular subclass of C spaces which are conformally related to Einstein spaces. (author)

Conformal Gravity

International Nuclear Information System (INIS)

Hooft, G.

2012-01-01

The dynamical degree of freedom for the gravitational force is the metric tensor, having 10 locally independent degrees of freedom (of which 4 can be used to fix the coordinate choice). In conformal gravity, we split this field into an overall scalar factor and a nine-component remainder. All unrenormalizable infinities are in this remainder, while the scalar component can be handled like any other scalar field such as the Higgs field. In this formalism, conformal symmetry is spontaneously broken. An imperative demand on any healthy quantum gravity theory is that black holes should be described as quantum systems with micro-states as dictated by the Hawking-Bekenstein theory. This requires conformal symmetry that may be broken spontaneously but not explicitly, and this means that all conformal anomalies must cancel out. Cancellation of conformal anomalies yields constraints on the matter sector as described by some universal field theory. Thus black hole physics may eventually be of help in the construction of unified field theories. (author)

Switching power supplies with multiple isolated output and unitary power factor with an only switch; Fonte chaveada com multiplas saidas isoladas e fator de potencia unitario com um unico interruptor

Energy Technology Data Exchange (ETDEWEB)

Canesin, Carlos Alberto

1990-09-01

The analysis and implementation of switching power supplies with multiple output, through the use of the D C/D C Single Ended Primary Inductance Converter - SEPIC is presented. The structure has a single switch mode processing stage, improved input power factor, with the use of the variable current hysteresis control, or, constant on time control. The analysis of the D C/D C SEPIC, output characteristics and computer simulation is presented. A switching power supply practical design and experimental results are presented to demonstrate the validity of the theoretical analysis. (author)

Conformational inversion-topomerization mechanism of ethylcyclohexyl isomers and its role in combustion kinetics

KAUST Repository

Bian, Huiting

2016-07-26

With the "strain-free" cyclic structure, cyclohexane and alkyl cyclohexanes (and their radicals) have various conformers (e.g. chair, boat, and twist etc.) by pseudorotation of the alkyl ring. Noting that different conformers will undergo different types of H-migration reactions, the mechanism of conformational change may impact the distribution of cyclohexyl and the branched cyclohexyl radical isomers during cyclohexane and alkyl cyclohexanes combustion. Consequently, it will influence the formation of subsequent decomposition products. In this work, the conformational inversion-topomerization mechanism and H-migration reactions for six ethylcyclohexyl radical isomers were systematically studied by ab initio calculations and the transition state theory. The updated sub-mechanism of these conformational changes is incorporated into an ethylcyclohexane pyrolysis model. By comparing the simulated results of the "complete" model including the sub-mechanism of conformational changes and the simplified model ignoring these processes, the effect of inversion-topomerization mechanism on the relative concentrations of various ethylcyclohexyl radicals and the formation of subsequent decomposition products were revealed. © 2016.

Fuzzy-Based Adaptive Hybrid Burst Assembly Technique for Optical Burst Switched Networks

Directory of Open Access Journals (Sweden)

Abubakar Muhammad Umaru

2014-01-01

Full Text Available The optical burst switching (OBS paradigm is perceived as an intermediate switching technology for future all-optical networks. Burst assembly that is the first process in OBS is the focus of this paper. In this paper, an intelligent hybrid burst assembly algorithm that is based on fuzzy logic is proposed. The new algorithm is evaluated against the traditional hybrid burst assembly algorithm and the fuzzy adaptive threshold (FAT burst assembly algorithm via simulation. Simulation results show that the proposed algorithm outperforms the hybrid and the FAT algorithms in terms of burst end-to-end delay, packet end-to-end delay, and packet loss ratio.

Application of time series analysis on molecular dynamics simulations of proteins: a study of different conformational spaces by principal component analysis.

Science.gov (United States)

Alakent, Burak; Doruker, Pemra; Camurdan, Mehmet C

2004-09-08

Time series analysis is applied on the collective coordinates obtained from principal component analysis of independent molecular dynamics simulations of alpha-amylase inhibitor tendamistat and immunity protein of colicin E7 based on the Calpha coordinates history. Even though the principal component directions obtained for each run are considerably different, the dynamics information obtained from these runs are surprisingly similar in terms of time series models and parameters. There are two main differences in the dynamics of the two proteins: the higher density of low frequencies and the larger step sizes for the interminima motions of colicin E7 than those of alpha-amylase inhibitor, which may be attributed to the higher number of residues of colicin E7 and/or the structural differences of the two proteins. The cumulative density function of the low frequencies in each run conforms to the expectations from the normal mode analysis. When different runs of alpha-amylase inhibitor are projected on the same set of eigenvectors, it is found that principal components obtained from a certain conformational region of a protein has a moderate explanation power in other conformational regions and the local minima are similar to a certain extent, while the height of the energy barriers in between the minima significantly change. As a final remark, time series analysis tools are further exploited in this study with the motive of explaining the equilibrium fluctuations of proteins. Copyright 2004 American Institute of Physics

Nanoscale mechanical switching of ferroelectric polarization via flexoelectricity

Energy Technology Data Exchange (ETDEWEB)

Gu, Yijia; Hong, Zijian; Britson, Jason; Chen, Long-Qing [Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802 (United States)

2015-01-12

Flexoelectric coefficient is a fourth-rank tensor arising from the coupling between strain gradient and electric polarization and thus exists in all crystals. It is generally ignored for macroscopic crystals due to its small magnitude. However, at the nanoscale, flexoelectric contributions may become significant and can potentially be utilized for device applications. Using the phase-field method, we study the mechanical switching of electric polarization in ferroelectric thin films by a strain gradient created via an atomic force microscope tip. Our simulation results show good agreement with existing experimental observations. We examine the competition between the piezoelectric and flexoelectric effects and provide an understanding of the role of flexoelectricity in the polarization switching. Also, by changing the pressure and film thickness, we reveal that the flexoelectric field at the film bottom can be used as a criterion to determine whether domain switching may happen under a mechanical force.

Optimal control of switching time in switched stochastic systems with multi-switching times and different costs

Science.gov (United States)

Liu, Xiaomei; Li, Shengtao; Zhang, Kanjian

2017-08-01

In this paper, we solve an optimal control problem for a class of time-invariant switched stochastic systems with multi-switching times, where the objective is to minimise a cost functional with different costs defined on the states. In particular, we focus on problems in which a pre-specified sequence of active subsystems is given and the switching times are the only control variables. Based on the calculus of variation, we derive the gradient of the cost functional with respect to the switching times on an especially simple form, which can be directly used in gradient descent algorithms to locate the optimal switching instants. Finally, a numerical example is given, highlighting the validity of the proposed methodology.

Atmel Microcontroller Based Soft Switched PWM ZVS Full Bridge DC to DC Converter

Directory of Open Access Journals (Sweden)

DEEPAK KUMAR NAYAK

2010-12-01

Full Text Available This paper deals with the simulation and implementation of soft switched PWM ZVS full bridge DC to DC converter. The 48V DC is efficiently reduced to 12V DC using a DC to DC converter. This converter has advantages like reduced switching losses, stresses and EMI. Input DC is converted into high frequency AC and it is stepped down to 12V level. Later it is rectified using a full wave rectifier. Laboratory model of microcontroller based DC to DC converter is fabricated and tested. The experimental results are compared with the simulation results.

Toward TeV Conformality

International Nuclear Information System (INIS)

Appelquist, T.; Fleming, G. T.; Neil, E. T.; Avakian, A.; Babich, R.; Brower, R. C.; Cohen, S. D.; Rebbi, C.; Schaich, D.; Cheng, M.; Vranas, P.; Clark, M. A.; Kiskis, J.; Osborn, J. C.

2010-01-01

We study the chiral properties of an SU(3) gauge theory with N f massless Dirac fermions in the fundamental representation when N f is increased from 2 to 6. For N f =2, our lattice simulations lead to a value of /F 3 , where F is the Nambu-Goldstone-boson decay constant and is the chiral condensate, which agrees with the measured QCD value. For N f =6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N f increases further, toward the critical value for transition from confinement to infrared conformality.

Transient-Switch-Signal Suppressor

Science.gov (United States)

Bozeman, Richard J., Jr.

1995-01-01

Circuit delays transmission of switch-opening or switch-closing signal until after preset suppression time. Used to prevent transmission of undesired momentary switch signal. Basic mode of operation simple. Beginning of switch signal initiates timing sequence. If switch signal persists after preset suppression time, circuit transmits switch signal to external circuitry. If switch signal no longer present after suppression time, switch signal deemed transient, and circuit does not pass signal on to external circuitry, as though no transient switch signal. Suppression time preset at value large enough to allow for damping of underlying pressure wave or other mechanical transient.

Simulating molecular mechanisms of the MDM2-mediated regulatory interactions: a conformational selection model of the MDM2 lid dynamics.

Directory of Open Access Journals (Sweden)

Gennady M Verkhivker

Full Text Available Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications and length of the lid. We found that the dynamic equilibrium between "closed" and "semi-closed" lid forms may be a fundamental characteristic of MDM2 regulatory interactions, which can be modulated by phosphorylation, phosphomimetic mutation as well as by the lid size. Our results revealed that these factors may regulate p53-MDM2 binding by fine-tuning the thermodynamic equilibrium between preexisting conformational states of apo-MDM2. In agreement with NMR studies, the effect of phosphorylation on MDM2 interactions was more pronounced with the truncated lid variant that favored the thermodynamically dominant closed form. The phosphomimetic mutation S17D may alter the lid dynamics by shifting the thermodynamic equilibrium towards the ensemble of "semi-closed" conformations. The dominant "semi-closed" lid form and weakened dependence on the phosphorylation seen in simulations with the complete lid can provide a rationale for binding of small p53-based mimetics and inhibitors without a direct competition with the lid dynamics. The results suggested that a conformational selection model of preexisting MDM2 states may provide a robust theoretical framework for understanding MDM2 dynamics. Probing biological functions and mechanisms of MDM2

label.switching: An R Package for Dealing with the Label Switching Problem in MCMC Outputs

Directory of Open Access Journals (Sweden)

Panagiotis Papastamoulis

2016-02-01

Full Text Available Label switching is a well-known and fundamental problem in Bayesian estimation of mixture or hidden Markov models. In case that the prior distribution of the model parameters is the same for all states, then both the likelihood and posterior distribution are invariant to permutations of the parameters. This property makes Markov chain Monte Carlo (MCMC samples simulated from the posterior distribution non-identifiable. In this paper, the label.switching package is introduced. It contains one probabilistic and seven deterministic relabeling algorithms in order to post-process a given MCMC sample, provided by the user. Each method returns a set of permutations that can be used to reorder the MCMC output. Then, any parametric function of interest can be inferred using the reordered MCMC sample. A set of user-defined permutations is also accepted, allowing the researcher to benchmark new relabeling methods against the available ones.

Design of photonic phased array switches using nano electromechanical systems on silicon-on-insulator integration platform

Science.gov (United States)

Hussein, Ali Abdulsattar

This thesis presents an introduction to the design and simulation of a novel class of integrated photonic phased array switch elements. The main objective is to use nano-electromechanical (NEMS) based phase shifters of cascaded under-etched slot nanowires that are compact in size and require a small amount of power to operate them. The structure of the switch elements is organized such that it brings the phase shifting elements to the exterior sides of the photonic circuits. The transition slot couplers, used to interconnect the phase shifters, are designed to enable biasing one of the silicon beams of each phase shifter from an electrode located at the side of the phase shifter. The other silicon beam of each phase shifter is biased through the rest of the silicon structure of the switch element, which is taken as a ground. Phased array switch elements ranging from 2x2 up to 8x8 multiple-inputs/multiple-outputs (MIMO) are conveniently designed within reasonable footprints native to the current fabrication technologies. Chapter one presents the general layout of the various designs of the switch elements and demonstrates their novel features. This demonstration will show how waveguide disturbances in the interconnecting network from conventional switch elements can be avoided by adopting an innovative design. Some possible applications for the designed switch elements of different sizes and topologies are indicated throughout the chapter. Chapter two presents the design of the multimode interference (MMI) couplers used in the switch elements as splitters, combiners and waveguide crossovers. Simulation data and design methodologies for the multimode couplers of interest are detailed in this chapter. Chapter three presents the design and analysis of the NEMS-operated phase shifters. Both simulations and numerical analysis are utilized in the design of a 0°-180° capable NEMS-operated phase shifter. Additionally, the response of some of the designed photonic phased

Multi states electromechanical switch for energy efficient parallel data processing

KAUST Repository

Kloub, Hussam; Smith, Casey; Hussain, Muhammad Mustafa

2011-01-01

We present a design, simulation results and fabrication of electromechanical switches enabling parallel data processing and multi functionality. The device is applied in logic gates AND, NOR, XNOR, and Flip-Flops. The device footprint size is 2μm by 0.5μm, and has a pull-in voltage of 5.15V which is verified by FEM simulation. © 2011 IEEE.

Multi states electromechanical switch for energy efficient parallel data processing

KAUST Repository

Kloub, Hussam

2011-04-01

We present a design, simulation results and fabrication of electromechanical switches enabling parallel data processing and multi functionality. The device is applied in logic gates AND, NOR, XNOR, and Flip-Flops. The device footprint size is 2μm by 0.5μm, and has a pull-in voltage of 5.15V which is verified by FEM simulation. © 2011 IEEE.

Molecular insight into conformational transmission of human P-glycoprotein

International Nuclear Information System (INIS)

Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

2013-01-01

P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp

Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

Science.gov (United States)

Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

2014-03-01

Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

A Novel Four-Step Commutation for Bidirectional Switch Cells of AC-AC Matrix Converter

DEFF Research Database (Denmark)

Guo, Yougui; Zeng, Ping; Blaabjerg, Frede

2012-01-01

on or off of output current happens on the second and third steps. Here the second step is equal to the third one. This method is implemented with four steps by programming in VHDL language. First, the special flip-flop, 74AHC16373, is obtained by programming so as to make input sector signals, output...... sector ones and active switching time PWM ones synchronize. Second, the required switching states are flexibly realized in the form of the look-up table by programming in VHDL language for 36 switching combinations of input sectors with output ones. Third, the obtained switching states are judged whether...... they need commutation by delayers. Finally, the novel method proposed is implemented by switching sequencers. The simulation results have verified its feasibility....

Optimization of photovoltaic energy production through an efficient switching matrix

Directory of Open Access Journals (Sweden)

Pietro Romano

2013-09-01

Full Text Available This work presents a preliminary study on the implementation of a new system for power output maximization of photovoltaic generators under non-homogeneous conditions. The study evaluates the performance of an efficient switching matrix and the relevant automatic reconfiguration control algorithms. The switching matrix is installed between the PV generator and the inverter, allowing a large number of possible module configurations. PV generator, switching matrix and the intelligent controller have been simulated in Simulink. The proposed reconfiguration system improved the energy extracted by the PV generator under non-uniform solar irradiation conditions. Short calculation times of the proposed control algorithms allow its use in real time applications even where a higher number of PV modules is required.

Performance of highly connected photonic switching lossless metro-access optical networks

Science.gov (United States)

Martins, Indayara Bertoldi; Martins, Yara; Barbosa, Felipe Rudge

2018-03-01

The present work analyzes the performance of photonic switching networks, optical packet switching (OPS) and optical burst switching (OBS), in mesh topology of different sizes and configurations. The "lossless" photonic switching node is based on a semiconductor optical amplifier, demonstrated and validated with experimental results on optical power gain, noise figure, and spectral range. The network performance was evaluated through computer simulations based on parameters such as average number of hops, optical packet loss fraction, and optical transport delay (Am). The combination of these elements leads to a consistent account of performance, in terms of network traffic and packet delivery for OPS and OBS metropolitan networks. Results show that a combination of highly connected mesh topologies having an ingress e-buffer present high efficiency and throughput, with very low packet loss and low latency, ensuring fast data delivery to the final receiver.

Nearly reversible conformational change of amyloid fibrils as revealed by pH-jump experiments.

Science.gov (United States)

Yamaguchi, Kei-ichi; Kamatari, Yuji O; Fukuoka, Mayuko; Miyaji, Reiji; Kuwata, Kazuo

2013-10-01

pH-jump induced conformational transitions between substates of preformed amyloid fibrils made by a fragmented peptide of helix 2 (H2 peptide) of MoPrP were detected, and their kinetics were analyzed using a novel pH-jump apparatus specially designed for observing amyloids. Previously, we reported that H2 peptide formed ordered fibrils with a minimum at 207 nm on CD spectra at pH 2.9 (named pH 2.9 fibrils), but formed aggregate-like fibrils with a minimum at 220 nm at pH 7.5 (named pH 7.5 fibrils). When pH-jump from 2.9 to 7.5 was performed, the CD spectrum changed instantly, but the finally observed ellipticities were clearly distinct from those of pH 7.5 fibrils. Thus, the finally observed state is termed 'pH 7.5-like fibrils'. However, pH 7.5-like fibrils reverted to the conformation very similar to that of the pH 2.9 fibrils when the pH of the solution was restored to 2.9. Then, we examined the kinetics of the nearly reversible conformational changes between pH 2.9 fibrils and pH 7.5-like fibrils using ANS fluorescence stopped-flow, and we observed relatively fast phases (0.7-18 s(-1)). In contrast, the conversion between pH 7.5-like fibrils and pH 7.5 fibrils never occurred (<0.2 day(-1)). Thus, H2 fibrils can be switched readily between distinct conformations separated by a low energy barrier, while a large energy barrier clearly separated the different conformations. These conformational varieties of amyloid fibrils may explain the physical basis of the diversity in prion.

Simulation of the Plasma Afterglow in the Discharge Gap of a Subnanosecond Switch Based on an Open Discharge in Helium

Science.gov (United States)

Alexandrov, A. L.; Schweigert, I. V.

2018-05-01

The phenomenon of subnanosecond electrical breakdown in a strong electric field observed in an open discharge in helium at pressures of 6-20 Torr can be used to create ultrafast plasma switches triggering into a conducting state for a time shorter than 1 ns. To evaluate the possible repetition rate of such a subnanosecond switch, it is interesting to study the decay dynamics of the plasma remaining in the discharge gap after ultrafast breakdown. In this paper, a kinetic model based on the particle-in-cell Monte Carlo collision method is used to study the dynamics of the plasma afterglow in the discharge gap of a subnanosecond switch operating with helium at a pressure of 6 Torr. The simulation results show that the radiative, collisional-radiative, and three-body collision recombination mechanisms significantly contribute to the afterglow decay only while the plasma density remains higher than 1012 cm-3; the main mechanism of the further plasma decay is diffusion of plasma particles onto the wall. Therefore, the effect of recombination in the plasma bulk is observed only during the first 10-20 μs of the afterglow. Over nearly the same time, plasma electrons become thermalized. The afterglow time can be substantially reduced by applying a positive voltage U c to the cathode. Since diffusive losses are limited by the ion mobility, the additional ion drift toward the wall significantly accelerates plasma decay. As U c increases from 0 to +500 V, the characteristic time of plasma decay is reduced from 35 to 10 μs.

Covariant Conformal Decomposition of Einstein Equations

Science.gov (United States)

Gourgoulhon, E.; Novak, J.

It has been shown1,2 that the usual 3+1 form of Einstein's equations may be ill-posed. This result has been previously observed in numerical simulations3,4. We present a 3+1 type formalism inspired by these works to decompose Einstein's equations. This decomposition is motivated by the aim of stable numerical implementation and resolution of the equations. We introduce the conformal 3-``metric'' (scaled by the determinant of the usual 3-metric) which is a tensor density of weight -2/3. The Einstein equations are then derived in terms of this ``metric'', of the conformal extrinsic curvature and in terms of the associated derivative. We also introduce a flat 3-metric (the asymptotic metric for isolated systems) and the associated derivative. Finally, the generalized Dirac gauge (introduced by Smarr and York5) is used in this formalism and some examples of formulation of Einstein's equations are shown.

Realization of a four-step molecular switch in scanning tunneling microscope manipulation of single chlorophyll-a molecules

Science.gov (United States)

Iancu, Violeta; Hla, Saw-Wai

2006-01-01

Single chlorophyll-a molecules, a vital resource for the sustenance of life on Earth, have been investigated by using scanning tunneling microscope manipulation and spectroscopy on a gold substrate at 4.6 K. Chlorophyll-a binds on Au(111) via its porphyrin unit while the phytyl-chain is elevated from the surface by the support of four CH3 groups. By injecting tunneling electrons from the scanning tunneling microscope tip, we are able to bend the phytyl-chain, which enables the switching of four molecular conformations in a controlled manner. Statistical analyses and structural calculations reveal that all reversible switching mechanisms are initiated by a single tunneling-electron energy-transfer process, which induces bond rotation within the phytyl-chain. PMID:16954201

Conformal symmetry in two-dimensional space: recursion representation of conformal block

International Nuclear Information System (INIS)

Zamolodchikov, A.B.

1988-01-01

The four-point conformal block plays an important part in the analysis of the conformally invariant operator algebra in two-dimensional space. The behavior of the conformal block is calculated in the present paper in the limit in which the dimension Δ of the intermediate operator tends to infinity. This makes it possible to construct a recursion relation for this function that connects the conformal block at arbitrary Δ to the blocks corresponding to the dimensions of the zero vectors in the degenerate representations of the Virasoro algebra. The relation is convenient for calculating the expansion of the conformal block in powers of the uniformizing parameters q = i π tau

Statistical study of overvoltages by maneuvering in switches in high voltage using EMTP-RV

International Nuclear Information System (INIS)

Dominguez Herrera, Diego Armando

2013-01-01

The transient overvoltages produced by maneuvering of switches are studied in a statistical way and through a variation the sequential closing times of switches in networks larger than 230 kV. This study is performed according to time delays and typical deviation ranges, using the tool EMTP- RV (ElectroMagnetic Trasient Program Restructured Version). A conceptual framework related with the electromagnetic transients by maneuver is developed in triphasic switches installed in nominal voltages higher than 230 kV. The methodology established for the execution of statistical studies of overvoltages by switch maneuver is reviewed and evaluated by simulating two fictitious cases in EMTP-RV [es

MUFASA: the strength and evolution of galaxy conformity in various tracers

Science.gov (United States)

Rafieferantsoa, Mika; Davé, Romeel

2018-03-01

We investigate galaxy conformity using the MUFASA cosmological hydrodynamical simulation. We show a bimodal distribution in galaxy colour with radius, albeit with too many low-mass quenched satellite galaxies compared to observations. MUFASA produces conformity in observed properties such as colour, specific star formation rate (sSFR), and H I content, i.e. neighbouring galaxies have similar properties. We see analogous trends in other properties such as in environment, stellar age, H2 content, and metallicity. We introduce quantifying conformity using S(R), measuring the relative difference in upper and lower quartile properties of the neighbours. We show that low-mass and non-quenched haloes have weak conformity (S(R)≲ 0.5) extending to large projected radii R in all properties, while high-mass and quenched haloes have strong conformity (S(R)˜ 1) that diminishes rapidly with R and disappears at R ≳ 1 Mpc. S(R) is strongest for environment in low-mass haloes, and sSFR (or colour) in high-mass haloes, and is dominated by one-halo conformity with the exception of H I in small haloes. Metallicity shows a curious anticonformity in massive haloes. Tracking the evolution of conformity for z = 0 galaxies back in time shows that conformity broadly emerges as a late-time (z ≲ 1) phenomenon. However, for fixed halo mass bins, conformity is fairly constant with redshift out to z ≳ 2. These trends are consistent with the idea that strong conformity only emerges once haloes grow above MUFASA's quenching mass scale of ˜1012 M⊙. A quantitative measure of conformity in various properties, along with its evolution, thus represents a new and stringent test of the impact of quenching on environment within current galaxy formation models.

Conformational Entropy of FK506 Binding to FKBP12 Determined by Nuclear Magnetic Resonance Relaxation and Molecular Dynamics Simulations.

Science.gov (United States)

Solomentsev, Gleb; Diehl, Carl; Akke, Mikael

2018-03-06

FKBP12 (FK506 binding protein 12 kDa) is an important drug target. Nuclear magnetic resonance (NMR) order parameters, describing amplitudes of motion on the pico- to nanosecond time scale, can provide estimates of changes in conformational entropy upon ligand binding. Here we report backbone and methyl-axis order parameters of the apo and FK506-bound forms of FKBP12, based on 15 N and 2 H NMR relaxation. Binding of FK506 to FKBP12 results in localized changes in order parameters, notably for the backbone of residues E54 and I56 and the side chains of I56, I90, and I91, all positioned in the binding site. The order parameters increase slightly upon FK506 binding, indicating an unfavorable entropic contribution to binding of TΔ S = -18 ± 2 kJ/mol at 293 K. Molecular dynamics simulations indicate a change in conformational entropy, associated with all dihedral angles, of TΔ S = -26 ± 9 kJ/mol. Both these values are significant compared to the total entropy of binding determined by isothermal titration calorimetry and referenced to a reactant concentration of 1 mM ( TΔ S = -29 ± 1 kJ/mol). Our results reveal subtle differences in the response to ligand binding compared to that of the previously studied rapamycin-FKBP12 complex, despite the high degree of structural homology between the two complexes and their nearly identical ligand-FKBP12 interactions. These results highlight the delicate dependence of protein dynamics on drug interactions, which goes beyond the view provided by static structures, and reinforce the notion that protein conformational entropy can make important contributions to the free energy of ligand binding.

Software-Controlled Next Generation Optical Circuit Switching for HPC and Cloud Computing Datacenters

Directory of Open Access Journals (Sweden)

Muhammad Imran

2015-11-01

Full Text Available In this paper, we consider the performance of optical circuit switching (OCS systems designed for data center networks by using network-level simulation. Recent proposals have used OCS in data center networks but the relatively slow switching times of OCS-MEMS switches (10–100 ms and the latencies of control planes in these approaches have limited their use to the largest data center networks with workloads that last several seconds. Herein, we extend the applicability and generality of these studies by considering dynamically changing short-lived circuits in software-controlled OCS switches, using the faster switching technologies that are now available. The modelled switch architecture features fast optical switches in a single hop topology with a centralized, software-defined optical control plane. We model different workloads with various traffic aggregation parameters to investigate the performance of such designs across usage patterns. Our results show that, with suitable choices for the OCS system parameters, delay performance comparable to that of electrical data center networks can be obtained.

Efficient round-robin multicast scheduling for input-queued switches